Carnitine as a dietary supplement

• PRINCIPAL PROPOSED USES: Angina, chronic obstructive pulmonary disease, congestive heart failure, diabetic peripheral neuropathy, heart attack, hyperthyroidism, intermittent claudication, male infertility, male sexual dysfunction, Peyronie’s disease
• OTHER PROPOSED USES: Alzheimer’s disease, attention deficit disorder, celiac disease, chronic fatigue syndrome, depression, diabetes, diabetic cardiac autonomic neuropathy, enhancing mental function in older adults, fibromyalgia, high cholesterol, human immunodeficiency virus infection, hyperactivity in fragile X syndrome, liver cirrhosis, sports performance, weight loss

Overview

Carnitine is a substance used by the body to turn fat into energy. It is not considered an essential nutrient because the body can manufacture all it needs. However, supplemental carnitine may improve the ability of certain tissues to produce energy. This has led to the use of carnitine for various muscle diseases and heart conditions.

Requirements and Sources

There is no dietary requirement for carnitine. However, some people have genetic defects that hinder the body’s ability to make carnitine. In addition, diseases of the liver, kidneys, or brain may inhibit carnitine production. Certain medications, especially the antiseizure drugs valproic acid (Depakene) and phenytoin (Dilantin), may reduce carnitine levels; however, whether taking extra carnitine would be helpful has not been determined. Because heart muscle tissue has a high energy requirement, it is particularly vulnerable to carnitine deficiency.

The principal dietary sources of carnitine are meat and dairy products. To obtain therapeutic dosages, however, a supplement is necessary.

Therapeutic Dosages

Typical adult dosages for the diseases described here range from 500 to 1,000 milligrams (mg) three times daily. For children, one study used fifty milligrams per kilogram twice daily, up to a maximum of four grams daily, which can be taken for up to six months.

Carnitine is taken in several forms for different purposes. L-carnitine is taken for heart and other conditions, propionyl-L-carnitine is taken for heart conditions, acetyl-L-carnitine is taken for brain health and neurodegenerative diseases like Alzheimer’s disease, D-carnitine is taken in an inactive form, and L-carnitine L-tartrate is often added to sports supplements for muscle recovery. The dosage is the same for all forms, and they are available in pills ranging from 3 to 5,000 mg.

Therapeutic Uses

Carnitine is primarily used for heart-related conditions. Some evidence suggests that it can be used along with conventional treatment for angina to improve symptoms and reduce medication needs. When combined with conventional therapy, it may or may not help prevent medical complications or sudden cardiac death in the months following a heart attack.

Lesser evidence suggests that it may be helpful for a condition called intermittent claudicationpain in the legs after walking due to narrowing of the arteriesand for congestive heart failure. In addition, a few studies suggest that carnitine may be useful for cardiomyopathy.

Carnitine may also be helpful for improving exercise tolerance in people with chronic obstructive pulmonary disease (COPD), also known as emphysema. One should not attempt to self-treat any of the foregoing serious medical conditions or use carnitine as a substitute for standard drugs.

Growing, if not entirely consistent, evidence suggests that L-carnitine or acetyl-L-carnitine, or their combination, may be helpful for improving sperm function and thereby provide benefits in male infertility. Two studies found evidence that carnitine is helpful for Peyronie’s disease, a condition affecting the penis.

Carnitine has also shown promise for improving mental and physical fatigue in older adults. Some studies have found evidence that one particular form of carnitine, acetyl-L-carnitine, might be helpful in Alzheimer’s disease, but the two most recent and largest studies found no benefit. One review evaluated published and unpublished double-blind, placebo-controlled trials and concluded that acetyl-L-carnitine may only be helpful for very mild Alzheimer’s disease.

Acetyl-L-carnitine has shown promise for the treatment of depression or dysthymiaa milder condition related to depressionnd for the identification of individuals at the highest risk of developing these conditions. Researchers at Stanford University linked low blood levels of acetyl-L-carnitine to depression. In their study, they found that the lower the level of carnitine, the worse the depression symptoms. With this genetic biomarker, physicians can better address depression in their patients.

Some evidence suggests that carnitine may be useful for improving blood sugar control in people with type 2 diabetes. Better evidence suggests the benefits of acetyl-L-carnitine for a major complication of diabetes, diabetic peripheral neuropathy (injury to nerves of the extremities caused by diabetes). Acetyl-L-carnitine might help prevent diabetic cardiac autonomic neuropathy, and injury to the nerves of the heart caused by diabetes. However, one study found that carnitine supplements had an adverse effect on triglyceride levels in people with diabetes.

Much weaker evidence suggests possible benefits for neuropathy caused by the chemotherapy drugs cisplatin and paclitaxel. Weak evidence hints that carnitine might help reduce liver and heart toxicity caused by the chemotherapy drug adriamycin.

Some evidence suggests that carnitine may be able to improve cholesterol profile. One small study demonstrated a beneficial effect of L-carnitine on anemia and high cholesterol in persons on hemodialysis for chronic renal failure.

A genetic condition called fragile X syndrome can cause behavioral disturbances such as hyperactivity, learning disabilities, cognitive impairment, and alterations in appearance. A preliminary study of seventeen boys found that acetyl-L-carnitine might help to reduce hyperactive behavior associated with this condition. Evidence for the effectiveness of L-carnitine in attention deficit hyperactivity disorder (ADHD) has been mixed. Many studies have failed to find positive results in human trials.

Celiac disease is an autoimmune disease affecting the digestive tract. Fatigue is a common symptom of the disease. One small double-blind trial found evidence that the use of L-carnitine at a dose of two grams daily might help alleviate this symptom.

Weak evidence hints that carnitine may help people with degeneration of the cerebellum (the structure of the brain responsible for voluntary muscular movement). One small study suggests carnitine may be helpful for reducing symptoms of chronic fatigue syndrome. Another study suggests that carnitine may be of value for treating hyperthyroidism and for severe liver disease. A substantial study marred by poor design (specifically, far too many primary endpoints) found equivocal evidence that L-carnitine, taken at dose of 500 mg three times daily, might be more effective than placebo for the treatment of fibromyalgia.

Other weak evidence suggests that carnitine may be helpful for decreasing the muscle toxicity of Zidovudine (ZDV), also known as azidothymidine (AZT), a drug used to treat human immunodeficiency virus (HIV) infection. Other weak evidence hints that acetyl-L-carnitine might reduce nerve-related side effects caused by HIV drugs in general.

One study failed to find carnitine effective for promoting weight loss, although another found that carnitine might lead to improvements in body composition (fat-muscle ratio). Carnitine is widely touted as a physical performance enhancer, but there is no real evidence that it is effective, and some research indicates that it is not.

Little to no evidence supports other claimed benefits, such as treating irregular heartbeat, Down syndrome, muscular dystrophy, and alcoholic fatty liver disease. However, in a randomized trial involving twenty-five persons with liver cirrhosis and early brain dysfunction (hepatic encephalopathy) associated with severe forms of this condition, carnitine appeared to significantly improve the function of both the liver and the brain after three months of treatment.

Scientific Evidence

Angina. Carnitine might be a good addition to standard therapy for angina. In one controlled study, two hundred persons with angina (the exercise-induced variety) either took 2 g daily of L-carnitine or were left untreated. All the study participants continued to take their usual medication for angina. Those taking carnitine showed improvement in several measures of heart function, including a significantly greater ability to exercise without chest pain. They were also able to reduce the dosages of some of their heart medications, under medical supervision, as their symptoms decreased.

The results of this study cannot be fully trusted because researchers did not use a double-blind protocol. Another trial with a double-blind, placebo-controlled design tested L-carnitine in fifty-two people with angina and found evidence of benefit.

In addition, several small studies (some of them double-blind) tested propionyl-L-carnitine for the treatment of angina and also found evidence of benefit.

Intermittent claudication. People with advanced hardening of the arteries, or atherosclerosis, often have difficulty walking because of a lack of blood flow to the legs, a condition called intermittent claudication. Pain may develop after walking less than half a block. Although carnitine does not increase blood flow, it appears to improve the muscle’s ability to function under difficult circumstances.

A twelve-month, double-blind, placebo-controlled trial of 485 persons with intermittent claudication evaluated the potential benefits of propionyl-L-carnitine. Participants with relatively severe disease showed a 44 percent improvement in walking distance, compared with placebo. However, no improvement was seen in those persons with mild disease. Another double-blind study followed 245 people and also found benefit.

Similar results have been seen in most other studies of L-carnitine or propionyl-L-carnitine. Propionyl-L-carnitine may be more effective for intermittent claudication than plain carnitine.

Congestive heart failure. Several small studies have found that carnitine, often in the form of propionyl-L-carnitine, can improve symptoms of congestive heart failure. In one trial, benefits were maintained for sixty days after treatment with carnitine was stopped.

After a heart attack. L-carnitine has shown inconsistent promise for use after a heart attack. A double-blind, placebo-controlled study followed 101 people for one month after those persons had experienced a heart attack. The study found that the use of L-carnitine, in addition to standard care, reduced the size of the infarctdead heart tissue.

In the months following a severe heart attack, the left ventricle of the heart often enlarges, and the pumping action of the heart becomes less efficient. Some evidence suggests that L-carnitine can help prevent heart enlargement but that it does not improve heart function. In a twelve-month, double-blind, placebo-controlled study of 472 persons who had just had a heart attack, the use of carnitine at a dose of 6 g per day significantly decreased the rate of heart enlargement. However, heart function was not significantly altered.

A three-month, double-blind, placebo-controlled study of sixty persons who had just had a heart attack also failed to find improvements in heart function. Heart enlargement was not studied.

Results consistent with the foregoing studies were seen in a six-month double-blind, placebo-controlled study of 2,330 people who had just had a heart attack. Carnitine failed to produce significant reductions in mortality or heart failure over the six-month period. However, the study did find reductions in early death. For statistical reasons, the meaningfulness of this last finding is questionable. Reduction in early death was a secondary endpoint rather than a primary one. Carnitine is used with conventional treatment, not as a substitute for it.

Diabetic neuropathy. High levels of blood sugar can damage the nerves, leading to the extremities, causing pain and numbness. This condition is called diabetic peripheral neuropathy. Nerve damage may also develop in the heart, a condition called cardiac autonomic neuropathy. Acetyl-L-carnitine has shown considerable promise for diabetic peripheral neuropathy and some promise for cardiac autonomic neuropathy.

Two fifty-two-week, double-blind, placebo-controlled studies involving a total of 1,257 people with diabetic peripheral neuropathy evaluated the potential benefits of acetyl-L-carnitine taken at 500 or 1,000 mg daily. The results showed that the use of acetyl-L-carnitine, especially at the higher dose, improved sensory perception and decreased pain levels. In addition, the supplement appeared to promote nerve fiber regeneration. A small study found some potential benefits for cardiac autonomic neuropathy.

Male sexual function. Carnitine has shown promise for improving male sexual function. One double-blind, placebo-controlled study of 120 men compared a combination of propionyl-L-carnitine (two grams per day) and acetyl-L-carnitine (two grams per day) with testosterone for the treatment of male aging symptoms such as sexual dysfunction, depression, and fatigue. The results indicated that both testosterone and carnitine improved erectile function, mood, and fatigue, compared with placebo. However, no improvements were seen in the placebo group. This is an unusual occurrence in studies of erectile dysfunction, so it casts some doubt on the study results.

A double-blind study of forty men evaluated propionyl-L-carnitine (two grams per day) in diabetic men with erectile dysfunction who had not responded well to Viagra. The results indicated that carnitine significantly enhanced the effectiveness of Viagra. In another double-blind study, a combination of the propionyl and acetyl forms of carnitine enhanced the effectiveness of Viagra in men who had erectile dysfunction caused by prostate surgery.

Male infertility. Growing evidence suggests that L-carnitine or acetyl-L-carnitine, or their combination, may be helpful for improving sperm quality and function, thereby benefiting male infertility. For example, in one double-blind, placebo-controlled study of sixty men, the use of combined L-carnitine (two grams per day) and acetyl-L-carnitine (two grams per day) significantly improved sperm quality.

Chronic obstructive pulmonary disease (COPD). Evidence from three double-blind, placebo-controlled studies enrolling a total of forty-nine people suggests that L-carnitine can improve exercise tolerance in COPD, presumably by improving muscular efficiency in the lungs and other muscles.

Alzheimer’s disease. Numerous double-blind or single-blind studies involving a total of more than fourteen hundred people have evaluated the potential benefits of acetyl-L-carnitine in the treatment of Alzheimer’s disease and other forms of dementia. However, while early studies found evidence of modest benefit, two large and well-designed studies failed to find acetyl-L-carnitine effective.

The first of these studies was a double-blind, placebo-controlled trial that enrolled 431 participants for one year. Overall, acetyl-L-carnitine proved no better than placebo. However, because a close look at the data indicated that the supplement might help people who develop Alzheimer’s disease at an unusually young age, researchers performed a follow-up trial. This one-year, double-blind, placebo-controlled trial evaluated acetyl-L-carnitine in 229 persons with early-onset Alzheimer’s. No benefits were seen here either. One review of the literature concluded that acetyl-L-carnitine may be helpful for mild cases of Alzheimer’s disease but not for more severe cases.

Mild depression. A double-blind study of sixty older persons with dysthymia found that treatment with three grams of carnitine daily for two months significantly improved symptoms compared with placebo. Positive results were seen in two other studies, too, one on depression and one on dysthymia.

Hyperthyroidism. Enlargement of the thyroid (goiter) can be due to many causes, including cancer and iodine deficiency. In some cases, thyroid enlargement occurs without any known cause, resulting in benign goiter. Treatment of benign goiter generally consists of taking thyroid hormone pills. This causes the thyroid gland to become less active, and the goiter shrinks. However, undesirable effects may result. Symptoms of hyperthyroidismtoo much thyroid hormonecan develop, including heart palpitations, nervousness, weight loss, and bone breakdown.

A double-blind, placebo-controlled trial found evidence that the use of L-carnitine could alleviate many of these symptoms. This six-month study evaluated the effects of L-carnitine in fifty women who were taking thyroid hormone for benign goiter. The results showed that a dose of two or four grams of carnitine daily protected participants’ bones and reduced other symptoms of hyperthyroidism.

Carnitine is thought to affect thyroid hormone by blocking its action in cells. This suggests a potential concern—carnitine might be harmful for people who have low or borderline thyroid levels to begin with. This possibility has not been well explored.

Peyronie’s disease. Peyronie’s disease is an inflammatory condition of the penis that develops in stages. In the first stage, penile pain occurs with erection; next, the penis becomes curved; finally, erectile dysfunction may occur. Many medications have been tried for Peyronie’s disease, with some success. One such drug is tamoxifen, which is better known as a treatment to prevent breast cancer recurrence. A three-month, double-blind study compared the effectiveness of acetyl-L-carnitine to the drug tamoxifen in forty-eight men with Peyronie’s disease. Acetyl-L-carnitine at a dose of one gram daily reduced penile curvature, while tamoxifen did not. In addition, the supplement reduced pain and slowed disease progression to a greater extent than tamoxifen.

Safety Issues

L-carnitine appears to be quite safe. However, persons with low or borderline-low thyroid levels should avoid carnitine because it might impair the action of thyroid hormones. Persons on dialysis should not receive this, or any other supplement, without a physician’s supervision. The maximum safe dosages for young children, pregnant or nursing women, and those with severe liver or kidney disease have not been established. Some studies have reported that L-carnitine passing from mother to child in breast milk has no side effects, but scientific studies have not confirmed the safety of using these supplements when nursing.

Important Interactions

Persons taking antiseizure medications, particularly valproic acid (Depakote, Depakene) but also phenytoin (Dilantin), may need extra carnitine. Persons taking thyroid medication should not take carnitine except under a physician’s supervision because it may reduce the drug’s effectiveness and make symptoms of hypothyroidism worse. The risk of bleeding may increase when taking carnitine with blood thinners.

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