Weight Loss [Discontinued] by 24bio

POSSIBLY EFFECTIVE

• Depression. Oral 5-HTP seems to improve symptoms of depression. Details: A meta-analysis of preliminary clinical research shows that taking 5-HTP for up to 8 weeks might improve symptoms of depression in some patients. The pooled remission rate across 13 studies was 65%, and the pooled effect size across 7 studies assessing the change in depressive symptom scores from baseline was large (102854). In most studies, the dose of 5-HTP administered ranged from 150-800 mg daily, although doses as high as 3 grams daily have been used (903,30000,30125,30138,102854). Some research has compared 5-HTP to conventional antidepressants. In one clinical trial of adults experiencing a first episode of depression, taking 5-HTP orally, titrated up to a daily dose of 400 mg, decreased depression symptoms similarly to fluoxetine titrated up to 40 mg daily (30112). Limited research also suggests that taking 5-HTP 300-800 mg daily seems to work similarly to fluvoxamine 50 mg (2203) or imipramine 150 mg daily (30125). Adding 5-HTP 300 mg orally daily to clomipramine 50 mg daily for 28 days has also been shown to reduce depressive symptoms when compared with clomipramine alone (6245).

POSSIBLY INEFFECTIVE

• Down syndrome. Oral 5-HTP does not seem to improve muscle tone or cognitive skills in patients with this condition. Details: Although early reports suggested that 5-HTP might improve muscle tone and activity levels in infants with Down syndrome (88172), other research has shown no benefit. One small clinical study suggests that taking 5-HTP 0.5-5 mg/kg daily orally from early infancy until 3-4 years of age does not improve muscle tone or developmental ability scores in children with Down syndrome when compared with a control group (88173). Also, a prospective, double-blind study shows that taking 5-HTP 1-2 mg/kg daily orally, alone or with pyridoxine 5-10 mg/kg daily orally, beginning at birth and continuing until 3 years of age, does not improve muscle tone or development of cognitive, social, or language skills when compared with placebo (30153).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Oral 5-HTP has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a food supplement containing 5-HTP 5 mg, phenylalanine 300 mg, and glutamine 150 mg daily for 40 days during alcohol detoxification therapy reduces withdrawal symptoms when compared with alcohol detoxification therapy alone (30100). However, taking a combination of 5-HTP 25-100 mg with carbidopa 25 mg four times daily for one year does not seem to improve alcohol abstinence rates when compared with placebo (30007). The effect of 5-HTP alone is unclear.
• Alzheimer disease. Although there has been interest in using oral 5-HTP for Alzheimer disease, there is insufficient reliable information about the clinical effects of 5-HTP for this condition.
• Anxiety. It is unclear if oral 5-HTP is beneficial in patients with anxiety disorders. Details: A small clinical study in people with anxiety disorders shows that taking 5-HTP 25-150 mg daily with carbidopa 150 mg daily for 8 weeks reduces anxiety when compared with baseline, but not when compared with clomipramine 25-150 mg daily (30124).
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral 5-HTP for ADHD, there is insufficient reliable information about the clinical effects of 5-HTP for this condition.
• Cerebellar ataxia. It is unclear if oral 5-HTP reduces cerebellar ataxia symptoms. Details: One small clinical trial in people with cerebellar ataxia of various etiologies shows taking 5-HTP orally 10 mg/kg daily for 4 months improve quantitative ataxia scores when compared with placebo. Further improvement was noted in subjects continuing treatment for another 8 months (916). However, in a subsequent trial in this population, taking 5-HTP orally 1 gram daily for 10 months did not improve symptom scores when compared with placebo (30164). Also, a small clinical study in people with Friedreich's ataxia shows that taking 5-HTP 200-300 mg daily for 1 month, then 600-900 mg daily for 5 months (depending on body weight), does not improve symptoms when compared with placebo (30165).
• Fibromyalgia. Small clinical studies suggest that oral 5-HTP may improve symptoms of primary fibromyalgia syndrome. Details: Small clinical studies in people with primary fibromyalgia syndrome suggest that taking 5-HTP 100 mg orally three times daily for 30-90 days might improve pain, tenderness, sleep, anxiety, fatigue, and morning stiffness when compared with baseline or placebo (913,10286).
• Inflammatory bowel disease (IBD). It is unclear if oral 5-HTP is beneficial for IBD. Details: Preliminary clinical research in adults with stable IBD and fatigue shows that taking a specific 5-HTP (Levotonine, Panpharma) 100 mg orally twice daily for 8 weeks does not improve fatigue scores when compared with placebo. However, the validity of this study is limited by high patient drop-out (111311).
• Menopausal symptoms. It is unclear if oral 5-HTP is beneficial for symptoms of menopause. Details: A small clinical study in postmenopausal patients shows that taking 5-HTP orally 50 mg three times daily for 4 weeks does not reduce hot flash frequency when compared with placebo (30061).
• Migraine headache. It is unclear if oral 5-HTP reduces frequency of migraines. Details: Preliminary clinical research shows that taking 5-HTP 600 mg daily decreases migraine attack frequency similarly to methysergide 3 mg daily (30129). However, other small clinical studies show that taking 5-HTP 400 mg daily does not reduce the frequency or severity of migraine attacks when compared with placebo (30130,30184). Also, in children 6-12 years of age, one very small clinical study shows that taking 5-HTP 5 mg/kg daily in 3 divided doses for 12 weeks does not reduce the frequency or severity of migraine attacks when compared with placebo (30128).
• Obesity. It is unclear if oral 5-HTP is beneficial in for weight loss. Details: Some very small clinical studies show that taking 5-HTP orally, 300 mg three times daily 30 minutes before meals for 2-12 weeks, improves early satiety and decreases daily caloric intake in females with obesity when compared with placebo (914,30018). 5-HTP was also associated with a mean weight loss of 1.7 kg over 6 weeks when caloric intake was not restricted, and a mean weight loss of 3.3 kg over 6 weeks when caloric intake was restricted to about 1200 calories daily (914,30114). In moderately overweight adults with type 2 diabetes, taking 5-HTP 250 mg three times daily 30 minutes before meals for 2 weeks reduces caloric intake by about 22% and decreases body weight by about 2 kg when compared to baseline (30175).
• Obsessive-compulsive disorder (OCD). It is unclear if oral 5-HTP is beneficial in patients with OCD. Details: A small clinical study in patients with moderate to severe OCD shows that adding 5-HTP 200 mg orally daily to fluoxetine, titrated up to 60 mg daily, for 12 weeks reduces symptom severity when compared with placebo and fluoxetine. A complete response, defined as greater than or equal to 35% improvement in overall Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, was seen in 54% of those taking 5-HTP at week 12, compared with only 12% of those taking placebo (104250). These results were not observed until week 12, which indicates that a longer treatment period may be needed to see the full effects of the intervention.
• Opioid withdrawal. Oral 5-HTP has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in Chinese males undergoing detoxification for heroin addiction shows that taking 5-HTP 200 mg orally daily for 6 days, in combination with tyrosine, phosphatidylcholine, and L-glutamine, might reduce insomnia and withdrawal symptoms and improve mood when compared with a control group (88178).
• Panic disorder. It is unclear if intravenous 5-HTP is beneficial for reducing anxiety in panic disorder. Details: A small clinical trial in females with panic disorders shows that receiving an intravenous (IV) infusion of 5-HTP, 60 mg over 30 minutes after premedication with carbidopa 100 mg orally, does not appear to reduce anxiety when compared with control (30093).
• Parkinson disease. It is unclear if oral 5-HTP is beneficial for improving Parkinson disease symptoms. Details: Two preliminary clinical trials show that taking 5-HTP 50 mg daily for 1 month seems to improve levodopa-induced dyskinesia and symptoms of depression, but not motor functioning or apathy, when compared with placebo in patients with Parkinson disease (102853,104251). Both studies used a crossover design to correct for the small sample size, but may still have been inadequately powered to detect small changes in these outcomes. However, in another study, taking larger doses of 5-HTP, 275-1500 mg orally daily along with carbidopa 150-1000 mg daily for up to 38 days, worsened rigidity, bradykinesia, and functional disability (30140). Other research has evaluated 5-HTP in patients with Parkinson disease and REM sleep behavior disorder (RBD). A small crossover study in these patients shows taking oral 5-HTP 50 mg daily for 4 weeks does not improve the percentage of REM sleep without atonia or the frequency of RBD events when compared with baseline or placebo. Patients taking 5-HTP report modest improvements in part II (motor function; e.g. swallowing, walking, and dressing) of the Unified Parkinson Disease Rating Scale (UPDRS), but not other parts of the UPDRS, when compared with placebo (107793). This study may have been inadequately powered to detect a difference between groups.
• Premenstrual syndrome (PMS). Although there is interest in using oral 5-HTP for PMS, there is insufficient reliable information about the clinical effects of 5-HTP for this condition.
• Seizures. Although there is interest in using oral 5-HTP for seizures, there is insufficient reliable information about the clinical effects of 5-HTP for this condition.
• Tension headache. It is unclear if oral 5-HTP reduces tension headache severity. Details: A small clinical study in adults with a history of chronic tension headaches suggests that taking 5-HTP 100 mg three times daily for 8 weeks does not reduce pain intensity or the number of days with headache when compared with placebo (2204).
• Tinnitus. Oral 5-HTP has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Research has evaluated a specific capsule formulation (Tinnitan Duo; Laboratorios Salvat) containing 5-HTP, ginkgo extract, magnesium, melatonin, pantothenic acid, vitamin B6, and zinc at undeclared doses. A small clinical trial in patients with subjective tinnitus shows taking this product as one capsule twice daily for 3 months improves Tinnitus Handicap Inventory (THI) total score and THI emotional subscale score at 3 months when compared with baseline. Patients also report improvement in tinnitus-related distress (107792). The validity of this study is limited by the lack of randomization and placebo-control; additionally, it is unclear if any effects are due to 5-HTP, other ingredients, or the combination. More evidence is needed to rate 5-HTP for these uses.

(Read more about 5-HTP)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral garcinia is beneficial for improving athletic performance. Details: Two very small, exploratory studies in untrained females and in elite athletes show that taking hydroxycitric acid (HCA), the active ingredient of garcinia, 250 mg daily for 5 days increases time to exhaustion and lowers the respiratory exchange ratio when compared with taking placebo (19151,26858).
• Hyperlipidemia. It is unclear if oral garcinia is beneficial in patients with hyperlipidemia. Details: A small open-label study of adults with obesity shows that taking garcinia 600 mg twice daily for 3 months may reduce total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides when compared to baseline (111243). The validity of these findings is limited by a lack of a comparator group and blinding.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral garcinia is beneficial in patients with NAFLD. Details: A small clinical study in females with obesity and NAFLD shows that taking a specific product containing garcinia bark leaf extract (HCA Garcinia Vita Plus, Vitamin House) 312.5 mg daily for 8 weeks in combination with a calorie-restricted diet improves body weight, body mass index (BMI), triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol when compared to baseline. However, liver enzyme levels increased slightly (111240). While a calorie-restricted control group was included, a lack of appropriate statistical comparison limits the validity of any between-group findings. Thus, it is unclear if these results are due to garcinia, the calorie-restricted diet, or the combination.
• Obesity. Despite contradictory evidence, oral garcinia seems to produce a very modest weight reduction in some people who are obese or overweight. Details: A meta-analysis of 8 small clinical trials shows that taking garcinia for 8-12 weeks seems to reduce weight by about 1.3 kg and body mass index (BMI) by about 1 kg/m2 when compared with control (104432). This analysis is limited by prominent heterogeneity in the included studies and a lack of sensitivity analyses. Most studies included in the analyses used garcinia 1000-4667 mg (standardized to 50% or 60% hydroxycitric acid) in divided doses daily as non-branded extracts or as specific branded supplements (Super CitriMax, InterHealth Nutraceuticals; Citrin, Sabinsa Corporation) (728,19152,19153,88158,104432). It is unclear which dose, if any, may be most beneficial. More recently, a small, open-label trial in adults with obesity shows that taking garcinia 600 mg twice daily for 3 months reduces body weight and BMI by 1.7 kg and 0.7 kg/m^2 when compared to baseline (111243). The validity of these findings is limited by a lack of a comparator group and blinding. Limited research has also studied garcinia in combination with glucomannan for 6 months, with evidence of moderate benefit for weight loss (96536). More evidence is needed to rate garcinia for these uses.

(Read more about GARCINIA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there has been interest in using oral green coffee for Alzheimer disease, there is insufficient reliable information about the clinical effects of green coffee for this condition.
• Diabetes. Although there has been interest in using oral green coffee for diabetes, there is insufficient reliable information about the clinical effects of green coffee for this condition.
• Hypercholesterolemia. It is unclear if oral green coffee is beneficial for hypercholesterolemia. Details: A meta-analysis of small clinical trials shows that taking green coffee extract modestly reduces levels of total and low-density lipoprotein (LDL) cholesterol, and increases levels of high-density lipoprotein (HDL), when compared to placebo. There was no effect on triglyceride levels (111048). These changes are unlikely to be clinically significant. In addition, this analysis is limited by the significant heterogeneity of the patient populations and any effect of green coffee extract in patients with hyperlipidemia is unclear. A small preliminary clinical study included in this meta-analysis in patients with hypercholesterolemia shows that drinking a beverage containing soluble green coffee 0.7 grams and soluble roasted coffee 1.3 grams (containing chlorogenic acids 148.4 mg per serving) three times daily for 8 weeks reduces LDL cholesterol, total cholesterol, and triglycerides when compared with baseline (103957). The validity of this finding is limited by the lack of a comparator group. Furthermore, it is unclear if the benefits are due to green coffee, roasted coffee, or the combination.
• Hypertension. It is unclear if oral green coffee extract is beneficial for lowering blood pressure. Details: Two small clinical studies in Japanese adults with mild, untreated hypertension show that taking green coffee extracts providing 50-140 mg chlorogenic acids daily for 4-12 weeks reduces systolic blood pressure by 5-10 mmHg and diastolic blood pressure by 3-7 mmHg when compared with placebo (17971,17972).
• Metabolic syndrome. Oral green coffee extract seems to improve some, but not all, measures of metabolic syndrome. Details: In patients with metabolic syndrome, clinical research shows that taking green coffee extract (Arjuna Natural Extracts Ltd) 400 mg twice daily for 8 weeks improves some measures of metabolic syndrome when compared with placebo. Systolic blood pressure, fasting blood glucose, insulin resistance, and waist circumference were reduced by a small amount, but there was no effect on glycated hemoglobin, lipid profile, or diastolic blood pressure (104831).
• Obesity. Oral green coffee extract may have a small effect on weight loss. Details: A meta-analysis of 13 clinical studies in patients with overweight or obesity shows that taking either green coffee extract 90-1000 mg, containing chlorogenic acids 30-500 mg, or pure chlorogenic acid 1200 mg daily for 8-12 weeks reduces weight by about 2 kg and body mass index (BMI) by 0.56 kg/m2 when compared with placebo (103954). Individual clinical studies have used a specific green coffee extract (Svetol, Naturex) (17982,17983). In the meta-analysis, there was no clear dose-response relationship (103954). This weight loss is unlikely to be clinically significant. In addition, this analysis is limited by the significant heterogeneity of the included studies and patient populations. In 2014 a trial reporting efficacy of a green coffee extract for treatment of obesity was determined to be "seriously flawed" by the Federal Trade Commission (FTC), resulting in its retraction by the authors and payment of a significant fine by the sponsoring company (Applied Food Sciences, Inc.) (88168,88169). This flawed study was not included in the 2020 meta-analysis (103954). In contrast to these findings, some clinical research has shown that taking green coffee does not reduce body weight. In one study, taking polyphenols 300 mg twice daily alone or in combination with oat-derived beta-glucans does not affect body weight or body composition when compared to baseline (109208). Also, in overweight or obese patients with breast cancer, a small clinical trial shows that taking green coffee extract (Arjuna Natural Extracts Ltd) 400 mg twice daily for 12 weeks does not affect body weight, body composition, or glycemic indices, when compared with placebo (111046).
• Polycystic ovary syndrome (PCOS). It is unclear if oral green coffee extract is beneficial for PCOS. Details: A small clinical trial in patients with PCOS shows that taking green coffee extract (Bonyan Salamat Kasra Company, Iran) 400 mg daily for 6 weeks modestly decreases total cholesterol and triglyceride levels when compared with taking placebo. However, there was no effect on glycemic indices, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or body weight (111047). More evidence is needed to rate green coffee for these uses.

(Read more about GREEN COFFEE)

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.
• Benign prostatic hyperplasia (BPH). Oral L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients in Iran with BPH shows that taking L-carnitine 1000 mg plus coenzyme Q10 daily in addition to finasteride 5 mg daily for 8 weeks modestly improves subjective assessment of sexual function when compared with placebo plus finasteride. There was no effect on prostate symptoms, prostate specific antigen levels, or quality of life (113226). It is unclear if these effects are due to L-carnitine, coenzyme Q10, 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.
• Hypertension. It is unclear if oral L-carnitine is beneficial for reducing systolic or diastolic blood pressure. Details: A meta-analysis of low-quality clinical studies in adults, both healthy and with underlying health conditions,shows that taking oral L-carnitine 0.5 to 3 grams daily for 4 to 52 weeks does not reduce systolic blood pressure (SBP) or diastolic blood pressure (DBP) when compared with control(115352). The validity of this study is limited by heterogenous methods between clinical trials, including population, dose, and outcome measurements.
• 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.
• Malnutrition. It is unclear if oral L-carnitine is beneficial in children with severe malnutrition. Details: A moderate-sized clinical study conducted in Bangladesh in children aged 9 to 24 months hospitalized with severe acute malnutrition shows that administering oral L-carnitine syrup 100 mg/kg daily for 15 days in addition to standard care does not improve rates of weight gain or reduce durations of hospital stays when compared with placebo (115351).
• 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 (IVF) and intracytoplasmic sperm injection (ICSI). Two small clinical studies in patients with PCOS receiving ART in combination with a gonadotropin-releasing hormone antagonist protocol shows that adding L-carnitine 3000 mg daily starting on the second day of menstruation and continuing until the day of oocyte triggering or embryo transfer does not improve rates of oocyte maturity or retrieval, implantation, or pregnancy when compared with control (107409,115353). 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 (96935,107402,107404,115353).
• 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.

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POSSIBLY SAFE ...when used orally and appropriately. 5-HTP has been used safely in doses up to 400 mg daily for up to one year (913,30007,30130). Doses up to 1.2 grams daily have been used with apparent safety for up to 10 months (914,30018,30125,30164,30165). Doses of 3 grams daily have been used safely for 3 weeks (30138). There is some controversy about the safety of 5-HTP due to concerns for eosinophilia myalgia syndrome (EMS) (902,919,7067,10084,30178). There is speculation that only certain, contaminated 5-HTP products may cause this serious adverse effect (88174). So far, there is not enough evidence to know if EMS is caused by 5-HTP, contaminants, or other unknown factors (919,7067,10084).

POSSIBLY UNSAFE ...when used orally in large doses. Doses of 6-10 grams daily have been associated with severe gastrointestinal effects and hyperkinesis (30139,30183). The risk may be reduced if the dose is increased gradually.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Doses of 5-HTP up to 5 mg/kg daily have been used safely for up to 3 years in infants and children up to 12 years old (30128,30153,88173). There is some controversy about the safety of 5-HTP due to concerns for eosinophilia myalgia syndrome (EMS) (902,919,7067,10084,30178). There is speculation that only certain, contaminated 5-HTP products may cause this serious adverse effect (88174). So far, there is not enough evidence to know if EMS is caused by 5-HTP, contaminants, or other unknown factors (919,7067,10084).

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There is insufficient reliable information available about the safety of garcinia extract when used orally. However, there is some concern about liver toxicity. There are numerous case reports of elevated liver enzymes and symptoms of liver toxicity in patients who have taken garcinia alone or in combination with other ingredients for as little as one week. In at least two reports, hepatotoxicity occurred in patients who were taking garcinia alone. Most other reports occurred in patients taking multi-ingredient products (13037,53511,93380,93381,93384,93385,93392,93393,93394,96535)(102544,102545,111241).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately. Green coffee extracts taken in doses up to 1000 mg daily, providing up to 500 mg chlorogenic acid, have been used with apparent safety for up to 12 weeks in clinical research (17971,17972,103954). A specific green coffee extract (Svetol, Naturex) has been used with apparent safety in doses up to 200 mg five times daily for up to 12 weeks (17981,17982,17983). Green coffee also contains caffeine, although in lower amounts than regular coffee. One cup of green coffee contains about 20-50 mg of caffeine, compared with about 100 mg in one cup of regular coffee. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of caffeine up to 400 mg daily are not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green coffee, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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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 (1433,3622,58166,58502,58981,59188,111887,111900,115351). 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).

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CARBIDOPA (Lodosyn) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Combining 5-HTP and carbidopa can increase the risk of serotonergic side effects.  Details Carbidopa is sometimes used with 5-HTP to minimize peripheral 5-HTP metabolism and boost the amount that reaches the brain. However, this combination might also increase the risk of some side effects including hypomania, restlessness, rapid speech, anxiety, insomnia, and aggressiveness (30076,30132,30158). Combining carbidopa and 5-HTP might also increase the risk of scleroderma-like skin changes due to elevated serotonin levels (1403).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of 5-HTP with medications that cause sedation might have additive effects.  Details In clinical trials, 5-HTP has been associated with drowsiness and somnolence (914,30093,30129,30130).

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Combining serotonergic drugs with 5-HTP might cause additive serotonergic effects.  Details 5-HTP can increase serotonin levels and cause serotonergic effects (901). Theoretically, combining serotonergic drugs with 5-HTP might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders (8056). However, serotonin syndrome with 5-HTP has not yet been reported in humans (104941). Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using 5-HTP with serotonergic drugs.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details HCA inhibits platelet aggregation in vitro. The inhibitory effect seems to be greater in platelets extracted from diabetic subjects than non-diabetic subjects (26862).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.  Details HCA reduces fasting and postprandial blood glucose levels in animal models, theoretically by delaying glucose absorption (26863,26867,26868). This effect has not been reported in humans.

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage.  Details There have been reports of acute hepatitis with elevated liver enzymes associated with garcinia, when taken alone or in combination with other ingredients (13037,53511,93380,93381,93384,93392,93393,93394,102544,102545). Case reports collected from the Drug Induced Liver Injury Network suggest this risk may be greater in people who carry the HLA B*35:01 allele (108401).

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining garcinia with other serotonergic drugs might increase the risk of serotonergic side effects, including serotonin syndrome.  Details In one report, a patient experienced serotonin syndrome after taking garcinia extract (60% hydroxycitric acid) 1000 mg daily in combination with escitalopram 20 mg, which had been taken for a year. The patient was switched to sertraline 50 mg daily and again experienced serotonin syndrome (23545).

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ADENOSINE (Adenocard) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, green coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.  Details Green coffee can contain caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products, be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alcohol might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370,24693).

ALENDRONATE (Fosamax) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, green coffee may decrease the levels and effects of alendronate.  Details In human research, drinking coffee with alendronate reduces the bioavailability of alendronate by 60% (11735). Whether green coffee reduces the bioavailability of alendronate has not been investigated. Separate green coffee ingestion and alendronate administration by two hours.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, green coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Green coffee can contain caffeine. Caffeine is reported to have antiplatelet activity (8028,8029). Theoretically, caffeine in green coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood (8030).

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, taking green coffee and antidiabetes drugs might interfere with blood glucose control.  Details In clinical research, green coffee extract results in modest reductions in blood glucose levels in various populations (17982,19327,111049). However, other reports claim that caffeine might increase or decrease blood sugar levels (6024,8646,19329,19330,19331,19332).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking green coffee with antihypertensive drugs might increase the risk of hypotension.  Details Clinical studies have shown that green coffee extract decreases blood pressure (17971,17972). When used with antihypertensive drugs, green coffee might have additive blood pressure-lowering effects. However, this has not been shown in clinical research.

BETA-ADRENERGIC AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of large amounts of green coffee might increase cardiac inotropic effects of beta-agonists.  Details Green coffee can contain caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).

CIMETIDINE (Tagamet) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = B Theoretically, cimetidine might increase the effects and adverse effects of caffeine in green coffee.  Details Green coffee can contain caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736,24700).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, green coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.  Details Green coffee can contain caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine (13741).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green coffee.  Details Green coffee can contain caffeine. Oral contraceptives decrease the rate of caffeine clearance by 40% to 65% (2714,11737).

DIPYRIDAMOLE (Persantine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, green coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.  Details Green coffee can contain caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as green coffee, be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, disulfiram might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of hypokalemia.  Details Green coffee can contain caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Diuretics can also cause lower potassium levels.

EPHEDRINE Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might increase the risk of stimulant adverse effects.  Details Green coffee can contain caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, estrogens might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Estrogen inhibits caffeine metabolism (2714).

FLUCONAZOLE (Diflucan) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, fluconazole might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022,24978).

FLUVOXAMINE (Luvox) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Fluvoxamine reduces caffeine metabolism (6370,38287).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, abrupt green coffee withdrawal might increase the levels and adverse effects of lithium.  Details Green coffee can contain caffeine. Abrupt caffeine withdrawal can increase serum lithium levels (609). Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported (609,610).

MEXILETINE (Mexitil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, mexiletine might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Mexiletine can decrease caffeine elimination by 50% (1260,11741,24981).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of a hypertensive crisis.  Details Green coffee can contain caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15).

NICOTINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the risk of hypertension.  Details Green coffee can contain caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, green coffee might reduce the effects of pentobarbital.  Details Green coffee can contain caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOTHIAZINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574).

PHENYLPROPANOLAMINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PIOGLITAZONE (Actos) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.  Details Green coffee contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Concomitant use of quinolones can decrease caffeine clearance and increase effects and risk of adverse effects (606,607,608,23554,23555,23556,24695,24696,24697).

RILUZOLE (Rilutek) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.  Details Green coffee can contain caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use might increase stimulant adverse effects.  Details Green coffee can contain caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).

TERBINAFINE (Lamisil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, terbinafine might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, green coffee might increase the levels and adverse effects of theophylline.  Details Green coffee can contain caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).

VERAPAMIL (Calan, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).

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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.

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General ...Orally, 5-HTP is generally well tolerated, short-term.
Most Common Adverse Effects:
Orally: Abdominal pain, anorexia, dizziness, diarrhea, drowsiness, fatigue, headache, insomnia, nausea, and vomiting. Severity appears to be dose-dependent.
Serious Adverse Effects (Rare):
Orally: Aggression, hallucinations, mania, severe gastrointestinal complaints.

Cardiovascular ...Orally, palpitations have been reported with 5-HTP (30076,30130,30167). Conversely, bradycardia has been reported in patients taking 5-HTP 0.4-2 grams daily in combination with carbidopa 100-300 mg daily (30132). In patients with schizophrenia, a combination of 5-HTP in doses up to 6 grams daily and carbidopa 150 mg daily was associated with diaphoresis and mild diastolic hypotension, especially when doses were increased at a rate faster than 200 mg per day (30183).

Dermatologic ...Orally, 5-HTP has been reported to cause urticaria, other allergic-type skin reactions, and flushing (2204,30000,30140). A scleroderma-like illness was reported in a 70-year-old man who had been taking 5-HTP 1400 mg daily and carbidopa 150 mg daily for 20 months. Elevated serotonin levels may be linked to this condition (1403).

Gastrointestinal ...Orally, 5-HTP has been reported to cause gastrointestinal side effects such as nausea, vomiting, abdominal or epigastric pain, heartburn, constipation, diarrhea, flatulence, anorexia, and taste alteration at any dose (2203,2204,30000,30112,30114,30125,30132,30139,30140)(30165,30183,104250). Severity may be dose-dependent and also related to how quickly doses are increased (30183). Some data suggests that these effects may diminish or disappear with continued use of 5-HTP (30132).

Hematologic ...Symptoms suggestive of eosinophilia myalgia syndrome (EMS) have been reported in some patients using 5-HTP (902,10084,30178,88174,90927). In one case, a woman was exposed to 5-HTP, tetrahydrobiopterin, carbidopa, and levodopa while administering them to her children for 2 years (90927). Her diagnosis was not confirmed, and the validity of the tests performed on the 5-HTP product has been questioned (88174). Other cases of eosinophilia or EMS in patients taking 5-HTP have been attributed to impurities that resemble previously identified contaminants found in L-tryptophan products (902,919,7067,10084). The L-tryptophan contaminants associated with EMS were linked to a specific manufacturer's production method that is not used in the preparation of 5-HTP (88174). Although 5-HTP supplements have been associated with EMS, it seems that this adverse effect is likely due to the presence of contaminants in the 5-HTP products, not 5-HTP itself.

Musculoskeletal ...Orally, rhabdomyolysis was noted in one patient with progressive myoclonus epilepsy who was treated with 5-HTP 300 mg daily for 21 days (30162).

Neurologic/CNS ...Orally, 5-HTP has been reported to cause drowsiness, dizziness, insomnia, fatigue, and headache (30076,30112,30132).

Psychiatric ...Orally, 5-HTP has been associated with euphoria, hypomania and mania, anxiety, insomnia, and aggressiveness (30076,30132,30158,88179). In patients with schizophrenia, a combination of high-dose 5-HTP, up to 6 grams daily, and carbidopa 150 mg daily was associated with transient increases in hallucinations, delusions, marked confusion, looseness of associations, flight of ideas, and a hyperkinetic syndrome consisting of restlessness, hand wringing, pacing, and an inability to sit quietly in a chair (30183).

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General ...Orally, garcinia and its constituent, hydroxycitric acid (HCA), seem to be generally well tolerated in clinical research.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal discomfort, headache, and nausea.
Serious Adverse Effects (Rare):
Orally: Garcinia has been linked with cases of hepatotoxicity and liver failure. There have also been rare cases of mania and pancreatitis.

Cardiovascular ...There is a case report of a 48-year-old female who developed acute necrotizing eosinophilic myocarditis (ANEM) after using a garcinia supplement orally for 2. 5 weeks. On admission to hospital, she was hypotensive and had an elevated serum troponin level, progressing to fulminant heart failure, acute kidney failure, and sustained ventricular arrhythmias. She recovered after treatment with extra-corporeal membrane oxygenation (ECMO) and high-dose corticosteroids (88160). Although the patient had no prior medical history and was not taking any medications, this cannot conclusively be attributed to garcinia.
When taken orally, a specific formulation of the multi-ingredient product Hydroxycut (Iovate Health Sciences Inc.), which was available until 2009, has been associated with malignant hypertension and hypertensive retinopathy. Hydroxycut contains caffeine, garcinia, gymnema, green tea, glucomannan, guarana extract, and willow bark. The suspected causal agent is caffeine, which is dosed at 600 mg daily if Hydroxycut is taken as recommended; however, the responsibility of the other ingredients cannot be ruled out (16527).

Endocrine ...In one case report, a 56-year-old female with pre-existing diabetes, hepatitis C, and hypertension developed diabetic ketoacidosis (DKA) and pancreatitis after taking an unknown amount of garcinia and African mango for one month. Upon admission, she presented with altered mental status, elevated serum glucose and lipase, and high anion gap metabolic acidosis. After 3 days of intensive supportive care, the DKA and pancreatitis resolved. The suspected probable causal agent was garcinia; however, African mango cannot be ruled out (97341). There have been at least 3 other cases of acute pancreatitis associated with use of garcinia (unknown dose) for 2 weeks and up to 7 months in adults ages 36-82 years (105056,105058,105071).

Gastrointestinal ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) have caused mild and infrequent nausea, diarrhea, and other gastrointestinal symptoms (728,11977,19153,88158,88159).

Hepatic ...Orally, garcinia and its constituent hydroxycitric acid (HCA) might cause liver toxicity. Several cases of acute liver toxicity have been reported in patients taking garcinia supplements (93392,93393,93394,95573,102544,102545,104431,111241). Reported doses of garcinia extract range from 480-1800 mg daily, providing up to 900 mg HCA daily (93392,93394,95573,102544,104431). However, not all experts agree that HCA plays a causal role in the hepatotoxicity associated with garcinia supplements; some suggest other mechanisms may be in play, such as immune-mediated processes (95576,108401). In most cases, patients presented with a hepatocellular pattern of toxicity and symptoms of abdominal pain, coagulopathy, jaundice, and elevated transaminases after taking garcinia for several weeks to several months (93393,93394,95573,102544,102545,104431,108401,111241). In most of these cases, there was no evidence of other natural causes of liver disease, such as viral hepatitis. Some of these patients used acetaminophen at recommended doses for limited durations, suggesting that a potential synergistic effect may occur when multiple hepatotoxic agents are used concomitantly.
The Drug-Induced Liver Injury Network has identified 22 cases (11 moderate; 7 severe) of liver injury from garcinia, with 5 cases occurring with garcinia alone, 16 cases occurring in combination with green tea, and 1 case occurring in combination with ashwagandha. Clinical presentations of liver injury related to garcinia closely resemble green tea-related liver injury. Most patients (82%) presented with a hepatocellular pattern of enzyme elevations. The median age of these case reports was 35 years, 41% identified as Hispanic, and most patients were overweight but not obese. In case reports involving garcinia alone, the carrier frequency on HLAB*35:01 was 60%, which is higher than the carrier frequency found in reports of liver injury due to other supplements (19%) and in population controls (11%). Within 3 months of injury onset, 1 patient required liver transplantation and 1 patient died from liver injury (108401).
There have been at least four cases of liver failure requiring transplantation associated with garcinia supplements (93392,95573,98425,104431). In one case related specifically to garcinia, a 52-year-old female had been taking a combination product (USA Nutra Labs) providing garcinia 1000 mg daily, standardized to 60% HCA. The supplement also provided calcium 50 mg, chromium 200 mcg, and potassium 50 mg. Symptoms started within a few weeks of initiation of the product (93392). In another case, a 34-year-old Hispanic male experienced acute liver failure requiring transplant after taking a specific garcinia product (Garcinia Cambogia 5:1 Extract, Swanson Vitamins) 160 mg three times daily before meals for 5 months (95573). In other reports, one 26-year-old male and one female presented to the emergency room with liver failure after 2-7 months of taking a supplement containing garcinia and green tea, with or without whey protein, Veldt raisin, and coffea arabica (98425,104431).
There have also been numerous cases of acute liver toxicity associated with combination products containing garcinia, such as Hydroxycut (Iovate Health Sciences Inc) (13037,53511,93380,93381,93384,93385,96535,98425,104431). Available until 2009, Hydroxycut contained garcinia, green tea, chromium, caffeine, calcium, potassium, and gymnema. A currently available garcinia-containing combination product called Seryburn Day Triple has also been associated with supplement-induced liver injury. (13037,93380,93381,95570,95572,95575,111241). In most of these cases, patients had elevated levels of liver enzymes without evidence of chronic liver disease. Patients usually developed symptoms within 1-12 weeks of taking the product. The clinical pattern of liver damage was often hepatocellular. Most cases reported altered liver enzyme values including ALT, AST, bilirubin, alkaline phosphatase, and international normalized ratio. In most cases, symptoms resolved with near normalization of enzyme levels once the garcinia-containing combination product was discontinued (13037,53511,93380,93381,93384,95567,95572,95575,111241).
However, there is one report of transplant related to Hydroxycut use (93381). As the suspected causal agents, garcinia and green tea were removed from the product during reformulation in 2009 (13037,53511,93380,93381,93384). Hepatotoxicity has been reported in at least one new formulation of Hydroxycut not containing garcinia (93394). Consequently, some experts believe that there is not enough information to attribute hepatotoxicity from this product to garcinia or HCA (95576). Also, in some cases, causality of hepatotoxicity was less clear because patients were taking many other supplements and drugs (95570).There is also a report of fatal liver failure in an obese female taking montelukast while also taking two dietary supplements containing multiple ingredients, including garcinia, gymnema, chromium, bitter orange, and many others. The authors speculated that the combination of montelukast with one or more ingredients in these dietary supplements may have resulted in liver failure (93385).

Musculoskeletal ...Orally, garcinia-containing products have been associated with rhabdomyolysis. There is a case report of a patient who developed rhabdomyolysis 3 hours after ingestion of an herbal product containing ephedra, guarana, chitosan, gymnema, garcinia, and chromium (19154). Since there were multiple ingredients, the effect cannot be conclusively attributed to garcinia. Another case of rhabdomyolysis has been reported for a patient taking an undetermined formulation of Hydroxycut at a dose of 4 caplets daily, naproxen sodium 220 mg as needed for pain, dextroamphetamine daily for 5 days, and hydrocodone-acetaminophen and cyclobenzaprine for pain. Two weeks later, after stopping Hydroxycut and receiving supportive care, the rhabdomyolysis resolved. Hydroxycut was determined to be possibly associated with the rhabdomyolysis (95566). Since Hydroxycut contains multiple ingredients and garcinia content was possible but not confirmed, a causal relationship with garcinia could not be determined.

Neurologic/CNS ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) may cause headache and dizziness (11977). A 35-year-old female reported ocular complications, headache, dizziness, and nausea after taking garcinia extract, providing more than 500 mg of HCA, three times daily for one week. The patient's neurologic symptoms resolved one day after discontinuing the garcinia extract (102546). It is unclear if these neurologic adverse effects were separate from or related to the patient's visual disturbances.

Ocular/Otic ...In one case, a 35-year-old female presented with ocular pain in both eyes, decreased vision in the left eye, headache, dizziness, and nausea after taking garcinia extract orally for one week. Ophthalmologic testing was consistent with adverse ocular effects, showing myopic shift with anterior chamber shallowing and swelling of retinal nerve fiber and macula. The patient reported taking a garcinia product containing hydroxycitric acid 500 mg three times daily, which was more than double the recommended dose per the product label. Symptoms resolved upon discontinuation of the garcinia extract and treatment with oral and topical steroids (102546).

Psychiatric ...Orally, garcinia supplements have been linked to several cases of mania. Typically, symptoms develop 1-8 weeks after starting garcinia. In a report of three patients, symptoms included reduced need for sleep, increased activities and spending, delusions of grandiosity, pressured speech, and agitation. Two of the patients were previously diagnosed with bipolar disorder, and use of garcinia was believed to precipitate episodes during stable phases of the disease. The third patient had no history of bipolar disorder, and use of garcinia was thought to possibly have unmasked previously undiagnosed primary bipolar disorder. In all three cases, recovery included discontinuation of garcinia (95568). In a separate case report, a 23-year-old male taking a specific combination product containing garcinia (Hydroxycut) 1-2 capsules daily for 1 month presented to the emergency room with mania. The patient had no history of bipolar disorder. Although the patient was started on risperidone and clonazepam, symptoms resolved following discontinuation of the supplement. Treatment was discontinued within 4 days of initiation, and the patient remained asymptomatic (95574). A 22-year-old female with no history of bipolar disorder developed mania and psychosis, presenting 10 days after starting Garcinia Cambogia Plus (Apex Vitality Health) 500-1500 mg daily, and Cleanse and Detox (Apex Vitality Health). The latter supplement contains raspberry ketones, licorice root, pumpkin seed, buckthorn root, Cascara sagrada, Irvingia gabonensis, rhubarb, pectin, Lactobacillus acidophilus, and aloe. Symptoms improved upon stopping the supplements and starting lithium and quetiapine (99421).

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General ...Orally, green coffee appears to be well-tolerated. Although green coffee contains caffeine, it is present in small quantities which are less likely to cause adverse effects. Green coffee contains about 20-50 mg caffeine per cup, compared with about 100 mg caffeine per cup of brewed coffee.

Cardiovascular ...Although acute administration of caffeine, a constituent of green coffee, can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722,13739). Drinking one or more cups daily of caffeinated coffee, such as green coffee, also doesn't seem to increase the risk of developing hypertension in habitual coffee drinkers (8033,13739).
Chlorogenic acids found in green coffee extracts may adversely affect plasma homocysteine levels. In one randomized controlled trial, 2 grams of chlorogenic acids (the amount found in about 1.5 L of strong coffee) daily for one week resulted in a 12% increase in plasma homocysteine levels (8035). However, in another trial of green coffee extract in a dose equivalent to 140 mg of chlorogenic acids daily for 4 months, there was a slight decrease in plasma homocysteine levels from baseline, but this did not differ significantly from placebo treatment (17970).
The diterpenes cafestol and kahweol found in green coffee beans have been implicated in the hypercholesterolemic effects of unfiltered coffee (19336,53599). However, these compounds are removed from some green coffee extracts. For instance, Svetol (Naturex, South Hackensack, NJ) is reported to contain less than 4 ppm of cafestol and kahweol (88171).

Dermatologic ...Positive skin tests and symptoms of contact allergy have been reported in workers exposed to green coffee bean dust (53568,53653).

Endocrine ...Some evidence shows that caffeine, a constituent of green coffee, is associated with fibrocystic breast disease, breast cancer, and endometriosis in females; however, this is controversial since findings are conflicting (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
Clinical research in healthy adults shows that increased consumption of caffeine results in increased insulin resistance (91023).

Gastrointestinal ...Orally, stomach irritation was reported by one person in a clinical trial of green coffee extract (104831).

Musculoskeletal ...Epidemiological evidence regarding the relationship between caffeine, which is found in green coffee, and the risk of osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified with a genetic variant of the vitamin D receptor appear to be at an increased risk of the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake, less than 300 mg per day, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).

Neurologic/CNS ...Orally, dizziness was reported by one person in a clinical trial of green coffee extract (104831).

Ocular/Otic ...Conjunctivitis caused by green coffee bean dust in coffee workers has been described in case reports (53657,53589).

Psychiatric ...Chronic use of caffeine, especially in large amounts, may produce tolerance, habituation, and psychological dependence (3719). Abrupt discontinuation of caffeine may result in physical withdrawal symptoms, including headache, fatigue, drowsiness, decreased physical energy, difficulty concentrating, depression, anxiety, irritability, and reduced alertness (13738). Certain populations such as children and the elderly may be more susceptible to the adverse effects of caffeine (13736).

Pulmonary/Respiratory ...Occupational exposure to green coffee beans has been documented to cause numerous adverse respiratory reactions, including bronchial reactivity, asthma, and rhinitis (53589,53641,53644,53648,53650,53665). Healthy subjects exposed experimentally to green coffee dust displayed acute decreases in expiratory flow rates (53653). In one study, green coffee workers displayed numerous acute respiratory symptoms when exposed to dust; these included coughing, increased sputum, sneezing, difficulty in breathing, running nose, and wheezing; these symptoms resolved after leaving work (53647).

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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).

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