Lipoic Acid

The Alpha of Antioxidants: Slow Aging, Fight Disease, Balance Blood Sugar, and Increase Energy

Lipoic acid, often referred to as alpha-lipoic acid or thioctic acid, is joining the reputable ranks of well-respected nutrients like vitamins E and C. This vitamin-like nutrient has a powerful role in quenching disease-causing free radicals and regenerating other antioxidants. It is also showing real promise for slowing the aging process, helping stabilize blood sugar, as well as protecting and supporting the health of eyes, nerves, heart, and liver. There’s more! This unique nutrient is often referred to as the “universal” antioxidant due to its ability to impact both water and fat-soluble tissues. Combine these notable attributes, and this nutrient deserves a standing ovation!

What, When, and Where

Back in the 1950s, lipoic acid was first identified as a co-factor for energy production, similar in function to many of the B vitamins. However, lipoic acid is not classified as a vitamin because it can be synthesized in small amounts by the body.[1] Since it has the ability to dissolve in lipids (fats), it was named lipoic acid. As research continued, it became obvious that symptoms appeared in those with a lipoic acid deficiency, leading to the conclusion that its role in health went beyond energy production.[2]

In terms of the trace amount of lipoic acid that is produced by the body, it becomes less and less as we age.[3] Ideally, food should be able to provide a source of this nutrient; however, little is known about its content and absorption through food, and other factors complicate the issue. Red meat is believed to be the best dietary source of lipoic acid, with smaller amounts being found in spinach, broccoli, carrots, potatoes, yams, and sweet potatoes.[4],18 Even for those who eat the foods that are supposedly rich in lipoic acid, food quality makes an difference. For example, grass-fed, naturally-raised beef and other game meat offer the best nutrition. Once the animals have been tainted with steroids, hormones, and chemical-laden food, their nutrient levels begin to plummet. Luckily, grass-fed, naturally-raised meats and organically-grown vegetables are readily available. Nevertheless, lipoic acid supplements are available in order to insure a sufficient intake of this nutrient and provide its health giving benefits.

Lipoic Acid’s Role as an Antioxidant

Lipoic acid provides antioxidant protection throughout all body systems.[5],[6] An antioxidant is a substance that has the ability to scavenge the body for disease-causing free radicals, which are unruly molecules that cause oxidation of cells. Free radicals contain one or more unpaired electrons and cause damage by “stealing” electrons from other molecules such as DNA, proteins, and fats. This oxidative damage leaves us vulnerable to accelerated aging, wrinkles, eye deterioration, heart dysfunction, and much more. Antioxidants prevent this damage by donating electrons to the radical, preempting its need to “steal,” and thus preventing the damage it can cause. Certain antioxidants may sound familiar – C, E, selenium, CoQ10, and polyphenols in green tea. However, there are a few characteristics to lipoic acid that make it special. For example, antioxidant substances typically come in either water-soluble (e.g. vitamin C) or fat-soluble (e.g. vitamin E), but lipoic acid is both.[7] This dual nature allows lipoic acid to function in both fatty and watery parts of the body, which is why it is sometimes referred to as the “universal antioxidant.”1

Lipoic acid also enhances the effectiveness and synergism of other antioxidants. Once an antioxidant neutralizes a free radical, it usually loses its electron-donating abilities. In living systems, however, antioxidants can be regenerated, often with the help of other antioxidants. Lipoic acid directly recycles or regenerates vitamin C,[8] glutathione,[9] coenzyme Q10,[10]and indirectly renews vitamin E.[11],[12] It does this without damaging its own chemistry.[13] By making these nutrients serviceable again, there is more antioxidant power working in our bodies, fighting the good fight against the free radical rebels that cause cellular damage and disease. In fact, studies suggest that a deficiency in lipoic acid may result in other antioxidant compounds not working properly.[14]

This antioxidant is one of the most versatile known and is capable of neutralizing a wide variety of free radicals, such as singlet oxygen, superoxides, and peroxyl and hydroxyl radicals.[15] These types of radicals are believed to play a significant role in many disease processes.1 Finally, lipoic acid has been shown to repair cells and tissues that have been damaged by oxidation.[16] Because of the attributes described above, coupled with the fact that this nutrient is rapidly absorbed, many scientists consider lipoic acid the ideal antioxidant.3,[17]

Specific Benefits of Lipoic Acid

There are mounds of research showing lipoic acid’s impact on health. Below is a brief look at some of the exciting ways this powerhouse nutrient can support the body and its functions.

Blood Sugar Stability

One of lipoic acid’s most notable functions in the body is its ability to stabilize glucose and insulin levels, reduce insulin resistance, and improve insulin sensitivity. It has long been understood that lipoic acid increases glucose (sugar) metabolism. It also enhances the efficiency of insulin, which moves glucose into cells and tissues of the body. Without the action of lipoic acid, glucose remains in the blood.[18] This is an important function because elevated blood glucose can have severe health consequences, since it is a potent generator of free radicals.18 It is now becoming quite common for people to become insulin resistant due to excess sugar consumption and poor lifestyle choices. Essentially, the cells become insensitive to insulin and will not take up the glucose as normal. Elevated blood glucose also encourages glycation, which is the process where proteins react with excess glucose. This not only accelerates aging, but also increases one’s susceptibility to most degenerative diseases. Research has shown that lipoic acid reduces glycation.18,[19] Overall, lipoic acid’s role in sugar and insulin balance in the body reduces a major source of free radicals, as well as supports conditions like hypoglycemia, Syndrome X, and diabetes.[20],[21],[22],[23]

Slow Aging

The most accepted theory of why we age is the accumulation of free radicals.[24] We actually have the genetic potential to live to about 120 years; however, it is the “wear and tear” on our organs and tissues from free radical damage that undercuts this genetic potential. Fortunately, we can prevent cell-deterioration with the right tools – antioxidants. Besides the obvious free radicals we are exposed to everyday (e.g. pesticides, air pollution, etc.), glycation is another factor that speeds the aging process and tends to occur more rapidly as we get older.[25] Therefore, as an age-slowing nutrient, lipoic acid’s function is two-fold by offering abundant free radical protection and reducing glycation.

Eye Protection

Lipoic acid has also been shown to support healthy vision.[26],[27] This double-duty nutrient penetrates the fat and water-soluble tissues of the eye and destroys free radicals. Animal experiments have demonstrated that this nutrient increases the levels of glutathione, vitamin C, and vitamin E in eye lens tissue.36 Additionally, lipoic acid can neutralize chemicals that cloud the lens.[28] Another proposed mechanism for lipoic acid’s impact on eye health is the stimulation and regeneration of glutathione within the lens,25 one of the primary antioxidants in the fluid surrounding the eye.18 Animal studies have found that supplementing with lipoic acid actually reduces the risk of cataracts.3,18

Nerve Health

Lipoic acid offers nerve support in several ways. First, nerve cells are readily damaged by free radicals, thus the strong antioxidant effects of this nutrient protect and repair.[29] Elevated blood sugar levels also damage nerve fiber; therefore, lipoic acid offers support due to its ability to stabilize blood glucose levels. This nutrient also boosts blood circulation, thus facilitating nutrient delivery to nerve cells. Additional research has found that lipoic acid enhances nerve conduction, which is the speed nerve signals are transmitted.18 Finally, it has been reported that lipoic acid actually stimulates the sprouting of new fibers on nerve cells.[30] Essentially, this nutrient helps improve the communication between the nerve cells, which may lead to less pain and numbness. In fact, physicians around the world have used this nutrient to support nerve health in such conditions as diabetes and sciatica.18

Chelation

Lipoic acid also functions as a heavy metal chelating agent, which has the ability to grab and bind metallic substances, neutralize them, and carry them to a place where they can be excreted from the body. This may reduce the toxicity from mercury,[31] cadmium,[32] and lead.[33] Excess heavy metals contribute to our oxidative stress load, which play into cellular damage and disease.1 Heavy metal toxicity is more common than you might think. Up to 25 percent of the U.S. population suffers, to some extent, from heavy metal poisoning.[34] Animal trials have demonstrated that lipoic acid can effectively prevent intoxication and liver damage by these metals.[35]

Energy

Lipoic acid works on the cellular level to help produce energy by working as a coenzyme – a helper of enzymes – in the cell’s major energy cycle. It takes part in a multi-enzyme process, preparing the fuel for the mitochondria, the powerhouse of the cell. Therefore, a shortage of lipoic acid is a contributing factor in slowing down the energy process.[36] It is believed by many scientists that an increase in lipoic acid levels can boost the amount of fuel burned in the cell, thereby augmenting the amount of energy available to your body for tasks such as muscle movement, growth, and tissue repair.3

Additional Benefits

Lipoic acid has been shown to enhance immune system function,[37] protect the liver,3 as well as support and help oxygenate the heart.3,36 There is also mounting evidence that this nutrient can protect brain neurons from damage and improve memory.[38],[39],[40] Recent research also finds it can help reduce inflammation throughout the body.[41] Finally, due to lipoic acid’s role in recycling and simulating glutathione,[42] it becomes a powerful tool for the body’s detoxification pathways. This is because glutathione plays an important role in the elimination of hazardous compounds.1

Supplementing with Lipoic Acid

Although the body makes some lipoic acid, there is substantial evidence that it makes barely enough for its metabolic functions, and inadequate amounts for optimal antioxidant needs.36 One’s ideal level varies depending on biochemical individuality, lifestyle, age, health status, exercise habits, and oxidative stress exposure and production. Because so little is understood about lipoic acid’s content in foods, it is practical to supplement. Overall, supplementation with this nutrient is very safe. For healthy people, 40 to 100 mg daily is a recommendation for general health and maintenance. To help support glucose intolerance and other conditions, 100 to 300 mg on a daily basis may be appropriate.18 One caution does exist for those who are dealing with conditions like diabetes or hypoglycemia because of this nutrient’s ability to lower glucose levels. [43],[44] These individuals should be monitored under doctor supervision while supplementing with higher amounts of lipoic acid since it may reduce drug requirements.18

Do I believe lipoic acid should replace all other antioxidants and be the only one taken as a supplement? No, every antioxidant has an important and unique role in the body. However, I do believe that the evidence stacked up in favor of this nutrient makes it a candidate for most every supplement regime. Take control of your health and vitality!

References

[1] Wolfson, David N.D. Lipoic Acid: The Universal Antioxidant. Nutrition Science News. Oct. 2000. Found at http://exchange.healthwell.com/nutritionsciencenews/NSN_backs/Oct_00/lipoic.cfm?path=ex on January 14, 2003.

[2] Fuchs J, et al., editors. Lipoic acid in health and disease. New York: Marcel Dekker Inc.; 1997.

[3] Berkson, Burt, M.D., Ph.D. The Alpha Lipoic Acid Breathrough. Prima Publishing. 1998.

[4] Dietary Supplement Information Bureau. Alpha-Lipoic Acid. Found at http://content.intramedicine.com/dse/consumer/monoAll-style.asp?objID=100010&ctype=ds&mtyp=4 on January 14, 2003.

[5] Kagan VE, Shvedova A, Serbinova E, et al. Dihydrolipoic acid–a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem Pharmacol.

[6] Monograph:Alpha-Lipoic Acid. Altern Med Rev. Aug1998;3(4):308-11.

[7] Kagan V, Khan S, Swanson C, et al. Antioxidant action of thioctic acid and dihydrolipoic acid. Free Radic Biol Med 1990;9S:15.

[8] 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 1998;12:1183–9.

[9] Busse E, Zimmer G, Schorpohl B, et al. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung1992;42:829–31.

[10] Kagan V, Serbinova E, Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 1990;169:851–7.

[11] Scholich H, Murphy ME, Sies H. Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol. Biochem Biophys Acta 1989;1001:256–61.

[12] Packer, Lester, Ph.D., et al. “Alpha-lipoic Acid As A Biological Antioxidant,” Free Radical Biology and Medicine 19:227-250, 1995.

[13] Rogers, Sherry. M.D. Detoxify or Die. Sand Key Company, Inc. 2002.

[14] Elkins, Rita. M.H. Alpha Lipoic Acid. Nature’s Supreme Antioxidant. Woodland Publishing. 1998.

[15] Biewanga G, et al. The pharmacology of the antioxidant lipoic acid. Gen Pharmac 1997;29(3):315-31.

[16] Spector A, et al.Thioredoxin fragment 31-36 is reduced by dihydrolipoamide and reduces oxidized protein. Biochem Biophys Res Commun 1988;150:156-62.

[17] Harrison, EK, McCormick, DC. The metabolims of dl-(1-6-14C) lipoic acid in the rat. Arch Biochem Biophys 160:514-522, 1974.

[18] Challem, Jack. Berkson, Burton, Diane Smith, Melissa. Syndrome X. John Wiley & Sons, Inc. 2000.

[19] Schleicher E. Wagner E, Nerlick A. Increased accumulation of the glucoxidation protein N (epsilon)-(carboxymethyl) lysine in human tissues in diabetes an aging. J Clin Invest 99:457-68. 1997.

[20] Jacob S, et al. Enhancement of Glucose Disposal in Patients with Type 2 Diabetes by Alpha-lipoic Acid. Arzneimittelforschung. Aug1995;45(8):872-74.

[21] Packer L. Antioxidant Properties of Lipoic Acid and Its Therapeutic Effects in Prevention of Diabetes Complications and Cataracts. Ann N Y Acad Sci. Nov1994;738:257-64.

[22] Nagamatsu M, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995;18:1160-167.

[23] Low PA, et al. The Roles of Oxidative Stress and Antioxidant Treatment in Experimental Diabetic Neuropathy. Diabetes. Sep1997;46(Suppl 2):S38-42.

[24] Harman, D. Free-radical theory of aging: the free-radical diseases. Age 7:111-113. 1984.

[25] Sahelain, Ray. M.d. Lipoic Acid. Longevity Research Center. 1998.

[26] Kilic F, et al. Modelling Cortical Cataractogenesis XX. In Vitro Effect of Alpha-lipoic Acid on Glutathione Concentrations in Lens in Model Diabetic Cataractogenesis. Biochem Mol Biol Int. Oct1998;46(3):585-95.

[27] Filina AA, et al. Lipoic Acid as a Means of Metabolic Therapy of Open-angle Glaucoma. Vestn Oftalmol. Dec1995;111(4):6-8.

[28] Suzuki, Y. Tsuchiiya, M. and Packer, L. 1991. Thioctic acid and dihydrolopic acid are novel antioxidants with interact with reactive oxygen species. Free Radical Research Communications. 15:255-263. 1991.

[29] Nagamatsu, M. Nickander, K, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress and improves distal nerve condition in experimental diabetic neuropathy. Diabetes Care 18:1160-1167.

[30] Dimpfer, W., Spuler, M. et al. Thioctic acid induces dose-dependent sprouting of neutries in cultured rate neuroblastoma cells. Developmental Pharmacological Therapeutics. 14:193-199. 1990.

[31] Anuradha B, Varalakshmi P. Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Pharmacol Res. Jan1999;39(1):67-80.

[32] Sumathi R, Baskaran G, Varalakshmi P. Relationship between glutathione and DL alpha-lipoic acid against cadmium-induced hepatotoxicity. Jpn J Med Sci Biol. Apr1996;49(2):39-48.

[33] Gurer H, Ozgunes H, Oztezcan S, Ercal N. Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med. Jul1999;27(1-2):75-81.

[34] Murray, M.T. & Pizzorno J. The Encyclopedia of Natural Medicine: p. 32. Rocklin, Calif.: Prima Publishing, 1998.

[35] Sumathi R, et al. Relationship between glutathione and DL alpha-lipoic acid against cadmium-induced hepatotoxicity.Jpn J Med Sci Biol 1996;49(2):39-48.

[36] Passwater, Richard, Ph.D. Lipoic Acid: The Metabolic Antioxidant. Keats Pub. 1995.

[37] Bustamante, J. et al. Antioxidant inhibition of thymocyte aprptosis by dihydrolipoic acid. Free Radical Biology and Medicine. 19:339-347.

[38] Prehn JK, Karkoutly C, Nuglisch J. Dihydrolipoate reduces neuronal injury after cerebral ischemia. J Cerb BloodFflow Meta. 12:78-87.1992.

[39] Greenamyre, J. T. et al. Neurosci. Letters 171:17-20. 1994.

[40] Stoll, S, et al. Parmacol. Biochem. 46:799-85. 1993.

[41] Lee HA, et al. Experimental Gerontology. 37:401-410. 2002.

[42] Busse E. Zimmer G, Schopohl B, Kornhuber B. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimitterlforschung 42:829-831. 1992.

[43] Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther. 2000;2(3):401-13.

[44] Konrad D. The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes. Jun2000;50(6):1464-71.