Antioxidant-rich diets and antioxidant supplements have been recommended for the prevention and treatment of a range of serious diseases associated with free radical damage including stroke, cancer, diabetes, cataracts, Parkinson's disease, Alzheimer's disease and arthritis. The success of this message is illustrated by figures showing that around half the adult US population take antioxidant pills every day.
The value of antioxidants has recently been called into question following negative findings.
Some studies have indicated that antioxidants' ability to neutralise free radicals may be lost or significantly reduced by the time they have been digested. Other studies suggest that antioxidant supplements may only be important in patients with a deficiency, and that they may even be harmful in some cases.
A large-scale trial carried out by the US National Cancer Institute was stopped before completion when it was observed that beta carotene supplements increased the incidence of lung cancer and mortality in those at risk through smoking or asbestos exposure.
Studies of vitamin E in cardiovascular disease (CVD) have had contradictory results. Studies of vitamin E in cancer prevention and in the progression of mild cognitive impairment to Alzheimer's disease have been negative.
In a further twist to the tale, it has been noted that tea, especially green tea, is associated with a reduced risk of CVD and cancer, even though during brewing antioxidants present in the tea react with oxygen in the water to produce free radicals.
Our research group at Exeter reviewed the evidence for the use of antioxidants in arthritis. We confined our research to the antioxidant vitamins taken as dietary supplements (vitamins A, C and E) together with selenium, an essential component of the body's own antioxidant enzyme glutathione peroxidase.
We found 20 randomised clinical trials testing these supplements in the treatment of any arthritis, falling into three main clusters: studies of selenium for rheumatoid arthritis; studies of vitamin E in rheumatoid arthritis and studies of vitamin E for osteoarthritis.
In five studies comparing selenium with placebo for up to six months in the treatment of rheumatoid arthritis, findings were almost universally negative. This was despite concentrations of selenium in the blood being significantly raised during the course of the trial.
There were four studies comparing vitamin E with either placebo or diclofenac in rheumatoid arthritis. Of the two placebo-controlled trials, one suggested that there might be a beneficial effect upon pain but not on inflammation and the other found no effect.
The trials comparing vitamin E with diclofenac found no difference between the treatment regimens, suggesting that vitamin E is as useful as diclofenac.
However, these trials lasted only three weeks, so the changes seen with both vitamin E and diclofenac might be attributable to a short-term placebo effect.
Lack of evidence
There were seven clinical trials of vitamin E in osteoarthritis; four comparing it with placebo, two with diclofenac and one with vitamin A.
Of the placebo-controlled trials, two suggested that vitamin E was effective in reducing pain but one of these was methodologically weak.
The second found greater effectiveness for both the whole patient sample and for a subgroup with osteoarthritis of the knee and hip.
However, this finding was not supported by two placebo-controlled trials in patients with osteoarthritis of the knee, which both had largely negative results. These studies were more recent, had larger sample sizes and longer treatment periods.
There were also single clinical trials of vitamin E in ankylosing spondylitis, vitamin A in psoriatic arthritis, vitamin C in osteoarthritis, selenium with vitamins A, C and E in RA, selenium with vitamins A, C and E in osteoarthritis and a trial comparing vitamins E, A or both in spondylosis.
None of these trials produced good evidence for a positive and clinically relevant effect of the supplement on symptoms of arthritis. In the case of psoriatic arthritis, vitamin A supplementation were associated with numerous adverse reactions.
We were forced to conclude that there is no good evidence for a positive effect of any of the supplements in the treatment of any type of arthritis.
Larger and more robust studies could still find some of these supplements effective, but it seems more likely that diets rich in antioxidants will be shown to play an important role in the prevention and treatment of arthritis, because the antioxidants contained in fruit and vegetables are bound into fibrous material that lingers in the stomach and colon where they can neutralise free radicals.
The best recommendation therefore is to eat plenty of fruit and vegetables, which will provide general health benefits, even if evidence for specific effects in arthritis is presently lacking, and to avoid possible adverse effects of taking vitamin supplements.
Dr Canter is a research fellow in complementary medicine at the Peninsula Medical School, Universities of Exeter & Plymouth
- The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994; 330: 1,029-35.
- Canter P H, Wider B, Ernst E. The antioxidant vitamins A, C, E and selenium in the treatment of arthritis - a systematic review of randomised clinical trials. Rheumatology 2007: 46; 1,223-33.