Alpha-lipoic acid is a naturally-occurring sulphur-containing cofactor. It is synthesised in humans.
Alternative names include alpha-lipoate, thioctic acid, lipoic acid, 2-dithiolane-3-pentatonic acid, and 1,2-dithiolane-3-valeric acid.
Alpha-lipoic acid functions as a potent antioxidant and as a cofactor for various enzymes (e.g. pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase) in energyproducing metabolic reactions of the Krebs cycle.
In addition, it appears to improve recycling of other antioxidant compounds, including vitamins C and E, coenzyme Q and glutathione. It may also protect against arsenic, cadmium, lead6and mercury poisoning.
Alpha-lipoic acid is present in foods such as spinach, meat (especially liver) and brewer’s yeast, but it is difficult to obtain amounts used in clinical studies (i.e. possibly therapeutic amounts) from food.
Alpha-lipoic acid is both fat-soluble and watersoluble, and this facilitates its diffusion into lipophilic and hydrophilic environments. It is metabolised to dihydrolipoic acid (DHLA), which also demonstrates antioxidant properties.
As a dietary supplement, alpha-lipoic acid is claimed to improve glucose metabolism and insulin sensitivity in diabetes, and to reduce replication of the human immunodeficiency virus (HIV). It has been investigated for possible use in patients with diabetes mellitus, glaucoma, HIV, hypertension and Alzheimer’s disease.
Alpha-lipoic acid has long been of interest as a potential therapeutic agent in diabetes, including both the microvascular and neuropathic pathologies. This stems from alpha-lipoic acid’s metabolic role and also because diabetes results in chronic oxidative stress. Alpha-lipoic acid appears to increase muscle cell glucose uptake and increase insulin sensitivity in individuals with type 2 diabetes mellitus. In vitro, alphalipoic acid has been found to stimulate glucose uptake by muscle cells in a manner similar to insulin.
In an uncontrolled study, patients with type 2 diabetes given 1000 mg lipoic acid intravenously experienced a 50% improvement in insulin-stimulated glucose uptake. In a further uncontrolled pilot study, 20 patients with type 2 diabetes were given 500 mg lipoic acid intravenously for 10 days. Glucose uptake increased by an average of 30%, but there were no changes in either fasting blood glucose or insulin levels.
In a study involving 10 lean and 10 obese patients with type 2 diabetes, alpha-lipoic acid improved glucose effectiveness and prevented hyperglycaemia-induced increases in serum lactate and pyruvate. In the lean diabetic patients, but not the obese patients, alpha-lipoic acid resulted in improved insulin sensitivity and lower fasting glucose.
In a placebo-controlled, multicentre pilot study, 74 patients with type 2 diabetes were randomised to receive alpha-lipoic acid 600 mg once, twice or three times a day, or placebo. When compared to placebo, significantly more patients had an increase in insulin-stimulated glucose disposal. As there was no dose effect, all three treatment groups were combined into one active group and compared with placebo. The increase in insulin-stimulated glucose disposal was then statistically significant, suggesting that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type 2 diabetes.
Alpha-lipoic acid has been used extensively in Germany for the treatment of diabetic neuropathy. An in vitro study showed that lipoic acid reduced lipid peroxidation of nerve tissue. A study in rats with diabetes induced by streptozotocin showed that alpha-lipoic acid reversed the reduction in glucose uptake that occurs in diabetes, and that this change was associated with an improvement in peripheral nerve function.
In a randomised, double-blind, placebo controlled multicentre trial, 73 patients with non-insulin-dependent diabetes mellitus were assigned to receive oral alpha-lipoic acid 800 mg daily or placebo for 4 months. Of the total, 17 patients dropped out of the study, but the results suggested that alpha-lipoic acid might slightly improve cardiac autonomic neuropathy (assessed by measures of heart rate variability) in non-insulin-dependent diabetic patients.
In a randomised, placebo-controlled study involving 24 patients with type 2 diabetes, oral treatment with 600 mg alpha-lipoic acid three times a day for 3 weeks appeared to reduce the chief symptoms of diabetic neuropathy. A further placebo-controlled, randomised, double-blind trial showed that oral alpha-lipoic acid 600 mg once or twice a day appeared to have a beneficial effect on nerve conduction in patients with both type 1 and type 2 diabetes.
A review of the evidence of the effect of alpha-lipoic acid in the treatment of diabetic neuropathy concluded that short-term treatment with oral or intravenous alpha-lipoic acid appears to reduce the chief symptoms of diabetic neuropathy, but this needs to be confirmed by larger studies.
A meta-analysis of four trials of alpha-lipoic acid involving 1258 patients found a benefit of 16–25% (compared with placebo) in signs and symptoms of neuropathy (e.g. ankle reflexes, pain, burning, numbness, pin-prick and touch-pressure sensation) after 3 weeks of treatment. This is supported by three more recent trials, which have also shown favourable results with alpha-lipoic acid in diabetic neuropathy. Three non-blinded trials (one in Korea and two in Bulgaria) tested alpha-lipoic acid in a dose of 600 mg daily. In the Korean study, total symptom score was significantly reduced at 8 weeks, as were individual symptom scores for pain, burning sensation, paraesthesia and numbness. In one of the Bulgarian trials, there was a significant improvement in several aspects of autonomic function, including postural blood pressure change and overall cardiovascular autonomic neuropathy score. In the second Bulgarian study, alpha-lipoic acid was found to be effective in peripheral and autonomic diabetic neuropathy and also diabetic mononeuropathy of the cranial nerves, leading to full recovery of the patients.
In a study involving 75 patients with open-angle glaucoma, alpha-lipoic acid was administered in a dose of either 75 mg daily for 2 months or 150 mg daily for 1 month. Improvements in biochemical parameters and visual function were found, particularly in the group receiving 150 mg lipoic acid. Human immunodeficiency virus Alpha-lipoic acid blocks activation of NF-kappa B, which is required for HIV virus transcription, and has also been noted to improve antioxidant status, T-helper lymphocytes, and the T-helper/suppressor cell ratio in HIV-infected T-cells. However, it is not known whether supplementation would improve survival in individuals who are HIV-positive.
Results of preliminary studies suggest that alpha-lipoic acid may lower blood pressure,25 improve the symptoms of burning mouth syndrome and improve T-cell functions in vitro in advanced stage cancer patients. Alphalipoic acid has also been investigated for a potential role in dementia, but there is only very limited evidence available.Alpha-lipoic acid has been investigated for an effect in conditions such as cancer cachexia, liver disease, ischaemia reperfusion injury, photoageing of the skin and cataract. However, there is no convincing data as yet from human randomised controlled trial (RCT) data.
Alpha-lipoic acid should be used with caution in patients predisposed to hypoglycaemia, including patients taking antidiabetic agents.
Pregnancy and breast-feeding
No problems have been reported, but there have not been sufficient studies to guarantee the safety of alpha-lipoic acid in pregnancy and breast-feeding.
None reported, apart from occasional skin rashes. Studies investigating the effect of alphalipoic acid have suggested that it is a safe supplement at reasonable doses. However, there are no long-term studies assessing the safety of alpha-lipoic acid.
Oral hypoglycaemics and insulin: Theoretically, alpha-lipoic acid could enhance the effects of these drugs.
Alpha-lipoic acid is available in the form of tablets and capsules. The dose is not established. Studies have used 300–600 mg daily. Dietary supplements provide 50–300 mg daily.
There is evidence that alpha-lipoic acid might have a role in patients with diabetes mellitus in improving glucose utilisation, insulin sensitivity and diabetic neuropathy. Very limited evidence also exists that alphalipoic acid may be helpful in glaucoma, dementia, hypertension and slow replication of HIV and cancer cells, but evidence of benefit in all these conditions, including diabetes, is too limited to make recommendations for supplementation.
(extracted from) Dietary Supplements, Third Edition, by Pamela Mason, BSc, MSc, PhD, MRPharmS, published by Pharmaceutical Press, London, 2007