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L-carnitine is a trimethylated amino acid that plays essential roles in many areas of the body, including fatty acid translocation and muscle function. Carnitine is also acetylated into the ester Acetyl-L-carnitine (ALCAR) in the brain, liver, and kidney. ALCAR also plays a variety of roles in the body, including increasing acetylcholine production and stimulation of protein and membrane phospholipid synthesis. Orally administered L-carnitine and ALCAR have profound anti-aging and nutrient repartitioning properties, and the effects of supplementing with them have been extensively researched in many areas, including exercise performance, weight loss, treatment of Alzheimer's, Parkinson's, diabetic neuropathy, depression and many other neurological disorders, treatment of alcoholism, treatment of cardiovascular diseases, insulin resistance, and many others.
2. What form is best?
Pharmacologically speaking, there is little difference between supplementing with L-carnitine and supplementing with ALCAR. This is because ALCAR is deacetylated during or immediately after intestinal cell uptake, and then a certain amount of free carnitine is later reacetylated (1, 2). Similarly, it has been shown that supplementation with both L-carnitine and ALCAR increase tissue levels of both substances, and that the intestine creates significant amounts of ALCAR from carnitine (2, 3).
3. What application does carnitine have?
The carnitines are excellent supplements for athletes, as well as anyone who wants to look and feel thier best. Studies with both ALCAR and L-carnitine have shown that they have potent nutrient repartitioning effects, and there are some studies indicating that L-carnitine can increase exercise performance.
In one study, both young and old rats were supplemented with ALCAR and compared with age-matched controls. Nutrient partitioning and muscle mass and function were among the factors measured. Body weight did not differ significantly between the two groups, but there were strong differences in the fat to protein ratios. The young rats fed ALCAR had slightly higher body protein levels (not statistically significant) and significantly less body fat, while the old rats fed ALCAR had much high body protein levels and the same amount of body fat (1). ALCAR may be especially useful for older people, as one rat study found that long-term administration prevents the progressive increase in the size of fat cells that normally occurs with age (4).
Another study looked at the effects of carnitine (.68 g) and choline (.94 g) supplementation on fat metabolism in healthy women. In the treatment groups, body fat decreased .7-1.3% over 35 days (as opposed to no difference in the placebo group). They also found that when the supplemented groups exercised, the ability to utilize fat as energy substrate increased (5). Animal studies have also shown L-carnitine to reduce obesity (6) and improve nitrogen utilization (7). However, there has been one human study in moderately obese premenopausal women in which no weight loss or repartitioning effect was found with L-carnitine (13).
When looking at the effects of the carnitines on exercise performance, we no longer have to rely so much on animal studies. Various studies have shown that L-carnitine improves exercise performance in people with heart problems or impaired exercise tolerance, as well as people recovering from hemodialysis (8-12). However, the influence on exercise performance on healthy individuals is less clear. L-carnitine definitely changes the response and effects of exercise, as evidenced by decreased muscle soreness and decreased pyruvate and lactate concentrations and higher ALCAR concentrations post-exercise (14, 15), as well as studies showing it to increase utilization of fat as a fuel source during exercise (5, 16). A study with L-carnitine L-tartrate also showed it to favorably effect many markers of recovery from squat exercises (19). The real world effect of this is not conclusively known, and two recent reviews stated that further studies are needed before the effect can be determined on healthy individuals (17, 18). Regardless of the present lack of human studies showing a definite ergogenic effect, the nutrient partitioning properties and improved recovery alone make carnitine a worthwhile supplement, and there are also many added benefits.
4. How does carnitine work?
Carnitine's primary job is in the regulation of cellular metabolism, and it closely interacts with coenzyme A in a variety of reactions. It is required for fatty acid oxidation, and this is the primary theoretical reason for improved exercise performance, as improved fatty acid oxidation will preserve muscle glycogen and improve ATP production (17, 18). It was recently confirmed that supplemental carnitine increases long-chain fatty acid oxidation in healthy individuals without carnitine deficiency (20), providing more evidence for an ergogenic benefit. Enhanced fatty acid oxidation and cellular metabolism is also the proposed mechanism of action for the nutrient partitioning benefits (1).
Additionally, carnitine is a potent antioxidant (especially in combination with ALA) (21) and there is evidence that it increases exercise performance for this reason. A Russian study found that both L-carnitine and ALCAR increased running speed and endurance in trained animals, and that the increase was proportional to their antioxidative activity (22). Another strong antioxidant is melatonin, and ALCAR has also been shown to increase melatonin levels (23).
5. What other benefits does carnitine have?
- Improved cognitive function - ALCAR plays a strong role in the
brain in many ways, and has beneficial effects in many conditions including
Alzheimer's and Parkinson's (24, 25). Studies in aged rodents show markedly
improved memory and learning capacities (32, 35-37), while studies in younger
rodents show a variety of promising effects as well (40, 41). Other rodent
studies have shown that ALCAR significantly protects the brain against a
variety of stresses, such as ischemia and repurfusion (26) and mitochondrial
uncoupling (27). It also protects against peripheral nerve trauma, "almost
eliminating neuron loss" (28), and in vitro neuronal apoptosis (29, 30).
ALCAR also increases levels of dopamine, amino acids, and acetylcholine in
the brain, as well as facilitating cholinergic activity (31, 32).
One of the primary mechanisms for the improved cognitive function and anti-aging properties seen with ALCAR is its ability to prevent oxidation and inflammation. Administering ALCAR reduces lipid peroxidation (33, 36, 39), prevents or reverses many age-related increases in markers of oxidative and inflammatory events in the cortex (34, 38), reduces damage to nucleic acids (DNA/RNA) (35) and proteins (35, 37), and also increases the levels of other antioxidants in the brain (37). Administering ALCAR also prevents mitochondrial decay (33, 35, 37), restores depleted ATP levels (28), and restores the activity of many key enzymes that decline with age such as carnitine acetyltranferase (33, 37), mitochondrial complexes III and IV (37), sodium potassium adenosine triphosphatase (39), and glutathione-S-transferase (39).
ALCAR supplementation is also accompanied by many positive structural changes in the brain in both the young and the old. It stimulates nerve growth factor (NGF) binding (28, 42), and rodent studies indicate significantly more regenerative elements and reduced degenerative elements (40, 43). A study that measured the regenerative capacity of myelinated fibers in young and old rats found that ALCAR significantly increased the density of regenerating myelinated fibers (RMF) and increased the density of axon diameters in both, as well as reducing degenerative elements (40), and another rat study with ALCAR found increased synaptic numeric densities and improvements in energy provision at nerve terminals in both young and old rats, as well as 10-20% increases in synapses smaller than .08 microns (41).
- Cardiovascular benefits - The carnitines have considerable potential
in the treatment of cardiovascular disease. Rodent studies with L-carnitine
have shown decreased triglyceride and cholesterol levels and protection against
arrhythmia and ischemia (51-54), and a study with ALCAR found a reversal
of the age-related decline in mitochondrial function in the heart (55). A
study on the three-year survival rate of patients with dilated cardiomyopathy
supplemented with L-carnitine (n=37) or placebo (n=33) found one death in
the L-carnitine group and six in the placebo group, and concluded that L-carnitine
had a considerable effect (56). Another study found over a 10% reduction
in cardiac events following suspected myocardial infarction (57), and other
human studies have found reduced arrhytmia (58), significant improvement
in patients with congestive heart failure (59), and reduced cholesterol and
triglycerides (59)
- Improved hearing and visual function - Two animal studies indicate
a significant reduction in noise-induced and age-induced hearing loss with
ALCAR. One measured outer hair cell (OHC) density after three weeks of noise
exposure, and found less than a 10% reduction with ALCAR as opposed to 60%
with placebo, and noise induced threshold shifts were less than 10 dB in
the ALCAR group as opposed to 30-35 dB with placebo (60). A six-week study
with aged rats found ALCAR to improve auditory thresholds by upregulating
mitochondrial function and reducing oxidative stress (61).
Improvements in visual function have been noted as well. A preliminary study on guinea pigs found an improvement in alignment to ocular responses and enhancement of optical nerve growth, and hypothesized that ALCAR can increase visual function (62). In vitro, ALCAR also prevents the buildup of advanced glycation end products (AGEs) in the eye, which are a known cause of macular degeneration (63).
- Reduced stress and depression - In rats, ALCAR protects against the decreases in dopamine and testosterone that normally occur after exposure to both acute and chronic stress and decreases other markers of stress (44-46), and no tolerance develops to this effect (45, 47). Preliminary human studies in the elderly and those undergoing treatment for certain conditions indicate a reduction in depression and fatigue and an improvement in quality of life (10, 48-50).
6. Are there any side effects?
Carnitine has no toxicity, teratogenicity, contraindications, or drug interagions (65). There are very few side effects associated with carnitine use, and no serious side effects have been reported (58, 64, 65). Some users report nausea or stimulation, but these tend to be transient and disappear with time (65). There are also many anecdotal reports of more vivid dreams.
7. How should carnitine be taken?
The typical dosage for carnitine is 1-4 g/day (65). A study on the pharmacokinetics of oral L-carnitine in human subjects found no differences in plasma carnitine after 2 g vs. 6 g, indicating that 2 g is already more than the saturable dose (66). The half-life of the 2 gram dose was 6.5 hours, and this would imply that the ideal dosing schedule would be 1-2 grams 2-3 times daily, although many studies indicate beneficial effects with only .5-1.5 grams daily.
8. What are some good supplements to stack with carnitine?
- Alpha lipoic acid
- Studies show that carnitine and ALA or R-ALA have additive benefits in
protecting against oxidative damage, improving substrate utilization, improving
neurological function, and improving the function of mitochondria (21, 33,
35, 55). They also may have an additive benefit in improving hearing function
(61).
- L-ornithine - A widely quoted study found 500 mg of ALCAR and 25-100 mg of L-ornithine taken before bed after a three hour fast to improve GH release, but this regimen must be followed exactly (69), and the effects of fasting for three hours before bed every night should be weighed against improved GH release.
- Choline - Two studies, one in human and one in rats (which also
included caffeine), indicate that carnitine and choline have synergistic
effects in decreasing body fat (5, 67). The dosage of choline is generally
1-2 times that of carnitine.
- Caffeine - The rat study with carnitine, choline and caffeine found that it produced body fat reductions and physiological responses similar to those induced by exercise, and that the rats subjected to both regimens (supplementation and exercise) had improved substrate utilization during exercise (67). Another study in endurance athletes found a carnitine and caffeine combination to improve exercise times more than either substance alone (68).
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