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Lipoic Acid
by Jim English
Alpha-lipoic Acid is a vitamin-like antioxidant
used in Europe to restore liver health, treat diabetes-related neuropathy
and radiation sickness, and confer protective benefits against oxidative
processes involved in degenerative diseases and premature aging.
Alpha-lipoic acid (ALA), also called thioctic
acid, is more potent than vitamins C and E, and CoQ10, and, according
to Dr. Lester Packer, Professor of Molecular Biology at UC, Berkeley,
may be the most important antioxidant ever discovered. "The
therapeutic potential of alpha-lipoic acid is just beginning to
be explored,' observed Packer, 'but this compound holds great promise."
Though lipoic acid is produced naturally in the body, researchers
weren't aware of the existence of this unique antioxidant until
the 1930s. When first purified and isolated in the 1950s, ALA was
thought to be a vitamin, but later was classified as an essential
coenzyme when researchers discovered it was a vital component of
the mitochondrial electron transport (energy) reactions that facilitate
the metabolism of glucose into energy (ATP).
Alpha-lipoic acid is normally synthesized in exceedingly
tiny amounts that are tightly bound to mitochondrial complexes.
Researchers didn't learn that alpha-lipoic acid is also a powerful
biological antioxidant until 1988.
What really caught the researchers' attention
was the realization they had discovered the only antioxidant known
to be both fat and water soluble. Furthermore, unlike any other
antioxidant, alpha-lipoic acid is easily transported across cell
membranes, enabling it to confer free radical protection both inside
and outside cell structures.
In recent years, Dr. Packer, a ground-breaking researcher who has
studied vitamin E and exercise-induced free radical production,
has focused on how lipoic acid and other antioxidants interact in
a complex recycling process in the body. He first discovered several
years ago how vitamin E is 'recycled' by vitamin C in the body.
Vitamin E is a potent antioxidant that works primarily
to stabilize dangerous free radicals (lipid peroxyl radicals and
lipid alkoxyl radicals) that form in fatty (lipid) tissues and membranes.
In order to quench these reactive molecules, vitamin E first absorbs
the excess unpaired electrons, but in so doing vitamin E becomes
a free radical itself, though far less reactive or damaging than
the original radicals. At this point, vitamin C now interacts with
the free radical form of vitamin E, and by absorbing the excess
electrons, converts it back to its natural form as stable vitamin
E.
The newly regenerated vitamin E molecule can now
go back to work, leaving behind a new free radical in the form of
unstable vitamin C (a semiascorbyl radical). In the next stage of
the recycling process the semiascorbyl radical is regenerated into
vitamin C by a class of sulfur-containing compounds called thiols.
Glutathione, the body's primary protective antioxidant inside of
cells and the most important member of the thiol group, is next
in line to be recycled by another antioxidant coenzyme called NADPH.
From here the cycle continues in a step-by-step process until all
free radicals are quelled.
Up to this point we've seen how vitamins E, C and glutathione work
together to deactivate and prevent free radicals from causing uncontrolled
damage in the body. But at this stage we run into a limiting factor
regarding availability of glutathione, which is an important free-radical
deactivator offering protection against cataract formation, as well
as immune enhancement, liver protection, cancer protection and heavy-metal
detoxification.
Despite a detailed understanding of the antioxidant
regeneration cycle, when Dr. Packer and other researchers tried
to boost antioxidant levels, they ran into problems trying to find
a way to increase cellular glutathione levels. Whereas vitamin E
and vitamin C levels can be elevated by increasing intake directly
from dietary or supplemental sources, cellular glutathione is only
produced in the body. Glutathione, when taken orally, is broken
down in the stomach before it reaches the bloodstream. What does
end up being absorbed can raise serum levels, but the effect inside
of cells is minimal.
'Alpha-lipoic acid proved to be the missing link,' Packer says.
Not only is ALA a powerful antioxidant in its own right, but it
also regenerates glutathione, giving cells a double dose of antioxidant
protection. It is easily absorbed when taken orally, and once inside
cells is quickly converted to its most potent form, dihydrolipoic
acid, an even more potent free-radical neutralizer than ALA. Because
both alpha-lipoic acid and dihydrolipoic acid are antioxidants,
their combined actions give them greater antioxidant potency than
any other natural antioxidant now known, according to Packer.
Another important property of alpha-lipoic acid
is that, since it is both water and fat soluble, ALA can move into
all parts of a cell to neutralize free radicals. Vitamin C (ascorbic
acid), on the other hand, is soluble only in water; while vitamin
E is soluble only in fat and sticks to the fatty parts of cells.
Packer remarked that alpha-lipoic acid also is
important in cell metabolism for the production of energy inside
the cell. Without alpha-lipoic acid, cells could not metabolize
sugars for energy and would just shut down. This makes alpha-lipoic
acid a metabolic antioxidant, able to draw on the cell's own metabolism
to magnify its protective effects and that of other antioxidants.
Other researchers have reported that not only does ALA increase
the efficiency of insulin, it also reduces insulin resistance, a
major factor in diabetes, obesity and coronary disease.
Alpha-lipoic acid could also have much broader
use in treating other diseases and may have general health benefits
when taken as a daily supplement like other antioxidants. 'Alpha-lipoic
acid could have far-reaching consequences in the search for prevention
and therapy of chronic degenerative diseases such as diabetes and
cardiovascular disease,' says Dr. Packer. "And because it's
the only antioxidant that can easily get into the brain, it could
be useful in preventing damage from a stroke," he says.
Currently, lipoic acid is used in Europe to treat and prevent complications
associated with diabetes, including neuropathy (painful peripheral
nerve degeneration), cataracts and macular degeneration. Researchers
have found that ALA can actually reverse neuropathy, aid in glucose
utilization, and, in some cases, help diabetics reduce their reliance
on insulin.
Researchers in Germany have reported that ALA
administration resulted in a 50% increase in insulin-stimulated
glucose disposal in patients with Type II diabetes (NIDDM). A Mayo
Foundation study also found that nerve conduction improved, and
after one month patients taking alpha-lipoic acid exhibited normal
blood flow.
While the normal dosage of lipoic acid is 50 to
100 mg per day, in Germany ALA has been medically approved in higher
dosages for treating adult-onset diabetes and diabetic complications.
Doctors at the Rostock Sudstadt Clinic have reported that 600 mg
of ALA per day significantly reduced symptoms of diabetic neuropathy.
Alpha-lipoic acid has been shown to protect tissues from damage
associated with low oxygen supply that can occur following heart
attack and stroke. Reperfusion, the reinstitution of blood flow
to tissues previously deprived, causes excessive production of free
radicals and is more destructive than the original trauma. What
scientists have found is that animals pretreated with ALA have only
1/3 the death rate of those not treated with ALA. Similar studies
have found a similar role for lipoic acid in preventing tissue damage
and death after a heart attack.
Scientists have also found that lipoic acid can inhibit replication
of HIV-1 and other viruses through its ability to bind directly
to DNA. Dr. Packer and Chandan K.Sen, a researcher from Finland,
have described how lipoic acid regulates aspects of the immune system,
and in particular, the T-lymphocytes. They, along with other scientists,
have reported how alpha-lipoic acid may help people with HIV.
ALA inhibits growth of HIV more effectively than NAC (N-Acetyl Cysteine).
Dr. Packer found that in test tube experiments, alpha-lipoic acid
"completely inhibited activation of a gene in the AIDS virus
that allows it to reproduce."
In a recent study, 12 people with AIDS were given
ALA. Glutathione levels were increased by 100%, vitamin C levels
by 90%, T4cells by 66%, and oxidative stress declined in 70% of
the participants.
German researchers have found that ALA has a positive effect on
long-term memory in aged mice, yet younger mice showed no such benefit.
In interpreting their data the researchers suggested that "alpha-lipoic
acid compensates age-related, long-term memory deficits rather than
improving memory in general."
Other researchers have found similar evidence
that ALA protects brain tissues from oxidative damage. Scientists
at the University of Rochester Medical Center have stated that '(the
result) suggests a possible role of these endogenous compounds in
the treatment of acute and chronic neurological disorders such as
Parkinson's and Huntington's diseases.'
The interior of the eye is an aqueous environment, and fat-soluble
antioxidants like vitamin E and beta-carotene don't offer much protection.
Given the dual water and fat soluble antioxidant properties of ALA,
scientists are investigating the effects of alpha-lipoic on cataracts.
Researchers have found that ALA is of potential therapeutic use
in preventing cataracts and their complications, noting that biochemical
changes in the lens showed major increases in levels of glutathione,
ascorbate, vitamin E and certain protective enzymes. In another
study involving animals given ALA, over 60 percent were protected
from cataract formation, leading researchers to conclude that ALA
had restored some of the protective functions of glutathione.
Free radicals created by the oxidation of low-density lipoproteins
(LDL) accumulate in arterial cholesterol deposits associated with
atherosclerosis. Vitamin E plays a critical role in protecting against
this LDL oxidation. Since ALA and dihydrolipoic acid both support
the regeneration cycle of vitamin E, it follows that higher concentrations
of vitamin E in LDL can be achieved by vitamin E recycling with
ALA.
'Just 10 years ago scientists had a simplistic view of free radicals
and antioxidants,' Packer says. "Today knowledge of a global
antioxidant network has emerged which is linked to the metabolic
energy producing process--a new perspective that is leading to an
explosion of basic research and therapeutic studies."
References
1. Packer L, Witt EH, Tritschler EJ. Free
Rad Biol and Med. 1995; 19-227-250
2. Packer L. Free Rad Biol. 1996. |
