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LE Magazine August 2002
The Benefits of
Carnitine and DHEA for Fat Metabolism
People want energy efficiency in their homes; they
need it for their bodies as well. Carnitine is an amino acid that's critical
for converting fatty acids into fuel. Because of this, it has the potential
to help people lose weight. Muscles, liver, kidney and heart all require
carnitine to convert fat into energy. If carnitine is not available, fatty
acids will accumulate in the body. Japanese researchers have demonstrated
the concept using high-fat diets. Normally this type of diet elevates
cholesterol and triglyceride levels. But adding carnitine reverses the
effect. Carnitine works by transporting fatty acids into mitochondria
where they are used for energy production. Where fat goes, carnitine must
follow.
Fats are one of three sources of energy the body utilizes. Muscles, including
the heart, plus the kidney, and the liver depend heavily on fatty acids
for fuel. Carnitine functions as a carrier system for fatty acids, shuttling
them into mitochondria so they can be oxidized. The "carnitine shuttle"
is well-known in biochemistry where it's recognized as critical for the
metabolism of fatty acids. The shuttle relies on several carnitine-related
enzymes to work. If any of them are nonfunctional, a build-up of fatty
acids in the blood and organs will occur, as the shuttle screeches to
a halt. This problem has been documented in people with insulin resistance.
Studies show that defective carnitine-related enzymes are involved in
this condition. But although dysfunctional enzymes would suggest something
genetic, it's not necessarily the case. Some research suggests that supplemental
carnitine may get the enzymes working again.
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| Fatty acid metabolism requires carnitine.
Fatty acids are converted to fatty acyl CoA, then combined with
carnitine before they're carried into the cells' power plants,
mitochondria, to be oxidized. |
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In addition to insulin resistance, obesity, fatty blood, fatty liver
and diabetes also involve abnormal fatty acid utilization. As a consequence,
energy production falters, and fatty acids build up in the body. What
can be done to get at this problem? There are two supplements and a stack
of scientific papers that may provide answers.
Carnitine lowers lipids
The effect of carnitine on lipids is dramatically illustrated by experiments
on cats. Felines quickly develop a life-threatening condition called "hepatic
lipidosis" if they don't eat. Although it sounds paradoxical, not eating
causes fat to build up in the liver. With it, the mitochondria begin to
die off, and the energy system collapses. The break-down in metabolism
occurs, at least in part, because of insufficient carnitine, which is
critical for fatty acid utilization. Without carnitine, which comes from
protein, fatty acids cannot be moved into mitochondria where they are
used for fuel. Force-feeding is the treatment for this condition. Once
protein (a source of carnitine) gets back in the system, lipid levels
fall, and the condition reverses itself.
Weight loss
Because carnitine moves fatty acids into mitochondria for fuel, it has
potential as a weight-loss supplement. Its beneficial effects have been
demonstrated in cats where it promotes faster weight loss during dieting.
However, a study in humans on an aerobic exercise program showed no results.
One of the reasons may be that carnitine's ability to energize lipids
depends on other factors. Hormones are one of those factors.
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Your Cat May
Need Supplemental Carnitine
• A new study shows that the amount of L-carnitine in commercial
cat food is insufficient to protect the liver. Researchers
gave obese cats approximately 150 mg of L-carnitine per quarter
pound of food versus the approximate 5 mg approved for commercial
cat food. The higher amount approaches what cats would get
from a natural diet. The added carnitine had significant effects
on liver function, specifically the utilization of fatty acids.
For obese cats, supplemental carnitine is essential. They
are prone to developing anorexia, which leads to the life-threatening
condition, hepatic lipidosis, where fat builds up in the liver.
Cats with this condition have drastic alterations in fatty
acids, with liver triglycerides off the chart. Cats given
adequate amounts of L-carnitine have a much better ability
to weather this metabolic crisis. Supplement L-carnitine suppresses
these drastic alterations in lipids.
• L-carnitine also maintains good metabolic function during
obesity. When cats become obese on a commercial diet, carnitine
levels shoot up drastically in the liver. This is apparently
because the amino acid is not being utilized: normally it
carries fat for fuel. But cats maintained on natural high
levels of L-carnitine everyday in their diet don't have drastic
increases of unused carnitine in their liver when they become
obese. Their carnitine levels remain steady, indicating less
stress on the system, and better metabolism.
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Insulin and glucagon are two hormones that affect the metabolism of fatty
acids. DHEA (dehydroepiandrosterone) is another. DHEA upregulates carnitine-related
enzymes that promote fatty acid utilization. In a study on humans, it
was shown that age-related declines in DHEA levels cause carnitine to
accumulate and not be utilized. This is similar to the fatty acid problem
in cats, where lipids build up in the liver for lack of carnitine to move
them. In this case, the lack of DHEA causes enzymes to lie idle, and the
carnitine shuttle doesn't move. When supplemental DHEA is given to the
rat equivalent of a postmenopausal woman, carnitine utilization is increased,
and so is energy production. Similarly, when DHEA and/or carnitine is
added to bone cells that depend on energy to multiply, energy and the
production of bone protein are increased. DHEA clearly promotes fatty
acid metabolism.
A lack of DHEA may be one of the primary causes of insulin resistance.
This condition interferes with insulin's ability to regulate glucose.
Since insulin is one of the hormones that affects fatty acid metabolism,
insulin resistance turns up frequently where fatty acid metabolism is
abnormal. And, although it is usually associated with obesity, obesity
is not always present at the same time as insulin resistance. A study
was done on nondiabetic, normal weight men with high blood pressure and
insulin resistance. It showed that insulin resistance coincides with insufficient
DHEA.
The positive effects of DHEA on insulin resistance have been proven in
genetically diabetic mice where it restores insulin sensitivity and reduces
the severity of diabetes. In humans, or at least in women, the level of
testosterone appears to be critical to whether DHEA will ameliorate insulin
resistance and improve fat utilization. This was dramatically illustrated
in a study on a woman in Tennessee who had non-insulin dependant diabetes.
When she was given the testosterone-suppressing drug, dexamethasone at
the same time as supplemental DHEA, there was a 30% increase in insulin
binding, and improvement in her diabetic condition. Dexamethasone alone
did not have this effect. It was the increase in the ratio of DHEA-to-testosterone
that had the beneficial effect on insulin binding.
DHEA reduces body weight in humans and increases lean body mass. It even
acts directly on developing fat cells, reducing their size and number
when combined with insulin. Its ability to reduce blood lipids has been
compared to the drug, clofibrate.
Supplemental carnitine and DHEA both increase fat utilization through
different, yet complimentary, mechanisms. Unfortunately, no human studies
have been published using the two together. Despite this, all signs point
to good effects on fat metabolism with this combination.
Find out more about Carnitine
and DHEA
References
Abadie JM, et al. 2001. Dehydroepiandrosterone alters
Zucker rat soleus and cardiac muscle lipid profiles. Exp
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Abadie JM, et al. 2001. Dehydroeipandrosterone alters phospholipid profiles
in Zucker rat muscle tissue. Lipids 36:1383-6.
Blanchard G, et al. 2002. Dietary L-Carnitine supplementation in obese
cats alters carnitine metabolism and decreases ketosis during fasting
and induced hepatic lipidosis. J Nutr 132:204-10.
Brady LJ, et al. 1991. Regulation of carnitine acyltransferase synthesis
in lean and obese Zucker rats by dehydroepiandrosterone and clofibrate.
J Nutr 121:525-31.
Buffington CK, et al. 1993. Case report: amelioration of insulin resistance
in diabetes with dehydroepiandrosterone. Am
J Med Sci 306:320-24.
Center SA, et al. 1993. Ultrastructural hepatocellular features associated
with severe hepatic lipidosis in cats. Am
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Center SA, et al. 2000. The clinical and metabolic effects of rapid weight
loss in obese pet cats and the influence of supplemental oral L-carnitine.
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Chiu KM, et al. 1997. Effect of dehydroepiandrosterone sulfate on carnitine
acetyl transferase activity and L-carnitine levels in oophorectomized
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Chiu KM, et al. 1999. Correlation of serum L-carnitine and dehydro-epiandrosterone
sulphate levels with age and sex in healthy adults [see comments]. Age
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Chiu KM, et al. 1999. Carnitine and dehydroepiandrosterone sulfate induce
protein synthesis in porcine primary osteoblast-like cells. Calcif
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Coleman DL, et al. 1982. Therapeutic effects of dehydroepiandrosterone
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Gomez FE, et al. 2002. Molecular differences caused by differentiation
of 3T3-L1 preadipocytes in the presence of either dehydroepiandrosterone
(DHEA) or 7-Oxo-DHEA. Biochem 41:5473-82.
Hall JA, et al. 1997. Lipid composition of hepatic and adipose tissues
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Inokuchi T, et al. 1995. Changes in carnitine metabolism with ketone body
production in obese glucose-intolerant patients. Diab
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Lea-Currie YR, et al. 1997. Effects of acute administration of dehydroepiandrosterone-sulfate
on adipose tissue mass and cellularity in male rats. Int
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Peluso G, et al. 2002. Decreased mitochondrial carnitine translocase in
skeletal muscles impairs utilization of fatty acids in insulin-resistant
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Shimura S, et al. 1993. Changes of lipid concentrations in liver and serum
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Suzuki M, et al. 1999. A close association between insulin resistance
and dehydroepiandrosterone sulfate in subjects with essential hypertension.
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Villani RG, et al. 2000. L-carnitine supplementation combined with aerobic
training does not promote weight loss in moderately obese women. Int
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Yamada J, et al. 1991. Characteristics of dehydroepiandrosterone as a
peroxisome proliferator. Biochim Biophys Acta 1092:233-43.
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