Better clinical trials may produce ‘optimal clinical rewards’ for antioxidants

Stricter clinical trials and a multifaceted approach may unlock the clinical potential of antioxidants, Japanese reviewers report.

Writing in Maturitas, Keiichiro Suzuki and co-workers from the Department of Biochemistry at Hyogo College of Medicine state that the failure of antioxidants supplements to produce benefits in many clinical trials merely “represent a challenge to design more sensitive antioxidant trials in order to confirm or alter these conclusions”.

An antioxidant is defined as a “substance (such as beta-carotene or vitamin C) that inhibits oxidation or reactions promoted by oxygen, peroxides, or free radicals”, according to the Merriam-Webster dictionary.

A vast body of epidemiological studies has linked increased dietary intake of antioxidants from fruits and vegetables to reduced risks of a range of diseases including cancer, cardiovascular disease and diabetes.

However, when such antioxidants have been extracted and put into supplements the results, according to the randomized clinical trials (RCTs), do not always produce the same benefits, and may even be harmful.

“Conclusions reached in some clinical trials suggest that antioxidants appear to have little or no benefit,” wrote the Japanese researchers. “However, a lack of beneficial effects does not disprove the central role of oxidative stress in cardiovascular diseases. On the contrary, these trials have stimulated us to design better antioxidant trials in the future,” they added.

Review details

The Japanese reviewers looked at the effects of vitamins C and E and polyphenols on various age-related diseases. In terms of vitamin C the researchers report that there is “some encouraging but not overwhelming support for vitamin C as a protective factor against cardiovascular diseases”.

However, for vitamin E, the researchers point to the controversial meta-analysis from 2005 which “suggest that high-dosages of vitamin E supplements have the potential to be harmful”.

“A large body of evidence suggests that more strict clinical trial designs will be necessary to effectively assess the utility of antioxidants and that a multifaceted antioxidant approach to atherosclerosis may produce optimal clinical rewards,” wrote the reviewers. “[Reactive oxygen species] production in our bodies is unavoidable, and hence the use of antioxidants may be very important in preventing, reversing, or delaying the onset of pathological disorders.

“However, at the present time, no practical antioxidants are available for therapeutic use.

“Further studies aimed at identifying the molecular mechanism for the protection afforded by various antioxidants against oxidative-induced vascular damage are needed, if antioxidants are to be used in a clinical setting,” they concluded.

‘Antioxidants inside’

Antioxidants are big business. The number of products with ‘antioxidants inside’ style labels is mushrooming, according to Mintel’s Global New Products Database (GNPD). In 2009, there were 409 launches globally with ‘antioxidants’ flagged on the labels, compared with 154 in 2005 and 299 in 2007 – and that is just in marquee supplement formats such as vitamin A, C E, selenium, CoQ10, and zinc.

The overall market for antioxidants was valued at a whopping $12bn (€8.8bn) in 2009, according to Euromonitor International.

Source: Maturitas

October 2010, Volume 67, Issue 2, Pages 103-107

“Antioxidants: Benefits and risks for long-term health”

Authors: Daisaku Yoshihara, Noriko Fujiwara, Keiichiro Suzuki