(R)-Lipoic Acid Unique Mitochondrial Antioxidant Fights Premature Aging
Glutathione is the most important member of the thiol group and the bodys primary intracellular antioxidant. In addition to being an important free-radical deactivator, glutathione also plays a vital role in protecting against cataract formation, enhancing immune function, preventing liver damage, slowing the initiation of cancers and eliminating heavy metals. Glutathione is quickly depleted when the body experiences high levels of oxidative stress from causes such as illness, infection, trauma, medication or surgery. Glutathione deficiency is also associated with low protein intake, diabetes, liver disease, cataracts, HIV infection, respiratory distress syndrome, cancer, and idiopathic pulmonary fibrosis.
ALA Boosts Glutathione Levels
Dr. Lester Packer, senior scientist at Lawrence Berkeley Laboratory and head of the Packer Lab at the University of California, has spent over 35 years studying how antioxidants like vitamins C, E and glutathione interact in the body. Dr. Packer first discovered several years ago how vitamin E is recycled by vitamin C.
Despite their detailed understanding of the antioxidant regeneration cycle, when Dr. Packer and other researchers tested methods for boosting antioxidant levels they ran into a problem when attempting to increase cellular glutathione levels. Whereas increasing ones intake of dietary or supplemental sources can readily elevate levels of vitamins E and C, cellular glutathione is only produced in the body. Glutathione, when taken orally, is broken down in the stomach before reaching the bloodstream. What does end up being absorbed can raise serum levels, but the effect inside of cells is minimal.
This problem was solved when Packer and his team turned to ALA. Alpha-lipoic acid proved to be the missing link, Packer said. They discovered that in addition to being a powerful antioxidant in its own right, ALA is able to raise intracellular glutathione levels. ALA is easily absorbed when taken orally, and once inside cells it is quickly converted to its most potent form, dihydrolipoic acid, an even more potent free-radical neutralizer. 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.
The Most Potent Antioxidant
According to Dr. Packer, ALA is more potent than vitamins C and E, and CoQ10, and may, in fact, 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.
ALA also is important in cell metabolism and is required for production of energy inside cells. Without ALA, 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 cells own metabolism to magnify its protective effects and that of other antioxidants.
Experiments carried out by Dr. Packer and colleagues suggest that ALA may 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, stated Dr. Packer. And because its the only antioxidant that can easily get into the brain, it could be useful in preventing damage from a stroke.
(R)-Lipoic Acid More Effective
Natural ALA, referred to as R-lipoic acid or (R)-ALA, is found in exceedingly miniscule amounts in animal and plant tissues, tightly bound to mitochondrial complexes. Because of the extreme difficulty (and high cost) of isolating natural (R)-ALA, researchers in the US and Europe originally conducted studies with synthetic lipoic acid. Unlike natural (R)-ALA, synthetic lipoic acid contains a 50/50 mixture of two forms (enantiomers) called (R)-ALA and (S)-ALA. Both (R)- and (S)- forms of ALA are isomers—essentially mirror-image molecular formulas, with the atomic arrangements reversed.
Working with synthetic ALA, researchers were able to gain valuable insights into its role as a coenzyme in mitochondrial energy production, and an antioxidant and antioxidant-recycling nutrient. They then began to map out the impressive range of protective health benefits conferred by supplemental ALA (see sidebar). In time researchers had access to pure samples of the natural, biological version, (R)-ALA. They quickly learned that while the body can utilize both forms of ALA, there is a strong preference for the natural, more biologically active (R) form. For example, researchers in Germany reported that, unlike the natural form, (S)-ALA does not improve ATP synthesis in isolated cells. Furthermore, the R-form increased membrane fluidity and transport, while the S-form tended to decrease fluidity.
R-lipoic acid is the biologically active form of the key mitochondrial antioxidant, alpha lipoic acid. R-lipoic acid is directly involved in cellular metabolism and is a vital component of the intracellular antioxidant cycle, able to scavenge a variety of free radicals and reactive oxygen species (ROS) while recycling vitamins C, E and glutathione. R-lipoic readily crosses the blood brain barrier and has been shown effective for elevating intracellular glutathione levels. R-LA helps regulate neuronal calcium homeostasis, regulates pro-inflammatory cytokines, and alters the expression of toxic genes. R-lipoic acid has been used to treat diabetes and has been recommended as a neuroprotective agent. Because R-lipoic is the naturally occurring form found in mitochondrial complexes it offers substantially greater antioxidant and neuroprotective benefits at substantially lower doses than the synthetic forms of lipoic acid currently available.
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