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What is L-Carnitine?
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.
What is the best form of L-Carnitine?
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. 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.
What benefits does L-Carnitine have?
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, and a study with ALCAR found a reversal of the age-related
decline in mitochondrial function in the heart. 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.
Another study found over a 10% reduction in cardiac events
following suspected myocardial infarction, and other human
studies have found reduced arrhytmia, significant improvement
in patients with congestive heart failure, and reduced cholesterol
and triglycerides.
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. Studies
in aged rodents show markedly improved memory and learning
capacities, while studies in younger rodents show a variety
of promising effects as well. Other rodent studies have shown
that ALCAR significantly protects the brain against a variety
of stresses, such as ischemia and repurfusion and mitochondrial
uncoupling. It also protects against peripheral nerve trauma,
"almost eliminating neuron loss", and in vitro neuronal
apoptosis. ALCAR also increases levels of dopamine, amino
acids, and acetylcholine in the brain, as well as facilitating
cholinergic activity.
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, prevents or reverses many age-related
increases in markers of oxidative and inflammatory events
in the cortex, reduces damage to nucleic acids (DNA/RNA) and
proteins, and also increases the levels of other antioxidants
in the brain. Administering ALCAR also prevents mitochondrial
decay, restores depleted ATP levels, and restores the activity
of many key enzymes that decline with age such as carnitine
acetyltranferase, mitochondrial complexes III and IV, sodium
potassium adenosine triphosphatase, and glutathione-S-transferase.
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, and
rodent studies indicate significantly more regenerative elements
and reduced degenerative elements. 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, 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.
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. A six-week
study with aged rats found ALCAR to improve auditory thresholds
by upregulating mitochondrial function and reducing oxidative
stress.
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.
In vitro, ALCAR also prevents the buildup of advanced glycation
end products (AGEs) in the eye, which are a known cause of
macular degeneration.
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, and no tolerance develops to this
effect. 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.
What application does L-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. 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.
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
and improve nitrogen utilization. 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.
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.
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, as well as
studies showing it to increase utilization of fat as a fuel
source during exercise. A study with L-carnitine L-tartrate
also showed it to favorably effect many markers of recovery
from squat exercises. 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. 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.
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. It was recently confirmed that supplemental
carnitine increases long-chain fatty acid oxidation in healthy
individuals without carnitine deficiency, 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.
Additionally, carnitine is a potent antioxidant (especially
in combination with ALA) 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. Another strong antioxidant
is melatonin, and ALCAR has also been shown to increase melatonin
levels.
Are there any side effects?
Carnitine has no toxicity, teratogenicity, contraindications,
or drug interagions. There are very few side effects associated
with carnitine use, and no serious side effects have been
reported. Some users report nausea or stimulation, but these
tend to be transient and disappear with time. There are also
many anecdotal reports of more vivid dreams.
How should carnitine be taken?
The typical dosage for carnitine is 1-4 g/day. 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.
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.
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.
They also may have an additive benefit in improving hearing
function.
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, 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.
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.
Another study in endurance athletes found a carnitine and
caffeine combination to improve exercise times more than either
substance alone.
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