Tri-Metabolic Control by Douglas Laboratories

POSSIBLY EFFECTIVE

• Age-related cognitive decline. Oral acetyl-L-carnitine may improve age-related cognitive decline. Details: Clinical research shows that taking acetyl-L-carnitine 1500-2000 mg daily for 3 months seems to improve some measures of cognitive function and memory in elderly people with age-related cognitive decline (42,3600,3601).
• Age-related fatigue. Oral acetyl-L-carnitine may improve age-related physical and mental fatigue. Details: One clinical trial shows that taking acetyl-L-carnitine 2 grams twice daily for 180 days reduces physical fatigue by 52% and mental fatigue by 43%, compared with only 4% and 8%, respectively, for elderly patients taking placebo. Fatigue after exercise is also reduced by 51% in those taking acetyl-L-carnitine, compared with only 4% in those taking placebo (58375).
• Alcohol use disorder. Intravenous acetyl-L-carnitine may reduce cravings and other symptoms of withdrawal during alcohol detoxification. It is unclear if oral acetyl-L-carnitine is beneficial for managing withdrawal or complications of alcohol use disorder. Details: Clinical research in adults with alcohol use disorder who are in withdrawal shows that acetyl-L-carnitine 1-3 grams daily, administered as a slow intravenous infusion over 3-4 hours for 10 days, followed by 3 grams daily orally for an additional 80 days, improves cravings, the inability to feel pleasure (anhedonia), and melancholic symptoms and increases the time to the first drink when compared with placebo. However, most symptom improvement appears to occur during the first week, so it is unclear if taking acetyl-L-carnitine 3 grams daily orally for an additional 80 days is beneficial (90766,90767). One small clinical trial in adults with chronic alcohol use disorder and cognitive impairment shows that taking acetyl-L-carnitine 2 grams daily for 90 days seems to improve memory and visuospatial capacity when compared with placebo (1589).
• Alzheimer disease. Oral acetyl-L-carnitine may slow the progression of Alzheimer disease and improve some measures of cognitive function. Details: Clinical research shows that taking acetyl-L-carnitine 1.5-3 grams daily for 3-12 months might slow the rate of Alzheimer disease progression and improve memory, some measures of cognitive function, and behavioral performance. It is more likely to show some effect in those with early-onset Alzheimer disease who are less than 66 years of age and have a faster rate of disease progression and mental decline (1594,1595,1596,1597,1598,1599,9105,10391). It is unclear how acetyl-L-carnitine compares with prescription medications.
• Depression. Oral acetyl-L-carnitine may reduce symptoms of depression, with comparable effects to conventional antidepressants, in patients with dysthymia and depression. It may be most effective in elderly patients and at higher doses. Details: Several clinical trials addressing the use of acetyl-L-carnitine in elderly patients with dysthymia and depression have been conducted (3602,3603,3604). A meta-analysis of these and other studies, all conducted in Europe, shows that taking acetyl-L-carnitine 1-4 grams daily for 3-24 weeks moderately reduces depressive symptoms when compared with placebo, and appears to have similar effects as conventional antidepressants. Acetyl-L-carnitine seems to be most effective when used at higher dosages. Duration of follow-up and baseline symptoms do not appear to influence results (95065).
• Diabetic neuropathy. Oral acetyl-L-carnitine may reduce pain in patients with diabetic neuropathy when taken at doses of at least 2-3 grams daily. It is unclear if oral acetyl-L-carnitine can improve nerve conduction velocity in these patients. Details: Although most clinical research evaluating acetyl-L-carnitine for use in diabetic neuropathy has shown benefit, this evidence is of overall low quality. A meta-analysis shows that taking acetyl-L-carnitine 2-3 grams daily for up to 12 months modestly reduces pain scores by about 15 points on a 100-point visual analog scale, while lower doses of 1.5 grams daily improve pain scores to a similar extent as placebo. Some research included in this analysis shows that acetyl-L-carnitine seems to increase nerve fibers, regenerate nerve fiber clusters, and improve vibratory sensations. In two studies, vibration sensation improved after 12 months when compared with placebo, but numerical data are lacking (102126). Other clinical research shows that taking acetyl-L-carnitine 1000 mg 2-3 times daily decreases pain within 6 months. Acetyl-L-carnitine seems to be most effective for reducing pain in patients with a shorter duration of diabetes and in patients with poorly controlled type 2 diabetes. Some research shows that taking acetyl-L-carnitine 500 mg (Liaoning Haisike Pharmaceutical Co. Ltd.) three times daily for 24 weeks is as effective as methylcobalamin 0.5 mg three times daily for improving electrophysiological parameters and symptoms as measured by the Neuropathy Disability Score (95067,102126). However, research on the use of acetyl-L-carnitine to improve nerve conduction velocity in patients with diabetic neuropathy is conflicting (1593,12743,12753,13007,95067).
• Male infertility. Oral acetyl-L-carnitine, taken in combination with L-carnitine, may increase sperm motility in males with infertility. It is unclear if oral acetyl-L-carnitine alone can improve sperm function or pregnancy outcomes. Details: Although some research disagrees (111861), taking acetyl-L-carnitine in combination with L-carnitine, usually in doses of 1 gram and 2 grams, respectively, daily for 3-6 months seems to increase sperm motility in males with infertility of various etiologies. The evidence related to the effect of this combination on sperm count and morphology is mixed (12352,58182,58194,58469,101560,107394,111459,111890). However, it is unclear if taking L-carnitine increases the odds of pregnancy. One meta-analysis of randomized controlled trials shows that taking these carnitines 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). Taking acetyl-L-carnitine 500 mg and L-carnitine 1 gram twice daily after taking nonsteroidal anti-inflammatory drugs for 2 months seems to increase sperm count and motility in those with abacterial prostatovesiculoepididymitis, an inflammation of the prostate gland, seminal vesicles, and epididymis (9791). Acetyl-L-carnitine has also been evaluated in combination with other ingredients. One study shows that taking acetyl-L-carnitine 50 mg in combination with L-carnitine 150 mg, L-arginine 1660 mg, and Panax ginseng 200 mg daily for 3 months increases sperm motility and sexual satisfaction in those with asthenospermia 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 treatment with prulifloxacin alone in patients with chronic prostatitis due to Chlamydia trachomatis infection (59006). Other small and preliminary Iclinical studies have investigated the effects of a specific combination product providing acetyl-L-carnitine 500 mg twice daily for 6 months, along with 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.

POSSIBLY INEFFECTIVE

• Chemotherapy-induced peripheral neuropathy. The evidence related to the effect of oral acetyl-L-carnitine on symptoms of chemotherapy-induced peripheral neuropathy is mixed. Some research shows that it may actually worsen symptoms. Details: High quality clinical research in females treated with taxane-based therapy for early-stage breast cancer shows that taking acetyl-L-carnitine 1000 mg three times daily for 24 weeks does not improve symptoms of neuropathy when compared with placebo. In fact, acetyl-L-carnitine treatment may actually make symptoms worse in some patients, with worsened symptoms persisting for up to at least 2 years (90758,96938,111882). Also, a small clinical trial in patients with multiple myeloma receiving bortezomib, doxorubicin, and dexamethasone shows that taking acetyl-L-carnitine 1.5 grams daily does not reduce symptoms of peripheral neuropathy when compared with not taking acetyl-L-carnitine (90756). A small clinical trial in patients with ovarian cancer or castration-resistant prostate cancer receiving sagopilone shows that taking acetyl-L-carnitine 1000 mg every three days appears to reduce the more severe symptoms of peripheral neuropathy; however, the overall incidence or duration of peripheral neuropathy is not reduced when compared with placebo (90757). Some research disagrees. One clinical trial in patients with taxoid-related neuropathy shows that taking acetyl-L-carnitine3 grams daily for 8 weeks modestly improves the severity of neuropathy by at last one grade in 51% of patients compared with 24% of those taking placebo. Functional improvement was also modestly improved (111862). Based on the available research, the American Society of Clinical Oncology strongly discourages the use of acetyl-L-carnitine for the prevention of chemotherapy-induced peripheral neuropathy, noting that the harms outweigh the potential benefits (104168).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related testosterone deficiency. Oral acetyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in older males shows that taking acetyl-L-carnitine 2 grams, in combination with propionyl-L-carnitine 2 grams, daily for 6 months seems to attenuate symptoms of androgen decline. The combination appears to be similar to testosterone for improving sexual dysfunction, depression, and fatigue (12353). It is unclear if these findings are due to acetyl-L-carnitine, propionyl-L-carnitine, or the combination.
• Aging skin. Although there has been interest in using oral acetyl-L-carnitine for aging skin, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Amenorrhea. Although there has been interest in using oral acetyl-L-carnitine for amenorrhea, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral acetyl-L-carnitine is beneficial in patients with ALS. Details: One small clinical trial in patients with ALS shows that taking acetyl-L-carnitine 1000 mg three times daily for 48 weeks, along with riluzole 50 mg twice daily, reduces the number of patients who lose self-sufficiency by about 17%, increases patient survival by a median of 23 months, and improves some measures of physical function when compared with riluzole alone (90755).
• Antiretroviral toxic neuropathy. Small clinical studies suggest that oral acetyl-L-carnitine may modestly improve symptoms in patients with antiretroviral toxic neuropathy. It is unclear if intramuscular or intravenous acetyl-L-carnitine is beneficial in patients with this condition. Details: Small clinical trials show that taking acetyl-L-carnitine 1000-1500 mg twice daily for up to 33 months might relieve symptoms of distal symmetrical polyneuropathy caused by antiretroviral treatment in HIV-positive patients (12745,58342). Also, a small, uncontrolled clinical study shows that intramuscular or intravenous administration of acetyl-L-carnitine 500-1000 mg daily for 3 weeks reduces pain intensity when compared to baseline in some HIV-positive patients receiving antiretroviral therapy (12747). However, another clinical study shows that intramuscular acetyl-L-carnitine 500 mg twice daily for 14 days does not reduce pain when compared with placebo (58342).
• Athletic performance. Although there has been interest in using oral acetyl-L-carnitine for athletic performance, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Small clinical trials suggest that oral acetyl-L-carnitine is not beneficial in children with ADHD. Details: One small clinical trial in children and adolescents with ADHD shows that taking acetyl-L-carnitine 1-3 grams daily, based on body weight, in two divided doses along with methylphenidate 20-30 mg daily for 3 weeks does not reduce symptoms of ADHD when compared with methylphenidate alone (90754). Based on this and another small trial, Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that acetyl-L-carnitine in doses of 1-3 grams daily is not recommended for adjunctive or monotherapy use for ADHD in children (110318).
• Bell palsy. Although there has been interest in using oral acetyl-L-carnitine for Bell palsy, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Bipolar disorder. Oral acetyl-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 type I or type II bipolar disorder shows that taking acetyl-L-carnitine 1000 mg plus alpha-lipoic acid 600 mg up to three times daily for 12 weeks does not improve depression when compared with placebo (90441).
• Cancer-related fatigue. Although there has been interest in using oral acetyl-L-carnitine for cancer-related fatigue, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Carpal tunnel syndrome. It is unclear if oral acetyl-L-carnitine is beneficial in patients undergoing surgery for carpal tunnel syndrome. Details: A small clinical study in adults undergoing carpal tunnel release surgery shows that taking acetyl-L-carnitine 3000 mg daily for 2 months postoperatively does not improve nerve regeneration or functional recovery when compared with placebo (100349). However, this study may have been inadequately powered to detect a difference between groups. Acetyl-L-carnitine has also been investigated in combination with other ingredients. In patients with mild to moderate symptoms awaiting carpal tunnel release, preliminary clinical research shows that taking acetyl-L-carnitine as part of a multi-ingredient formulation for 60 days reduces pain by 31%, but does not improve function, when compared with no treatment. The formulation provided a total of 600 mg twice daily of acetyl-L-carnitine with alpha-lipoic acid, phosphatidylserine, curcumin, thiamine, riboflavin, and vitamins C, E, B6, and B12 (111702).
• Cataracts. Although there has been interest in using oral acetyl-L-carnitine for cataracts, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Chronic fatigue syndrome (CFS). It is unclear if oral acetyl-L-carnitine is beneficial in patients with CFS. Details: Preliminary clinical research in patients with CFS shows that taking acetyl-L-carnitine 2 grams daily for 6 months improves general fatigue in up to 59% of patients when compared with baseline. The combination of acetyl-L-carnitine and propionyl-L-carnitine appears to be less effective than either supplement alone, with only 37% of patients taking this combination achieving improvement when compared with baseline (11788).
• Diabetes. It is unclear if oral acetyl-L-carnitine improves glycemic control in people with type 2 diabetes. Details: Clinical research in patients with type 2 diabetes, hypertension, and dyslipidemia shows that taking acetyl-L-carnitine 1 gram twice daily for 6 months does not improve blood glucose levels, glycated hemoglobin, fasting insulin levels, insulin resistance, or glucose disposal rate when compared with placebo. Most patients were already taking one or more antidiabetes drug, as well as medication for hypertension and dyslipidemia (96937). It is unclear if acetyl-L-carnitine improves glycemic profile in patients with uncontrolled diabetes.
• Down syndrome. Although there has been interest in using oral acetyl-L-carnitine for Down syndrome, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Dyslipidemia. It is unclear if oral acetyl-L-carnitine reduces lipid levels in adults with dyslipidemia. Details: Clinical research in patients with dyslipidemia, type 2 diabetes, and hypertension shows that taking acetyl-L-carnitine 1 gram twice daily for 6 months does not improve cholesterol, triglycerides, or lipoprotein(a) levels when compared with placebo. All patients were taking statins prior to treatment with acetyl-L-carnitine, and most were receiving medication for hypertension and diabetes (96937). It is unclear if acetyl-L-carnitine is beneficial in patients not taking statins.
• Fibromyalgia. It is unclear if oral and/or intramuscular acetyl-L-carnitine can improve symptoms of fibromyalgia. Details: One clinical study in patients with fibromyalgia shows that taking acetyl-L-carnitine 1000 mg daily orally plus acetyl-L-carnitine 500 mg daily intramuscularly for 2 weeks, followed by acetyl-L-carnitine 1500 mg daily orally for 8 weeks, reduces muscle pain and improves mood, general health, and quality of life when compared with placebo (90768). A smaller clinical study in patients with fibromyalgia shows that taking acetyl-L-carnitine 500 mg three times daily for 12 weeks improves quality of life (physical) scores and symptoms of depression, but not pain, anxiety, or quality of life (mental) scores when compared with baseline (90761). The validity of these findings is limited by the lack of a comparator group. Acetyl-L-carnitine has also been investigated in combination with other ingredients. Clinical research shows that taking acetyl-L-carnitine 500 mg and palmitoylethanolamide (PEA) 600 mg twice daily for 12 weeks increases the proportion of patients with at least a 30% reduction in pain by 86% when compared with not taking this combination. There was also a modest improvement in the overall assessment of status. All patients were on stable treatment with duloxetine and pregabalin for 3 months prior to the initiation of acetyl-L-carnitine and PEA, and this treatment continued throughout the study (111901).
• Fragile X syndrome. Small clinical studies suggest that oral acetyl-L-carnitine is not beneficial in children with fragile X syndrome. Details: Two small clinical studies in children with fragile X syndrome shows that acetyl-L-carnitine 20-50 mg/kg daily for one year does not improve intellectual function when compared with placebo. Also, while it may reduce hyperactive behavior in these patients based on parent assessment, it does not appear to reduce hyperactive behavior based on teacher assessment (9956,93063).
• Frailty. It is unclear if oral acetyl-L-carnitine prevents frailty. Details: Clinical research in pre-frail older adults shows that taking acetyl-L-carnitine 1.5 grams twice daily for 3 months modestly improves cognition and the distance walked in 6 minutes when compared with taking placebo (111889). It is unclear whether taking acetyl-L-carnitine is beneficial for frailty treatment or prevention.
• Hepatic encephalopathy. Small clinical studies suggest that oral acetyl-L-carnitine may not improve quality of life or fatigue in patients with hepatic encephalopathy due to cirrhosis. Details: The benefits of acetyl-L-carnitine in the management of hepatic encephalopathy due to cirrhosis are unclear (58922,58949,59002,90759). A meta-analysis of the available clinical research shows that taking acetyl-L-carnitine 2 grams twice daily for 90 days does not improve quality of life or fatigue in this population when compared with placebo. However, major clinical outcomes, such as all-cause mortality, days of hospitalization, and serious adverse events, have not been evaluated. Additionally, the validity of these findings is limited by the small size, high risk for bias, and heterogeneity of the included studies (100350).
• Hypertension. It is unclear if oral acetyl-L-carnitine lowers blood pressure in adults with hypertension. Details: Clinical research in patients with hypertension, type 2 diabetes, and dyslipidemia shows that taking acetyl-L-carnitine 1 gram twice daily for 6 months does not improve systolic or diastolic blood pressure when compared with placebo. Most patients were already being treated with antihypertensive drugs prior to treatment with acetyl-L-carnitine, in addition to medications for dyslipidemia and diabetes (96937). It is unclear if acetyl-L-carnitine reduces blood pressure in patients with uncontrolled hypertension.
• Infertility. Although there has been interest in using oral acetyl-L-carnitine for infertility in females, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Lyme disease. Although there has been interest in using oral acetyl-L-carnitine for Lyme disease, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Multiple sclerosis-related fatigue. It is unclear if oral acetyl-L-carnitine is beneficial in patients with multiple sclerosis-related fatigue. Details: One small clinical study in patients with multiple sclerosis shows that taking acetyl-L-carnitine 1 gram twice daily for one month reduces fatigue by approximately 25% when compared with placebo (90760).
• Obesity. Although there has been interest in using oral acetyl-L-carnitine for obesity, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Peripheral neuropathy. Although there has been interest in using oral acetyl-L-carnitine for peripheral neuropathy, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Peyronie disease. A small clinical study suggests that oral acetyl-L-carnitine may modestly improve symptoms of Peyronie disease. Details: One small clinical trial in patients with acute and early chronic Peyronie disease shows that taking acetyl-L-carnitine 1 gram twice daily for 3 months reduces pain and slows disease progression when compared with tamoxifen 20 mg twice daily (10076).
• Polycystic ovary syndrome (PCOS). It is unclear if acetyl-L-carnitine is beneficial in patients with PCOS. Details: A clinical study in patients with PCOS shows that taking acetyl-L-carnitine 1.5 grams, in combination with metformin and pioglitazone, twice daily for 12 weeks improves menstrual irregularity and insulin resistance when compared with baseline. The lack of statistical comparison to placebo, as well as the combined use with metformin and pioglitazone, limits the validity of these findings (107396).
• Schizophrenia. It is unclear if oral acetyl-L-carnitine is beneficial in patients with schizophrenia. Details: A very small, open-label clinical study in patients with schizophrenia who partially responded to clozapine therapy shows that taking acetyl-L-carnitine 1 gram daily, in combination with clozapine 300-600 mg daily, for 12 weeks reduces positive symptoms of schizophrenia, but not cognitive function or other clinical symptoms, when compared with baseline (95063). The validity of these findings is limited by the lack of a comparator group.
• Sciatica. It is unclear if oral acetyl-L-carnitine is beneficial in patients with sciatica. Details: One small clinical trial in patients with sciatica secondary to a herniated disc shows that taking acetyl-L-carnitine (Nicetile, SigmaTau Ind. Farm. Riunite SpA,) 1180 mg daily for 60 days decreases the use of analgesics when compared with baseline. However, acetyl-L-carnitine appears to be less effective than alpha-lipoic acid (Byodiniral 300 QR, MDM SpA,) 600 mg daily for reducing lower limb pain and the use of analgesics (21671).
• Stroke. It is unclear if oral acetyl-L-carnitine is beneficial following a stroke. Details: Clinical research in patients with an acute ischemic stroke given routine care shows that oral or nasogastric acetyl-L-carnitine 1 gram three times daily for 3 days modestly improves stroke impairment and overall function 3 months after the stroke when compared with taking placebo. The proportion of patients taking acetyl-L-carnitine with no symptoms or obvious disability at 3 months was 53%, compared with 29% of patients taking placebo. The patients in this study were not candidates of reperfusion therapy and initiated acetyl-L-carnitine within 24 hours of the stroke (111894).
• Toxin-induced liver damage. Oral acetyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients being treated with anti-tuberculosis drugs shows that taking acetyl-L-carnitine 250 mg, along with coenzyme Q10 and alpha-lipoic acid, twice daily for 2 weeks reduces the risk of drug-induced liver injury by 73% when compared with placebo (107445). It is unclear if these findings are due to acetyl-L-carnitine, other ingredients, or the combination. More evidence is needed to rate acetyl-L-carnitine for these uses.

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LIKELY SAFE ...when used orally and appropriately. Acetyl-L-carnitine has been used safely in doses up to 3 grams daily in clinical trials lasting up to 33 months (42,1589,1594,1595,1596,1597,1598,1599,3600,3601) (9105,9791,10076,12743,12745,58375,90755,90756,90759,90761)(90766,90767,90768,95063,95067,111862).

POSSIBLY SAFE ...when used parenterally and appropriately under medical supervision (1591,1592,12743).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Acetyl-L-carnitine has been safely used orally in children for up to 6 weeks (90754).

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

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ACENOCOUMAROL (Sintrom) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.  Details L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. 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). It is unclear if such an interaction would also occur with acetyl-L-carnitine.

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.  Details Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain (95065).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, acetyl-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). It is unclear if such an interaction would occur with acetyl-L-carnitine.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.  Details L-carnitine, the parent compound of acetyl-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 acetyl-L-carnitine and warfarin.

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General ...Orally, acetyl-L-carnitine is generally well tolerated.
Most Common Adverse Effects:
Orally: Agitation, dry mouth, headache, insomnia, and reduced appetite. A metabolite of acetyl-L-carnitine has been reported to cause a fishy odor of the urine, breath, and sweat.

Cardiovascular ...Orally, one patient in a pharmacokinetic study reported high blood pressure 8 hoursafter taking acetyl-L-carnitine 500 mg; however, it is unclear if this was due to acetyl-L-carnitine or another factor (95061).

Dermatologic ...Orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause rash (90441).

Gastrointestinal ...Orally, acetyl-L-carnitine may cause nausea, vomiting, diarrhea, constipation, hiccups, abdominal distension and gastrointestinal upset or pain. However, gastrointestinal symptoms do not usually occur more often in patients receiving acetyl-L-carnitine than in patients receiving placebo (1596,1599,12743,13007,58922,90755,95063,95067,111889,111894). Acetyl-L-carnitine may also cause dry mouth and anorexia (58342). When taken orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause diarrhea, constipation, and dyspepsia (90441).

Neurologic/CNS ...Orally, acetyl-L-carnitine may cause headache and insomnia (90760,90767,95063). In one clinical trial, two patients with antiretroviral toxic neuropathy reported paresthesia, pain, and neuropathy after taking acetyl-L-carnitine 1000 mg daily (58342). A case of mania has been reported for a patient with bipolar I disorder currently in remission. The patient presented with symptoms after taking multiple supplements for the past 4 weeks including acetyl-L-carnitine 1000 mg twice daily. The symptoms appeared 3 days after beginning to take acetyl-L-carnitine and worsened over the next week. The patient had increased speech rate and volume and reported increased energy levels and racing thoughts. The patient's parent reported irritability and an increase in loud behaviors at home, similar to a previous episode of mania. The patient was advised to discontinue acetyl-L-carnitine, and the manic symptoms disappeared 3 days later (95062).

Psychiatric ...Orally, acetyl-L-carnitine may cause agitation (restlessness and motor overactivity) (1596,1599,12743,13007). Side effects reported in people with Alzheimer disease include psychiatric disturbances such as depression, mania, confusion and aggression, but it is not clear whether these are due to acetyl-L-carnitine or the condition itself (1594,1595,1596,1597,1598,1599,9105,10391).

Other ...One of the metabolites of acetyl-L-carnitine can cause the urine, breath, and sweat to have a fishy odor (12756). Also, foul smelling urine has been reported following oral use of a combination of acetyl-L-carnitine and alpha-lipoic acid (90441).

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