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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intermittent claudication (IC) is defined by leg muscle pain, cramping and fatigue brought on by ambulation/exercise; relieved on rest; and caused by inadequate blood supply and is the primary symptom of peripheral arterial disease (PAD). PAD has a detrimental effect on the quality of life. PAD is a debilitating atherosclerotic disease of the lower limbs and is associated with an increased risk of cardiovascular morbidity and mortality. IC is an extremely important marker of atheroma. Up to 60% patients with IC have significant underlying coronary and/or carotid disease and 40% of all patients suffering from IC die or suffer a stroke within 5 years of presentation. The therapeutic intervention of IC essentially aims at providing symptomatic relief and reducing the systemic cardiovascular complications. Although exercise therapy is one of the most efficacious conservative treatments for claudication, the pharmacotherapeutic goals can be best achieved through an increase in the walking capacity to improve quality of life and a decrease in rates of amputation. In the development of treatment for IC, an aggressive non-pharmacological intervention and pharmacological treatment of the risk factors associated with IC are considered. In the next 2 years, the results of major trials of drugs that stabilize and regress atherosclerosis such as statins and angiotensin converting enzyme inhibitors, and anti-platelet agents, recombinant growth factors and immune modulators will be available for IC. Levocarnitine (l-carnitine) and a derivative, propionyl levocarnitine, are emerging agents that increase the pain-free walking and improve the quality of life in IC patients by working at the metabolism and exercise performance of ischemic muscles. This article provides a comprehensive review of the pathophysiology involved, diagnosis of IC and existing and emerging pharmacotherapies with rationale for their use in its treatment.
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PMID:Intermittent claudication: an overview. 1638 60

L-Carnitine (L-beta-hydroxy-gamma-N,N,N-trimethylaminobutyric acid) plays an essential role in fatty acid transport in the mitochondrion. Conditions that appear to benefit from exogenous supplementation of L-carnitine include anorexia, chronic fatigue, cardiovascular disease, hypoglycemia, male infertility, muscular myopathies, renal failure and dialysis. D-Carnitine is not biologically active and might interfere with the proper utilization of the L isomer, and so there are claims that the racemic mixture (DL-carnitine) should be avoided. Despite the fact that it is known about the systemic manifestations of oral intake of this compound, oral supplementation with DL-carnitine for treatment of primary and secondary carnitine deficiency syndromes has been used in Russia for 25 years. The purpose of the present review was to contrast the differences in pharmacokinetics, phannacodynamics, biochemistry, and toxicity between treatments of L- and DL-carnitine. There is some evidence that L-carnitine and D-carnitine compete for uptake in small intestine and tubular re-absorption in kidneys. After intestinal absorption, L- and D-carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle, and D-carnitine competitively depletes muscle level of L-carnitine. Whereas L-carnitine is found to be essential for the oxidation of fatty acids, D-carnitine causes a depletion of L-carnitine, and hindered fatty acid oxidation and energy formation. Pharmacological effects of carnitine are stereospecific, since L-carnitine was effective in various animals and clinical studies, while D- and DL-carnitine was found to be ineffective or toxic, for example, to muscle cells and to the myocardium. DL-Carnitine causes symptoms of myasthenia and cardiac arrhythmias, which disappeared after L-carnitine administration. Clinically toxic effect of D-carnitine was described in patients with renal failure on long-term haemodialysis, in adriamycin (doxorubicin) cardiotoxicity and in stable angina pectoris.
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PMID:[Stereopharmacology of carnitine]. 1649 28

Cancer-related fatigue (CRF) is either a symptom or a syndrome depending on criteria for diagnosis. CRF is present in 20% to 30% of long-term cancer survivors and 80% to 90% during treatment and at the end of life. Assessment requires determining the presence, severity, and interference with daily activities. Different descriptors for fatigue (eg, tiredness, lack of vigor) measure different patient experiences. Associated factors such as depression, pain, insomnia, dyspnea, anemia, and deconditioning worsen CRF and should be treated if present. Associated factors that contribute to the severity of fatigue differ depending on the stage of cancer. Pharmacologic interventions include recombinant erythropoietin, psychostimulants, corticosteroid, anti-inflammatory drugs other than steroids, and L-carnitine. Advances in the management of CRF will require an understanding of the underlying mechanism before target-specific therapies can be developed.
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PMID:Management of fatigue in cancer patients. 1683 40

Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous L-carnitine may hold promise as a treatment for this common symptom. Little is known about L-carnitine safety, tolerability, and dose-response in patients with cancer. We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous L-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials. Adult patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 microM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score > or =50 were entered by groups of at least three into a standard maximum tolerated dose design. Each successive group received a higher dose of L-carnitine (250, 750, 1250, 1750, 2250, 2750, 3000 mg/day, respectively), administered in two daily doses for 7 days. To compare symptom outcomes before and after supplementation, patients completed validated measures of fatigue (Brief Fatigue Inventory [BFI]), depressed mood (Center for Epidemiologic Studies Depression Scale [CES-D]), quality of sleep (Epworth Sleeplessness Scale [ESS]), and KPS at baseline and 1 week later. Of the 38 patients screened for carnitine levels, 29 were deficient (76%). Twenty-seven patients participated ("intention to treat, ITT") (17 males, 10 females), and 21 completed the study ("completers"); 17 of these patients ("responders," mean+/-[SD] age=57.9+/-15) had increased carnitine levels at the end of the supplementation period. The highest dose achieved was 3000 mg/day. No patient experienced significant side effects and no toxicities were noted. Analysis of all the patients accrued (ITT, n=27) showed a total carnitine increase from 32.8+/-10 to 54.3+/-23 microM/L (P<0.001) and free carnitine increase from 26.8+/-8 to 44.1+/-17 microM/L (P<0.001). BFI decreased significantly, from 66+/-12 to 39.7+/-26 (P<0.001); ESS decreased from 12.9+/-12 to 9+/-6 (P=0.001); and CES-D decreased from 29.2+/-12 to 19+/-12 (P<0.001). A separate analysis of the 17 "responders" showed a dose-response relationship for total- (r=0.54, P=0.03), free-carnitine (r=0.56, P=0.02) levels, and fatigue (BFI) scores (r=-0.61, P=0.01). These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/day and that positive effects may be more likely at relatively higher doses in this range. This study provides the basis for the design of future placebo-controlled studies of l-carnitine supplementation for cancer-related fatigue.
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PMID:Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. 1715 57

Fatigue is one of the conditions most frequently complained by the elderly. There are few effective treatment options for patients with chronic fatigue syndrome. To determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl L-carnitine (ALC), 96 aged subjects (>70 years, range 71-88) were investigated (50 females and 46 males; mean age 76.2+/-7.6 and 78.4+/-6.4 years, respectively). They met four or more of the Holmes major criteria or at least six of Fukuda minor criteria. Fatigue was measured with the Wessely and Powell [Wessely, S., Powell, R., 1989. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J. Neurol. Neurosurg. Psychiatry 52, 940-948] scores, with the fatigue severity scale. At the end of the treatment, we observed a decrease of physical fatigue: 6.2 (p<0.001), of mental fatigue: 2.8 (p<0.001), of severity fatigue: 21.0 (p<0.001) and improvements in functional status: 16.1 (p<0.001) and cognitive functions: 2.7 (p<0.001). By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain -27% versus -3% (p<0.05); prolonged fatigue after exercise: 51% versus -4% (p<0.0001); sleep disorders: 28% versus 4% (p<0.05); physical fatigue: 7 versus -0.5 (p<0.0001); mental fatigue: -3.3 versus 0.6 (p<0.0001); fatigue severity scale: -22.5 versus 1.2 (p<0.0001); functional status 17.1 versus 0.6 (p<0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5 (p<0.0001). Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions.
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PMID:Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. 1765 28

It has been widely established that patients with end-stage renal disease undergoing chronic haemodialysis therapy exhibit low endogenous levels of L-carnitine and elevated acylcarnitine levels; however, the clinical implication of this altered carnitine profile is not as clear. It has been suggested that these disturbances in carnitine homeostasis may be associated with a number of clinical problems common in this patient population, including erythropoietin-resistant anaemia, cardiac dysfunction, and dialytic complications such as hypotension, cramps and fatigue. In January 2003, the Centers for Medicare and Medicaid Services (USA) implemented coverage of intravenous L-carnitine for the treatment of erythropoietin-resistant anaemia and/or intradialytic hypotension in patients with low endogenous L-carnitine concentrations. It has been estimated that in the period of 1998-2003, 3.8-7.2% of all haemodialysis patients in the USA received at least one dose of L-carnitine, with 2.7-5.2% of patients receiving at least 3 months of supplementation for one or both of these conditions. The use of L-carnitine within Australia is virtually non-existent, which leads us to the question: Are Australian haemodialysis patients missing out? This review examines the previous research associated with L-carnitine administration to chronic dialysis patients for the treatment of anaemia, cardiac dysfunction, dyslipidaemia and/or dialytic symptoms, and discusses whether supplementation is warranted within the Australian setting.
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PMID:L-carnitine supplementation in the dialysis population: are Australian patients missing out? 1819 95

The purpose of this study was to evaluate the effect of glycine propionyl-L-carnitine (GPLC) supplementation and endurance training for 8 wk on aerobic- and anaerobic-exercise performance in healthy men and women (age 18-44 yr). Participants were randomly assigned to 1 of 3 groups: placebo (n=9), 1 g/d GPLC (n=11), or 3 g/d GPLC (n=12), in a double-blind fashion. Muscle carnitine (vastus lateralis), VO(2peak), exercise time to fatigue, anaerobic threshold, anaerobic power, and total work were measured at baseline and after an 8-wk aerobic-training program. There were no statistical differences (p> .05) between or within the 3 groups for any performance-related variable or muscle carnitine concentrations after 8 wk of supplementation and training. These results suggest that up to 3 g/d GPLC for 8 wk in conjunction with aerobic-exercise training is ineffective for increasing muscle carnitine content and has no significant effects on aerobic- or anaerobic-exercise performance.
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PMID:Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance. 1827 31

The concept of L-carnitine (L-CAR) supplementation to improve muscular performance is based on the role of L-CAR in regulating aerobic metabolism. L-CAR has also been found to attenuate free radical-induced oxidative stress in various pathological conditions. Thus, it was hypothesized that L-CAR may reduce intermittent hypoxia (IH)-induced oxidative stress and thereby benefit skeletal muscle performance. Thirty-six adult male Sprague-Dawley rats were divided into three groups: unexposed control; IH exposed (6 h day(-1) for 7 consecutive days), IH exposed with L-CAR supplementation (100 mg (kg body weight)(-1) day(-1)). Electrical stimulation was used to induce six tetanic muscular contractions in the gastrocnemius muscle after completion of exposure. Percentage mean performed work (PW), time of decay to 50% peak force of contraction (T50), and peak force of contraction (FPeak) were measured during tetanic contractions. Mean frequency (MF) was measured using electromyography between tetanic contractions. Muscle damage was indirectly measured from plasma creatine kinase (CK) and lipid hydroperoxide (LHP) levels. The levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC) and LHP were estimated in the muscle tissue to investigate the efficacy of L-CAR in attenuating oxidative stress. Significant reduction in TBARS, PC and LHP levels and CK activity in the L-CAR-supplemented IH group as compared to the IH placebo group suggests that L-CAR reduces oxidative damage and thereby delays muscular fatigue, which was evident from MF, T50, PW and FPeak. From these studies, we conclude that L-CAR delays muscle fatigue by the reducing free radical-induced oxidative damage of IH exposure.
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PMID:L-carnitine supplementation attenuates intermittent hypoxia-induced oxidative stress and delays muscle fatigue in rats. 1856 3

Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly improved FACT-An functional well-being subscale (P<0.03), and KPS (P<0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients.
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PMID:L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. 1880 75

The use of nutritional supplements in sport is widespread and few serious athletes do not, at some stage in their career, succumb to the temptation to experiment with one or more nutritional supplements. Nutritional ergogenic aids are aimed primarily at enhancing performance (either by affecting energy metabolism or by an effect on the central nervous system), at increasing lean body mass or muscle mass by stimulation of protein synthesis and at reducing body fat content. Although not strictly ergogenic (i.e. capable of enhancing work performance), supplements aimed at increasing resistance to infection and improving general health are seen by athletes as important in reducing the interruptions to training that minor illness and infection can cause. Creatine is perhaps the most widely used supplement in sport at the moment. Supplementation can increase muscle creatine phosphate levels and, although not all published studies show positive results, there is much evidence that performance of short-term high-intensity exercise can be improved by supplementation. Ingestion of large doses of bicarbonate can enhance performance of exercise where metabolic acidosis may be a limiting factor, but there is a significant risk of adverse gastrointestinal side effects. Caffeine can also improve performance, in part by a stimulation of fatty acid mobilization and sparing of the body's limited carbohydrate stores, but also via direct effects on muscle and possibly by central nervous system effects on the perception of effort and fatigue. Carnitine plays an essential role in fatty acid oxidation in muscle but, although supplements are used by athletes, there is no good evidence of a beneficial effect of supplementation. None of these products contravenes the International Olympic Committee regulations on doping in sports, although caffeine is not permitted above a urine concentration of 12 mg/l. Supplementation is particularly prevalent among strength and power athletes, where an increase in muscle mass can benefit performance. Protein supplements have not been shown to be effective except in those rare cases where the dietary protein intake is otherwise inadequate. Individual amino acids, especially ornithine, arginine and glutamine, are also commonly used, but their benefit is not supported by documented evidence. Cr and hydroxymethylbutyrate are also used by strength athletes, but again there are no well-controlled studies to provide evidence of a beneficial effect. Athletes use a wide variety of supplements aimed at improving or maintaining general health and vitamin and mineral supplementation is widespread. There is a theoretical basis, and limited evidence, to support the use of antioxidant vitamins and glutamine during periods of intensive training, but further evidence is required before the use of these supplements can be recommended.
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PMID:Nutritional ergogenic aids and exercise performance. 1908 54


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