L-Carnitine and its derivatives, acetyl-L-carnitine and propionyl-L-carnitine have increasingly favorable research as more studies are done.  I now have 76 double-blind studies showing some benefit for human diseases.  Admittedly, some of the studies were very small and some of the benefits were minor, but 76 is a very impressive number.  Some of the studies were very large with over 400 participants and some lasted a full year.  There are many additional animal and supporting human research studies.

How interchangeable these three carnitines are is unclear, but they appear equally effective in various disorders and are interchangeable as best I can tell.  Acetyl-l-carnitine is formed by the reversible acetylation of carnitine.  The carnitines form an important part of the mitochondrial energy production system.  Of course, mitochondia are present in every cell of your body since without mitochondria a cell cannot produce energy to carry out its various functions.  

Although the carnitines are most heavily promoted on the internet for dementia, that is one condition that they do not appear to help (see the studies under acetyl-L-carnitine).  However, two large studies did find acetyl-L-carnitine of benefit for mild cognitive impairment in the elderly, a common precursor to dementia.  These are older, Italian studies that were only 3 months long.

L-Carnitine is a naturally occurring amino acid derivative found in meat and diary products.  It can also be produced by the human liver and kidney by combining two essential amino acids, methionine and lysine.  Dietary intake does influence blood levels.  Carnitine is found in high concentrations in human heart, muscles, and liver tissue, where it participates in metabolizing fatty acids into energy by transporting long-chain fatty acids into the mitochondria. L-carnitine enhances the rate of oxidative phosphorylation (ATP or energy production), working synergistically with CoQ10 in the inner membrane of the mitochondria. 

Double-blind studies have shown benefits from l-carnitine for ADHD, chronic fatigue syndrome, heart attack victims, heart failure, intermittent claudication, kidney dialysis, fatigue, liver encephalopathy, male infertility, muscle fatigue in elderly, exercise-induced muscle fatigue and soreness, and childhood hyperactivity, although the number of studies completed for each disorder is sometimes quite limited.  Carnitines are reported to have few side-effects when taken at the recommended doses.  Although L-carnitine is not a medication and no prescription is needed, it has been approved by the FDA for a variety of childhood genetic diseases which block the production of carnitine.

Carnitine deficiency can cause serious heart and liver problems. This may occur in inborn errors of metabolism, renal tubular dysfunction (Fanconi's syndrome), chronic renal failure, or with valproic acid (Depakene, Depakote) and zidovudine (Retrovir)

L-carnitine can be somewhat expensive, usually being sold in 500 mg capsules.  For 2-4 grams per day, a month's supply of 500 mg. capsules would cost in the range of $35-100 depending on the supplier.  However, bulk L-carnitine can lower this cost to $10-$20 per month, if a $100 1000 g bottle is purchased ( www.dextersportscience.com; 3-6 g of L-carnitine L-tartrate equals 2-4 g of carnitine; carnitine base is also sold and I don't know which is better).

Acetyl-L-Carnitine (ALC): ALC is also found in animal products and is manufactured by the body fairly easily from L-carnitine and probably vice-versa. An acetyl group taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate (Neuroimage. 2002 Nov;17(3):1256-65). Acetyl-L-Carnitine is an ester of the trimethylated amino acid, L-carnitine, and is synthesized in the human brain, liver, and kidney by the enzyme ALC-transferase. Acetyl-L-carnitine facilitates the uptake of acetyl CoA into the mitochondria during fatty acid oxidation, enhances acetylcholine production, and stimulates protein and membrane phospholipid synthesis. ALC, similar in structure to acetylcholine, also exerts a cholinomimetic effect.  

Acetyl-L-carnitine is being heavily promoted as a wonderful anti-aging pill.  That is an huge exaggeration.  Still, there are quite a few double-blind studies showing ALC helped ADHD, chronic fatigue syndrome, erectile dysfunction, depression, fatigue in multiple sclerosis, diabetic neuropathy,  macular degeneration, Peyronie's disease, male sexual dysfunction, mild cognitive impairment, sperm motility, and depression in the elderly.  It doesn't appear to help already established Alzheimer's disease.

The cost of ALC is about $30 per month for 1 gram/day at Wal-Mart, but as little as $9 per month in tablet form from iherb.com.  In powder form, it's $133 for 1000 g in bulk or just $4 per month for 1 gram/day.  Most studies use twice as much.  One half rounded teaspoon (roughly 2 grams) of the bulk powder is hardly noticeable in orange juice or grape juice.  The powder form has a mildly undesirable taste with a strong odor of vinegar.

Propionyl-L-Carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism (J Vasc Surg. 1999 Jun;29(6):1097-103).  It has been shown to help angina, chronic fatigue syndrome, congestive heart failure, Peyronie's disease, sexual dysfunction, and intermittent claudication in a small number of studies.  It has no clear advantage and is harder to obtain.

Both acetyl- and L-carnitine can cause diarrhea is some individuals, especially at higher dosages.  I don't know if this is more common with the powdered form.  

Chronic Fatigue Syndrome and Hepatitis C: Carnitine Low: Both serum acylcarnitine (ACR) and free carnitine (FCR) levels in normal healthy subjects were quite different between Japanese (n=131) and Swedish people (n=46) (p<0.001). However, Swedish patients with CFS (n=57) had serum ACR deficiency (p<0.001) similar to Japanese CFS. In Japanese patients with CFS, hematological malignancies, chronic pancreatitis, hypertension, diabetes mellitus, chronic hepatitis type C, and psychiatric diseases, a significant decrease in the levels of serum ACR was only found in patients with CFS and chronic hepatitis type C (p<0.001). Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Kuratsune H, et al. Osaka University, Japan. Int J Mol Med. 1998 Jul;2(1):51-6

Genetics: Carnitine Palmitoyltransferase (CPT) Deficiencies: These are uncommon genetic disorders of mitochondrial fatty acid oxidation. The CPT system is made up of two separate proteins located in the outer (CPT1) and inner (CPT2) mitochondrial membranes. While CPT2 is an ubiquitous protein, three tissue-specific CPT1 isoforms--the so-called "liver" (CPT1-A), "muscle" (CPT1B) and "brain" (CPT1-C) exist. CPT1-A deficiency presents as recurrent attacks of fasting hypoketotic hypoglycemia. Twenty four CPT1A mutations have been reported to date. CPT1-B and -C deficiencies have not been identified. CPT2 deficiency has several clinical presentations. The "benign" adult form (more than 200 families reported) is characterized by episodes of muscle breakdown, rhabdomyolysis, triggered by prolonged exercise. The prevalent S113L mutation is found in about 50% of mutant alleles. The infantile-type CPT2 presents as severe attacks of hypoketotic hypoglycemia, occasionally associated with cardiac damage commonly responsible for sudden death before 1 year of age. In addition to these symptoms, features of brain and kidney dysorganogenesis are frequently seen in the neonatal-onset CPT2 deficiency, almost always lethal during the first month of life. Around 40 CPT2 mutations (private missense or truncating mutations) have been detected. Treatment is based upon avoidance of fasting and/or exercise, a low fat diet enriched with medium chain triglycerides and carnitine. Prenatal diagnosis may be offered for pregnancies at a 1/4 risk of infantile/severe-type CPT2 deficiency.

Decreased Carnitine Only in Chronic Fatigue and Hepatitis C: Swedish patients with CFS (n=57) had serum acylcarnitine (ACR) deficiency (p<0.001). The levels of serum ACR and FCR in Japanese patients with various kinds of diseases (CFS, hematological malignancies, chronic pancreatitis, hypertension, diabetes mellitus, chronic hepatitis type C, psychiatric diseases) found a significant decrease in ACR only in patients with CFS and chronic hepatitis type C (p<0.001). Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Kuratsune H, Yamaguti K, et al. Osaka University. Int J Mol Med. 1998 Jul;2(1):51-6.

Carnitine Eliminated Slowly: In a single dose PC study of 12 healthy students, 2 g of L-carnitine increased blood carnitine levels (the free form by 81%, and the total by 57%) to a maximum at 3.5 hours and then slowly decreased. Twenty-four hours after ingestion, blood carnitine concentrations had still not returned to their initial levels. The half-life of the carnitine was 15 hours. During the 24 h after the administration of the 2 g of L-carnitine, 7% was eliminated in the urine. Free and total carnitine in human serum after oral ingestion of L-carnitine. Bach AC, Schirardin H, Sihr MO, Storck D. Diabete Metab. 1983 May-Jun;9(2):121-4. Also: After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the half life was 4.2 hours and maximum blood levels were reached in 3.1 hours. Arch Pharm Res. 2004 Jun;27(6):676-81. Ed: This study suggests that once a day dosing is probably just as good at twice a day and 3 times a day is pointless.

Carnitine Down in Severe Diabetics: L-carnitine levels in the diabetic patients with complications were lower than in those with no complications. Asia Pac J Clin Nutr. 2004;13(Suppl):S155

Carnitine Down in Hepatitis B in Children: The plasma carnitine levels of 31 children with chronic HBV infection were significantly lower than that of 20 controls (P < 0.001) Plasma carnitine level was inversely correlated with portal inflammation (P < 0.05). Liver carnitine level was inversely correlated with fibrosis score (P < 0.05). Plasma and liver carnitine levels of children with chronic hepatitis B. Selimoglu MA, Yagci RV., Erzurum, Turkey. J Clin Gastroenterol. 2004 Feb;38(2):130-3

Prefrontal Brain Damage in Chronic Fatigue: Sixteen patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex vs. 49 controls on MRIs. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects. These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. BMC Neurol. 2004 Oct 04;4(1):14.

High Mitochondrial Metabolism Increases Longevity in Mice: In a group of outbred mice, there was a positive association between metabolic intensity (kJ daily food assimilation as g/body mass) and lifespan, but no relationships of lifespan to body mass, fat mass or lean body mass. Mice in the upper quartile of metabolic intensities had greater resting oxygen consumption by 17% and lived 36% longer than mice in the lowest intensity quartile. Mitochondria isolated from the skeletal muscle of mice in the upper quartile had higher proton conductance vs. the lowest quartile. The higher conductance was caused by higher levels of endogenous activators of proton leak through the adenine nucleotide translocase and uncoupling protein-3. Individuals with high metabolism were therefore more uncoupled, had greater resting and total daily energy expenditures and survived longest - supporting the 'uncoupling to survive' hypothesis. Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Speakman JR, et al. University of Aberdeen, Scotland Aging Cell. 2004 Jun;3(3):87-95.

Thomas E. Radecki, M.D., J.D.

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