Lipoic acid (LA) (figure 1) is a thiol compound that acts as a very important antioxidant. It is present in foods such as spinach, peas, tomatoes, brussel sprouts and broccoli, but is also synthesised in liver cells. Because it is both water and fat soluble, LA is present in both phospholipid membranes and the cytosol of cells. If you have read my previous article ‘The Antioxidant Merry-go-round’ (here), you will already be aware of the synergistic effect shared between LA, glutathione, vitamin C, vitamin E and co-enzyme Q10 in protecting cells from oxidative damage. Many antioxidant compounds are protective of cardiovascular disease because it is thought that free radical damage plays a role in the aetiology of the condition. Supplemental LA raises cellular levels of glutathione and so it may play a role in protecting against cardiovascular disease.
Figure 1. The molecular structure of lipoic acid (top) and dihydrolipoic acid (bottom). Lipoic acid is transported into the cell where it is reduced to dihydrolipoic acid. Dihydrolipoic acid can then scavenge free radicals by donating electrons and as a result becomes oxidised to lipoic acid. Lipoic acid can be reduced back to dihydrolipoic acid via enzymatic reaction using NAD(P)H as a hydrogen donor. Oral supplemntation with several grams of lipoic acid is tolerated in humans. Lipioc acid exists in two enantiomers. The (R)-isomer is biologically active and the (S)-isomer is part of the synthetic racemic mixture in supplements. Bioavailability ranges from 20 % to 38 % depending on the mix of (R)-isomers and (S)-isomers.
Despite the bad reputation cholesterol has acquired, it is likely that cholesterol in blood only becomes problematic if oxidised by free radicals. On this basis, LA has been investigated for its ability to prevent oxidative damage to LDL cholesterol in healthy adults. Research has demonstrated that 600 mg of LA reduces markers of oxidative damage, which may delay atherosclerosis. In addition, LA has been shown to favourable alter blood lipid levels and decrease atherosclerotic plaques, at least in animal models. Interestingly in rabbits, LA also intensifies the tissue respiration levels in heart, liver and blood vessels, suggesting it may have other important metabolic effects. In other animal experiments, LA has been shown to be beneficial in the reduction of hypertension in rats, possibly by increasing glutathione levels which may have reduced oxidation in the aortic vessels, thus dilating them.
Dietary LA is incorporated into cells where it increases cellular uptake of cysteine which promotes the formation of cytosolic glutathione. Glutathione and LA are two important cellular thiol reducing agents that are known to recycle vitamin C and vitamin E, and both of these vitamins have been extensively researched for their protective effect against cardiovascular disease. The jury is still out on the extent and mechanism for the protective effect of LA on cardiovascular disease, because much of the research has been conducted in animals. However LA appears to show promising effects and so increasing intakes to the 600 mg dose in human feeding studies is a sensible step to provide good cellular antioxidant protection. However, supplements will be necessary because food sources are likely not rich enough in LA to provide the high doses required.
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