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Sports Supplements & Nutritional Supplement Reviews > Alpha Lipoic Acid (ALA)Review of Alpha Lipoic Acid
What is Alpha Lipoic Acid? Alpha-lipoic acid (ALA) is a powerful antioxidant that is synthesized within the liver and other tissues. Antioxidants are known to protect biological systems from oxidative damage. Lipoic Acid is believed to protect against the development of artherosclerosis (hardening of the arteries), hypertension, strokes, diabetes, protects against ageing, and improves memory. It has also been shown to increase the level of creatine stored within muscle cells, stabilises blood sugar levels and may enhance weight loss. It is found naturally in our diets, within vegetables such as spinach, broccoli, sprouts and tomatoes. However, it is only through supplementation that Alpha Lipoic Acid reaches potentially therapeutic levels (Wollin and Jones, 2003). Who Should Consider Taking Alpha Lipoic Acid? ALA may be of benefit to anyone looking to improve their health, and well-being, by protecting against the damaging effects of free-radicals (damaging by-products of metabolism). In this way, it may be of benefit to hard training individuals, looking to reduce the negative effects of prolonged, or intense, training. It may also be of benefit to athletes looking to enhance muscle creatine levels, for people looking to control/lower blood sugar levels, and to maintain a healthy bodyweight. Summary of Alpha Lipoic Acid's Phyiological Effects:
Alpha Lipoic Acid Research Alpha Lipoic Acid is known to be a very potent antioxidant (Midaoui and Champlain, 2002). In fact, it is several times more potent than other common antioxidants like vitamin C and E. Antioxidants protect against the damaging effects of free-radicals that are produced during normal metabolic processes. Free-radicals cause many damaging effects within our bodies, including: interference with normal cellular processes, damage to cell membranes and structures, damage and breakage of DNA strands. Free-radicals are believed to play a role in the development of many chronic diseases such as cancer, atherosclerosis, heart disease, diabetes, and play a major role in the processes of ageing (Stephanie and Jones, 2003). Within the body Alpha Lipoic Acid is often reduced to dihydrolipoic acid (DHLA). ALA and DHLA are some of the most powerful biological antioxidant systems (Moini et al., 2002). Alpha Lipoic Acid has a further positive effect in that it is known to be able to re-synthesize vitamins C, E, and glutathionine, and therefore enhances the effectiveness of these antioxidant systems (Biewenga et al., 1997; Kagan et al., 1992). Unlike most other antioxidants, Lipoic Acid is both water and fat soluble, and therefore can have protective effects in all parts of the human body – it is able to have positive effects in parts of the body made mainly of water (heart, muscles etc.) and parts of the body made mainly of fats (nervous system, brain etc.). Research, looking at the effect of Alpha Lipoic Acid supplementation on the rate of artherosclerosis (hardening, and eventually, blocking of the arteries) has found that the supplementation of 600mg of Lipoic Acid prevents premature arterosclerosis (Marangon et al., 1999). The reduced in artherosclerosis is thought to be primarily due to ALA’s antioxidant effect (Marangon et al., 1999). By reducing the amount of artherosclerosis, supplementing with Alpha Lipoic Acid will reduce the risk of heart disease, stroke and hypertension (Leaf and Halleq, 1992; Wollin and Jones, 2003). It has also been shown to combat some of the negative effects that some anti-tumour drugs have on the heart (Balachandar et al., 2003). Research has shown that Alpha Lipoic Acid supplementation can prevent hypertension (Midaoui and Champlin, 2002; Midaoui et al., 2003) and reduce free-radical production, within the heart, through its antioxidant action (Midaoui et al., 2003). Alpha Lipoic Acid may also prove to be useful in the treatment of some types of liver disease, specifically: alcohol induced damage, mushroom poisoning, and metal intoxification (Bustamante et al., 1998). ALA may prove to be a useful supplement for people suffering with type II diabetes. It has been shown to improve insulin sensitivity (Jacob et al., 1995; Jacob et al., 1999), improve the effects of insulin on skeletal muscle glucose transport (Peth et al., 2000), and reduce the synthesis of fatty acids (Wagh et al., 1987). Alpha Lipoic Acid supplementation enhances the removal of glucose from the blood, thereby helping to stabilise blood sugar levels, and increases muscle uptake of glucose instead of uptake by fat cells (Packer et al., 1995). The enhanced glucose uptake is believed to be because Lipoic Acid increases the number of glucose transporters on the surface of cells (Bustamente et al., 1998). The ability of Alpha Lipoic Acid to enhance the uptake of glucose, within muscle cells, may have a positive effect for athletes by helping to ensure that muscle glycogen levels remain high. This could prove useful if athletes want to enhance glucose muscle uptake, after exercise. It is for this reason that Alpha Lipoic Acid supplements are commonly taking by bodybuilders and many athletes, in combination with heavy training. ALA supplementation has also been shown to enhance the uptake of creatine within muscle cells (Burke et al., 2003). This is likely to be due to ALAs ability to enhance the uptake of glucose within muscles. Lipoic Acid has this effect by enhancing insulin sensitivity (Lee et al., 2005a; Lee et al., 2005b). Creatine has traditionally been combined with a high sugar drink, which increases insulin levels, and helps to enhance creatine uptake by muscle fibres. Because Alpha Lipoic Acid increases the muscles sensitivity to insulin it further increases the uptake of creatine by the muscles. By enhancing insulin sensitivity, and stabilising blood sugar levels Alpha Lipoic Acid shows promise as an anti obesity supplement (Lee et al., 2005a; Lee et al., 2005b). Lipoic Acid has two positive effects that influence weight loss: 1) Firstly, it decreases food intake, and; 2) Secondly, it increases energy expenditure (Kim et al., 2004). It has this effect by decreasing the levels of a key enzyme (AMPK), within the hypothalamus, whilst increasing AMPK activity within muscles. AMPK is a major regulator of cellular energy metabolism. When activated, AMPK inhibits the synthesis of fatty acids, whilst increasing both fat, and glucose metabolism, which will further aid weight loss (Lee et al., 2005a; Lee et al., 2005b). Another interesting area of research concerning Alpha Lipoic Acid supplementation is that it posesses anti-ageing properties. Two of the key factors involved in ageing are: decreased metabolism particularly through decreased mitochondrial function; and increased levels of oxidative stress (Hagen et al., 2002a; Hagen et al., 2002b; Liu et al., 2002). Supplementing with Lipoic Acid, has been shown to enhance memory function – particularly when combined with acetyl-l-carnitine – primarily by lowering oxidative damage and reversing some of the age associated reductions in mitochondrial function (Hagen et al., 2002a; Hagen et al., 2002b; Liu et al., 2002). Alpha Lipoic Acid is known to pass easily into the brain, where it has many positive effects including a significant reduction in the accumulation of the heavy metals copper and iron, in the brain (Midaoui and Champlain, 2002). It is through this process that ALA may enhance brain function by lowering iron and copper induced oxidative stress. A combination of Alpha Lipoic Acid and acetyl-l-carnitine has proved very effective at reversing the effects of ageing (Hagen et al., 2002). This research found significant improvements in metabolic rate, physiological activity, and reductions in the level of cellular damage by free-radicals. Research looking at a combination of Hyperbaric oxygen (HBO) therapy and Lipoic Acid supplementation found that ALA supplementation may also enhance the healing process from injury (Alleva et al., 2005) . HBO treatment has proved to be an effective treatment for speeding up the healing process. However, the high levels of oxygen used in HBO treatment, leads to increased levels of free radicals, and thus increased levels of cellular damage. When Alpha Lipoic Acid supplements were used in conjunction HBO treatment, the level of both lipid and DNA oxidation decreased, indication reduced levels of cellular damage. This was believed to be due to ALA's antioxidant ability (soaking up of free-radicals) and/or a recycling of vitamin E. Is Alpha Lipoic Acid effective? A large number of research papers have highlighted many benefits to taking Alpha Lipoic Acid, including: protecting against cellular damage and recycling vitamins C and E; reducing the build up of fatty deposits on artery walls; normalising blood pressure; improved insulin sensitivity; anti-obesity effect; anti-ageing effect, and; a memory protecting effect. How to take Alpha Lipoic Acid? Current research is not clear as to which dose of Alpha Lipoic Acid is optimum (Wollin and Jones, 2003). Research has found Alpha Lipoic Acid to be effective when taken at between 200-1800mg. For general health benefits, and to enhance insulin sensitivity/glucose uptake, consider taking 200mg, 2-3 times per day. Alleva, R., Nasole, e., Di donato, F., Borghi, B., Neuzil, J. and Tomasetti, M. (2005) Alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy. Biochem Biophys Res Commun. 333 (2), 404-410. Balachandar, A. V., Malarkodi, K. P. and Varalakshmi, P. (2003) Protective role of DLalpha-lipoic acid against adriamycin-induced cardiac lipid peroxidation. Hum Exp Toxicol. 22 (5), 249-254. Biewenga, G. P., Haenen, G. R. M. M. and Bast, A. (1997) The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 29, 315-331. Burke, D. G., Chilibeck, P. D., Parise, G., Taranopolsky, M. A. and Candow, D. G. (2003) Effect of alpha-lipoic combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. Int J sport Nutr Exerc Metab. 13 (3), 294-302. Bustamante, J., Lodge, J. K., Marcocci, L., Tritschler, H. J., Packer, L. and Rihn, B. H. (1998) Alpha-lipoic acid in liver metabolism and disease. Free Radicol Biol Med. 24, 1023-1039. Hagen, T. M., Liu, J., Lykkesfeldt, J., Wehr, C. M., Ingersoll, R. T., Vinarsky, V., Bartholomew, J. C. and Ames, B. N. (2002a) Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A. 99 (4), 1870-1875. Hagen, T. M., Moreau, R., Suh, J. H. and Visioli, F. (2002b) Mitochondrial decay in the ageing rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Ann N Y Acad Sci. 959, 491-507. Jacob, S., Henriksen, E. J., Schiemann, A. L., Simon, I., Clancy, D. E., Tritschler, H. J., Jung, W. I., Augustin, H. J. and Dietze, G. J. (1995) Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung. 45, 872-874. Jacob, S., Ruus, P., Herman, R., Tritschler, H. J., Maerker, E., Renn, W., Augustin, H. J., Dietze, G. J. and Rett, K. (1999) Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radical Biology and Medicine. 27, 309-314. Kagan, W., Kuhlinski, B., Ruhlmann, C. and Plotz, C. (1992) Recycling of Vitamin E in human low lipoproteins. J Lipid Res. 33, 385-397. Kim, M. S., Park, J. Y., Namkoong, C., Jang, P. G., Ryu, J. W., Song, H. S., Yun, J. Y., Namgoong, I. S., Ha, J., Park, I. S., Lee, I. K., Viollet, B., Youn, J. H., Lee, H. K. and Lee, K. U. (2004) Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. 10, 727-733. Leaf, A. and Halleq, H. A. (1992) The role of nutrition in the functioning of the cardiovascular system. Nutr Rev. 50, 402-406. Lee, W. J., Koh, E. H., Won, J. C., Kim, M-S., Park, J-Y. and Lee, K-U. (2005a) Obesity: The role of hypothalamic AMP-activated protein kinase in body weight regulation. The International Journal of Biochemistry and Cell Biology. 37, 2254-2259. Lee, W. J., Song, K-H., Koh, E. H., Won, J. C., Kim, H. S., Park, H-S., Kim, M-S., Kim, S-W., Lee, K-U. and Park, J-Y. (2005b) Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochemical and Biophysical Research Communications. 332, 885-891. Liu, J., Head, E., Gharib, A. M., Yuan,W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W. and Ames, B. N. (2002) Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-aplha-lipoic acid. Proc Natl Acad Sci U S A. 99 (4), 2356-2361. Marangon, K., Devaraj, S., Tirosh, O., Packer, L. and Jialal, I. (1999) Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radical Biol Med. 27, 1114-1121. Midaoui, A. and De Champlain, J. (2002) Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Hypertension. 39, 303-307. Midaoui, A. E., Elimadi, A., Wu, L., Haddad, P. S. and De Champlain, J. (2003) Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens. 16 (3), 173-179. Moini, H., Tirosh, O., Park, Y. C., Cho, k. –J. and Packer, L. (2002) R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys. 397, 384-391. Paker, L., Witt, E. H. and Tritschler, H. J. (1995) Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine. 19, 227-250. Peth, J. A., Kinnick, T. R., Youngblood, E. B., Tritschler, H. J. and Henriksen, E. J. (2000) effects of a unique conjugate of alpha-lipoic acid and alpha-linoleic acid on insulin action in obese Zucker rats. Am J Physiol Regul integr Comp Physiol. 278, R453-459. Wagh, S. S., Natraj, C. V. and Menon, K. K. G. (1987) Mode of action of lipoic acid in diabetes. J Biosc. 11, 59-74. Wollin, S. D. and Jones, P. H. (2003) Recent Advances in Nutritional Sciences: Alpha-Lipoic Acid and Cardiovascular Disease. J Nutr. 133, 3327-3330.
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