The Importance of High L-Carnitine Levels
L-carnitine is an amino acid synthesized by the body from the essential amino acids lysine and methionine, and can also be obtained from red meat - particularly lamb. For this reason, l-carnitine deficiency is quite common among vegetarians and even health-conscious people who simply avoid red meat, and an l-carnitine deficiency as a result of this can have some ironic consequences for such a health-conscious segment of the population. This is because l-carnitine plays a central role in the metabolic breakdown of long-chain fatty acids and their subsequent transport into the mitochondria for their oxidation and use in the production of cellular energy. This makes l-carnitine essential to maintaining a healthy metabolism, which in turn is critical for avoiding such age and lifestyle-associated disorders such as Metabolic Syndrome, Type II diabetes, cardiovascular disease, and others. L-carnitine deficiencies were not identified until 1972, making the study of l-carnitine's crucial importance to metabolism an ongoing topic of research.

Clinical studies have clearly demonstrated that GBB dramatically increases endogenous l-carnitine production. In fact, one study conducted on infants (saying much about GBB's safety) increased plasma carnitine concentrations by more than 300%. In another study using adult subjects, GBB increased carnitine excretion (another marker for carnitine production) by nearly 40-fold. Another study (this one using laboratory mice) determined that gamma-butyrobetaine supplementation equaled exogenous l-carnitine supplementation in the ability to raise l-carnitine levels in all tissues. Most studies examining the clinical potential of l-carnitine have used exogenous, supplemental l-carnitine, and these have produced significant findings.

The Research
These findings include human studies on anorexia nervosa, athletic performance, angina, ischemia, peripheral vascular disease, cardiomyopathy, myocardial infarctions, hyperlipidemia, diabetes, chronic fatigue syndrome, hepatitis, HIV, hyperthyroidism, and renal failure. In the latter, l-carnitine use is even recommended by the National Kidney Foundation for the alleviation of anemia associated with chronic renal failure. Anemia is a symptom targeted by l-carnitine supplementation in anorexia nervosa patients as well, improving weight gain, physical performance and appetite in combination with adenosylcobalamin (a cofactor of B12).

L-carnitine also increased walking time for peripheral vascular disease patients by nearly 80% in one double-blind, placebo-controlled study, while significantly increasing the survival rate among cardiogenic shock patients in two others. Long-term supplementation among patients of heart failure have produced improvements in ejection fraction, Weber classification (a standardized test of cardiac performance), peak VO2 consumption, arterial and pulmonary blood pressure, and cardiac output. This is in addition to decreasing the mortality rate among myocardial infarction survivors by 12.5% after a year of l-carnitine supplementation at 4 grams daily, according to one study.

Hyperlipidemia, a condition characterized by excess levels of fat in the blood (and a major force behind a poor HDL/LDL ratio of cholesterol), has also been targeted by l-carnitine research, with most studies showing 2 grams to be an effective daily dose for reducing triglyceride levels, either as an adjuvant or stand-alone therapy. Injections of l-carnitine have also been used among diabetics to successfully improve insulin sensitivity and alleviate the symptoms of diabetic neuropathy.

L-carnitine has long been theorized to have energy-enhancing, fat-loss, and athletic performance-enhancing properties, but studies contradicting these claims are as numerous as those supporting them. However, these claims do flow into the similar vein of chronic fatigue syndrome (CFS), where studies with l-carnitine have been successful. One such study was a crossover trial where l-carnitine was directly compared to the drug amantadine (often prescribed to treat CFS in Multiple Sclerosis [MS] patients). The results were that amantadine was poorly tolerated by the CFS patients, forcing 15 of the 30 to drop out of the treatment due to side effects - with no statistically significant improvements among those who remained. After a 2-week washout period, the second 8-week phase of the study began - this time with l-carnitine as the intervention. Only one patient withdrew from this phase of the study, and significant improvements were recorded in 12 of the 18 standard parameters used to measure the degree of CFS symptoms.

L-carnitine has also been linked to liver health, particularly through its ability to control serum ammonia levels. In fact, several studies with hepatic encephalopathy patients have confirmed not only this ability on the part of l-carnitine, but also the ability to improve mental function in this condition as measured by NCT-A, an accepted psychometric test for mental status in such patients. L-carnitine supplementation has also been studied in HIV-positive patients, both as stand-alone and adjuvant therapy; l-carnitine enhances CD4 immune cells in the former while protecting them in the latter, thus effectively making l-carnitine an immune system enhancer.

Hyperthyroidism and male infertility have also been subjects for l-carnitine supplementation. Since endogenous l-carnitine plays a marginally inhibitory role in the activity of thyroid hormones, it was hypothesized that increasing l-carnitine levels via supplementation would have a positive effect on hyperthyroid patients. The hypothesis proved correct in at least one study, where daily doses as low as 2 grams (for 6 months) prevented and reversed symptoms of hyperthyroidism, including the latter's effect on bone mineralization. L-carnitine has also been linked to increased sperm counts, leading to a number of studies with it among infertile males. These studies, which used 2-3 grams of l-carnitine daily in periods generally ranging from 2 to 4 months, were successful in increasing both sperm count and motility.

As mentioned earlier, l-carnitine supplementation in patients with renal failure has been so extensive that its use has even been advocated by the National Kidney Foundation. In one eight-month study, only 3 grams of intravenously administered l-carnitine per week was required to improve left ventricular ejection fraction (which is taxed heavily during renal failure) by more than 30%. Finally, there is also some evidence to suggest that l-carnitine might be useful for women during prenatal periods; one short-term study (5 days) showed that 4 grams of l-carnitine combined with the drug betamethasone reduced the incidence of respiratory distress syndrome as well as mortality in premature newborns.

Gamma-Butyrobetaine as an L-Carnitine Pre-Cursor
The efficiency of gamma-butyrobetaine in its conversion to l-carnitine in the body is such that it can adequately serve as a substitute for exogenous, supplemental l-carnitine with regard to any of the aforementioned conditions.

References:

Monograph. L-carnitine. Altern Med Rev. 2005 Mar;10(1):42-50.
Sandor A. Butyrobetaine is equal to L-carnitine in elevating L-carnitine levels in rats. Biochim Biophys Acta. 1991 May 8;1083(2):135-8.

Olson AL, Rebouche CJ. gamma-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant. J Nutr. 1987 Jun;117(6):1024-31.

Rebouche CJ, Bosch EP, Chenard CA, Schabold KJ, Nelson SE. Utilization of dietary precursors for carnitine synthesis in human adults. J Nutr. 1989 Dec;119(12):1907-13.