Lipoic acid, or more technically alpha-lipoic acid, is an increasingly recognized dietary supplement that has demonstrated a variety of beneficial effects. Lipoic acid occurs naturally in small amounts in the body where it is involved in a variety of processes but is primarily important in aerobic metabolism and various enzymatic actions. Lipoic acid is known to be involved in the energy-producing processes in cells. Lipoic acid is found in many foods, including liver, kidney, and heart meat and in broccoli, spinach, beets, yeast, yams, carrots, and potatoes. Scientists discovered lipoic acid in the 1950s, but the importance of this compound and its critical role as an antioxidant in the body was not defined until 1988. Lipoic acid is readily converted in the body to another compound called dihydrolipoic acid. Dihydrolipoic acid, or R-Dihydrolipoic acid, is the reduced form of lipoic acid that has more immediate effects than lipoic acid and has even more significant antioxidant effects than lipoic acid. Both of these antioxidants are particularly effective in destroying free radicals known as peroxynitrite radicals. These damaging compounds contain both oxygen and nitrogen and have been implicated in the development of chronic inflammation, nervous system diseases, pulmonary diseases, and arteriosclerosis.

Lipoic acid acts as an antioxidant in the body and has been shown to have protective effects against nerve damage in diabetics, among other beneficial effects. Lipoic acid is believed to increase the antioxidant activity of other antioxidants, such as vitamin C and vitamin E. It has the unusual effect of acting as an antioxidant both in water-soluble and fat-soluble domains in cells and tissues. This is in contrast to vitamin C, which is only water soluble, and vitamin E, which is only fat soluble. When lipoic acid is combined with these other antioxidants, the ability of the body to fight free radicals is increased. Lipoic acid is also known to amplify the positive effects of two other factors, glutathione and coenzyme Q10, which are important in the fight against oxidative stress and the development of disease. Researchers have found that lipoic acid only acts as an antioxidant only when there is an excessive amount freely circulating in the body. There is generally an excess of lipoic acid in the body only when great quantities of the compound are consumed in food or in supplements. The amount of lipoic acid produced internally in the body naturally decreases with age, and this may be one of the reasons why free radicals begin to inflict damage and cause disease as one ages.

In addition to its ability to protect against the oxidative stress caused by free radicals, lipoic acid also assists the B vitamin family in generating energy in the body from carbohydrates, proteins, and fats obtained from food sources. Lipoic acid has been used extensively in Europe for a variety of reasons, including the maintenance of liver health. Germany has approved lipoic acid for the treatment of nerve diseases associated with diabetic and alcoholism complications. In addition, Germany has also approved lipoic acid as a treatment for a variety of liver diseases. Lipoic acid has been shown to improve blood flow in the aorta following a period where there was little oxygen available.

Diabetic Neuropathy

Lipoic acid has been shown to be effective in the treatment of diabetic nephropathy, the type of nerve damage that occurs as a result of diabetic complications.1 Research indicates that lipoic acid can prevent some of the damage that occurs when nerves are deprived of oxygen in diabetics. In addition to this ability to prevent nerve damage, lipoic acid appears to improve the ability of cells to uptake glucose, which is a critical component in diabetes disease processes. Furthermore, lipoic acid appears to promote the general health of nerves and chelate, or remove, harmful metals in the body that are damaging to nerves. An experiment in diabetic rats found that lipoic acid administered for up to three months improved blood flow to nerves.2 The ability of nerves to function normally was completely restored in many of these rats. Likewise, studies in diabetic humans have been promising. Human diabetic subjects that received 200 milligrams of lipoic acid daily for 21 days had a significant reduction in pain associated with diabetic nephropathy.3

A large randomized, placebo-controlled, multicenter, double-blind study involving 328 patients with type 2 diabetes mellitus found that lipoic acid, given in doses of 600 and 1200 milligrams daily five times weekly for three weeks, significantly improved a variety of diabetic nephropathy symptoms, including burning sensations, numbness, itching, tingling and pain.4 One of the main theories of how lipoic acid improves the health status of diabetics is that blood glucose is stabilized with the long-term use of lipoic acid. There is also evidence that lipoic acid decreases the effects of an enzyme that is related to hunger. This led to decreased appetite in a group of study animals. Decreased appetite can help diabetics decrease food intake and lose weight, which helps slow the progression of disease.

Arteriosclerosis, Hypertension and Stroke

One of the complications of diabetes is the increased risk developing of arteriosclerosis. Lipoic acid is believed by many to reduce the risk of developing arteriosclerosis. This may occur because lipoic acid appears to have positive effects on the arterial walls where arteriosclerosis develops. The positive effects are likely related to the overall positive activity lipoic acid has on anti-oxidative and metabolic functions in the body. This has been verified in various animal studies, but a study in humans had added weight to this evidence. A four-month randomized study concluded that 600 milligrams of lipoic acid per day for eight weeks significantly reduced harmful LDL-cholesterol oxidation in healthy subjects.5 The researchers also found evidence that lipoic acid significantly reduced levels of oxidative stress in these subjects.

Researchers also believe that lipoic acid can reduce some of the harmful effects on various cells and tissues following myocardial infarction and stroke. Lipoic acid passes readily into the brain where it can produce its beneficial effects on nerve tissues and blood vessels in the brain. Animal studies have shown that lipoic acid reduced brain damage in animals that had suffered a stroke and those receiving lipoic acid had a survival rate four times greater than those animals that did not receive this compound.6 Some of the positive protective effects of lipoic acid in these cases may be related to its ability to increase the levels of a compound called glutathione in the body. Glutathione levels are often significantly depleted by harmful oxidative stress activity associated with these cardiovascular events.

A study of 36 patients with coronary artery disease found that a combination of lipoic acid with the compound acetyl-L-carnitine reduced blood pressure and may be an effective regimen to treat some patients with hypertension.7 The researchers also found that the tone of the brachial artery improved with this treatment.

Metal Chelation

There is strong evidence that lipoic acid can chelate, or chemically-inactivate, metals in the body. This includes the ability to chelate toxic metal elements and compounds and help remove them from the body. Animal studies have shown that lipoic acid can help protect against arsenic poisoning. It has also been shown to decrease levels of liver toxicity following exposure to the heavy metal cadmium.8 Other studies have shown that lipoic acid has the ability to chelate harmful mercury stores from kidney tissues.9

Cataracts

An important factor in the development of cataracts is the action of the enzyme aldose reductase. Evidence now exists that lipoic acid blocks the actions of aldose reductase in the lens of the eye and may help prevent cataracts. Additional evidence of this preventive effect has been found in an additional study.10

Glaucoma

A study in patients with open-angle glaucoma found that visual function and other measures of glaucoma were improved in a group that received 75 milligrams of lipoic acid daily for two months or 150 milligrams of lipoic acid daily for one month compared to a control group that received no lipoic acid.11

Ischemia

Ischemia is the lack of blood supply to a tissue or organ. When the blood supply is re-established to the deprived tissue, a considerable number of damaging free radicals are released. This process often occurs when a person has been treated for strokes or blood clots. These free radicals have the potential to cause negative changes in the body that lead to additional disease. Several studies in animals have demonstrated that lipoic acid administration can reduce the harmful effects of these free radicals.12

Mushroom Poisoning
Research performed in the 1970s found that lipoic acid can help improve outcomes in patients with mushroom poisoning. A total of 75 patients who had suffered amanita mushroom poisoning received lipoic acid infusions.13 Typically, between 10 and 50 percent of individuals will recover from amanita poisoning without therapy. The researchers found that 89 percent of those who had received lipoic acid recovered without additional therapy.

Liver Diseases

There is accumulating evidence that lipoic acid may benefit those with liver diseases, such as hepatitis and cirrhosis.14 It may accomplish this by helping to break down toxins in the body that are normally processed by the liver. However, when the liver is in a weakened state, lipoic acid can help shield the liver from the effects of these toxins. There has been no conclusive evidence that lipoic acid can improve outcomes in patients with alcoholic liver disease, but there is some anecdotal and other evidence that these patients could benefit from such therapy.

Chronic Fatigue Syndrome

Because lipoic acid assists B vitamins in the body in the production of energy, patients with chronic fatigue syndrome may benefit from lipoic acid supplementation. At this point, the evidence for these benefits has not been collected.

Skin

Lipoic acid has been used in a variety of situations to improve the health of the skin. A study of 33 women with an average age of 54 years found that a cream containing 5% lipoic acid reduced the roughness of the skin and decreased the appearance of photoaging compared to a control group.15

Additional Benefits

There is some evidence that lipoic acid may be protective against the harmful effects of radiation. Other researchers believe that lipoic acid may prevent the formation or progression of a variety of neurological diseases based on the idea that lipoic acid has such a strong neutralizing effect on oxidative stress.16 A different study found that lipoic acid disables the enzyme that is responsible for the replication of the HIV virus.17 Additional research has suggested that lipoic acid may prevent some of the negative effects of cigarette smoke. Yet another study found that lipoic acid might help patients with muscle degeneration diseases caused by genetic defects.18 Researchers have identified a series of mechanisms that suggest lipoic acid may be beneficial in the prevention and treatment of Alzheimer’s disease.19

A different group of researchers believe that lipoic acid has the potential to be a general anti-aging compound based on the idea that it activates the cellular defenses of the body, improves overall immune system function, detoxifies a variety of cells and tissues and increases blood flow to these areas.20 These researchers have also found that lipoic acid supplementation in a group of older mice led to improvements in cognition and genetic processes that matched similar processes in younger mice. Other benefits include a restoration of cellular signaling processes, decreased mitochondrial breakdown in cells, and re-normalization of glutathione levels.

Investigators have found that lipoic acid supplementation improved a variety of inflammation measures that are associated with multiple sclerosis.21 A recent study found that the combination of vitamin E and lipoic acid helped reduce vision loss in mice with retinitis pigmentosa, which is a degenerative eye disease also found in humans.22

Safety and Adverse Effects

Lipoic acid has generally been found to be safe when administered in recommended doses. Among the rare reported side effects in humans has been the development of skin allergies and gastrointestinal distress.

Recommended Dosing
For general antioxidant protection, take 100-300 mg lipoic acid total per day. For the prevention of diabetic complications, take 200-300 mg lipoic acid twice per day. For the prevention and control of diabetic neuropathy, take 200-300 mg lipoic acid three times per day. When taking more than 100 mg lipoic acid per day, also supplement with biotin and a complement of B vitamins. When taking the reduced form of lipoic acid, R-Dihydrolipoic acid, doses are usually reduced by one-third to one-half because of the more efficient delivery of this form of the compound to cells.

1 Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-33.
2 Melhem MF, Craven PA, Derubertis FR. Effects of dietary supplementation of alpha-lipoic acid on early glomerular injury in diabetes mellitus. J Am Soc Nephrol 2001;12:124-33.
3 Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-33
4 Ibid
5 Packer L, Witt EH, Tritschler HJ. Alpha-lipoic as a biological antioxidant. Free Rad Biol Med 1995;19:227-50
6 Panigrahi M, Sadguna Y, Shivakumar BR, Kolluri SV, Roy S, Packer L, Ravindranath V. Alpha-Lipoic acid protects against reperfusion in jury following cerebral ischemia in rats. Brain res 1996;717 (102):184-88.
7 McMackin CJ, Widlansky ME, Hamburg NM, et al. Effect of combined treatment with alpha-lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in patients with coronary artery disease. J Clin Hyperten 2007;9:249-55
8 Muller L, menzel H. Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium2+ toxicity in isolated hepatocytes. Biochem Biophys Acta 1990;1052:386-91.
9 Anuradha B, Varalakshmi P. Protective role of DL alpha-lipoic acid against mercury-induced neural lipid peroxidation. Pharmacol Res 1999;39:67-80.
10 Maitra I, Serbinova L, Tritschler HJ, Packer L. Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats. Free rad Biol Med 1995;18:823-29.
11 Filina AA, Davydova NG, Endrikhovskii SN, Shamshinova AM. Lipoic acid as a means of metabolic therapy of open-angle glaucoma. Vetn Oftalmol 1995;111:6-8.
12 Scheer B, Zimmer G. Dihydrolipoic acid prevents hypoxic/reoxygenation and peroxidative damage in rat mitochondria. Arch Biochem Biophys 1993;302:385-90.
13 Bartter FC, Berkson BM, Gallelli J, et al. Thioctic acid in the treatment of poisoning with alpha-amanitin. In: Faulstich H, Kommerell B, Wieland T, eds. Amanita toxins and Poisoning. Baden-Baden, Germany Witzstrock:1980:197-202.
14 Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Age-associated decline in ascorbic acid concentration, recycling and biosynthesis in rat hepatocytes-reversal with R-alpha-lipoic acid supplementation. FASEB J 198;12:1183-89.
15 Beitner H. Therapeutics Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% alpha-lipoic acid related to photoaging of facial skin. Brit J Dermatol 2003;149:841-9.
16 Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Rad Biol Med 1997;22:359-378.
17 Baur A, Harrer T, Peukert M, et al. Alpha-lipoic acid is an effective inhibitor of human immunodeficiency virus (HIV-1) replication. Klin Wochenschr 1991;69:722-24.
18 Barbiroli B, et al. J of Neurology 1995;242:472-7.
19 Holmquist L, Stuchbury G, Berbaum K, et al. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacology and Therapeutics. 2007;113:154.
20 Hagen T, et al. Function outlined of lipoic acid as anti-aging compound. Ascribe Newswire 2007:pg. 5.
21 Marracci GH, McKeon GP, Marquardt WE, Winter RW, Riscoe MK, Bourdette DN. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res 2004 ;78:362-70.
22 Gaston R. Vitamin E, lipoic acid help slow vision loss. Life Extension 2006;12:17.