Lipoic acid (alpha-lipoic acid, thioctic acid) is a sulfur-containing enzyme helper involved in carbohydrate degradation. The body synthesizes this fat-soluble coenzyme; consequently it is not classified as a dietary essential. Lipoic acid is not a vitamin, nor is it derived from a vitamin. Nonetheless, it plays a critical metabolic role. Lipoic acid functions in the oxidation of carbohydrate by the mitochondria, subcellular particles devoted to energy production.
Key chemical transformations require lipoic acid: the oxidation of pyruvic acid (a small acid from glucose breakdown) to an activated form of acetic acid called acetyl coenzyme A and the oxidation of alpha ketoglutaric acid, a product of the Kreb’s cycle, which is the central energy-yielding pathway of the cell carbon dioxide released in both oxidations represents a major portion of the carbon dioxide expired by the lungs as a metabolic waste product. To accomplish such oxidations, lipoic acid must work together with four vitamin-related coenzymes: thiamin pyrophosphate, derived from Thiamin (vitamin B1); FAD (flavin adenine dinucleotide), derived from Riboflavin (vitamin B2); NAD (nicotinamide adenine dinucleotide), derived from Niacin (vitamin B3); and Coenzyme A, derived from Pantothenic Acid (vitamin B5). Lipoic acid is emerging as a versatile antioxidant. In the reduced form it is able to protect lipids from oxidation due to free radical attack and may protect vitamin E. It quenches superoxide and reactive oxygen compounds generated in the body during inflammation and it may play a role in regulating oxidation-reduction balance of cells.
Lipoic Acid (LA) as a fat-soluble enzyme operates as a cofactor in the metabolism of glucose and oxygen utilization. Soon after its discovery in 1950 it was shown to provide highly effective protection against toxin and radiation damage. Lipoic Acid is now recognized as a powerful antioxidant. It has a strong ability to disarm oxygen free radicals and a high affinity for chelating undesirable ionized metals.
In the past 49 years there have been over 800 research papers published on Lipoic Acid, and new discoveries continue to evolve. UC Berkeley researcher, Dr Lester Packer, has referred to Lipoic Acid as the “ideal antioxidant” not only because Lipoic Acid works as a powerful antioxidant on its own, but also because it acts in a synergistic fashion with other antioxidants.
Lipoic Acid works to recycle and reactivate such free radical scavengers as Vitamins C and E, thereby maximizing utilization of these vitamins as antioxidants. Lipoic Acid has the same effect on naturally occurring antioxidants such as thioredoxin and glutathione (the most abundant antioxidant, selenium-containing proteins in mammals). Even after these vitamins have already been oxidized, Lipoic Acid can reactivate them. So if you are not getting enough Vitamin C or E in your diet, Lipoic Acid supplements can help compensate for the difference.
Although Lipoic Acid is not currently considered to be a vitamin by most researchers, it was originally thought to be a vitamin. Most researchers currently believe that the liver synthesizes Lipoic Acid in small amounts. Due to the way it functions synergistically with certain vitamins (the antioxidant B vitamins, Vitamin C, and Vitamin E), some researchers suspect that it still might be an essential vitamin. However the ultimate answer to this question will be determined by whether it is an essential nutrient which is not synthesized in the body. Packer claims that, even though Lipoic Acid’s pathway is not clearly explained, lipoic acid is made in the body. But one thing researchers do agree on is that Lipoic Acid levels decrease with age, and with that decline many of the body’s rejuvenating abilities are lost.
Lipoic Acid supplementation has been shown to be beneficial in helping to treat a variety of medical problems. Beneficial results were found especially in the treatment of those with diabetes and neurodegenerative disorders. Lipoic Acid can also help lower elevated cholesterol levels, which may protect against cardiovascular dysfunctions. It can retard HIV activation and cataract formation. There is also evidence that Lipoic Acid helps to slow down numerous aspects of the aging process by protecting the brain, and by preserving intracellular mitochondria (which supply the basic energy that regulates every cell in the human body).
Lipoic Acid’s ability to recycle other antioxidants in the body makes it a great potential protector against atherosclerosis. Atherosclerosis is the condition that underlies both heart disease and stroke. There is good evidence that free radicals negatively modify LDL (low-density lipoprotein) cholesterol. LDL cholesterol is one of the primary contributors to the undesirable cholesterol deposits that form atherosclerotic plaques. That’s why LDL cholesterol is referred to as the “bad cholesterol.” There is also ample evidence that sufficient levels of Vitamin E can protect against this type of free radical damage. Since Lipoic Acid can extend the life of Vitamin E, it can also increase protection from this type of damage.
Several important research findings indicate that Lipoic Acid may offer some hope for those who suffer from AIDS. Research reveals HIV patients have low levels of a potent endogenous (from within the body) antioxidant called glutathione. One study demonstrates that when Lipoic Acid is administered to the body’s T cells (cells involved in immune protection), there is a dramatic rise in intracellular glutathione levels.
Another study found that Lipoic Acid has a buffering effect on detrimental gene activation, a process that is induced by the rampage of free radicals. Expression of HIV is dependent upon aberrant gene activation. In several studies Lipoic Acid and other antioxidants were effective in inhibiting the activation of this mechanism. Because of these findings, researchers have proposed using Lipoic Acid as a therapeutic adjunct to treating HIV infection.
Lipoic Acid may help to prevent brain damage when the brain is deprived of oxygen due to stroke or cardiac arrest. Damage to the brain commonly occurs during these situations because of the combination of ischemia (lack of oxygen) and reperfusion (rapid reoxygenation). Most of the brain damage usually occurs during reperfusion, which is primarily attributed to injury from oxygen free radicals. When experimental animals are treated with lipoic acid, before being exposed to both ischemia and reperfusion, there is a significant improvement in the reduction of brain damage.
Lipoic Acid may also help with age-related memory decline, and could also have the potential for enhancing or preserving cognitive abilities. In one experiment with mice, Lipoic Acid demonstrated an improvement in the long-term memory of older mice, after being administered for a period of 15 days. However, there was no change among the younger mice. It appears that Lipoic Acid alleviated certain neurotransmitter (NMDA) receptor deficits in the older animals.
There is reason to believe that Lipoic Acid may also be helpful in preventing cancer, since free radical damage to DNA is thought to be a main factor in causing cells to become cancerous.”
Lipoic Acid can revive and rejuvenate other antioxidant substrates present in the body, like the spent ascorbate and tocopherol radicals produced when Vitamin C and Vitamin E disarm higher-energy free radicals. Thus Lipoic Acid can maximize their utilization, giving you more miles per gallon on your health and a bigger bang for your buck, minimizing the draw on your pocketbook. Lipoic Acid stands alone as a powerful antioxidant.
Lipoic acid has the unique ability to remove mercury from inside our cells and the ability to cross the blood-brain barrier. If you use Lipoic Acid to help you remove mercury you need to maintain constant levels in your body for periods long enough that the mercury has time to be “escorted” out of your body and not reabsorbed. Thus, detoxing with Lipoic Acid for mercury requires that doses of 100mg be taken faithfully every 3 to 4 hours for one week. Off 7 to 10 days, then repeat. This process can be repeated several times per year.
There are growing numbers of studies substantiating the multiple benefits of Lipoic Acid and showing that doses as much as 600 – 1,000 mg/day produce the greatest benefits for health-maintenance and preventive purposes.
Gen Pharmacol 1997 Sep;29(3):315-31
The pharmacology of the antioxidant lipoic acid.
Biewenga GP, Haenen GR, Bast A
Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, Department of Pharmacochemistry, The Netherlands.
1. Lipoic acid is an example of an existing drug whose therapeutic effect has been related to its antioxidant activity. 2. Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant activity of lipoic acid is determined by its concentration and by its antioxidant properties. Four antioxidant properties of lipoic acid have been studied: its metal chelating capacity, its ability to scavenge reactive oxygen species (ROS), its ability to regenerate endogenous antioxidants and its ability to repair oxidative damage. 4. Dihydrolipoic acid (DHLA), formed by reduction of lipoic acid, has more antioxidant properties than does lipoic acid. Both DHLA and lipoic acid have metal-chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage. 5. As a metal chelator, lipoic acid was shown to provide antioxidant activity by chelating Fe2+ and Cu2+; DHLA can do so by chelating Cd2+. 6. As scavengers of ROS, lipoic acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro-oxidant activity has been observed. However, lipoic acid can act as an antioxidant against the pro-oxidant activity produced by DHLA. 7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione. 8. DHLA can provide peptide methionine sulfoxide reductase with reducing equivalents. This enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease. 9. Through the lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during oxidative stress. 10. Within drug-related antioxidant pharmacology, lipoic acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.
Ceska Slov Farm 1996 Sep;45(5):237-41
[alpha-Lipoic acid–a natural disulfide cofactor and antioxidant with anticarcinogenic effects].
[Article in Slovak] Dovinova I
Ustav experimentalnej onkologie SAV, Bratisliava.
The present survey summarizes the data about the structure, function and methods of investigation of the natural substance alpha-lipoic acid. This compound is an important growth factor of many microorganisms and at the same time a disulfide cofactor of dehydrogenases in oxidative phosphorylation. It is a physiological constituent of biological membranes, an efficient antioxidant and a scavenger of free radicals. Lipoic acid possesses anticarcinogenic and preventive effects which protect the cells from damage.
Altern Med Rev 1998 Aug;3(4):308-11
[Record supplied by publisher]
Alpha-Lipoic acid is a potent antioxidant in both fat- and water-soluble mediums. Furthermore, its antioxidant activity extends to both the oxidized form and its reduced form. DHLA is capable of regenerating ascorbic acid from dehydroascorbic acid, directly regenerating vitamin C and indirectly regenerating vitamin E. Researchers have found lipoic acid to increase intracellular glutathione levels as well as Coenzyme Q10. Clinically, it appears lipoic acid has the potential to prevent diabetes, influence glucose control, and prevent chronic hyperglycemia associated complications such as neuropathy and cataracts. Lipoic acid may also be useful in the treatment of glaucoma, ischemia-reperfusion injury, amanita mushroom poisoning, and cellular oxidative damage.