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CARNITINE

CARNITINE

WHAT IS CARNITINE

Carnitine is an amino acid found in almost of the cells of the body. It is typically found in things such as meat. The word Carnitine is used but often includes a number of other similar compounds such as L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine.

Carnitine is critical to the production of energy. It’s primary role is to transport long-chains of fatty acids into the mitochondria so they can be oxidized or burned as fuel to produce energy. It is also also a leading amino acid used in the transport of toxic compounds generated out of the cells of the body thus preventing their accumulation. Because of its key functions, Carnitine is concentrated in areas like skeletal and cardiac muscle where fatty acids are utilized as a dietary fuel.

The body typically makes sufficient carnitine to meet the needs of most people. There are many genetic or medical reasons why some individuals cannot produce enough, so in these individuals carnitine is a conditionally essential nutrient and needs to be supplements either my oral or injectable means. One of the most important medical needs that requires additional Carnitine is the body’s increased demand as in Athletics. Competitive and non-competitive athletes, runners, body builders, and weight trainers utilize large portions of Carnitine in their activities and benefit immensely from replacement therapy. Others that may require replacement are those individuals who cannot obtain Carnitine thru their diet.

Healthy children and adults do not necessarily need to consume carnitine from food or supplements, as the liver and kidneys produce sufficient amounts from the amino acids lysine and methionine to meet daily needs. But with increase demand and dietary restrictions, adding Carnitine is required.

CARNITINE SOURCES & ABSORPTION

Carnitine often comes from animal products such as meat, fish, poultry, and milk are the best sources. Some believe the redder the meat, the higher its carnitine content. Dairy is another product that contain carnitine primarily in the whey fraction. Carnitine occurs a form known as D and L carnitine. They are mirror images of each other and has similar characteristics. One major difference is that L-carnitine is active form in the body and is mostly found in food or taken exogenously (ie via oral or injections).

Most adults who eat a variety of food in their diet to include red meat or other sources of animal products can obtain where between 60–180 mg of carnitine per day. On the other hand, Vegans ingest a significant amount less approximately 10–12 mg because of the reduction in animal meats sources. One very important note is anywhere between 54–86% of dietary carnitine is absorbed in the small intestine and then enters the bloodstream. This step in the process can often malfunction during disease, illness and stress.

The breakdown and absorption continues in the kidneys where carnitine is reabsorbed. Rather than being metabolized any further, if there is an excess it is excreted in the urine.

FOOD ITEMMilligrams (mg)
Beef steak (4 oz)56–162
Ground beef (4 oz)87–99
Whole Milk (1 cup)8
Codfish (4 oz)4–7
Chicken breast (4 oz)3–5
Cheddar Cheese (2 oz)2
Ice cream (½ cup)3
Whole wheat bread (2 slices)0.2
Asparagus (½ cup)0.1

HOW CAN A DEFICIENCY OCCUR

There are several processes that go into taking what we eat and turning it into a version of Carnitine the body can absorb and then use. Anywhere in the process can lead to a lower overall Carnitine level. In addition, there are 2 types of known deficiencies: a genetic disorder of the cellular carnitine-transporter system which is often seen by the age of 5 and showing symptoms such as cardiomyopathy, skeletal-muscle weakness, and hypoglycemia and the secondary is a deficiencies related to another condition such as chronic kidney disease, certain antibiotics and medication. Therefore there is not only clinical evidence of deficiencies but data to support it’s replacement.

CARNITINE REPLACEMENT – FACT OR FICTION

Carnitine has been studied extensively because of its importance in the to production of energy and how well it is tolerated not to mention it therapeutic safety. Many including researchers prefer the use of acetyl-L-carnitine in research studies because it is better absorbed from the small intestine over that of L-carnitine and efficiently crosses the blood-brain barrier thus producing positive effects in the brain.

ATHLETIC PERFORMANCE


Many athletes take carnitine to improve performance. Still after many years of clinical research it is difficult to find consistent results because of so many variables ie weight, diet, exercise, genetic code, dosage of carditine and length of treatment. There is evidence that carnitine supplements can improve exercise or physical performance in healthy individuals with doses ranging from 2–6 grams/day over a 28 day period. To put this somewhat of a perspective, a man weighing 155 lbs would have a total body content of 20 grams of carnitine located in the muscle tissue. The thought as far as athletic performance is to increase the body’s use of oxygen and improve metabolism during exercise.

AGING & CARNITINE


It is thought a large portion of the aging process is due to a decline in mitochondrial function. Carnitine may be involved because its concentration in tissues declines with age and thereby reduces the integrity of the mitochondrial membrane. Research in aged rats found supplementation with high doses of acetyl-L-carnitine and alpha-lipoic acid (an antioxidant) to reduced mitochondrial decay. In addition these animals also moved about more freely and improved their performance on memory-requiring tasks. At present there are no equivalent studies of this kind in humans. However, a meta-analysis of double-blind, placebo-controlled studies suggests that supplements of acetyl-L-carnitine may improve mental function and reduce deterioration in older adults with mild cognitive impairment and Alzheimer’s disease. In these studies, subjects took 1.5–3.0 grams/day of acetyl-L-carnitine for 3–12 months. At present, there may appear to be a significant benefit to supplementation with Carnitine.

CARDIOVASCULAR & PERIPHERAL ARTERY DISEASE

Many studies have been done thus far to evaluate the effectiveness of supplemental carnitine in the management of cardiac ischemia (restriction of blood flow to the heart) and peripheral arterial disease (whose most important symptom is poor circulation in the legs, known as intermittent claudication). Because levels of carnitine are low in the failing heart muscle, supplemental amounts might counteract the toxic effects of free fatty acids and improve carbohydrate metabolism. Some short-term studies show that carnitine has had anti-ischemic properties when given orally and by injection. A double-blind, placebo-controlled, multicenter clinical trial in Italy assigned 2,330 patients experiencing an acute anterior myocardial infarction to receive either supplemental L-carnitine (9 g/day intravenously for 5 days, then 4 g/day orally for 6 months) or a placebo. Treatment with L-carnitine significantly reduced mortality 5 days after randomization but did not significantly affect the risk of heart failure or death at 6 months. The authors of a 2013 meta-analysis combined the results from this trial with those from 12 smaller trials. They concluded that treatment with L-carnitine in patients experiencing an acute myocardial infarction reduces all-cause mortality by 27%, ventricular arrhythmias by 65%, and angina by 40% over a median follow-up period of 2 months, but does not reduce the risk of heart failure or recurrence of myocardial infarction.

Claudication results from an inadequate supply of oxygen-rich blood to the legs and leads to an accumulation of acetylcarnitine in muscle due to its incomplete utilization. Patients with peripheral arterial disease who develop claudication have significant impairments in exercise performance and have difficulty walking even short distances at a slow speed. Research indicates that carnitine might improve the performance of skeletal muscles in the leg. In one European multicenter clinical trial, supplementation with L-carnitine (in the form of propionyl-L-carnitine at 2 g/day for 12 months) in patients with moderate to severe claudication significantly improved maximal walking distance and perceived quality of life compared to patients receiving placebo. A similar trial in the United States and Russia found that the same daily dose and form of carnitine administered for 6 months in patients with disabling claudication significantly improved walking distance and speed, reduced bodily pain, enhanced physical function, and improved perceived health state compared to patients in the control group. The authors of a systematic review and meta-analysis that included these and 12 other randomized clinical trials concluded that propionyl-L-carnitine significantly increases peak walking distance in patients with claudication.

These findings suggest that L-carnitine, when administered for up to 1 year, might have beneficial effects on the cardiovascular system in certain settings. Other research, however, has raised concerns about the cardiovascular effects of chronic exposure to carnitine. Due to differences in intestinal bacteria composition, omnivorous study participants produced more TMAO than vegans or vegetarians following consumption of L-cartinine. The study also found dose-dependent associations between fasting plasma L-carnitine concentration and risk of coronary artery disease, peripheral artery disease, and overall cardiovascular disease, but only among participants with concurrently high TMAO levels. The researchers noted that these findings could partly explain the link between high levels of consumption of red meat (a rich source of carnitine) and increased cardiovascular disease risk. More research is needed to fully understand the effects of carnitine on cardiovascular health.

CANCER

Many cancer patients experience fatigue from chemotherapy, radiation treatment, and poor nutritional status. They may also be deficient in carnitine. In one study, treatment with carnitine supplements (4 grams/day for one week) lowered fatigue in most chemotherapy-treated subjects and restored normal blood levels of carnitine. A separate trial, patients with terminal cancer patients were supplemented with carnitine (doses ranged from 250 milligrams to 3 grams/day). They experienced less fatigue and improved mood and quality of sleep. In both studies, most subjects were carnitine deficient before taking the supplements. So, one can draw a parallel between lower levels in the body and the reduction of fatigue once stores are replaced.

DIABETES & CARNITINE

One of the predominant factors in the development of diabetes is insulin resistance. This link may be associated with a defect in fatty-acid oxidation in muscle. This raises the question of whether mitochondrial dysfunction might be a factor in the development of the disease. One of the markers of insulin resistance is increased storage of fat in lean tissues. Early research suggests that supplementation with L-carnitine intravenously may improve insulin sensitivity in diabetics by decreasing fat levels in muscle and may lower glucose levels in the blood by more promptly increasing its oxidation in cells. A recent analysis of two multicenter clinical trials of subjects with either type 1 or type 2 diabetes found that treatment with acetyl-L-carnitine (3 grams/day orally) for one year provided significant relief of nerve pain and improved vibration perception in those with diabetic neuropathy. The treatment was most effective in subjects with type 2 diabetes of short duration.

HIV AND AIDS

The human immunodeficiency virus (HIV) causes a decline in the number of lymphocytes (one type of white blood cell), resulting in acquired immunodeficiency syndrome (AIDS). HIV-infected individuals often accumulate fat in some areas of the body and lose fat in others and develop high levels of blood fats (hyperlipidemia) and insulin resistance, which together constitute the lipodystrophy syndrome. This syndrome may represent mitochondrial toxicity brought about by the HIV infection and the antiretroviral drugs used to treat it, and can induce a carnitine deficiency that limits mitochondrial fat metabolism. The molecular mechanisms by which this occurs are poorly understood but early research suggests that supplementation with carnitine both intravenously and orally (at doses of 2–6 grams/day for weeks or months) in HIV-infected individuals may slow the death of lymphocytes (which in turn may slow HIV progression), reduce neuropathy, and favorably affect blood lipid levels.

END STAGE KIDNEY DISEASE AND DIALYSIS

Balance within the body of Carnitine among individuals with renal diseases can be substantially impaired by several factors, particularly reduced synthesis and increased elimination of the compound by the kidneys as well as reduced intake from food due to poor appetite and consumption of fewer animal products. Many patients with end-stage renal disease, particularly those on hemodialysis, become carnitine insufficient. Carnitine blood levels and muscle stores are low, which may contribute to anemia, muscle weakness, fatigue, altered levels of blood fats, and heart disorders. Numerous studies suggest that high doses of supplemental carnitine (often injected) in patients on maintenance hemodialysis can correct some or all of these symptoms, though most involve small numbers of patients and are not double-blinded trials. A recent meta-analysis of these studies concludes that carnitine supplements may aid anemia management.

MALE INFERTILITY

Carnitine may be of value in male infertility. Carnitine levels found in seminal fluid is directly related to sperm count and motility. Several studies indicate that carnitine supplementation (2–3 grams/day for 3–4 months) may improve sperm quality. A randomized, double-blind crossover trial found that 2 grams/day of carnitine taken for 2 months by 100 infertile men increased the concentration and both total and forward motility of their sperm. The reported benefits may relate to increased mitochondrial fatty-acid oxidation (providing more energy for sperm) and reduced cell death in the testes.

SIDE EFFECTS FROM CARNITINE

Typically persons do not exhibit any side effects from doses approximately 3 g/day. Although infrequent carnitine supplements can cause:

  • nausea, vomiting
  • abdominal cramps
  • diarrhea
  • a “fishy” body odor
  • muscle weakness in uremic patients (kidney disease)
  • seizures in those with seizure disorders.

Some research indicates that intestinal bacteria metabolize carnitine to form a substance called TMAO that might increase the risk of cardiovascular disease. This effect appears to be more pronounced in people who consume meat than in vegans or vegetarians. The implications of these findings are not well understood and require more research.

CARNITINE & MEDICATION INTERACTIONS

Treatment with the anticonvulsants valproic acid, phenobarbital, phenytoin, or carbamazepine has been shown to significantly reduce blood levels of carnitine. In addition, the use of valproic acid with or without other anticonvulsants may cause hepatotoxicity and increase plasma ammonia concentrations, leading to encephalopathy. This toxicity may also occur following acute valproic acid overdose. L-carnitine administration may help treat valproic acid toxicity in children and adults, though the optimal regimen has not been identified.

SUPPLEMENT SOURCES

L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine are available over-the-counter as oral dietary supplements. Quality carnitine is significantly important as its potency is severely reduced by amount per serving, form of carnitine and absorption once injected. Carnitine is often promoted as an aid for weight loss, to improve exercise performance, and to enhance a sense of well-being. It is also a drug approved by the Food and Drug Administration to treat primary and certain secondary carnitine-deficiency syndromes. IV and injectable administration appear to be superior methods of repleting lost stores.