Lucia Zappi IRCCS Universitagrave San Martino IST

luciazappiistgeit

ldquohelliptutto ersquo una grande fatica Sembra assurdo ma anche solo pettinarmi o vestirmi richiede uno sforzo immane Scendere dal letto o andare al bagno egrave il massimo che possa fare Fare le faccende egrave veramente troppo non sarei neppure capace di sollevare lrsquoaspirapolverehelliprdquo

NCCN Definizione

Cancer related fatigue is a distressing persistent subjective sense of physical emotional andor cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning

La cancer-related fatigue egrave stata riconosciuta come

entitagrave nosologica a seacute stante dalla ICD 10 (X classificazione internazionale delle malattie)

Incidenza

78-96 della popolazione oncologica 50 prima del trattamento Aumenta durante il trattamento e persiste

anche dopo la terapia (17- 30 dei survivors)

Incidenza trattamento correlata

Chemioterapia 60-90 Radioterapia 65-100 Immunoterapia 70-81

Classificazione

GRADO 1 GRADO 2 GRADO 3 GRADO 4

Fatigue ingravescente ma non interferenza con le normali attivitagrave

Moderata incapacitagrave a svolgere alcune attivitagrave

Severa incapacitagrave a svolgere gran parte delle attivitagrave

Allettamento Grave disabilitagrave

NCI CTC 2004

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

ldquohelliptutto ersquo una grande fatica Sembra assurdo ma anche solo pettinarmi o vestirmi richiede uno sforzo immane Scendere dal letto o andare al bagno egrave il massimo che possa fare Fare le faccende egrave veramente troppo non sarei neppure capace di sollevare lrsquoaspirapolverehelliprdquo

NCCN Definizione

Cancer related fatigue is a distressing persistent subjective sense of physical emotional andor cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning

La cancer-related fatigue egrave stata riconosciuta come

entitagrave nosologica a seacute stante dalla ICD 10 (X classificazione internazionale delle malattie)

Incidenza

78-96 della popolazione oncologica 50 prima del trattamento Aumenta durante il trattamento e persiste

anche dopo la terapia (17- 30 dei survivors)

Incidenza trattamento correlata

Chemioterapia 60-90 Radioterapia 65-100 Immunoterapia 70-81

Classificazione

GRADO 1 GRADO 2 GRADO 3 GRADO 4

Fatigue ingravescente ma non interferenza con le normali attivitagrave

Moderata incapacitagrave a svolgere alcune attivitagrave

Severa incapacitagrave a svolgere gran parte delle attivitagrave

Allettamento Grave disabilitagrave

NCI CTC 2004

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

NCCN Definizione

Cancer related fatigue is a distressing persistent subjective sense of physical emotional andor cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning

La cancer-related fatigue egrave stata riconosciuta come

entitagrave nosologica a seacute stante dalla ICD 10 (X classificazione internazionale delle malattie)

Incidenza

78-96 della popolazione oncologica 50 prima del trattamento Aumenta durante il trattamento e persiste

anche dopo la terapia (17- 30 dei survivors)

Incidenza trattamento correlata

Chemioterapia 60-90 Radioterapia 65-100 Immunoterapia 70-81

Classificazione

GRADO 1 GRADO 2 GRADO 3 GRADO 4

Fatigue ingravescente ma non interferenza con le normali attivitagrave

Moderata incapacitagrave a svolgere alcune attivitagrave

Severa incapacitagrave a svolgere gran parte delle attivitagrave

Allettamento Grave disabilitagrave

NCI CTC 2004

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Incidenza

78-96 della popolazione oncologica 50 prima del trattamento Aumenta durante il trattamento e persiste

anche dopo la terapia (17- 30 dei survivors)

Incidenza trattamento correlata

Chemioterapia 60-90 Radioterapia 65-100 Immunoterapia 70-81

Classificazione

GRADO 1 GRADO 2 GRADO 3 GRADO 4

Fatigue ingravescente ma non interferenza con le normali attivitagrave

Moderata incapacitagrave a svolgere alcune attivitagrave

Severa incapacitagrave a svolgere gran parte delle attivitagrave

Allettamento Grave disabilitagrave

NCI CTC 2004

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Incidenza trattamento correlata

Chemioterapia 60-90 Radioterapia 65-100 Immunoterapia 70-81

Classificazione

GRADO 1 GRADO 2 GRADO 3 GRADO 4

Fatigue ingravescente ma non interferenza con le normali attivitagrave

Moderata incapacitagrave a svolgere alcune attivitagrave

Severa incapacitagrave a svolgere gran parte delle attivitagrave

Allettamento Grave disabilitagrave

NCI CTC 2004

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Classificazione

GRADO 1 GRADO 2 GRADO 3 GRADO 4

Fatigue ingravescente ma non interferenza con le normali attivitagrave

Moderata incapacitagrave a svolgere alcune attivitagrave

Severa incapacitagrave a svolgere gran parte delle attivitagrave

Allettamento Grave disabilitagrave

NCI CTC 2004

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

The impact of fatigue results of a survey by the Fatigue Coalition

Physical Impact Financial Impact Social and Emotional Impact

Difficulty in carryng out tasks 56

71 of patients lost one or more days of work

59 reported difficulty in socializing with friends and family

Difficulty in climbing stairs 56

31 lost an entire week of work

37 had difficulty in maintaing relationships

Difficulty in walking long distance 69

28 had to stop work 30 found intercourse with partner difficult

Difficulty in continuing exercise 67

A Iop Ann Oncol 2004

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

RILEVANZA CLINICA DELLA FATIGUE

Vogelzang NJ et al Semin Hematol 1997 34 (Suppl 2) 4-12

Lrsquoimportanza del trattamento di questo sintomo viene percepita in modo differente dal medico rispetto al paziente

0 20 40 60 80 100

Risposta ()

Oncologi

Pazienti

Fatigue

Dolore

Entrambi allo stesso modo

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Although fatigue is usually the most commonly reported adverse symptom during cancer therapy up until recently there was little effort directed at reducing fatigue before during or after cancer therapy

Von Roenn J H amp Paice J A

Control of common non-pain cancer symptoms Seminars in Oncology 32 200ndash210 - 2005

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

For clinical interventions to be effective patients with fatigue who would benefit from treatment must first be identified Vogelzang et al (1997) interviewed 419 cancer patients 50 did not discuss treatment options for fatigue with their oncologists only 27 reported that their oncologist offered treatment recommendations for their fatigue Curt et al (2000) similarly reported that 40 of patients with fatigue did not receive any treatment recommendations

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

bull fatigue severity temporal characteristics (eg onset duration) bull exacerbating and alleviating factors bull impact on functioning and quality of life symptom-related distress bull other symptoms pain menopausal symptoms sleep disturbances depression and cognitive dysfunction Since fatigue is a subjective sensation it is important to use validated standardised assessment instruments

Fatigue assessment

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

CANCER RELATED FATIGUE

Direct effects of cancer and tumour burden

Comorbid medical conditions bull Anemia bull Malnutrition bull Thyroid dysfunction bull Infection

Treatment side effects bull Chemotherapy bull Radiotherapy bull Surgery bull Medication sid effects

Exacerbating comorbid symptoms bull Chronic pain bull Sleep disturbances bull Deconditioning

Psychosocial factors bull Coping with chronic illness bull Anxiety bull Depression

Causes of fatigue (Atkinson et al 2002 Cella et al 1998 Portenoy and Itri 1999)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Meccanismi fisiopatologici

Peripheral fatigue originates in the muscles and related tissues( alterations in

adenosine triphosphate - ATP) Central fatigue develops in the central nervous system

Proposed mechanisms cytokine dysregulation hypothalamic-pituitary-adrenal (HPA) axis dysfunction 5 hydroxy tryptophan (5-HT) neurotransmitter

dysregulation circadian rhythm disruption and vagal afferent activation

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Cytokine Dysregulation

Proinflammatory cytokines such as interleukin (IL)-1β IL-6 and tumor necrosis factor (TNF)-α have been evaluated as markers of cancer-related fatigue

Specific cytokines may contribute to fatigue

through more specific pathways IL-1 and IL-6 and TNF-α have been shown to

suppress erythropoiesis TNF has been associated with alterations in

central nervous system neurotransmission interferon-γ can act as chachectins IL-6 have also been associated with depression

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Interventions

pharmacological interventions exercise behavioural management use of assistive devices lifestyle management nutritional support complementary or alternative therapy counselling

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

NCCN Guidelines Activity enhancement

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review

January 2000 and October 2006 English peer- reviewed nursing and health care journals age 18 or older literature search conducted in October 2006 using the

CINAHLreg Medlinereg Ovidreg and ProQuestreg databases

topics fatigue cancer and exercise Results 10 studies Sample size ranged from 12 to 108 Level of evidence moderate to high

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

focused question ldquoWhat is the relationship

between cancer treatment fatigue and exerciserdquo

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3

This systematic review considered the effect of

exercise on fatigue in patients with multiple myeloma breast lung prostate cancers both early and late stages of disease patients receiving chemotherapy or radiation

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

setting of interventions

home-based exercises (8 ) out-of home exercises (2)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Home-based exercise interventions

walking bicycling or swimming

RESULTS improvement in vigor and reduction in fatigue with a

trend toward improved body esteem Pinto 2005 improved sleep increased lean body weight and less

fatigue with exercise Coleman 2003 progressively increased time in minutes walked per day improved QOL and a significant decrease of fatigue

Courneya 2003 moderated aerobic exercise and resistance training

decreased the overall perception of fatigue Crowley 2003

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Out of home exercise interventions Controlled setting with professional instructors with a focus on

muscle strengthening flexibility and endurance Researchers found exercise to be well-tolerated and

feasible in a variety of malignancies No noticeable change in fatigue occurred but reported

bodily pain decreased Losito Murphy amp Thomas 2006 Improved physical and emotional well-being Borst 2005

Participation in a group exercise program was beneficial because patient support increased motivation

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Conclusions

Patients with cancer may be challenged to initiate and maintain an exercise program for more than 3 months without unswerving professional support

This support can be made more effective if the

recommended exercise program is regularly adjusted to the patientsrsquo health status and considers shifting hemoglobin levels vital signs respiratory health and subjective feelings that influence the outcomes of exercise

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Fatigue and the nutritional approaches

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

At the organism level cancer-associated fatigue involves the dysregulation of several interrelated physiological

biochemical and psychological systems At the tissue and cellular levels fatigue is

related to reductions in the efficiency of cellular energy systems mainly found in mitochondria

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants It results in oxidation of cellular structures such as membrane lipids and proteins and

mutation of nuclear DNA Maes M (2009) Inflammatory and oxidative and nitrosative

stress pathways underpinning chronic fatigue somatization and psychosomatic symptoms Current Opinions in Psychiatry 22 75ndash83

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

ROSRNS damage

Membrane oxidation induces permeability changes in mitochondria and this

loss of electron transport function essential requirement of mitochondrial oxidative phosphorylation (ATP)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

I Nutraceutici Acidi grassi polinsaturi essenziali (Omega 3

Omega 6) Acido Antranilico Acido ascorbico (o Vitamina C) Acido Folico (o Folacina o Vitamina M) Acido Lipoico (o Acido Tiottico o Vitamina N) Antocianine (o Antociani) Bioflavonoidi o (Flavonoidi o Vitamina C2) Caffeina L-Carnitina Carotenoidi Coenzima Q-10 (o Ubichinone o Vitamina Q) Colina (o Vitamina J) Creatina D-ribosio Ficocianine Fruttosio Glucosammina Inositolo (o Vitamina B7) Isoflavoni Licopene Lievito di birra Maltodestrine Octacosanolo Picnogenolo Policosanoli Proantocianidine (o PAC) Probiotici Resveratrolo Sali minerali (Calcio Cromo Fluoro Fosforo Iodio Magnesio Potassio Ferro Selenio Sodio Zinco) Steroli vegetali (o Fitosteroli) Taurina Teanina Teina Triptofano Vitamine 5-HTP (5-idrossitriptofano)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Lipid replacement therapy

NTFactorreg a lipid replacement oral

supplement containing phospholipids phosphoglycolipids cardiolipids

and other membrane lipids

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Ellithorpe R R Settineri R amp Nicolson G L (2003) Reduction of fatigue by use of a dietary supplement containing glycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28

NTFactor in patients with severe chronic fatigue

reduce their fatigue by approximately 405 in 8 weeks

405

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Nicolson G L Ellithorpe et al Lipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010

NTFactor plus vitamins minerals and other supplements

resulted in a 368 reduction in fatigue within 1 week

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III Study Ricardo A Cruciani 2006 Journal of Pain and Symptom Management

L-carnitine a micronutrient

important for the processing of long-chain fatty acids and energy production in mammalian cells

Dose escalation proceeded through all dose

levels (250 750 1250 1750 2250 2750 and 3000 mgdayrespectively)

mild nausea no other side effects

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Pharmacologic Treatment of Cancer-Related Fatigue Jennifer K Carroll The Oncologist 20071243-51

L-carnitine three studies open-label prospective designs with 12ndash50

participants Treatment with l-carnitine (500ndash600 mgday) for 1ndash4

weeks RESULTS increased plasma free carnitine concentrations

significantly improved fatigue and quality-of-life measures

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006

12 patients advanced tumors (50 at stage IV) mean age 60 y range 42ndash73 antineoplastic treatment L-Carnitina was administered orally at 6 gd for 4 wk outcome measures fatigue and quality of life in

relation to oxidative stress nutritional status and laboratory variables (reactive oxygen species glutathione peroxidase and proinflammatory cytokines)

Giulia Gramignano Nutrition Volume 22 February 2006

RESULTS Fatigue decreased significantly Nutritional variables (lean body mass and appetite)

increased significantly Levels of reactive oxygen species decreased and

glutathione peroxidase increased but not significantly

Proinflammatory cytokines did not change significantly

Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169 Garth L Nicolson AElig Kenneth A Conklin

Chemotherapy can displace important mitochondrial cofactors such as CoQ10

The concurrent administration of CoQ10 during chemotherapy can affect both acute and chronic cardiotoxicity caused by anthracyclines

Acute and chronic adverse effects of cancer chemotherapy can be reduced by molecular replacement of membrane lipids and enzymatic cofactors such as coenzyme Q10

Neuro Endocrinol Lett 2005 Dec26(6)745-51 In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation Maes M Mihaylova I Leunis JC

omega3 poly-unsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA)

docosahexaenoic acid (DHA) CFS was accompanied by increased levels of omega6

PUFAs linoleic acid arachidonic acid (AA)

mono-unsaturated fatty acids (MUFAs) ie oleic acid

Neuro Endocrinol Lett 2005 Dec26(6)745-51 In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation Maes M Mihaylova I Leunis JC

omega3 poly-unsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA)

docosahexaenoic acid (DHA) CFS was accompanied by increased levels of omega6

PUFAs linoleic acid arachidonic acid (AA)

mono-unsaturated fatty acids (MUFAs) ie oleic acid

ω6-PUFA ω3-PUFA

Acido Linoleico Acido Linolenico

Acido Arachidonico Acido Eicosapentaenoico e decosaesaenoico

Lipoossigenasi Cicloossogenasi

LT Serie 5

Prostanoidi Serie 3

Diminuzione attivazione piastrine Vasodilatazione

Inibizione cascata infiammazione

Fosfolipidi di membrana

Ac Arachidonico libero

Lipoossigenasi

Cicloossogenasi LT

Serie 4 Prostanoidi

Serie 2

Fosfolipasi A2 e C

Prostanoidi Serie 3

PG serie 2

TX Serie 2

Immuno- soppressione Radicali Liberi Carcinogenesi

Neuro Endocrinol Lett 2005 Dec26(6)745-51 Maes M Mihaylova I Leunis JC

Results decreased availability of omega3 PUFAs plays a

role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS

The results suggest that patients with CFS should

respond favourably to treatment with omega3 PUFAs such as EPA and DHA

Neuro Endocrinol Lett 2005 Dec26(6)745-51 Maes M Mihaylova I Leunis JC

Results decreased availability of omega3 PUFAs plays a

role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS

The results suggest that patients with CFS should

respond favourably to treatment with omega3 PUFAs such as EPA and DHA

Serotonin and central nervous system fatigue nutritional considerations J Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S

Increases in brain 5-HT concentration have been associated with increased physical and perhaps mental fatigue during endurance exercise

Carbohydrate (CHO) or branched-chain amino acid

(BCAA) feedings may attenuate increases in 5-HT and improve performance

Good theoretical rationale and data exist but the

strength of evidence is presently weak

Cochrane Database of Systematic Reviews 2012

Types of participants

Adults 18 years or older Advanced progressive illness Clinically significant fatigue andor weight loss in the

latter stages of illness degenerative neurological conditions such as

multiple sclerosis Parkinsonrsquos disease and dementia

irreversible organ failure cancer with distant metastasis acquired immune deficiency syndrome

Cancer - identified five systematic reviews (116 studies with 17342 participants) bull pharmacological interventions eicosapentaenoic acid (EPA) amantadina carnitinaeritropoietina bull non pharmacological interventions exercise physical training medically assisted hydration psychosocial interventions

Types of outcome measure

Primary outcomes 1 Clinically significant improvements in fatigue 2 Improvements in quality of life 3 Withdrawals due to adverse events

Cancer fatigue Pharmacological interventions RESULTS

Dewey 2007 (five studies 587 participants) failed to provide sufficient evidence of a benefit to

the use of EPA (ac Eicosapentaenoico) over placebo for the management of fatigue in advanced cancer

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cochrane Database of Systematic Reviews 2012

Types of participants

Adults 18 years or older Advanced progressive illness Clinically significant fatigue andor weight loss in the

latter stages of illness degenerative neurological conditions such as

multiple sclerosis Parkinsonrsquos disease and dementia

irreversible organ failure cancer with distant metastasis acquired immune deficiency syndrome

Cancer - identified five systematic reviews (116 studies with 17342 participants) bull pharmacological interventions eicosapentaenoic acid (EPA) amantadina carnitinaeritropoietina bull non pharmacological interventions exercise physical training medically assisted hydration psychosocial interventions

Types of outcome measure

Primary outcomes 1 Clinically significant improvements in fatigue 2 Improvements in quality of life 3 Withdrawals due to adverse events

Cancer fatigue Pharmacological interventions RESULTS

Dewey 2007 (five studies 587 participants) failed to provide sufficient evidence of a benefit to

the use of EPA (ac Eicosapentaenoico) over placebo for the management of fatigue in advanced cancer

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Types of participants

Adults 18 years or older Advanced progressive illness Clinically significant fatigue andor weight loss in the

latter stages of illness degenerative neurological conditions such as

multiple sclerosis Parkinsonrsquos disease and dementia

irreversible organ failure cancer with distant metastasis acquired immune deficiency syndrome

Cancer - identified five systematic reviews (116 studies with 17342 participants) bull pharmacological interventions eicosapentaenoic acid (EPA) amantadina carnitinaeritropoietina bull non pharmacological interventions exercise physical training medically assisted hydration psychosocial interventions

Types of outcome measure

Primary outcomes 1 Clinically significant improvements in fatigue 2 Improvements in quality of life 3 Withdrawals due to adverse events

Cancer fatigue Pharmacological interventions RESULTS

Dewey 2007 (five studies 587 participants) failed to provide sufficient evidence of a benefit to

the use of EPA (ac Eicosapentaenoico) over placebo for the management of fatigue in advanced cancer

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer - identified five systematic reviews (116 studies with 17342 participants) bull pharmacological interventions eicosapentaenoic acid (EPA) amantadina carnitinaeritropoietina bull non pharmacological interventions exercise physical training medically assisted hydration psychosocial interventions

Types of outcome measure

Primary outcomes 1 Clinically significant improvements in fatigue 2 Improvements in quality of life 3 Withdrawals due to adverse events

Cancer fatigue Pharmacological interventions RESULTS

Dewey 2007 (five studies 587 participants) failed to provide sufficient evidence of a benefit to

the use of EPA (ac Eicosapentaenoico) over placebo for the management of fatigue in advanced cancer

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Types of outcome measure

Primary outcomes 1 Clinically significant improvements in fatigue 2 Improvements in quality of life 3 Withdrawals due to adverse events

Cancer fatigue Pharmacological interventions RESULTS

Dewey 2007 (five studies 587 participants) failed to provide sufficient evidence of a benefit to

the use of EPA (ac Eicosapentaenoico) over placebo for the management of fatigue in advanced cancer

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer fatigue Pharmacological interventions RESULTS

Dewey 2007 (five studies 587 participants) failed to provide sufficient evidence of a benefit to

the use of EPA (ac Eicosapentaenoico) over placebo for the management of fatigue in advanced cancer

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer fatigue Pharmacological interventions RESULTS Minton 2008 (51 studies 10296 participants) small but significant improvement in fatigue over

placebo with the psychostimulant drug methylphenidate

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer fatigue Pharmacological interventions RESULTS

Glaspy 2010 Although erythropoietin and darbepoetin showed

evidence of an effect over standard care or placebo

they are no longer recommended in practice for this use especially if haemoglobin concentration is above 12 gdL

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer fatigue Pharmacological interventions RESULTS

No benefits over placebo were seen for fatigue with the use of the antidepressant drug paroxetine nor with progestational steroids

Megestrol acetate can provide a small statistically

significant weight gain for people with cancer versus placebo

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer fatigue Non pharmacological interventions RESULTS Cramp 2008 (28 studies 2083 participants) supported the use of exercise in the management

of cancer related fatigue No recommendations can be made for specific

exercise interventions that might best manage fatigue in advanced stages of cancer

The optimal management of fatigue is likely to be different for those in the advanced stages of

a non curative illness as compared with those who are in the early stages of chronic disease

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Cancer fatigue Non pharmacological interventions RESULTS

Goedendorp 2009 (27 studies with 3324 participants) For people undergoing cancer treatment at any

disease stage found Insufficient evidence that psychosocial

interventions were beneficial for fatigue management

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427

Irsquom so Tired Biological and Genetic Mechanisms of Cancer related Fatigue Andrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427 As the science continues

to progress toward individualized medicine understanding the genetic dimensions of CRF will become increasingly important

in order to identify persons at risk for this debilitating symptom as well as targets

for intervention to alleviate it

• Il Controllo della FATIGUEFarmaconutrizione E terapia fisica
• Diapositiva numero 2
• NCCN Definizione
• Incidenza
• Incidenza trattamento correlata
• Classificazione
• The impact of fatigue results of a survey by the Fatigue Coalition
• RILEVANZA CLINICA DELLA FATIGUE
• Diapositiva numero 9
• Diapositiva numero 10
• Fatigue assessment
• Diapositiva numero 12
• Meccanismi fisiopatologici
• Cytokine Dysregulation
• Interventions
• Diapositiva numero 16
• NCCN GuidelinesActivity enhancement
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3 Treatment-Related Fatigue and Exercise in Patients with Cancer A Systematic Review
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• Anne-Marie Kuchinski MEDSURG NursingmdashMayJune 2009mdashVol 18No 3
• setting of interventions
• Home-based exercise interventions
• Out of home exercise interventions
• Conclusions
• Fatigue and the nutritional approaches
• Diapositiva numero 26
• Oxidative stress intracellular excess of reactive oxygen (ROS) and nitrogen (RNS) free radical species over intracellular antioxidants
• ROSRNS damage
• I Nutraceutici
• Lipid replacement therapy
• Ellithorpe R R Settineri R amp Nicolson G L (2003)Reduction of fatigue by use of a dietary supplement containingglycophospholipids Journal of the American Nutraceutical Association 6(1) 23ndash28
• Nicolson G L Ellithorpe et alLipid replacement therapy with a glycophospholipidndash antioxidantndashvitamin formulation significantly reduces fatigue within one week Journal of the American Nutraceutical Association 13(1) 11ndash15 2010
• Diapositiva numero 33
• Safety Tolerability and Symptom Outcomes Associated with L-Carnitine Supplementation in Patients with Cancer Fatigue and Carnitine Deficiency A Phase III StudyRicardo A Cruciani 2006 Journal of Pain and Symptom Management
• Pharmacologic Treatment of Cancer-Related FatigueJennifer K Carroll The Oncologist 20071243-51
• Efficacy of l-carnitine administration on fatigue nutritional status oxidative stress and related quality of life in 12 advanced cancer patients undergoing anticancer therapy Giulia Gramignano Nutrition Volume 22 February 2006
• Giulia Gramignano Nutrition Volume 22 February 2006
• Reversing mitochondrial dysfunction fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy Clin Exp Metastasis (2008) 25161ndash169Garth L Nicolson AElig Kenneth A Conklin
• Neuro Endocrinol Lett 2005 Dec26(6)745-51In chronic fatigue syndrome the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activationMaes M Mihaylova I Leunis JC
• Diapositiva numero 40
• Neuro Endocrinol Lett 2005 Dec26(6)745-51Maes M Mihaylova I Leunis JC
• Serotonin and central nervous system fatigue nutritional considerationsJ Mark Davis Am J Clin Nutr 200072(suppl)573Sndash8S
• Cochrane Database of Systematic Reviews 2012
• Types of participants
• Diapositiva numero 45
• Types of outcome measure
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigue Pharmacological interventions RESULTS
• Cancer fatiguePharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Cancer fatigueNon pharmacological interventionsRESULTS
• Irsquom so Tired Biological and Genetic Mechanisms of Cancer related FatigueAndrea Barsevick PhD Qual Life Res 2010 December 19(10) 1419ndash1427