Carnitine 1000 + BCAA Orange Cream by GNC Pro Performance

POSSIBLY EFFECTIVE

• Hepatic encephalopathy. Oral and intravenous BCAAs improve symptoms and nutritional status in patients with hepatic encephalopathy, especially in those not tolerating protein supplementation. Details: Taking BCAAs 240 mg/kg (up to 25 grams) daily in 3 divided doses for up to 3 months can improve symptoms, liver function tests, and nitrogen balance in patients with chronic hepatic encephalopathy (68,69,82,690,92643,97531). Oral BCAAs are recommended for malnourished patients with chronic hepatic encephalopathy who cannot tolerate protein supplementation (69,4274). When the enteral route is unavailable and when patients cannot tolerate general purpose amino acid solutions, intravenous solutions with BCAAs can be used for nutritional support; however, most patients can tolerate standard amino acid mixtures (4274). Some clinical research also suggests that taking BCAAs orally improves psychomotor function, attention, intelligence, and driving ability in patients with latent hepatic encephalopathy (684,685,37131,97531). However, not all studies show a positive effect of BCAAs on psychometric outcomes (37135). There is also some preliminary evidence that intravenous BCAAs might be helpful for reversing coma in acute hepatic encephalopathy, although findings are conflicting (66,81,686,687,688,689,4274,37134). BCAAs do not appear to reduce the risk of mortality or improve quality of life in patients with hepatic encephalopathy (92643,97531).
• Tardive dyskinesia. Oral BCAAs might reduce symptoms of tardive dyskinesia precipitated by antipsychotic drugs. Details: Taking BCAAs orally seems to reduce symptoms of tardive dyskinesia (72,10146,13307). Clinical research in adult and pediatric patients who are taking antipsychotic drugs shows that taking a drink containing BCAAs 222 mg/kg three times daily for 3 weeks reduces tardive dyskinesia movements by 30% to 60% when compared with placebo (10146,13307).

POSSIBLY INEFFECTIVE

• Liver cancer. Oral BCAAs do not seem to improve outcomes or reduce the risk for recurrence in patients with liver cancer. Details: A meta-analysis of the available clinical research, as well as individual clinical studies, in patients with hepatocellular carcinoma show that consuming up to 50 grams of BCAAs twice daily for up to 4 years does not improve survival, reduce tumor recurrence, or reduce the risk of complications such as ascites following liver resection when compared with a control group receiving no intervention (37143,92646,97532,105578). However, one small clinical study suggests that BCAAs may be beneficial in patients recently diagnosed with hepatocellular carcinoma that does not require surgery. Taking two packets of a specific supplement (Aminoleban EN) daily containing a total of L-leucine 4 grams, L-isoleucine 3.8 grams, and L-valine 3.2 grams, starting two weeks before receiving transcatheter arterial chemoembolization and radiofrequency ablation and continuing for up to 5 years, reduces recurrence of liver cancer and increases event-free survival when compared with placebo (97533). However, the validity of these findings is limited by the high withdrawal rate in this study.

LIKELY INEFFECTIVE

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Overall, oral BCAAs are not beneficial and might even lead to worsened outcomes in patients with ALS. Details: Although early studies have indicated that taking BCAAs might be beneficial in ALS, more recent studies show no benefit and a possible increased loss of pulmonary function and higher rate of mortality among patients using BCAAs (678,679,680,681,37154).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if dietary BCAAs prevent Alzheimer disease. Details: Observational research has found that higher blood levels of BCAAs are associated with an 11% to 13% lower risk of Alzheimer disease; however, when research was adjusted for mortality, body mass index, and concomitant cholesterol-lowering medications, the association was no longer significant (100469).
• Athletic performance. Small clinical trials suggest that although oral BCAAs may not enhance athletic performance, they may modestly reduce perceived exertion and fatigue with some forms of exercise. Details: In most studies, taking BCAAs orally does not enhance athletic performance (692,1135,37080,37094,37106,37123,37141,37142,37151,92641). For instance, BCAAs do not appear to improve strength or work power or to reduce completion times for long-distance running or cycling trials (692,37106,37112,37141,37142,92641). However, most research shows that BCAAs are beneficial for reducing exercise-induced fatigue and perceived exertion after prolonged or intense exercise, exercise in the heat, or exercise following glycogen depletion (692,37112,37124,37144,92642,92644,92645,92648,97529,97530)(97535,105582). In many cases, this improvement is observed when BCAAs are taken in combination with arginine, citrulline, or green tea powder (37124,92642,92645,92648,97529,100462). However, some conflicting evidence exists (1135,37080,37094). Overall, the validity of these findings is limited because most studies differ widely in the amount and type of product consumed. For example, studied doses included BCAAs 0.17-0.3 mg/kg daily; or valine 0.5-1.7 grams, leucine 1-3.5 grams, and isoleucine 0.48-2.1 grams given before and/or after exercise (37108,37123,92642,92644,92645). Other limitations include variability in the studied endpoints and control comparisons used.
• Bipolar disorder. It is unclear if oral BCAAs are beneficial in patients with bipolar disorder. Details: One small clinical study shows that consuming a tyrosine-free amino acid drink containing 60 grams of the BCAAs leucine, isoleucine, and valine in a ratio of 3:3:4, reduces acute manic symptoms within 6 hours when compared with placebo. When taken daily for 7 days, it seems to continue to improve symptoms over a 2-week period (10117).
• Cachexia. Small clinical studies suggest that oral BCAAs are beneficial in patients with cachexia from various causes. Details: Preliminary clinical research in elderly malnourished patients receiving hemodialysis shows that taking a combination of BCAAs 4 grams three times daily improves appetite and caloric intake and increases plasma albumin levels and anthropometric measurements when compared with placebo (10147). Also, small clinical studies in adults with cachexia due to cancer or cirrhosis show that taking oral BCAAs 2.4 grams twice daily for 1 year or 4.8 grams 3 times daily for 1 week might be helpful when compared to baseline (71,37090). This finding is limited by the lack of a comparator group. A small clinical study in adults with congestive heart failure who have lost at least 7.5% of dry weight over the past 6 months or have a body mass index below 20 kg/m² shows that taking BCAAs 10 grams every evening at bedtime for 8 weeks improves physical and emotional quality of life scores, appetite, and fatigue when compared with placebo. Patients taking melatonin 20 mg nightly in addition to BCAA supplementation observed greater improvements in appetite and fatigue when compared with placebo (108478). However, a statistical comparison of outcomes between the groups taking BCAA alone or BCAA with melatonin was not provided.
• Cancer. It is unclear if dietary BCAA consumption improves cancer-related mortality. Details: Observational research in adults has found that consuming BCAAs 19 grams or more daily as part of the diet is not associated with a reduced risk of cancer-related mortality when compared with a lower dietary BCAA intake of less than 7.8 grams daily (108467). The validity of this finding is limited due to unclear reporting; additionally, dietary intake was recorded from a single survey.
• Cardiovascular disease (CVD). It is unclear if dietary BCAA consumption reduces the risk of CVD-related mortality. Details: Observational research in adults has found that CVD-related mortality is not associated with dietary BCAA intake or with individual leucine, isoleucine, or valine intake (108467). The validity of this meta-analysis is limited due to unclear reporting; additionally dietary intake was recorded from a single survey.
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral BCAAs can improve physical performance in adults with COPD. Details: A clinical study in adults with stable, stage 2 or 3 COPD undergoing a pulmonary rehabilitation program shows that taking a BCAA powder 4.3 grams, diluted in water and consumed once daily for 4 weeks, may improve recovery after exercise, but does not impact maximal exercise capacity, functional and muscular performance, or quality of life when compared with placebo (108464). The validity of these findings is limited due to the short duration of treatment.
• Cirrhosis. Most small studies suggest that BCAAs may modestly improve certain measures in some patients with liver cirrhosis. Details: One small clinical study shows that although taking BCAAs 14.4 grams daily for 12 months does not improve survival or liver function in patients with advanced liver cirrhosis, the number of hospitalizations and prevalence of cachexia are reduced and quality of life is improved when compared with control or whey protein (37090). A clinical study in patients with sarcopenia and liver cirrhosis shows that taking BCAAs 7.2 grams for 6 months decreases bilirubin levels and improves Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores when compared with baseline (108468). Although the study enrolled a control group (whey protein), the investigators did not provide a statistical comparison of outcomes between groups. In addition, a small study in Japanese patients with cirrhosis shows that taking BCAAs 12.45 grams daily for at least 12 months improves liver function and reduces liver complications by 50% to 60% over 3-5 years when compared with control (37120). Also, taking a specific product (Livact, Samil Pharmaceutical) providing the same dose for 11-22 months improves liver function by a small to moderate amount over a 24-month period when compared with not taking BCAAs. There was also a moderate reduction in the rate of developing or worsening major complications such as ascites or hepatic encephalopathy (103351). However, some research providing BCAAs as part of a late evening snack has found no benefit. In one small study, consuming BCAAs as part of a late evening snack in an undefined dose for 3 months does not seem to improve quality of life when compared with a late evening snack without BCAAs (37101). Also, a very small clinical study in patients with abnormal glucose metabolism related to cirrhosis shows that consuming BCAAs in an undefined dose as part of a late evening snack for 1 week does not improve glycemic control when compared with baseline. Instead, glucose levels increased in some patients (103348). It is possible that the doses provided in these latter studies were lower than those used in the studies showing benefit. Additionally, these very small studies may not have been adequately powered to detect a difference between groups.
• Colorectal cancer. It is unclear if dietary BCAAs are beneficial or harmful in patients with colorectal cancer. Details: An observational study in Italy has found that increased dietary intake of BCAAs is associated with a lower risk of developing sigmoid colon cancer, but not overall colorectal cancer risk, when compared with lower intake (105584). However, there's some concern that increased dietary BCAAs may have negative effects in patients who have been diagnosed with colorectal cancer. Observational research in patients living in the US has found that higher dietary intake of BCAAs is associated with a slightly higher risk of all-cause mortality when compared with lower intake (105581).
• Dementia. It is unclear if dietary BCAAs help to prevent dementia. Details: Observational research has found that higher blood levels of BCAAs are associated with a 13% to 17% lower risk of dementia. The lowered risk was maintained when research was adjusted for mortality, body mass index, and concomitant cholesterol-lowering medications (100469).
• Diabetes. It is unclear if dietary BCAAs reduce the risk for developing diabetes. Details: Some population research in Japanese females has found a decreased risk of diabetes associated with higher intake of BCAAs (97543). However, other observational research in people from the US has found that increased dietary intake of BCAAs is associated with an increased risk of diabetes (97536). Reasons for the conflicting finding are not entirely clear. Some evidence suggests that the dietary pattern of BCAA intake, rather than the total intake, may influence the risk of diabetes. Also, there is some speculation that differences in gut microbiota may attribute to the observed differences in diabetes risk associated with BCAA intake (100465). Prospective clinical research is needed to determine whether this association is causal or correlative.
• Exercise-induced muscle damage. Small studies suggest that BCAAs might reduce some, but not all, markers of muscle damage caused by exercise. Details: A meta-analysis of small clinical studies shows that supplementation with BCAAs reduces creatine kinase (CK) levels 24 hours post-exercise, but not 48 hours post-exercise. Additionally, this analysis shows that lactate dehydrogenase (LDH) levels are not affected by BCAA supplementation (97534). The validity of this analysis was limited because baseline dietary protein consumption was not taken into consideration as a potential confounder. A separate meta-analysis of clinical research in trained male athletes performing various resistance exercises shows that taking BCAAs 0.2-1.76 grams/kg for 1-28 days improves CK levels immediately following exercise, and at 24 and 48 hours post-exercise, but does not reduce LDH levels at any timepoint, when compared with placebo or control (108469). Most doses of BCAAs studied consisted of a 2:1:1 ratio of leucine, isoleucine, and valine, respectively. The validity of these findings is limited due to the short duration of treatment and various doses studied. Small individual clinical trials show that taking BCAAs does not affect urinary myoglobin after a marathon nor plasma myoglobin or CK levels after isotonic muscular exercise (37123,92641,100471). The benefits of BCAAs might depend on baseline protein consumption. A small clinical study in resistance trained males shows that adding BCAAs 0.22 grams/kg (MusclePharm BCAA) daily for 8 days to a high daily protein consumption of 1.2 grams/kg does not attenuate muscle damage or improve muscle recovery when compared with placebo (100471). Conversely, a meta-analysis of clinical research in adults completing various exercises shows that taking BCAAs consisting of any combination of valine, leucine, and isoleucine ratios modestly reduces CK, LDH, and myoglobin 24 and 48 hours post-exercise, but does not improve muscle recovery or muscle force after exercise, when compared with placebo (108471). The validity of these findings is limited due to unclear reporting.
• Exercise-induced muscle soreness. Limited evidence suggests that oral BCAAs may modestly attenuate exercise-induced muscle soreness. Details: One meta-analysis shows that taking BCAAs does not reduce delayed-onset muscle soreness after exercise when assessed at the individual time points of 24, 48, or 72 hours (97534). However, when results of all time points are pooled together in two separate meta-analyses, supplementation modestly reduces soreness after exercise (97534,103353). Most, but not all, individual trials also show that taking BCAAs in various doses, such as 0.087 grams/kg or 5-10 grams before and/or after exercise, modestly reduces muscle soreness after exercise (37108,37123,37124,92648,97530,97535,100467,100471,103346,108471). The validity of these individual trials is limited by their small sample sizes, variable dosing regimens, and enrolled populations, which were mainly limited to young untrained adult males (97534,103353). A separate meta-analysis of clinical research in trained male athletes performing various resistance exercises shows that taking BCAAs 0.2-1.76 grams/kg for 1-28 days may improve muscle soreness during the first 24 hours after exercise, but not at 24 or 48 hours post-exercise, when compared with placebo or control (108469). The validity of these findings is limited due to the short duration of treatment and various doses studied. Also, it is not clear whether taking BCAAs before or after a workout may be more beneficial. Some research found a nonsignificant trend toward reduced muscle soreness when consuming a specific product (Aminofeel, Seikatsu Bunkasya Co. Ltd.) containing BCAAs 3.2 grams three times daily starting 3 days before working out and continuing 3 days after, when compared to control (100467). More research is needed to determine the best dosing regimen and which populations, if any, may benefit.
• Heart failure. It is unclear if oral BCAAs are beneficial in patients with heart failure. Details: A small clinical study in patients with heart failure and hypoalbuminemia shows that taking a specific packet of BCAA granules (LIVACT, Ajinomoto Co) containing L-valine 1144 mg, L-leucine 1904 mg, and L-isoleucine 952 mg, three times daily for at least 7 days and stopping after discharge from the hospital, does not affect serum albumin or cardiothoracic ratio (CTR) when compared with placebo (100470). It is possible that this study was underpowered to detect differences between groups. Another small clinical study in adults with chronic heart failure participating in a cardiac rehabilitation program shows that taking a specific oral supplement (Meiji Mei Balance Rehasupport Mini; Meiji Group) containing BCAAs 2.5 grams and various vitamins, minerals, and whey protein, twice daily for 12 weeks increases fat mass, but has no effect on peak oxygen uptake, 6-minute walking distance, or strength parameters, when compared with no supplementation (108470). It is unclear if these effects are due to BCAAs, the other ingredients, or the combination.
• Hepatitis. It is unclear if oral BCAAs are beneficial in patients with hepatitis. Details: Preliminary clinical research in patients with alcoholic hepatitis shows that taking BCAAs 20 grams daily orally or enterally for 3 weeks or until discharge, in combination with a controlled diet, does not reduce the risk of mortality when compared with conventional protein or a controlled diet alone (37133).
• Inflammatory myopathies. It is unclear if oral BCAAs are beneficial in patients with polymyositis and dermatomyositis. Details: A small clinical study in adults with suspected or confirmed polymyositis or dermatomyositis who are receiving standard corticosteroid therapy shows that a BCAA-specific product containing L-isoleucine 952 mg, L-leucine 1904 mg, and L-valine 1144 mg for 12-28 weeks, taken as two packages three times daily for a total daily dose of 24 grams, does not improve manual muscle test scores or clinical response at 12 and 28 weeks when compared with placebo (108477).
• Obesity. It is unclear of oral BCAAs can reduce the likelihood of developing obesity or improve weight loss in adults with overweight or obesity. Details: Some observational research has found that higher dietary intake of BCAAs is associated with lower odds of obesity when compared with a lower intake (100466). Conversely, a large observational study in adults in Iran, including those who are overweight or obese, has found that the highest dietary intake of BCAAs is associated with a 24% higher likelihood of general obesity in males, but not in females, when compared with the lowest dietary BCAA intake (108465). This study did not report ranges for highest and lowest BCAA intake, limiting the validity of this study. BCAAs have also been evaluated in adults with overweight or obesity. A small clinical study in obese females that underwent a 4-week calorie-restricted diet shows that taking 6 caplets daily containing a total of L-leucine 3 grams, L-isoleucine 1.5 grams, and L-valine 1.5 grams in addition to vitamin B6 40 mg daily for 4 weeks does not further reduce weight, but may slightly preserve lean body mass, when compared with placebo (100464). Another small clinical study in overweight and obese adults shows that taking BCAAs 0.1 gram/kg daily in addition to starting a low-calorie diet for 16 weeks does not improve weight loss, but may preserve lean muscle mass, when compared with taking placebo while following the low-calorie diet (105583).
• Overall mortality. It is unclear if dietary BCAA consumption reduces the risk of all-cause mortality. Details: Observational research in adults has found that total BCAA intake, as well as isoleucine intake, is associated with a reduced risk of all-cause mortality, particularly in those with higher serum triglyceride concentrations (108467). However, this association was not present for leucine or valine intake. The validity of this meta-analysis is limited due to unclear reporting; additionally dietary intake was recorded from a single survey.
• Pancreatic cancer. The association between dietary BCAA intake and pancreatic cancer risk is unclear. Details: Observational research in adults in Italy has found that consuming BCAAs as part of the diet in quantities greater than 18 grams daily is associated with a 2-fold increased risk of pancreatic cancer when compared with less than 12 grams daily. This relationship was stronger in younger males, those with higher body mass indexes, and in those who smoke or have high alcohol intake (108476). Dietary information was recorded from a single, weekly consumption questionnaire.
• Phenylketonuria (PKU). It is unclear if oral BCAAs are beneficial in patients with PKU. Details: A small clinical trial in adolescents and young adults with PKU shows that taking BCAAs, consisting of valine 150 mg/kg, isoleucine 150 mg/kg, and leucine 200 mg/kg, with meals and at bedtime for up to 6 months seems to improve attention and processing when compared with a control group (37127).
• Physical performance. It is unclear if oral BCAAs are beneficial for improving physical function and muscle strength in older adults. Details: In malnourished elderly individuals, preliminary clinical research shows that taking a supplement providing BCAAs 5000 mg daily, in addition to other amino acids, vitamin B6, and vitamin B1 (Aminotrofic) for 2 months, does not improve muscle mass, muscle strength, or physical function to a greater extent than dietary advice intended to maximize nutritional intake from food and drink (103349). Similarly, a clinical study in middle aged and elderly adults shows that a specific product (Sarcojoint; Orient Euro Pharma, Inc) containing leucine 1 gram, arginine, vitamin D3, glucosamine, chondroitin, and calcium, taken twice daily in addition to regular resistance exercise for 12 weeks, does not improve muscle strength, muscle mass, or physical performance when compared with taking an unspecified vitamin B supplement twice daily with regular exercise (108472). Conversely, one small clinical study in older adults who have had a hip replacement shows that taking BCAAs 1.2 grams and lysine 1.8 grams (Amino-aile, Ajinomoto Co., Inc.) daily for one month after undergoing exercise therapy sessions modestly increases the strength of both legs and arms when compared with taking starch. However, there was no effect on hip abductor strength of the operated leg or on grip strength or measures of independence (103347).
• Postoperative infection. There is limited evidence on the intravenous and oral use of BCAAs for reducing infection after oncologic surgery. Details: A meta-analysis of 6 small heterogeneous clinical trials in patients after oncologic surgery, mostly for liver cancer, suggests that receiving oral or intravenous BCAAs reduces the risk of postoperative infection by 38% when compared with control (105577).
• Postoperative recovery. There is limited evidence on the intravenous and oral use of BCAAs for improving postoperative recovery after oncologic surgery. Details: A meta-analysis of small heterogeneous clinical trials in patients after oncologic surgery, mostly for liver cancer, suggests that receiving oral or intravenous BCAAs reduces hospital stay by about 2 days, but does not reduce mortality or post-operative complications, when compared with control (105577).
• Psychological well-being. It is unclear if oral BCAAs are beneficial for psychological well-being. Details: A cross-sectional observational study has found that higher dietary consumption of BCAAs is associated with a lower risk of anxiety and depression when compared with lower consumption (105579).
• Sarcopenia. It is unclear if oral BCAAs are beneficial in patients with primary sarcopenia or in those with sarcopenia related to liver cirrhosis. Details: A small clinical study in postmenopausal adults at risk for sarcopenia shows that consuming BCAAs 9 grams daily for 8 weeks in addition to resistance training increases strength and muscle mass when compared with baseline, but is no different than resistance training plus a placebo (105576). Another small clinical study in adults 65 years or older with sarcopenia shows that taking a supplement containing BCAAs 2500 mg, vitamin D 500 IU, protein, and other vitamins daily for 8 weeks in addition to resistance training does not improve physical function when compared with resistance training alone. The supplement did seem to slightly improve handgrip strength and body mass when compared with no supplementation (100468). However, overall the study was inadequately powered to detect smaller effects on physical function and muscle mass. There is also interest in using BCCAs in patients with sarcopenia and liver cirrhosis. A clinical study in this population shows that taking BCAAs 7.2 grams (containing 1.2 grams of L-leucine, 600 mg of L-isoleucine, and 600 mg of L-valine) daily for 6 months improves handgrip strength, gait speed, and muscle mass when compared with baseline (108468). Although the study enrolled a control group (whey protein), the investigators did not provide a statistical comparison of outcomes between groups. A separate meta-analysis of low-quality clinical research in this population shows that taking BCAAs has no effect on handgrip strength when compared with no supplementation (108473). Although other outcomes were evaluated, results are inconclusive due to the limited number of studies available for each outcome.
• Spinocerebellar ataxia (SCA). It is unclear if oral BCAAs are beneficial in patients with SCA. Details: Although there is some preliminary clinical evidence that oral BCAAs might have a beneficial effect on symptoms of SCA (73), a small clinical crossover study shows that taking a particular BCAA compound (Livact) 4.5-18 grams daily for 4 weeks does not improve ataxia in patients with SCA when compared with placebo (37088).
• Stroke. It is unclear if oral BCAAs are beneficial in patients recovering from stroke. Details:A small nonblinded, clinical study in elderly patients with subacute stroke and sarcopenia currently undergoing intensive inpatient rehabilitation therapy shows that administering a specific product (Seniup; Enterogenomics Co) containing BCAAs 6 grams, given twice daily orally or by feeding tube for 1 month, modestly improves skeletal muscle index, dysphagia, gait, balance, and handgrip strength, and may attenuate muscle loss in affected upper and lower extremities, when compared with rehabilitation alone (108474). The validity of these findings is limited by the short duration of treatment. Other research has compared BCAA dosing regimens. A small study in stroke patients taking part in exercise sessions shows that taking BCAAs 3.5 grams (Hepas, Clinico Co. Ltd) daily for 2 months with breakfast is more effective for improving leg strength and balance than when taken post-exercise in the mid-afternoon. However, there were no differences in most measures of strength or in skeletal muscle mass (103352). More evidence is needed to rate BCAAs for these uses.

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

EFFECTIVE

• L-carnitine deficiency. Oral and intravenous L-carnitine can treat primary and secondary L-carnitine deficiency. Details: Administering L-carnitine orally or intravenously is effective for acute or chronic treatment of primary L-carnitine deficiency or secondary L-carnitine deficiency due to inborn errors of metabolism. This is an FDA-approved indication for L-carnitine (4949,58611,59018). For primary or secondary deficiencies, oral L-carnitine 990 mg 2-3 times daily is used. For inborn errors of metabolism resulting in secondary L-carnitine deficiency, L-carnitine 50 mg/kg given as a slow (2-3 minute) bolus injection or by infusion followed by 50 mg/kg administered in divided doses every 3-4 hours over the next 24 hours is also used. Subsequent daily maintenance doses of intravenous L-carnitine are usually around 50 mg/kg (3616).

POSSIBLY EFFECTIVE

• Angina. Oral and intravenous L-carnitine may improve exercise tolerance and symptoms of angina during exercise in patients with angina. Details: Several small clinical trials in patients with chronic stable angina or cardiac syndrome X show that taking L-carnitine orally or intravenously seems to improve exercise tolerance and time to onset of angina when compared with placebo (3623,3624,58156,59096,59118,59216,59217,59230). Oral doses of L-carnitine have ranged from 900 mg to 2 grams daily in single or divided doses for 2 weeks to 6 months (3623,3624,58156,59096,59118,59217). Intravenous L-carnitine 3 grams in 500 mL of 5% dextrose, administered once daily for 14 days (59230), or intravenous DL-carnitine 40 mg/kg administered 30 minutes prior to exercise (59216) have also been used.
• Congestive heart failure (CHF). Oral and intravenous L-carnitine may improve exercise capacity and symptoms of heart failure in patients with CHF. Details: Several small clinical trials in patients with CHF show that taking L-carnitine 1.5-3 grams daily in single or divided doses for up to 34 months or administering intravenous L-carnitine 5 grams daily for 7 days seems to improve symptoms and increase exercise capacity when compared with placebo (3625,3626,58145,58771,58824). Also, taking a specific combination product containing L-carnitine 2250 mg and coenzyme Q10 270 mg (Carni Q-Gel, Tishcon Corporation) daily for 12 weeks appears to improve symptoms of CHF when compared with no treatment (58392).
• Hyperlipidemia. Oral or intravenous L-carnitine may slightly improve lipid levels. Oral, but not intravenous, L-carnitine may also improve lipoprotein(a) levels in patients with elevated lipoprotein(a). Details: Most meta-analyses of clinical research in patients with or without hyperlipidemia show that L-carnitine, given orally at a dose of 76 mg to 3 grams daily or intravenously at a dose of 15-20 mg/kg three times weekly, appears to reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels by up to 9.5 mg/dL, 8.3 mg/dL, and 11.2 mg/dL, respectively, while increasing high-density lipoprotein (HDL) cholesterol by up to 1.6 mg/dL. Sub-analyses in patients with elevated levels of specific lipids shows that L-carnitine might be most beneficial in these populations (95073,102019,111886). However, clinical research is generally very low to moderate quality. Also, any effects of L-carnitine on these lipids are modest and might not be considered clinically significant. An umbrella meta-analysis of meta-analyses of clinical research shows that taking L-carnitine orally reduces total cholesterol, LDL cholesterol, and triglyceride levels by only 1.1 mg/dL, 4.8 mg/dL, and 2.5 mg/dL, with increases in HDL cholesterol of 0.7 mg/dL (111896). More information is needed on the effects of L-carnitine on lipid levels specifically in patients with hyperlipidemia. Some research has also evaluated the benefits of L-carnitine in people with hyperlipidemia and elevated lipoprotein(a) levels or those undergoing hemodialysis. Preliminary clinical research and a meta-analysis of clinical research in these populations shows that taking L-carnitine 1-2 grams daily for 8-24 weeks reduces levels of lipoprotein(a) by about 9 mg/dL when compared with control (58155,95073). However, giving L-carnitine intravenously 1 gram three times weekly or 4 grams daily does not improve lipoprotein(a) levels in these patients (95073). Also, oral or intravenous L-carnitine does not improve LDL cholesterol, HDL cholesterol, or triglyceride levels in these patients (58155,95073). Whether L-carnitine reduces the risk of cardiovascular events in patients with hyperlipidemia is unknown.
• Kidney failure. Intravenous, but not oral, L-carnitine is FDA-approved for the prevention and treatment of L-carnitine deficiency in patients with kidney failure undergoing hemodialysis. Any other benefits with the use of L-carnitine in patients on hemodialysis are unclear. Details: Patients with kidney failure undergoing maintenance hemodialysis often experience L-carnitine deficiency, which can lead to lipid, red blood cell, cardiac muscle, and skeletal muscle abnormalities (26496). Use of intravenous L-carnitine for the prevention and treatment of L-carnitine deficiency in people with kidney failure who are undergoing hemodialysis is an FDA-approved indication for L-carnitine. L-carnitine 10-20 mg/kg is given as a slow (2-3 minute) bolus injection, with dose adjustments made based on subsequent pre-dialysis L-carnitine concentrations (3616). However, oral L-carnitine is not FDA-approved for this purpose. There is concern that long-term administration of high doses of oral L-carnitine may result in accumulation of toxic metabolites, including trimethylamine and trimethylamine-N-oxide, in patients with kidney failure (3616). Research in other areas are conflicting. Most clinical research shows that taking L-carnitine 0.7-3 grams or 10 mg/kg daily or administering L-carnitine 2-6 grams or 30-60 mg/kg weekly via intravenous infusion can improve cardiac function, intravenous fistula complications, red blood cell count, hemoglobin, and C-reactive protein levels in patients on hemodialysis (9790,26496,58257,58437,58842,59009,59178,111877). A meta-analysis of 18 clinical studies in adults with kidney-related anemia undergoing hemodialysis shows that receiving oral or intravenous L-carnitine reduces erythropoietin responsiveness and erythropoiesis stimulating agent (ESA) requirement, but not hemoglobin level, when compared with placebo or conventional therapy, regardless of treatment duration or route of administration (107406). Despite an earlier meta-analysis suggesting that L-carnitine does not reduce the incidence of dialysis-related hypotension or muscle cramping (58511), a more recent meta-analysis shows that L-carnitine reduces the incidence of dialysis-related hypotension by 74% when compared with placebo (111878). However, sub-analyses suggest that only oral L-carnitine, and doses of over 4.2 grams weekly for at least 12 weeks, are effective for preventing hypotension (111878). A meta-analysis and some preliminary clinical research also show that muscle cramping is reduced by up to 78% when compared with controls (104176,111878). Additionally, observational research has found that administering at least 1 gram of L-carnitine per dialysis session for at least 10 sessions monthly is associated with a 10% to 20% decrease in the number of hospitalization days during the subsequent month (58409). However, L-carnitine may not be beneficial for improving other measures in people with kidney failure receiving dialysis. While some research shows that L-carnitine decreases lipoprotein(a) levels (44187), low-density lipoprotein (LDL) cholesterol levels (26496,91723,107399), and total cholesterol levels (107399), most research shows that it does not improve serum lipid levels (9790,26496,44187,58257,58320,58842,58939,59009,59025,59031)(59036,59059,59080,90633,91723,107399). Additionally, while one small clinical trial shows that taking L-carnitine can improve performance on some exercise tests (104179), most research shows that L-carnitine does not improve respiratory function or exercise performance. The effect on quality of life is unclear (58154,58437,58472,58743,59031,90633,111867,111877).
• Male infertility. Oral L-carnitine, taken alone or in combination with acetyl-L-carnitine, may increase sperm motility in males with infertility, leading to a greater likelihood of pregnancy in female partners. Details: Although some clinical research has yielded conflicting results (58209,58588,59020,90627,111861), most clinical research shows that taking L-carnitine 1-3 grams daily in divided doses for up to 24 weeks, with or without acetyl-L-carnitine 1 gram daily, increases sperm count and motility, and improves sperm morphology, in males with infertility of various etiologies (12352,58167,58182,58194,58334,58469,58831,58849,59129,59189)(59190,101560,107394,111861,111459,111888,111890). However, it is unclear if taking L-carnitine increases the odds of pregnancy. One meta-analysis of randomized controlled trials shows that taking L-carnitine and acetyl-L-carnitine in combination increases the odds of pregnancy by 3.7-fold over placebo. However most clinical research investigating the effect of L-carnitine alone or with acetyl L-carnitine on pregnancy rates disagrees (12352,58182,101560,111861,111459,111888). The number of studies investigating the effect of L-carnitine alone or with acetyl-L-carnitine on pregnancy rate is small and the duration of supplementation may be inadequate. Taking L-carnitine 1 gram and acetyl-L-carnitine 0.5 grams twice daily after taking nonsteroidal anti-inflammatory drugs for 2 months seems to increase sperm count and motility in males with abacterial prostatovesiculoepididymitis, an inflammation of the prostate gland, seminal vesicles, and epididymis (9791). Some studies have also evaluated L-carnitine in combination with other ingredients. One clinical trial in males with asthenospermia shows that taking L-carnitine 150 mg, acetyl-L-carnitine 50 mg, L-arginine 1660 mg, and Panax ginseng 200 mg daily for 3 months increases sperm motility and sexual satisfaction when compared with no treatment (32189). Another small clinical trial shows that taking this combination along with prulifloxacin 600 mg daily for 6 months improves sperm concentration and motility when compared with prulifloxacin alone in patients with chronic prostatitis due to Chlamydia trachomatis infection (59006). Other small and preliminary clinical studies have investigated the effects of a specific combination product providing L-carnitine 1 gram twice daily for 6 months, along with acetyl-L-carnitine, coenzyme Q10, selenium, zinc, vitamin C, folic acid, vitamin B12, and citric acid (Proxeed Plus). Taking this combination product has been shown to improve measures of sperm quality such as sperm count, sperm concentration, total motility, and progressive motility when compared to baseline. The effect on sperm volume and morphology is unclear. Most research has been conducted in patients with oligoasthenozoospermia, although some benefit has also been shown in patients with varicocele-related infertility, especially those with more severe varicocele (102017,107395,111296). The validity of these findings is limited by the lack of comparator group. Also, it is unclear if these effects are due to L-carnitine, other ingredients, or the combination. The effect of L-carnitine in combination with other ingredients on pregnancy rate has also been examined. One meta-analysis of moderate-quality clinical research shows that taking L-carnitine in combination with micronutrients increases the odds of pregnancy by 3.5-fold over placebo or no treatment (111888).
• Myocarditis. Oral DL-carnitine may prevent myocarditis in children with diphtheria. Details: Myocarditis is a complication of diphtheria. Clinical research in children with diphtheria shows that taking DL-carnitine 100 mg/kg daily for 4 days reduces the risk of myocarditis and mortality when compared with no treatment (3620,3621).
• Valproic acid-induced toxicities. Although more well-designed research is needed to confirm these findings, oral and intravenous L-carnitine may improve neurologic and hepatic function and reduce ammonia levels in patients with these valproic acid-induced toxicities. Details: Valproic acid-induced toxicities are often associated with low plasma and tissue levels of L-carnitine. Preliminary clinical research and case reports in patients on valproic acid therapy who have neurologic or hepatic deterioration or hyperammonemia show that taking L-carnitine 50-100 mg/kg daily in divided doses or administering L-carnitine 150-500 mg/kg daily via intravenous infusion seems to improve neurologic and hepatic function and bring plasma ammonia levels within normal limits (1438,1914,1915,1916,1917,4523,5798,5799,95068). There is also some preliminary evidence that intravenous L-carnitine can prevent the development of severe valproic acid-induced hepatotoxicity when given to patients being treated for overdose and accidental ingestion of valproic acid (1438,4528,5798,5799), especially if treatment is initiated early (4528). Despite these results, most evidence consists of anecdotal individuals or small case series. A more recent retrospective cohort study suggests that treatment with an L-carnitine dosing regimen consisting of a 100 mg/kg intravenous loading dose followed by up to 3 grams daily in divided doses for 3 days or until ICU discharge does not enhance valproic acid elimination or prevent organ dysfunction when compared with patients not treated with L-carnitine (111869). Also, taking L-carnitine does not appear to reduce valproic acid-associated weight gain (58295). Well-designed clinical trials are still needed to determine the role of L-carnitine in the treatment or prevention of valproic acid toxicities.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with mild-to-moderate acne shows that applying a proprietary formulation containing L-carnitine, licochalcone, and 1,2-decanediol to the face twice daily for 8 weeks reduces the number of acne lesions and pustules and improves quality of life when compared to baseline. However, the improvements do not appear to be significant when compared with placebo (26493).
• Age-related fatigue. Small clinical studies suggest that oral L-carnitine may improve physical and mental fatigue associated with aging. Details: Two small clinical trials in elderly patients experiencing fatigue after slight physical activity shows that taking L-carnitine 2-4 grams daily for 1-6 months improves physical and mental fatigue, increases muscle mass, and decreases fat mass when compared with placebo (16109,16111).
• Aluminum phosphide poisoning. It is unclear if intravenous L-carnitine is beneficial in people with aluminum phosphide poisoning. Details: A meta-analysis of preliminary clinical research in patients with aluminum phosphide poisoning shows that intravenous L-carnitine does not reduce the odds of mortality when compared with control groups receiving routine treatments only (111892). However, only 2 studies were included in the analysis and both studies may have been underpowered to detect differences.
• Alzheimer disease. Oral L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with mild to moderate Alzheimer disease shows that taking L-carnitine tartrate 3.73 grams, in combination with serine, nicotinamide riboside, and N-acetyl cysteine, daily for 28 days and then twice daily for 56 days does not improve cognitive function when compared with taking placebo. However, in patients with the most severe symptoms, there was some modest improvement (110623). This study may have been underpowered to detect differences. Also, the effect of L-carnitine alone is unclear.
• Androgenic alopecia. It is unclear if topical L-carnitine is beneficial in people with androgenic alopecia. Details: One small clinical trial in individuals with androgenic alopecia shows that applying topical L-carnitine 2% solution to the scalp twice daily for 6 months significantly increases the number of terminal hair shafts on the scalp when compared with placebo (58390).
• Anorexia nervosa. Although there has been interest in using oral L-carnitine for anorexia nervosa, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Anthracycline cardiotoxicity. Oral and intravenous L-carnitine have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with breast cancer undergoing doxorubicin treatment shows that taking a combination of L-carnitine and vitamin E over 4 21-day treatment cycles decreases the proportion of patients with cardiac events by 24.2% when compared with chemotherapy treatment only. There were also modest beneficial effects on some enzyme measures of cardiac health. Patients received L-carnitine 3 grams intravenously on the first day of each cycle followed by an oral intake of 300 mg 4 times daily for the remaining 20 days. Vitamin E 1800 mg daily was taken orally in 3 divided doses (111891).
• Athletic performance. Oral L-carnitine has been evaluated for its effect on athletic performance in several small and short-term clinical studies, with mixed results. Details: Maximal exercise in trained athletes has been associated with a decrease in plasma L-carnitine levels (3648,58583). Theoretically, restoring these levels with L-carnitine supplementation might have beneficial effects. However, clinical studies examining the use of L-carnitine for athletic performance have reported conflicting results. Some clinical studies show that taking L-carnitine 2 grams, either before exercise or daily for up to 6 weeks, enhances athletic performance and endurance and reduces post-exercise muscle pain in male athletes and healthy untrained males (58450,59182,59185), but other studies do not support these findings (1947,59128,59134). Additionally, although some studies show that taking L-carnitine 1-2 grams or 40 mg/kg before exercise or 4 grams daily for 2 weeks can decrease lactate accumulation and increase oxygen uptake, power output, and time to anabolic threshold during exercise (3649,3650,59061,59184,59186), other studies show no improvement in these outcomes (58471,58775,59033,59045,59069,59128). These discrepancies may be related to the small study sizes, short treatment durations, and variable dosing regimens.
• Atrial fibrillation. It is unclear if oral L-carnitine is beneficial for preventing postoperative atrial fibrillation in patients undergoing aortic valve surgery. Details: A very small clinical study in patients undergoing aortic valve replacement or valve-sparing aortic root replacement shows that receiving oral L-carnitine (L-Cartin FF, Otsuka Pharmaceutical) 1 gram three times daily, beginning 2 days prior to surgery and continuing for 7 days after surgery, is associated with a postoperative atrial fibrillation rate of 20%, compared with a rate of 60% in a historical age-matched control group not receiving L-carnitine (107408).
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral L-carnitine is beneficial in children with ADHD. Details: One small crossover trial in children with ADHD shows that taking L-carnitine 50 mg/kg twice daily for 6 months improves parent and teacher assessments of behavior when compared with placebo (58166).
• Autism spectrum disorder. Small clinical studies suggest that oral L-carnitine may improve some symptoms of autism spectrum disorder. Details: Small clinical trials in children 3-16 years of age with autism spectrum disorder show that taking L-carnitine 50 mg/kg or 150 mg/kg daily for 8 to 12 weeks modestly improves overall symptoms of autism, especially lethargy, social isolation, hyperactivity, and irritability, when compared with taking placebo. However, there is inconsistency between studies with respect to rating scales used and specific endpoints showing improvement. In one study, children remained on any pre-existing medications; in the other two, all children were also taking risperidone (58981,111887,111900).
• Arrhythmia. Small clinical studies suggest that oral L-carnitine may reduce the incidence of arrhythmias in patients with premature ventricular contractions. Details: Small clinical trials in patients with premature ventricular contractions show that taking L-carnitine 2 grams twice daily for 45 weeks or 2 grams three times daily for 2 weeks might reduce the incidence of arrhythmias when compared to baseline (59043,59120,59143).
• Asthenopia (eye strain). Oral L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in videoterminal users with computer vision syndrome and without dry eye shows that taking a product containing L-carnitine 50 mg, along with zinc and extracts of elderberry, black currant, and eleuthero root (Meramirt CM) daily for 1 month modestly reduces severity of eye strain and sensitivity when compared with not taking this product (111295). It is unclear if these findings are due to L-carnitine, other ingredients, or the combination.
• Beta-thalassemia. Small clinical studies suggest that oral L-carnitine may improve symptoms and reduce complications of beta-thalassemia minor, intermedia, and major. Details: Several small clinical trials in children with beta-thalassemia major show that taking L-carnitine 50 mg/kg daily for 3-6 months might reduce pulmonary artery systolic pressure, increase cardiac output during exercise, and improve progression to puberty (58294,58502,58556). Clinical research in adults with beta-thalassemia intermedia shows that taking L-carnitine with hydroxyurea appears to increase hemoglobin and hematocrit and reduce left ventricular end-diastolic diameter, a measure of pulmonary hypertension (58679). In patients with beta-thalassemia major or intermedia aged 6 years and up, taking L-carnitine 50 mg/kg daily for 6 months normalized left ventricular dilatation and hypertrophy in 30% and 37% of patients, respectively, compared with only 10% in those taking placebo. Cardiac output was also improved, but there were no changes in blood parameters (101565). Clinical research in children with beta-thalassemia minor shows that taking L-carnitine 50 mg/kg daily, with or without folic acid 1 mg daily, for 3 months appears to reduce bone pain by 84% to 87% and increase the number of climbable stairs 3.1- to 5.2-fold when compared with baseline (90631).
• Cachexia. Small clinical studies suggest that oral L-carnitine may improve body composition and quality of life in patients with cancer-related cachexia. Details: One small clinical trial in patients with cancer-related cachexia shows that taking L-carnitine 4 grams daily for 12 weeks increases body mass index (BMI) when compared with placebo (59029). Other research shows that taking L-carnitine 4 grams daily with megestrol acetate, eicosapentaenoic acid (EPA), and thalidomide for 5 months is more effective than any single product alone for increasing lean body mass in patients with cancer-related cachexia (23437). Additionally, taking L-carnitine 4 grams daily with megestrol acetate, celecoxib, and antioxidants for 4 months appears more effective than megestrol acetate alone for improving lean body mass, fatigue, and quality of life in these patients (59012).
• Cancer-related fatigue. It is unclear if oral L-carnitine is beneficial for improving fatigue in patients with advanced cancer. Details: Some cancer patients have low blood levels of L-carnitine, which may reduce energy production and lead to fatigue. Some small clinical trials in patients with advanced cancer show that taking L-carnitine 3-4 grams daily for 7 days significantly improves some measures of fatigue when compared to baseline (16106,16110). However, other higher quality clinical research shows that taking L-carnitine 2-4 grams daily for 4-12 weeks is no more effective than placebo for improving fatigue in advanced cancer patients (26498,58523,59029).
• Celiac disease. It is unclear if oral L-carnitine is beneficial in patients with celiac disease. Details: Some research shows that L-carnitine blood levels are low in patients with celiac disease. One small clinical trial in patients with celiac disease shows that taking L-carnitine 2 grams daily for 6 months lowers some measures of fatigue when compared with placebo. However, L-carnitine does not significantly improve measures of depression or quality of life in these patients (16105).
• Chemotherapy-related fatigue. It is unclear if oral L-carnitine is beneficial in patients with fatigue due to sunitinib therapy. Details: A small clinical study in adults with renal cell carcinoma who are experiencing fatigue associated with sunitinib treatment shows that taking L-carnitine 1500 mg daily for 2 weeks modestly improves fatigue severity when compared to baseline (100352). The validity of this finding is limited by the small study size and lack of a comparator group.
• Chronic fatigue syndrome (CFS). It is unclear if oral L-carnitine is beneficial in patients with CFS. Details: One small clinical study in adults with CFS shows that taking L-carnitine 1 gram three times daily for 2 months can improve some symptoms of CFS when compared to baseline (3630). The validity of this finding is limited by the lack of a comparator group.
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral L-carnitine is beneficial in patients with COPD. Details: One small clinical study in adults with moderate to severe COPD shows that taking L-carnitine 2 grams daily for 6 weeks improves exercise performance and walking tolerance when compared with placebo (58213).
• Cirrhosis. Preliminary research suggests that oral L-carnitine may be beneficial in patients with cirrhosis. Details: One small clinical trial in patients with cirrhosis who are receiving branched-chain amino acids supplements to improve nutritional status shows that taking L-carnitine 1 gram orally daily for 6 months, in addition to increasing exercise by 2000 steps per day, does not improve muscle volume, handgrip strength, or leg strength, but does reduce complaints of muscle cramping, when compared to baseline (102124). Another small, uncontrolled clinical trial in patients with cirrhosis shows that taking L-carnitine 1800 mg daily for 6 months does not improve Child-Pugh scores, but may improve quality of life, when compared to baseline (104177). The validity of these studies is limited by the lack of comparator groups. The effect of L-carnitine has also been examined retrospectively in patients with cirrhosis. One retrospective study in matched patients that had been admitted to hospital for cirrhosis suggests that taking L-carnitine for more than 30 days is associated with an increase in survival length by about 21 months compared with not taking L-carnitine. Overall, L-carnitine use was also associated with a 36% to 48% increase in the proportion of patients surviving 1-5 years, with the greatest effect in patients with modest to severe liver dysfunction. The median dose of L-carnitine was 1000 mg daily for at least 6 months is associated with a reduced loss of skeletal muscle compared with not taking L-carnitine (111860). The validity of these studies is limited by their retrospective design.
• Cognitive function. It is unclear if oral L-carnitine is beneficial for improving cognitive function in healthy individuals. Details: Low-quality clinical research shows that taking L-carnitine 500 mg as a single dose or 250 mg twice daily for 3 days does not improve cognitive function or memory in otherwise healthy young adults when compared with placebo (58176,95070).
• Coronary heart disease (CHD). It is unclear if oral L-carnitine is beneficial in patients with CHD. Details: One small clinical trial in patients with CHD shows that taking L-carnitine 2 grams prior to exercise does not improve endurance when compared with placebo (58196). Another small clinical trial in patients with CHD shows that taking L-carnitine 1 gram daily for 12 weeks does not improve low-density lipoprotein (LDL) cholesterol, total cholesterol, or apolipoprotein-B when compared with placebo; however, it does appear to increase high-density lipoprotein (HDL) and apolipoprotein A-1 levels in these patients (95071).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral L-carnitine is beneficial for COVID-19 prevention or treatment. Details: Preliminary clinical research in patients hospitalized with mild to moderate COVID-19 shows that taking L-carnitine 1 gram 3 times daily for 5 days does not reduce the incidence of fever or cough when compared with standard treatments only. However, all patients taking L-carnitine survived compared with 86% of those given standard treatment only. Also, there were improvements in oxygen saturation and inflammatory measures (111874). Other clinical research in patients with confirmed asymptomatic or mild COVID-19 shows that taking L-carnitine tartrate (Carnipure) 1 gram 3 times daily for 21 days does not prevent the development of severe lung symptoms when compared with taking placebo. However, in a sub-group of patients, lung lesion improvement was significantly better between days 7 and 14. In adults without COVID-19 but living with someone with confirmed disease, taking this product does not prevent COVID-19 when compared with taking placebo. However, the total number of confirmed illnesses in the population was low (111898).
• Critical illness (trauma). It is unclear if oral or nasogastric L-carnitine is beneficial for critical illness. Details: One small clinical trial in critically ill patients in the ICU shows that receiving L-carnitine (BSK, Zist Takhmir Co, Tehran-Iran) 3 grams daily via a nasogastric tube for 7 days modestly improves disease severity, organ function, inflammatory and other laboratory measures when compared with receiving placebo. Also, mortality rate was reduced by approximately 50%. There was no effect on the duration of hospital or ICU stay (111883,111884). However, another small clinical trial in critically ill patients following an acute ischemic stroke shows that oral or nasogastric L-carnitine tartrate 500 mg every 8 hours for 6 days does not affect the duration of mechanical ventilation or hospital or ICU stay, the severity of illness, or 28-day mortality rates, when compared with taking placebo. There was a modest beneficial effect on insulin resistance (111881). This study was small and may have been underpowered to detect differences.
• Diabetes. Oral L-carnitine may improve glycemic control in patients with diabetes, but it is unclear if these improvements are clinically meaningful. It is also unclear if L-carnitine can improve lipid profiles or weight loss in these patients. Details: While individual study results are mixed (58169,58189,58514,58793,90632,96922,101561), meta-analyses of available clinical research in mixed populations shows that taking L-carnitine 200 mg to 4 grams daily reduces fasting plasma glucose and glycated hemoglobin (HbA1C) levels, and possibly insulin, and improves insulin resistance, when compared with taking placebo or a control diet, although the clinical significance of these improvements is unclear (102018,111875,111886). One meta-analysis shows that these benefits are generally specific to patients with high levels of fasting glucose, diabetes, or obesity, as well as studies investigating L-carnitine in doses of at least 2 grams daily for 12 weeks. However, a small number of studies included in this analysis investigated the effects of acetyl-L-carnitine (111875). Other research in obese patients with type 2 diabetes shows that, when taken with orlistat or sibutramine, L-carnitine 2 grams daily for 12 months decreases body weight and body mass index and improves glycemic control when compared with orlistat or sibutramine alone (58778,58830,58882). The effect of L-carnitine on lipids in people with diabetes is unclear. Some studies show significant reductions in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and/or lipoprotein(a) (58554,58647,58649,90632,101561,107397), while other studies show no improvement in lipid profiles (58169,58189).
• Dilated cardiomyopathy. Small clinical studies suggest that oral L-carnitine may improve ejection fraction in children with dilated cardiomyopathy and adults with ischemic cardiomyopathy. Details: Primary L-carnitine deficiency is a common cause of pediatric dilated cardiomyopathy. Additionally, patients with dilated cardiomyopathy of unknown etiology have been shown to have low cardiac levels of L-carnitine (59196,100351). Due to these findings, L-carnitine has been evaluated for the treatment of dilated cardiomyopathy in children and adults, but the small sizes of these studies and methodological limitations limit the reliability of the results. One small clinical study in children under 13 years of age with dilated cardiomyopathy shows that taking L-carnitine 50-100 mg/kg daily for 1 year in conjunction with standard care improves ejection fraction and reduces left atrial and ventricular diameters when compared with placebo and standard care (100351). The results of this study are limited by the small sample size, unclear etiology of dilated cardiomyopathy, and potential bias. Another small clinical study in children under 5 years of age with dilated cardiomyopathy and low serum levels of L-carnitine shows that taking L-carnitine 100 mg/kg daily for 3 months improves left ventricular ejection fraction (LVEF), cardiac output, and New York Heart Association (NYHA) classification when compared with baseline (59196). Further research is needed to clarify whether L-carnitine is beneficial for most children with dilated cardiomyopathy, or only those with carnitine deficiency. L-carnitine has also been evaluated in older adults. A meta-analysis of clinical studies in mostly older adults with dilated cardiomyopathy shows that addition of intravenous L-carnitine, alone or followed by oral L-carnitine, 1-6 grams daily to conventional therapy for a total of 10-28 days is associated with a 28% increased likelihood of overall efficacy, with improvements observed in both LVEF and cardiac output, when compared with conventional therapy alone (107405). The validity of these findings is limited by the heterogeneity of the included studies, potential publication bias, and unclear reporting. A small individual clinical study in older adults with ischemic cardiomyopathy shows that taking oral L-carnitine daily for 2 months improves LVEF when compared with baseline (58150). The validity of this finding is limited by the lack of a comparator group.
• Dry eye. Topical L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Evidence suggests that chronic use of eye drops containing benzalkonium chloride can cause tear film instability and lead to dry eye (90921). One small clinical trial in patients with glaucoma using eye drops containing benzalkonium chloride shows that using additional eye drops containing L-carnitine (1.017%), eledoisin (0.04%), taurine (0.49%), sodium hyaluronate (0.20 grams/100 mL), and vitamin E acetate (0.20 grams/100 mL) (Carnidrop Plus, Sigma-Tau) three times daily for 15 days reduces dry eye symptoms by approximately 50% when compared to baseline (90625). It is unclear if these findings are due to L-carnitine, other ingredients, or the combination.
• Endometriosis. Although there has been interest in using oral L-carnitine for endometriosis, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Exercise-induced muscle damage. It is unclear if oral L-carnitine tartrate is beneficial for exercise recovery. Details: A small clinical study in healthy males and females participating in moderate physical activity at least 3 days weekly shows that taking a specific product (Carnipure, Lonza Consumer Health, Inc.) providing elemental L-carnitine 2 grams daily for 5 weeks improves perceived recovery and soreness as well as serum creatine kinase levels by 33% and 28%, respectively, when compared with placebo (107398).
• Exercise-induced muscle soreness. Small clinical studies suggest that oral L-carnitine may slightly reduce exercise-induced muscle soreness. Details: Evidence from mostly small clinical trials, when considered alone or combined via meta-analysis, shows that taking L-carnitine 1-3 grams daily for around 3 weeks modestly reduces exercise-induced muscle soreness, especially in the period of 24-48 hours after exercise. Benefits may last up to 96 hours post-exercise. Levels of creatinine kinase, lactate dehydrogenase, and myoglobin also appear to improve with L-carnitine supplementation, reflecting a reduction in muscle damage (58326,58709,59148,101567).
• Hepatic encephalopathy. Oral or intravenous L-carnitine may improve biochemical markers of disease severity in patients with hepatic encephalopathy, but L-carnitine does not seem to improve clinically important outcomes such as fatigue, quality of life, or overall disease severity. Details: A meta-analysis of nine studies in adults with hepatic encephalopathy shows that taking L-carnitine 1-6 grams daily orally or intravenously for up to 90 days increases albumin levels and decreases plasma levels of ammonia, bilirubin, aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine, but does not improve fatigue or quality of life, when compared with placebo (102122). A more recent clinical trial shows that taking L-carnitine 2 grams daily for 24 weeks modestly improves bilirubin levels and some measures of cognitive and liver health, but not quality of life, when compared with taking placebo (111876). Two of the clinical trials included in this analysis also show that taking L-carnitine 2 grams daily for 60-90 days significantly improves cognitive function when compared with placebo in adults with hepatic encephalopathy (58174,58204). Another small clinical trial in patients with advanced liver cirrhosis shows that L-carnitine improves psychometric response to the ammonia tolerance test, suggesting that L-carnitine might be useful in the prevention of hepatic encephalopathy (58872). L-carnitine has also been evaluated in combination with rifaximin. A small clinical study in patients with overt hepatic encephalopathy shows that taking oral L-carnitine 1500 mg in combination with rifaximin 1200 mg three times daily for 12 weeks has no effect on the modified portal systemic encephalopathy index when compared with rifaximin alone. L-carnitine improved blood ammonia levels at 4 weeks, but not at 8 or 12 weeks (107410).
• Hepatitis-related fatigue. It is unclear if oral L-carnitine is beneficial in patients with hepatitis-related fatigue. Details: One small clinical trial in patients with hepatitis C who are receiving interferon-alpha treatment shows that taking L-carnitine 2 grams daily significantly reduces fatigue when compared with interferon-alpha alone. L-carnitine appears to reduce fatigue within the first 3 months of treatment, but not after 6 months (16104).
• Hepatitis B. Oral L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with hepatitis B shows that taking a specific vitamin complex providing L-carnitine 2472 mg (Godex, Celltrion Pharm) in combination with entecavir 0.5 grams daily for 12 months normalizes alanine transaminase (ALT) levels in 95% and 100% of patients after 3 months and 12 months, respectively, compared to 59% and 86% of patients taking entecavir alone. However, the L-carnitine complex does not appear to improve aspartate transaminase (AST) levels or reduce hepatitis B virus titers (91724). It is unclear if these findings are due to L-carnitine, other ingredients, or the combination.
• Hepatitis C. Small clinical studies suggest that oral L-carnitine may improve response to treatment and markers of liver function in patients with hepatitis C. Details: Two small clinical trials in patients with chronic hepatitis C show that taking L-carnitine 2 grams once or twice daily along with interferon-alpha and ribavirin for 12 months modestly improves response to treatment, increases hemoglobin and red blood cell counts, reduces aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and reduces steatosis when compared with interferon-alpha and ribavirin treatment alone (58405,59010).
• HIV/AIDS. Although there has been interest in using intravenous L-carnitine to increase CD4 counts in patients with HIV/AIDS, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Hyperthyroidism. It is unclear if oral L-carnitine is beneficial in patients with hyperthyroidism. Details: One small clinical trial in females with hyperthyroidism shows that taking L-carnitine 2-4 grams daily for 2-6 months seems to significantly improve symptoms associated with hyperthyroidism, such as palpitations, nervousness, tremors, and asthenia, when compared with placebo (8047).
• Hypertriglyceridemia. It is unclear if oral L-carnitine is beneficial in patients with hypertriglyceridemia. Details: Small clinical studies in patients with hypertriglyceridemia show that taking L-carnitine 1 gram daily for 12 weeks does not reduce triglyceride levels when compared with placebo (59028,59244).
• Hypothyroidism. It is unclear if oral L-carnitine is beneficial for improving fatigue in patients with hypothyroidism. Details: One small clinical trial in patients with secondary hypothyroidism shows that taking L-carnitine (Ildong Pharmaceutical Co.) 990 mg twice daily for 12 weeks in addition to adequate doses of levothyroxine does not reduce overall fatigue severity when compared with placebo. However, taking L-carnitine might improve physical and mental fatigue in patients with secondary hypothyroidism that are less than 50 years of age. L-carnitine might also improve mental fatigue in patients that underwent thyroidectomy for thyroid cancer (95069).
• Infertility. It is unclear if oral L-carnitine is beneficial for female infertility. Details: One uncontrolled clinical trial in females who had failed to conceive in previous in vitro fertilization (IVF) cycles shows that taking L-carnitine (L-CAR Basic Premium; AA Project Co. ltd.) 1000 mg daily for an average of 82 days does not improve the number of retrieved oocytes or fertilization rates when compared with previous IVF cycles. However, embryo quality at days 3 and 5 of insemination was improved, resulting in an increase in the rate of transferable embryos from 60% in previous cycles to 67%, morphologically good-quality embryos from around 46% to 54%, and blastocysts from around 11% to 21%. The most evidence of benefit was seen in those taking L-carnitine for the shortest time length of 7-44 days (96933).
• Intermittent claudication. Although there has been interest in using oral L-carnitine for intermittent claudication, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Liver disease. Small clinical studies suggest that oral L-carnitine may modestly improve some, but not all, lipid parameters in adults with liver disease. Details: A meta-analysis of six small, low-quality clinical trials in patients with hepatitis C, nonalcoholic steatohepatitis (NASH), and nonalcoholic fatty liver disease (NAFLD) shows that taking L-carnitine moderately reduces total cholesterol and slightly reduces triglyceride levels, but does not improve low-density lipoprotein (LDL) cholesterol or high-density lipoprotein (HDL) cholesterol levels, when compared with control. Studies evaluating L-carnitine doses of 2 grams daily or less and study durations of 24 months or longer showed the largest effect on lipid levels (104178). Another meta-analysis of preliminary clinical research in patients with hepatitis B or C, hepatic encephalopathy, NASH, or NAFLD shows that taking L-carnitine modestly reduces levels if aspartate aminotransferase (AST) and alanine aminotransferase (AST) when compared with taking placebo or no L-carnitine. Some of the studies included in this analysis used acetyl-L-carnitine. However, a meta-analysis of two studies investigating the effect of carnitine orotate shows that taking this compound increases the proportion of patients with normal ALT levels by 4.6 fold (111871).
• Liver transplant. It is unclear if oral L-carnitine is beneficial in patients awaiting a liver transplant. Details: One small clinical trial shows that taking L-carnitine 500 mg three times daily while awaiting a liver transplant does not reduce the incidence of primary graft dysfunction (PGD) or non-function (PNF) when compared with placebo. However, survival one month after surgery was 97% in those taking L-carnitine, compared with 74% in those taking placebo (101562). This study may have been inadequately powered to detect a difference in the incidences of PGD and PNF between groups.
• Low birth weight. It is unclear if oral or intravenous L-carnitine is effective for increasing body weight in preterm infants. Several small clinical studies show conflicting results. Details: Several very small clinical trials in preterm infants receiving total parenteral nutrition show that administering L-carnitine orally at a dose of 13-60 mcmol/kg or intravenously at a dose of 10 mg/kg or 50-100 mcmol/kg daily can improve fat utilization and weight gain when compared with control (3633,3634,3635,3636,3637,58902,59097). However, other small clinical studies show that supplementation with L-carnitine does not significantly increase body weight in preterm infants (58190,58800,59161). The reasons for the discrepant findings are unclear, but due to small study size, some of the studies may have been underpowered to detect significant differences between groups.
• Lyme disease. Although there has been interest in using oral L-carnitine for Lyme disease, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Metabolic syndrome. It is unclear if oral or intravenous L-carnitine is beneficial in patients with metabolic syndrome. Details: One very small clinical trial in patients with metabolic syndrome undergoing 2 days of moderate calorie restriction followed by a 5-day modified fasting period shows that intravenous L-carnitine 2 grams twice daily for 7 days increases weight loss by 1.4 kg and decreases waist circumference by 3.3 cm when compared with intravenous saline. Perceived hunger scores, physical fatigue, and insulin levels were also improved. However, there were no effects on blood pressure (90634). Other clinical research in patients with metabolic syndrome and a total carotid plaque volume of at least 50 mm³ shows that taking L-carnitine 2 grams daily for 6 months does not affect the progression of carotid plaque volume when compared with taking placebo. Also, taking L-carnitine increased the progression of carotid plaque stenosis by 9.3%, as well as levels of low-density lipoprotein (LDL) cholesterol, in this population (111879).
• Migraine headache. It is unclear if oral L-carnitine is beneficial in patients with migraine headaches. Details: One small clinical trial in patients with migraines shows that taking L-carnitine 500 mg daily, with or without magnesium oxide, for 12 weeks does not significantly reduce migraine frequency or severity when compared with a control (59030). However, another small preliminary clinical trial in children with episodic migraines shows that taking L-carnitine 25 mg per kg twice daily for 12 weeks prophylactically is as effective as taking propranolol 1 mg/kg once daily for reducing the frequency, severity, and duration of migraine headaches (111870). These studies were small and may have been underpowered to detect differences between groups.
• Muscle cramps. It is unclear if oral L-carnitine is beneficial in patients with muscle cramps. Details: One small, uncontrolled clinical trial in adults with type 2 diabetes shows that taking L-carnitine 300 mg twice daily for 4 months decreases the monthly frequency of muscle cramps from around 4 cramps per month at baseline to around 1 cramp per month after treatment. When compared with baseline, pain was also reduced by about 1 point on a 5-point scale (96922). However, the lack of a placebo control group limits the validity of these findings.
• Multiple sclerosis-related fatigue. It is unclear if oral L-carnitine is beneficial in patients with multiple sclerosis-related fatigue. Details: Some patients with multiple sclerosis have low blood levels of L-carnitine. Additionally, immunosuppressive therapy for multiple sclerosis can cause fatigue. One small, open-label clinical trial in patients with multiple sclerosis receiving immunosuppressive therapy and with low L-carnitine levels shows that taking L-carnitine 3-6 grams daily decreases some measures of fatigue when compared with no treatment (16107).
• Myocardial infarction (MI). It is unclear if oral or intravenous L-carnitine is beneficial in patients who have experienced an MI. Details: Some clinical research shows that taking L-carnitine orally or intravenously after MI reduces premature ventricular beats (58172,59044), improves myocardial viability (59248) and left ventricular function (3628), and reduces mortality (3627,3629,59037). However, other studies show no change in left ventricular functioning (58148) or mortality after taking L-carnitine (3628,58225,90630). The reasons for these discrepant findings are unclear, but may be due to differences in the dosing regimens and length of follow-up. Oral L-carnitine doses have ranged from 2-4 grams daily for up to 12 months (3627,3629,59248). Intravenous L-carnitine has been dosed at 5 grams within the first 36 hours after an MI followed by 3 grams twice daily on days 3-7 (58172), 100 mg/kg every 12 hours for 36 hours (59044), or 9 grams daily for 5 days followed by oral L-carnitine 6 grams daily for 12 months (3628).
• Narcolepsy. It is unclear if oral L-carnitine is beneficial in patients with narcolepsy. Details: One small clinical trial in patients with narcolepsy shows that taking L-carnitine 340 mg in the morning and 170 mg in the evening for 8 weeks reduces dozing off time during the day by about 9 minutes when compared with placebo. However, the number of naps needed, quality of life, and sleepiness are not affected (90624).
• Neonatal apnea. It is unclear if intravenous L-carnitine is beneficial for preventing neonatal apnea in premature infants. Details: One small clinical trial in premature infants shows that adding L-carnitine 30 mg/kg daily to total parenteral nutrition or oral feeds does not affect ventilator requirements or reduce the incidence of apnea when compared with placebo (58163).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral L-carnitine is beneficial in children and adults with NAFLD. Details: One small clinical study in adults with NAFLD shows that taking L-carnitine 600 mg daily for 3 months improves markers of liver function when compared with baseline. No improvements in liver function markers were reported in patients in the control group; however, no statistical comparisons were conducted between groups (58808). A small clinical study in children aged 5-15 years with NAFLD receiving vitamin E shows that taking L-carnitine 25 mg/kg twice daily (maximum of 500 mg twice daily) for 3 months has no effect on aminotransferase concentrations or sonographic grades of fatty liver when compared with placebo (107401).
• Nonalcoholic steatohepatitis (NASH). It is unclear if oral L-carnitine is beneficial in patients with NASH. Details: One small clinical trial in patients with NASH shows that taking L-carnitine 1 gram after breakfast and 1 gram after dinner daily along with following a specific diet improves markers of liver function when compared with diet alone (58715). Another small clinical trial in patients with obesity and nonalcoholic steatohepatitis taking simvastatin 20 mg daily and following a hypocaloric diet shows that taking L-carnitine 10 mL twice daily for 90 days modestly reduces BMI, and improves liver health, lipid, and glycemic indices, when compared with taking a product described as essential phospholipids (111893).
• Obesity. Oral L-carnitine seems to have a small effect on weight loss in overweight or obese individuals when taken for up to 6 months, but some conflicting results exist. Doses of 2 grams daily seem to offer the most benefit. Details: Meta-analyses of clinical trials show that taking L-carnitine 250 mg to 4 grams daily reduces weight and body mass index (BMI) by a small amount when compared with a control group not taking L-carnitine (95074,101563,101564). Subgroup analyses show that L-carnitine only reduces BMI and weight in overweight or obese patients. Taking L-carnitine did not affect weight or BMI in patients with a BMI of up to 25 kg/m2 or in patients undergoing hemodialysis (101563,101564). Another subgroup analysis shows that the largest benefit occurs at a dose of 2 grams daily (101564). In patients with obesity and nonalcoholic steatohepatitis taking simvastatin 20 mg daily and following a hypocaloric diet, one clinical trial shows that taking L-carnitine 10 mL twice daily for 90 days modestly reduces BMI, and improves liver health, lipid, and glycemic indices, when compared with taking a product described as essential phospholipids (111893). However, conflicting results exist. One subgroup analysis in overweight or obese individuals shows that there is no effect on BMI when L-carnitine is taken for 24 weeks or more (101563). One meta-analysis of two small clinical trials in patients with overweight or obesity shows that taking L-carnitine is no more effective than lifestyle modification for reducing body weight (111866). Also, some clinical research shows that taking L-carnitine does not reduce body weight in obese females. Doses used in these studies include L-carnitine 1 gram daily for 12 weeks or 2 grams twice daily for 8 weeks along with exercise (58151,111872). The effect of L-carnitine on cardiovascular risk has also been examined in patients with obesity. One small clinical trial shows that taking L-carnitine 1 gram daily for 12 weeks modestly reduces the lipid accumulation index, based on waist circumference and blood triglyceride levels, when compared with taking placebo. However, there was no effect on other cardiovascular risk indices based on ratios of triglycerides, high-density lipoprotein (HDL) cholesterol, and/or low-density lipoprotein (LDL) cholesterol levels (111872). L-carnitine has also been evaluated in combination with weight loss medications. Clinical research shows that taking L-carnitine 2 grams daily along with orlistat 360 mg daily or sibutramine 10 mg daily for 1 year decreases body weight and BMI when compared with orlistat or sibutramine alone in obese adults with type 2 diabetes (58778,58830,58882).
• Osteoarthritis. It is unclear if oral L-carnitine is beneficial in patients with knee osteoarthritis. Details: A small clinical study in females with knee osteoarthritis and overweight or obesity who are on a low-calorie diet shows that taking L-carnitine 1 gram daily for 12 weeks does not improve pain, stiffness, or physical function when compared with placebo (107403).
• Pemphigus. Although there has been interest in using oral L-carnitine for glucocorticoid-induced muscle wasting in patients with pemphigus, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Peripheral arterial disease (PAD). It is unclear if oral L-carnitine is beneficial in patients with PAD. Details: One small clinical trial in patients with PAD shows that taking L-carnitine 2 grams twice daily for 3 weeks may improve walking distances in people with PAD (3631). However, another small clinical trial in patients with PAD or coronary heart disease shows that taking L-carnitine 2 grams two hours before exercise does not improve endurance (58196). Also, adding L-carnitine 1 gram twice daily to cilostazol therapy for 180 days does not appear to confer additional benefit in this patient population (59023).
• Polycystic ovary syndrome (PCOS). It is unclear if oral L-carnitine is beneficial for improving pregnancy rates or cardiovascular risk in people with PCOS. The effect of L-carnitine on body composition has promising results. Details: Clinical research shows that adding L-carnitine 3 grams daily for 3 months to standard clomiphene plus metformin therapy improves menstrual regularity by 20%, ovulation rate by 24%, and pregnancy rate by 21% when compared with placebo (102123). Preliminary clinical research in patients with PCOS who are resistant to both clomiphene and human chorionic gonadotropin (HCG) shows that taking L-carnitine 2 grams twice daily from day 3 of clomiphene treatment until HCG injection results in the presence of a dominant follicle in 64% of cycles and pregnancy in 20% of cycles (96936). However, L-carnitine may not be beneficial in combination with assisted reproductive technology (ART), including in vitro fertilization and intracytoplasmic sperm injection. A small clinical study in patients with PCOS receiving ART in combination with a gonadotropin-releasing hormone antagonist protocol shows that adding L-carnitine 3000 mg daily during the induction of ovulation (from the second day of the cycle until the day of oocyte triggering) does not improve pregnancy rates in frozen-thawed embryo transfer cycles when compared with control (107409). The effect of L-carnitine has also been examined on anthropometric and cardiovascular risk indices in patients with PCOS. One small clinical study shows that taking L-carnitine 250 mg daily for 12 weeks reduces body weight by 2.8 kg, body mass index (BMI) by 1.2 kg/m2, waist circumference by 1.7 cm, and hip circumference by 2.2 cm when compared with placebo (96935). A meta-analysis of this and other small studies also shows that L-carnitine modestly reduces BMI when compared with placebo in patients with PCOS (111873). Although several studies also show improvements in markers of glycemic control and insulin sensitivity, most research does not support beneficial effects on lipid levels, cardiovascular risk, or liver fat content (96935,107402,107404).
• Rett syndrome. It is unclear if oral L-carnitine is beneficial in patients with Rett syndrome. Details: Two small clinical studies in children with Rett syndrome show that taking L-carnitine 100 mg/kg daily in two or three divided doses for up to 6 months modestly improves well-being, motor skills, sleep efficiency, and communication skills when compared with control or placebo (1433,58161).
• Sarcopenia. Oral L-carnitine may be beneficial for preventing sarcopenia in adults over 75 years of age, but not in healthy older females. Details: One small clinical trial in healthy, active, older females aged 65-70 years shows that taking L-carnitine, as L-carnitine-l-tartrate 1500 mg, daily for 24 weeks does not improve muscle strength or muscle mass when compared with placebo (96930). An additional preliminary clinical trial in females aged 60-75 years taking part in a twice weekly resistance exercise program shows that taking L-carnitine tartrate 1 gram daily with L-leucine 3 grams daily for 24 weeks does not improve muscle strength or volume when compared with taking L-leucine 4 grams daily or no supplementation (111880). These studies were small and may have been underpowered to detect differences. In contrast, in weaker adults 75 years of age and older, taking L-carnitine 2-4 grams daily for 1-6 months increases muscle mass by approximately 2-4 kg when compared with placebo (16109,16111).
• Sepsis. Small clinical studies suggest that intravenous L-carnitine may not reduce mortality in patients with sepsis, although patients with more severe sepsis may see some benefit. Details: Meta-analyses of generally low-quality small clinical trials in patients with sepsis shows that intravenous administration of L-carnitine, 2-6 grams as a bolus followed by a 4-12 gram infusion, does not reduce the risk of 28-day or 1-year mortality when compared with placebo (104180,111868). However, in a subgroup analysis of patients with more severe sepsis, classified as those with a sequential organ failure assessment score (SOFA) of greater than 12, the risk of 1-year mortality was reduced by 32% when compared with placebo (104180).
• Spinal muscular atrophy. Although there has been interest in using oral L-carnitine for spinal muscular atrophy, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Theophylline-induced cardiac toxicity. It is unclear if intravenous L-carnitine is beneficial in patients with theophylline-induced cardiac toxicity. Details: One small clinical trial shows that intravenous administration of L-carnitine 100 mg/kg over 30-60 minutes followed by 50 mg/kg every 8 hours along with intravenous propranolol within 24 hours of theophylline intoxication improves symptoms associated with theophylline-induced cardiac toxicity when given along with standard treatment. This combination led to greater improvements than either agent used alone. These included improvements in serum theophylline levels, heart rate, arrhythmia, mean arterial pressure, and duration of hospital stay. When L-carnitine was used without propranolol, only respiratory rate and theophylline levels over 24 hours were improved to a greater extent than with standard treatment alone (101566).
• Toxin-induced liver damage. Small clinical studies have evaluated oral and intravenous L-carnitine for the management of liver damage caused by different classes of drugs, including antimycobacterial antibiotics and asparaginase-based agents, with promising results. Details: The antimycobacterial antibiotics used to treat tuberculosis, including isoniazid, rifampicin, and pyrazinamide, have been associated with hepatotoxicity (90922). Clinical research shows that taking L-carnitine 2 grams in two divided doses daily for 4 weeks along with a standard treatment regimen for tuberculosis reduces the percentage of treatment-naïve patients with drug-induced hepatotoxicity by almost half when compared with placebo (26499). The asparaginase-based medications have also been associated with hepatotoxicity. Two case series of children with hyperbilirubinemia caused by treatment with L-asparaginase or pegaspargase show that administering intravenous L-carnitine 50-100 mg/kg daily improves bilirubin levels (100353,100354). One case series also suggests that taking oral L-carnitine 50-100 mg/kg daily can help to prevent hyperbilirubinemia in patients with a history of asparaginase-induced hepatotoxicity (100353).
• Traumatic brain injury (TBI). Although there has been interest in using oral L-carnitine for TBI, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose.
• Urinary tract infections (UTIs). It is unclear if oral L-carnitine is beneficial in children with UTIs. Details: One small clinical trial in children 6 months to 10 years of age shows that taking L-carnitine 50 mg/kg daily as a syrup along with antibiotics for 7 days prevents renal scarring associated with acute pyelonephritis. Kidney damage was resolved in 50% of children taking L-carnitine, compared with 13% of children taking placebo. There were no differences in urine cultures between groups (101568).
• Venous leg ulcers. Although there has been interest in using oral L-carnitine for venous leg ulcers, there is insufficient reliable information about the clinical effects of L-carnitine for this purpose. More evidence is needed to rate L-carnitine for these uses.

(Read more about L-CARNITINE)

LIKELY EFFECTIVE

• Cystic fibrosis. Long-term nebulized hypertonic sodium chloride improves lung function and reduces pulmonary exacerbations in patients with cystic fibrosis. Details: Meta-analyses of clinical research in adults with cystic fibrosis show that, when taken along with a bronchodilator and other standard therapies, nebulized hypertonic sodium chloride in concentrations of 3% to 7%, up to 10 mL twice daily for 4 weeks, increases forced expiratory volume at one second (FEV1) when compared with isotonic saline (sodium chloride 0.9%) (26230,26230). This benefit was not seen at 48 weeks. Other clinical research in adults with cystic fibrosis shows that inhaling sodium chloride 7%, 4 mL twice daily for 48 weeks, does not improve FEV1 when compared with isotonic saline. However, chronic treatment with hypertonic saline does reduce the number of pulmonary exacerbations and increase the number of patients without pulmonary exacerbations when compared with isotonic saline (29402). It is not clear if this benefit occurs in children with cystic fibrosis. The Pulmonary Clinical Practice Guidelines Committee of the Cystic Fibrosis Foundation recommends that individuals with cystic fibrosis aged 6 years or older use nebulized hypertonic saline long-term to improve lung function, reduce the number of exacerbations, and improve quality of life (29403).

POSSIBLY EFFECTIVE

• Amphotericin B nephrotoxicity. Oral sodium chloride seems to prevent nephrotoxicity associated with use of amphotericin B. Details: Clinical research shows that administering oral or intravenous sodium chloride 150 mEq daily during treatment with amphotericin B can attenuate the rise in serum creatinine levels and preserve renal function when compared to treatment with amphotericin B alone (26226).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bipolar disorder. It is unclear if oral sodium is beneficial in preventing lithium level fluctuations in patients with bipolar disorder. Details: A moderate-sized open-label clinical study in adults with type I bipolar disorder receiving lithium carbonate shows that taking sodium chloride 1 gram daily for 12 weeks along with dietary salt restriction of 1 gram daily reduces the percentage of patients with lithium level fluctuations above 0.8 mEq/L, but does not significantly affect serum sodium, potassium, aldosterone, or creatinine levels when compared with controls who were not salt restricted, but were advised not to consume additional salt at the table (112909). However, the interpretation of these findings is limited by missing data in both groups.
• Canker sores. Although there is interest in using topical sodium chloride for canker sores, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Congestive heart failure. It is unclear if oral sodium is beneficial in patients with acute decompensated heart failure requiring decongestive therapy with diuretics. Details: A moderate-sized clinical study in adults hospitalized with acute decompensated heart failure requiring high-dose intravenous furosemide shows that taking sodium chloride 2 grams three times daily for up to 96 hours does not affect patient weight or serum creatinine levels when compared with placebo (112911). However, the clinical relevance of this study is unclear and it may have been inadequately powered to detect a difference between groups.
• Conjunctivitis. Although there is interest in using ophthalmic sodium chloride for conjunctivitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Hyponatremia. Although there is interest in using oral sodium chloride for hyponatremia, there is insufficient reliable information about the clinical effects of oral sodium chloride for this condition.
• Pharyngitis. Although there is interest in using topical sodium chloride for pharyngitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Prematurity. It is unclear if oral sodium is beneficial for premature infants. Details: Preliminary clinical research in infants born at less than 32 weeks' gestation shows that adding sodium 4 mEq/kg daily to enteral feedings, starting from the 7th day after birth and continuing through the 35th day, reduces the risk of developing hyponatremia and improves weight gain when compared with adding water (98180). A small, open-label clinical study in newborns less than 35 weeks gestation shows that high sodium intake, defined as an average of 0.25% sodium in maintenance fluids, for 48 hours on day 2 and 3 after birth results in less weight loss within the first 72 hours of life when compared with control, but does not improve mortality, length of hospital stay, or complications from prematurity (112908). However, interpretation of these findings is limited by varied concentrations of sodium as an intervention. More evidence is needed to rate sodium for these uses.

(Read more about SODIUM)

LIKELY SAFE ...when used orally and appropriately. BCAAs 12 grams daily have not been associated with significant adverse effects in studies lasting for up to 2 years (68,72,73,74,10117,10146,10147,37120,92643,97531,103351,103352). ...when used intravenously and appropriately. BCAAs are an FDA-approved injectable product (13309).

CHILDREN: LIKELY SAFE
when used orally in dietary amounts of 71-134 mg/kg daily (11120,13308).

CHILDREN: POSSIBLY SAFE
when larger, supplemental doses are used orally and appropriately for up to 6 months (13307,13308,37127).

PREGNANCY:
Insufficient reliable information available; avoid using amounts greater than those found in food. Although adverse effects have not been reported in humans, some animal research suggests that consumption of supplemental isoleucine, a BCAA, during the first half of pregnancy may have variable effects on birth weight, possibly due to abnormal placental development (103350).

LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food. Although the safety of increased BCAA consumption during lactation is unclear, some clinical research suggests that a higher concentration of isoleucine and leucine in breastmilk during the first 6 months postpartum is not associated with infant growth or body composition at 2 weeks, 2 months, or 6 months (108466).

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

LIKELY SAFE ...when used orally and appropriately. L-carnitine has been safely used in clinical trials lasting up to 12 months (1947,3620,3621,3623,3624,3625,3626,3627,3628,3629) (3630,3639,4949,8047,9790,12352,16104,16105,16106,16107) (16109,16110,23437,26496,26499,58150,58156,58161,58169,58182) (58189,58204,58207,58209,58213,58294,58523,58554,58556,58647) (58679,58715,58778,58793,58830,58831,58882,59023,59029,59043) (90624,90633,104177,111872,111876,111883,111884,111891,111898). ...when used parenterally as an FDA-approved prescription medicine. Avoid using D-carnitine and DL-carnitine. These forms of carnitine can act as competitive inhibitors of L-carnitine and may cause symptoms of L-carnitine deficiency (1946).

CHILDREN: POSSIBLY SAFE
when used orally or intravenously and appropriately. L-carnitine has been safely used orally in children for up to 6 months (1433,3622,58166,58502,58981,59188,111887,111900). It has also been safely used orally and intravenously in preterm infants (3633,3634,3635,3636,3637,58163,58190,58800,58902,59097)(59161).

PREGNANCY:
Insufficient reliable information available; avoid using.

LACTATION: POSSIBLY SAFE
when used orally. Supplemental doses of L-carnitine have been given to infants in breast milk and formula with no reported adverse effects. The effects of large doses used while nursing are unknown, but L-carnitine is secreted in the breast milk (3616).

(Read more about L-CARNITINE)

LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310). Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses. Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).

(Read more about SODIUM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, BCAAs might alter the effects of antidiabetes medications.  Details Some evidence suggests that BCAAs might stimulate insulin release (10105,10110,10113,10114,10118). However, a small clinical study in adults with liver cirrhosis and high nocturnal levels of blood glucose suggests that BCAAs might increase blood glucose levels (103348).

LEVODOPA Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B BCAAs in large doses can reduce the effects of levodopa.  Details BCAAs may compete with levodopa for transport systems in the intestine and brain and decrease the effectiveness of levodopa (66,2719). Small clinical studies how that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease (3291,3292,3293,3294).

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

ACENOCOUMAROL (Sintrom) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, L-carnitine might increase the anticoagulant effects of acenocoumarol.  Details L-carnitine might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation with concomitant use. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, L-carnitine might decrease the effectiveness of thyroid hormone replacement.  Details L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, L-carnitine might increase the anticoagulant effects of warfarin.  Details L-carnitine might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin (9878,12165). There is not enough information to know whether this interaction occurs with L-carnitine and warfarin.

(Read more about L-CARNITINE)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.  Details High intake of dietary sodium can increase systolic and diastolic blood pressure (26222). Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease (26223).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.  Details Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Altering dietary intake of sodium might alter the levels and clinical effects of lithium.  Details High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

SODIUM-CONTAINING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.  Details The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

TOLVAPTAN (Samsca) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.  Details Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

(Read more about SODIUM)

General ...Orally or intravenously, BCAAs are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, diarrhea, nausea, vomiting.
All routes of administration: High doses can lead to fatigue and loss of motor coordination.

Cardiovascular ...Orally, a single case of hypertension following the use of BCAAs has been reported (37143).

Dermatologic ...Orally, a single case of skin blanching following the use of BCAAs has been reported (681). It is not known if this effect was due to use of BCAAs or other factors.

Gastrointestinal ...Orally, BCAAs can cause nausea, vomiting, diarrhea, and abdominal distension. Nausea and diarrhea has been reported to occur in about 10% of people taking BCAAs (10117,37143,92643,97531).

Neurologic/CNS ...Orally and intravenously, BCAAs can cause fatigue and loss of motor coordination due to increased plasma ammonia levels (693,694,10117). Short-term use of 60 grams of BCAAs containing leucine, isoleucine, and valine for 7 days in patients with normal metabolic function seems to increase levels of ammonia, but not to toxic plasma levels (10117). However, liver function should be monitored with high doses or long-term use (10117). Due to the potential of increased plasma levels of ammonia and subsequent fatigue and loss of motor coordination, BCAAs should be used cautiously before or during activities where performance depends on motor coordination (75). Orally, BCAAs may also cause headache, but this has only been reported in one clinical trial (681).

(Read more about BRANCHED-CHAIN AMINO ACIDS (BCAA))

General ...Orally and intravenously, L-carnitine is generally well tolerated.
Most Common Adverse Effects:
All routes of administration: Abdominal cramps, abdominal pain, diarrhea, gastritis, heartburn, nausea, reduced appetite, and vomiting. A fish-like body odor has also been reported.
Serious Adverse Effects (Rare):
All routes of administration: Seizures.

Cardiovascular ...According to population research, plasma L-carnitine levels are associated with increased risk of cardiovascular disease and major cardiac events (90635). However, oral supplementation with L-carnitine does not appear to be associated with an increased risk of cardiovascular disease. In fact, a meta-analysis of clinical research shows that L-carnitine supplementation is associated with a reduction in all-cause mortality, as well as ventricular arrhythmias and the development of angina and does not increase the development of heart failure or myocardial reinfarction (59037). Also, another meta-analysis suggests that L-carnitine does not affect mortality or cardiovascular outcomes in patients with a previous myocardial infarction (90630).

Dermatologic ...Orally, L-carnitine has been reported to cause skin rash in a small number of cases (16105,91724). Two patients in a hair growth study using topical carnitine reported mild itching and increased dandruff, while a third reported strong itching with reddish bumps and a burning sensation (58390). When a specific formulation containing L-carnitine, licochalcone, and 1,2-decanediol was applied to the face, mild skin dryness and tightness was reported by 12% of volunteers, compared with 4% to 8% of those in the vehicle-only control group (26493).

Gastrointestinal ...Orally and intravenously, L-carnitine has been associated with nausea, epigastric discomfort, vomiting, abdominal cramps, heartburn, gastritis, anorexia, and diarrhea (3616,3624,59030,95069,95070,101562,107410,111870,111887,111891). Orally, diarrhea or colitis symptoms (1433,3630,16105,16107,16111,23437,58523,58554,59020,90623), nausea and abdominal pain (16105,16106,26499,58169,58392,58554,90623,90634), indigestion (26703), and constipation (58523) have been reported in various clinical trials.

Hematologic ...In one case report, L-carnitine 990 mg twice daily was started in a female presenting to hospital with valproic acid toxicity. Blood phosphorous levels subsequently fell from 2.3 mg/dL to 1.3 mg/dL over 4 days. After discontinuation of L-carnitine, blood phosphorus levels increased to 1.8 mg/dL. The authors suggested that the role of L-carnitine in improved protein metabolism may play a role in the declining levels of phosphorous in the blood and increased risk of hypophosphatemia (90628).

Neurologic/CNS ...Orally or intravenously, L-carnitine has been associated with seizures (3616). Orally, use of L-carnitine in clinical trials has resulted in headache, although this event is rare (58554,95070,111891). L-carnitine may also cause agitation (95070).

Other ...Orally or intravenously, L-carnitine has been associated with a fish-like body odor (1433,3616,58166,59854,90623). One of its metabolites, trimethylamine N-oxide, can cause the urine, breath, and sweat to have a fishy odor (12756,58664).

(Read more about L-CARNITINE)

General ...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level. Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.

Cardiovascular ...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263). A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).

Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).

Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).

Musculoskeletal ...Observational research has found that low sodium levels can increase the risk for osteoporosis. One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).

Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).

Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).

Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).

(Read more about SODIUM)