Over the past two decades, large clinical trials of antioxidant supplements have been conducted with participants who had preexisting heart disease or some risk factors for heart disease such as smoking and diabetes. These studies focused primarily on the potential benefit of vitamins E, C, and/or the carotenoid beta-carotene for preventing cardiovascular disease. The studies did not specifically target diabetic populations, but the results are pertinent to people with diabetes because some were included in some of the studies and because the cardiovascular disease end points measured are some of the complications people with diabetes often develop.
A 1996 English study, the Cambridge Heart Antioxidant Study, found that vitamin E supplements given to 2,002 adults with preexisting heart disease significantly reduced the occurrence of heart attacks after one year of supplementation. These findings encouraged further studies of vitamin E. However, a number of subsequent studies did not show benefits for consumption of vitamin E supplements in amounts of 20 to 40 times the RDA (recommended dietary allowance, now 15 milligrams [mg] per day). More recently, a 2002 British study gave a trio of antioxidant supplements (vitamins E and C and beta-carotene) or placebo to 20,536 adults with cardiovascular disease or diabetes for five years. As compared to the placebo group, the people who took the supplements had substantially increased blood levels of the antioxidants, but the antioxidants had no effect on the occurrence of cardiovascular events (such as heart attack or stroke), cancer, or hospitalizations for nonvascular problems.
Some of the large antioxidant clinical trials enrolled enough people with Type 2 diabetes to assess the effects of antioxidant supplements in the diabetic group separately. In 2002, investigators from Canada, the United States, and Germany reported the effects of supplementing adults age 55 and over, who had either cardiovascular disease or Type 2 diabetes and an additional coronary risk factor, with vitamin E for an average of 4.5 years. For the group of 3,654 people with diabetes, vitamin E had no effect on incidence of heart attacks, strokes, or nephropathy (kidney disease)—all among the complications of diabetes. A 2003 Italian study tested vitamin E and low-dose aspirin for preventing heart disease and stroke in 4,495 adults age 50 and over with heart disease risk factors, including 1,031 people with diabetes. Over a median period of 3.7 years, there was no benefit found for vitamin E supplementation in either the subjects with diabetes or those without. (Low-dose aspirin was less effective for preventing cardiovascular events in the diabetic group as compared to the nondiabetic group.) Finally, a 2003 analysis and summary of 15 vitamin E and beta-carotene clinical trials (called a meta-analysis) concluded that the results showed no beneficial effect for various doses of the antioxidants in diverse populations for the prevention of cardiovascular diseases. In fact, beta-carotene supplements were shown to slightly increase risk of death from cardiovascular and all causes.
Alpha-lipoic acid (also called ALA or thioctic acid) is a unique, sulfur-containing compound that is made in small amounts in the body but is not obtained from the diet. It neutralizes a variety of reactive oxygen species and can “recycle” vitamins C and E in the body. In people with diabetes, ALA appears to enhance insulin action and blood vessel circulation, protect against diabetic neuropathy (nerve disease), and inhibit protein glycation (a reaction between excess glucose and protein that impairs the protein’s function and forms harmful end products in the body).