***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Ifosfamide and cisplatin cause urinary loss of carnitine , which is a fundamental molecule for energy production in mammalian cells . We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients . Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry . Patients were excluded if they had anaemia or other conditions thought to be causing asthenia .  Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life question naire . Treatment consisted of oral levocarnitine 4 g daily , for 7 days . Fifty patients were enrolled ; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients . In the whole group , baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 ( ±6.4 ; st and ard deviation ) and the mean plasma carnitine value was 20.9 μM ( ±6.8 ; st and ard deviation ) . After 1 week , fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 ( ±5.4 ; st and ard deviation ) ( P<.001 ) . All patients achieved normal plasma carnitine levels . Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy . In selected patients , levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue . This compound deserves further investigations in a r and omised , placebo-controlled study We examined the effect of macronutrient content on  glomerular filtration rate ( GFR ) , and excretion , reabsorption , and filtered load of carnitine .  Ten subjects consumed five diets [ high protein ( HP ) , low protein ( LP ) , control , high fat ( HF ) , and high carbohydrate ( HC ) ] of equal energy and carnitine content for 6 d each , in a r and omized crossover manner . The rate of carnitine excretion was lower after the LP diet than after the HP diet because of lower GFR after the LP diet . The rate of carnitine reabsorption was lower after the LP diet than after the HP diet , also because of the lower GFR after the LP diet . The rate of carnitine reabsorption was not different after the HF and HC diets , nor was GFR . The filtered load of carnitine , however , was greater after the HF diet , result ing in a higher rate of carnitine excretion Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment . Dexmethylpheni date ( D-MPH ; the D-isomer of methylpheni date ) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment . A r and omized , double-blind , placebo-controlled , parallel-group study evaluated the potential therapeutic effect and safety of D-MPH in the treatment of patients with chemotherapy-related fatigue . Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale ( FACIT-F ) total score at Week 8 was the primary outcome measure . One hundred fifty-four patients ( predominantly with breast and ovarian cancers ) were r and omized and treated . Compared with placebo , D-MPH-treated subjects demonstrated a significant improvement in fatigue symptoms at Week 8 in the FACIT-F ( P=0.02 ) and the Clinical Global Impression-Severity scores ( P=0.02 ) , without clinical ly relevant changes in hemoglobin levels . Cognitive function was not significantly improved . There was a higher rate of study drug-related adverse events ( AEs ) ( 48 of 76 [ 63 % ] vs. 22 of 78 [ 28 % ] ) and a higher discontinuation rate because of AEs ( 8 of 76 [ 11 % ] vs. 1 of 78 [ 1.3 % ] ) in D-MPH-treated subjects compared with placebo-treated subjects . The most commonly reported AEs independent of study drug relationship in D-MPH-treated subjects were headache , nausea , and dry mouth , and in placebo-treated subjects were headache , diarrhea , and insomnia .  D-MPH produced significant improvement in fatigue in subjects previously treated with cytotoxic chemotherapy . Further studies with D-MPH or other agents to explore treatment response in chemotherapy-associated fatigue should be considered Summary Background . Fatigue can significantly interfere with a cancer patient ’s ability to fulfill daily responsibilities and enjoy life . It commonly co-exists with depression in patients undergoing chemotherapy , suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly assigned to receive either  20 mg of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine ( Paxil ® , SmithKline Beecham Pharmaceuticals ) or an identical-appearing placebo . Patients began their study medication seven days following their first on- study treatment and continued until seven days following their fourth on- study treatment . Seven days after each treatment , participants completed question naires measuring fatigue ( Multidimensional Assessment of Fatigue , Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist ) and depression ( Profile of Mood States-Depression subscale [ POMS-DD ] and Center for Epidemiologic Studies -Depression [ CES-D ] ) . Results . Repeated- measures ANOVAs , after controlling for baseline measures , showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D ( p=0.006 ) and the POMS-DD ( p=0.07 ) but not in reducing fatigue ( all measures , ps > 0.27 ) . Conclusions . Although depression was significantly reduced in the 44 patients receiving paroxetine  compared to the 50 patients receiving placebo , indicating that a biologically active dose was used , no significant differences between groups on any of the measures of fatigued were observed . Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment BACKGROUND & AIMS A phase III , r and omized non-inferiority study was carried out to compare a two-drug combination ( including nutraceuticals , i.e. antioxidants ) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome ( CACS ) : the primary endpoints were increase of lean body mass ( LBM ) and improvement of total daily physical activity . Secondary endpoint was : increase of physical performance tested by grip strength and 6-min walk test . METHODS Sixty eligible patients were r and omly assigned to : arm 1 , L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2 , L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day , all orally . All patients received as basic treatment polyphenols 300 mg/day , lipoic acid 300 mg/day , carbocysteine 2.7 g/day , Vitamin E , A , C. Treatment duration was 4 months . Planned sample size was 60 patients . RESULTS The results did not show a significant difference between tre atment arms in both primary and secondary endpoints . Analysis of changes from baseline showed that LBM ( by dual-energy X-ray absorptiometry and by L3 computed tomography ) increased significantly in both arms as well as physical performance assessed by 6MWT . Toxicity was quite negligible and comparable between arms . CONCLUSIONS The results of the present study showed a non-inferiority of arm 1 ( two-drug combination ) vs arm 2 ( two-drug combination + megestrol acetate ) . Therefore , this simple , feasible , effective , safe , low cost with favorable cost-benefit profile , two-drug approach could be suggested in the clinical practice to implement CACS treatment OBJECTIVE In April 2005 a phase III r and omized study was started to establish which was the most effective and safest treatment of cancer-related anorexia/cachexia syndrome and oxidative stress in improving identified primary endpoints : increase of lean body mass , decrease of resting energy expenditure ( REE ) , increase of total daily physical activity , decrease of interleukin-6 and tumor necrosis factor-alpha , and improvement of fatigue assessed by the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) . METHODS All patients were given as basic treatment polyphenols plus antioxidant agents alpha-lipoic acid , carbocysteine , and vitamins A , C , and E , all orally . Patients were then r and omized to one of the following five arms : 1 ) medroxyprogesterone acetate/megestrol acetate ; 2 ) pharmacologic nutritional support containing eicosapentaenoic acid ; 3 ) L-carnitine ; 4 ) thalidomide ; or 5 ) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide . Treatment duration was 4 mo . The sample comprised 475 patients . RESULTS By January 2007 , 125 patients , well balanced for all clinical characteristics , were included . No severe side effects were observed . As for efficacy , an interim analysis on 125 patients showed an improvement of at least one primary endpoint in arms 3 , 4 , and 5 , whereas arm 2 showed a significant worsening of lean body mass , REE , and MFSI-SF . Analysis of variance comparing the change of primary endpoints between arms showed a significant improvement of REE in favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor of arms 1 , 3 , and 5 versus arm 2 . A significant inferiority of arm 2 versus arms 3 , 4 , and 5 for the primary endpoints lean body mass , REE , and MFSI-SF was observed on the basis of t test for changes . CONCLUSION The interim results obtained thus far seem to suggest that the most effective treatment for cancer-related anorexia/cachexia syndrome and oxidative stress should be a combination regimen . The study is still in progress and the final results should confirm these data Increased cytokine expression contributes to the pathogenesis of cancer anorexia – cachexia syndrome . Carnitine may reduce inflammation in chronic diseases . We tested the effects of L-propionylcarnitine ( PC group ) or saline ( C group ) on food intake ( FI ) , body composition , and inflammatory status of MCA-sarcoma-bearing rats . On tumor appearance , rats were r and omly assigned to daily i.p . injection of L-propionylcarnitine ( 250 mg/kgBW/d ; n = 8) or saline ( equal volume ; n = 8) . FI and fat-free mass wasting improved in PC rats only ( p < .01 vs. controls ) . Cytokines ’ levels decreased in PC rats vs. controls ( p < .02 ) . Results suggest that carnitine may ameliorate cancer anorexia – cachexia , via reduction of the inflammatory status Background Cachexia , a > 10 % loss of body-weight , is one factor determining the poor prognosis of pancreatic cancer . Deficiency of L-Carnitine has been proposed to cause cancer cachexia . Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospect i ve , multi-centre , placebo-controlled , r and omized and double-blinded trial to receive oral L-Carnitine ( 4 g ) or placebo for 12 weeks . At entry patients reported a mean weight loss of 12 ± 2,5 ( SEM ) kg . During treatment body-mass-index increased by 3,4 ± 1,4 % under L-Carnitine and decreased ( −1,5 ± 1,4 % ) in controls ( p < 0,05 ) . Moreover , nutritional status ( body cell mass , body fat ) and quality -of-life parameters improved under L-Carnitine . There was a trend towards an increased overall survival in the L-Carnitine group ( median 519 ± 50 d versus 399 ± 43 d , not significant ) and towards a reduced hospital-stay ( 36 ± 4d versus 41 ± 9d , n.s . ) . Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinical ly relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine We investigated the effect of antioxidant supplementation on mitochondrial function , fat distribution , and lipid and glucose metabolism in HIV-1-infected patients with antiretroviral therapy (ART)-related lipoatrophy . 61 ART-treated HIV-1-infected patients with lipoatrophy were r and omized to receive either n-acetyl-L-carnitine ( n = 21 ) , lipoic acid + n-acetylcisteine ( LA/NAC ) ( n = 20 ) , or no supplementation ( n = 20 ) for 48 weeks . At baseline and at the end of treatment , mitochondrial function was studied by (13)C 
    Output:
    
The results of this process favored L-carnitine supplementation in patients with cancer-related cachexia .
Nitrogen balance was improved either through the increase of protein synthesis or by reduction in proteolysis , inhibiting apoptosis or reversing inflammatory processes .
Although clinical studies are inconclusive , studies in animal models support L-carnitine administration to prevent oxidative stress and ameliorate mitochondrial function .
L-carnitine supplementation leads to beneficial effects on several critical mechanisms involved in pathologic skeletal muscle loss and improved fatigue-related parameters in patients with cancer .