• Alpha-lipoic Acid, Thioctic Acid
• Neuropathic Conditions: ]]>Diabetic Neuropathy (Peripheral Neuropathy and Cardiac Autonomic Neuropathy)]]>
• ]]>Burning Mouth Syndrome]]>, ]]>Cancer Prevention]]>, ]]>Cataract Prevention]]>, ]]>Diabetes (Blood Sugar Control)]]>, ]]>Glaucoma]]>, ]]>Heart Disease Prevention]]>, ]]>Liver Disease]]>, ]]>Migraine Headaches]]>, ]]>Sun-damaged Skin]]>
Lipoic acid, also known as alpha-lipoic acid, is a sulfur-containing fatty acid. It is found inside every cell of the body, where it helps generate the energy that keeps us alive and functioning. Lipoic acid is a key part of the metabolic machinery that turns glucose (blood sugar) into energy for the body's needs.
Lipoic acid is an ]]>antioxidant]]> , which means that it neutralizes naturally occurring but harmful chemicals known as free radicals. Unlike other antioxidants, which work only in water or fatty tissues, lipoic acid is unusual in that it functions in both water and fat. ]]>1,2]]> By comparison, vitamin E works only in fat and vitamin C works only in water. This gives lipoic acid an unusually broad spectrum of antioxidant action.
Antioxidants are a bit like kamikaze pilots, sacrificing themselves to knock out free radicals. One of the more interesting findings about lipoic acid is that it may help regenerate other antioxidants that have been used up. In addition, lipoic acid may be able to do the work of other antioxidants when the body is deficient in them. ]]>3,4]]>
It is thought that certain nerve diseases are at least partially caused by free radical damage. Thanks to its combined fat and water solubility, lipoic acid can get into all the parts of a nerve cell and potentially protect it against such damage. This is the rationale for studies on the potential benefits of lipoic acid for diabetic neuropathy.
A healthy body makes enough lipoic acid to supply its requirements; external sources are not necessary. However, several medical conditions appear to be accompanied by low levels of lipoic acid 5]]> —specifically ]]>diabetes]]> , ]]>liver cirrhosis]]> , and ]]>atherosclerosis]]> —which suggests (but definitely does not prove) that supplementation would be helpful.
Liver and yeast contain some lipoic acid. Nonetheless, supplements are necessary to obtain therapeutic dosages.
The typical dosage of oral lipoic acid for treating complications of diabetes is 100 to 200 mg 3 times daily. In studies that found benefits, several weeks of treatment were often necessary for full effects to develop.
For use as a general antioxidant, a lower dosage of 20 to 50 mg daily is commonly recommended, although there is no evidence that taking lipoic acid in this way offers any health benefit.
Lipoic acid has been widely used for decades in Germany to treat diabetic peripheral neuropathy]]> . This is a condition caused by diabetes in which nerves leading to the arms and legs become damaged, resulting in numbness, pain, and other symptoms. Free radicals are hypothesized to play a role in neuropathy, and, on this basis, lipoic acid has been tried as a treatment. However, the evidence for benefit is largely limited to studies that used the intravenous form of this supplement. ]]>6,7,8]]>
Another set of nerves may become damaged in diabetes, as well: the autonomic nerves that control internal organs. When this occurs in the heart (cardiac autonomic neuropathy), it leads to irregularities of heart rhythm. There is some evidence that lipoic acid supplements may be helpful for this condition. ]]>9]]>
Preliminary and sometimes contradictory evidence suggests that lipoic acid may improve other aspects of diabetes, including ]]>blood sugar control]]> and the development of long-term complications, such as diseases of the heart, kidneys, and small blood vessels. ]]>10-14,28,29]]>
One animal study suggests that lipoic acid might help prevent age-related hearing loss. ]]>15]]> Similarly weak evidence hints that lipoic acid might be helpful for glaucoma, ]]>31]]> as well as for reducing the side effects (specifically, cardiac toxicity) of the cancer chemotherapy drug ]]>doxorubicin]]> . ]]>34-35]]> Other uses for which lipoic acid has been proposed include preventing ]]>cancer]]> and ]]>heart disease]]> , and treating or preventing ]]>cataracts]]> .
What Is the Scientific Evidence for Lipoic Acid?
Diabetic Peripheral Neuropathy
There is some evidence that intravenous lipoic acid can reduce symptoms of diabetic peripheral neuropathy, at least in the short term. However, the evidence for oral lipoic acid remains weak and contradictory.
For example, a double-blind, placebo-controlled study]]> of 500 people with diabetic neuropathy found that intravenous lipoic acid helped reduce symptoms over a 3-week period; however, long-term oral supplementation did not prove effective. ]]>16]]>
Benefits were seen with oral lipoic acid in a study published in 2006. ]]>33]]> In this double-blind, placebo-controlled trial, 181 people with diabetic peripheral neuropathy were given either placebo or one of three doses of lipoic acid: 600, 1,200 or 1,800 mg daily. Over the five week study period, benefits were seen in all three lipoic acid groups as compared to the placebo group.
However, while this outcome may sound promising, one feature of the results tends to reduce the faith one can put in them: the absence of a dose-related effect. Ordinarily, when a treatment is effective, higher doses produce relatively better results. When such a spectrum of outcomes is not observed, one wonders if something went wrong in the study.
Other than this one study, the positive evidence for oral lipoic acid in diabetic peripheral neuropathy is limited to ]]>open studies]]> of minimal to no validity and double-blind trials too small to be relied upon. ]]>19-23]]>
There is some preliminary evidence that lipoic acid could be more effective if it is combined with ]]>gamma-linolenic acid (GLA)]]> , another supplement used for diabetic peripheral neuropathy. ]]>24,25]]>
Diabetic Autonomic Neuropathy
There is better evidence for oral lipoic acid in a form of diabetic neuropathy affecting the nerves that supply the heart: autonomic neuropathy.
Not only does diabetes damage the nerves in the arms and legs, but it can also affect deep nerves that control organs such as the heart and digestive tract. The Deutsche Kardiale Autonome Neuropathie (DEKAN) study followed 73 people with diabetes who had symptoms caused by nerve damage affecting the heart. Treatment with 800 mg daily of oral lipoic acid showed ]]>statistically significant]]> improvement compared to placebo and caused no significant side effects. ]]>26]]>
Burning Mouth Syndrome
Individuals with burning mouth syndrome (BMS) feel chronic scalding pain in the mouth, as if they had consumed an excessively hot drink. Although the cause of BMS is not known, the symptoms resemble those of neuropathy, and for that reason, researchers have investigated the potential benefits of lipoic acid.
In a 2-month, double-blind trial involving 60 people with BMS, use of lipoic acid significantly reduced symptoms as compared to placebo. ]]>30]]> However, 2 double-blind trials involving 52 and 39 patients respectively failed to find any benefit for lipoic acid. ]]>38,39]]>
Lipoic acid appears to have no significant side effects at dosages up to 1,800 mg daily. 27]]>
Safety for young children, women who are pregnant or nursing, or those with severe liver or kidney disease has not been established.
1. 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 . 1992;44:1637-1649.
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 . 1992;44:1637-1649.
6. Ziegler D, Hanefeld M, Ruhnau KJ, et al. The ALADIN III Study Group. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). Diabetes Care. 1999;22:1296-1301.
7. 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;38:1425-1433.
12. Nagamatsu M, Nickander KK, Schmelzer JD, et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care . 1995;18:1160-1167.
14. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med. 1999;27:309-314.
16. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Diabetes Care. 1999;22:1296-1301.
17. 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;38:1425-1433.
20. Kahler W, Kuklinski B, Ruhlmann C, et al. Diabetes mellitus—a free radical-associated disease. Results of adjuvant antioxidant supplementation [in German; English abstract]. Z Gesamte Inn Med . 1993;48:223-232.
21. 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;38:1425-1433.
23. Ruhnau KJ, Meissnert HP, Finn JR, et al. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med. 1999;16:1040-1043.
24. Hounsom L, Horrobin DF, Tritschler H, et al. A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy. Diabetologia . 1998;41:839-843.
27. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Diabetes Care. 1999;22:1296-1301.
32. Beitner H. Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5%alpha-lipoic acid related to photoageing of facial skin. Br J Dermatol . 2003;149:841-849.
Last reviewed April 2009 by EBSCO CAM Review Board]]>
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
Copyright © 2007 EBSCO Publishing All rights reserved.