‘No evidence’ for vitamin benefit

“Vitamin supplements ‘do us no good and may be harmful’”, the headline in The Independent reads. It, along with a wide range of other news sources, reports that a review has found there to be "no convincing evidence” that antioxidant supplements are of any benefit in preventing the risk of early death either in those with disease or in healthy people. Reportedly, one in three women and one in four men regularly take vitamin supplements and so the findings from this extensive study, which looked at the effects of a range of vitamins and selenium across numerous trials, will be of great interest to the public, medical communities and, not least, the dietary supplement industry.

This is a carefully conducted review and one of the largest to look into the effects of vitamin supplements as a whole. As the lead researcher is quoted as saying in The Guardian “the bottom line is current evidence does not support the use of antioxidant supplements in the general healthy population or in patients with certain diseases”. People take supplements for a wide range of reasons from believing they may be of benefit to treat a certain condition or to supplement their diet as part of a healthy lifestyle approach.

This review does not provide the reassurance that many would wish to hear, that taking nutrient supplements is good for us. For now, it would seem sensible for people to aim to achieve the recommended intakes of antioxidants from a balanced diet including fruit and vegetables.

Where did the story come from?

Goran Bjelakovic and colleagues at Copenhagen University, Denmark carried out this research, which is published in the Cochrane Database of Systematic Reviews . The study was funded by the Knowledge and Research Centre for Alternative Medicine, Denmark and The Copenhagen Trial Unit, Centre for Clinical Intervention Research.

What kind of scientific study was this?

This was a systematic review in which the authors have thoroughly examined the literature investigating the effects on mortality of antioxidant supplements.

The researchers searched through a range of medical databases from their date of inception onwards, they also looked at bibliographies of relevant papers and contacted pharmaceutical companies directly for additional research. They looked for all primary and secondary preventative (when there is no disease, or prevention when there is disease, respectively) randomised controlled trials conducted in adults, regardless of language, publication status or methods used. They looked at trials of any antioxidant supplement taken in any dose, form, combination or for any duration of time; this included vitamins A, C and E, beta-carotene and selenium compared with either an inactive placebo or no treatment. The outcome that they looked at in all of the trials was death from any cause. The researchers carefully reviewed all aspects of the individual studies and used statistical methods to combine the results of the trials where appropriate.

What were the results of the study?

The researchers identified 67 trials, involving 232,550 people, as being suitable for inclusion in the review. A third of these trials included healthy participants (164,439 people) and two-thirds of the trials involved people with a variety of different diseases (68,111 people). The average age of participants in the studies was 62 and the average length of follow-up in the studies was 3.4 years.

Overall, there was no reduction in mortality from taking antioxidant supplements. Of all the participants in the trials, 13.1% of those taking antioxidants died and 10.5% of those taking placebo or no treatment died. A statistical analysis combining all the studies found there was no significant effect of antioxidant supplements on mortality (neither an increased nor decreased risk).

The trials significantly differed from each other in terms of the type of supplement used and whether bias could have been introduced into the study. When they looked at trials with a low risk of bias only, the risk of mortality from taking supplements just reached statistical significance, showing a 5% increased risk of mortality. Looking at trials of different supplements separately, the researchers also found increased risk of death from any cause from vitamin A (16%), beta-carotene (7%) and vitamin E (4%), but all of these results only just reached statistical significance. There were no significant effects on mortality from either vitamin C or selenium.

What interpretations did the researchers draw from these results?

The researchers conclude that there is “no evidence to support antioxidant supplements for primary or secondary prevention [of mortality]” and that vitamins A, E and beta-carotene may even increase risk of mortality. Further trials should be closely monitored for potential harmful effects. They say that “antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.”

What does the NHS Knowledge Service make of this study?

This is a well-conducted and thorough review of the trials that have been conducted investigating the effects of antioxidant supplements upon mortality and the findings will be of great interest to the public, medical communities and, not least, the dietary supplement industry. However, some points that should be noted:

• The main point from this review was that there was no evidence to support antioxidant supplements for primary or secondary prevention of death. The overall result from combining all the studies was that antioxidants neither increased nor decreased the risk of death compared with no treatment. Increases in risk were only seen when smaller groups of studies were combined. 
• The research is compiled from many studies of variable quality, methods and inclusion criteria, using different doses and combinations of antioxidants, with some including other multivitamins and minerals. These differences mean that there could be some variation in the reliability of some of the individual study results and this will introduce some error when combining any of the studies. 
• The review has only looked at death from any cause. It has not examined other specific health benefits that may have been aimed for through supplement use, e.g. increased energy, increased resistance to illness etc. Therefore, from this review alone, it cannot be concluded that supplement use has been completely non-beneficial. 
• Similarly, this review has not looked or made assumptions about any direct harm from taking antioxidant supplements. 
• As the authors acknowledge, most trials used supplement doses that were much higher than those found in a normal diet and sometimes higher than recommended daily intake levels. 
• This review only addresses the effects of antioxidant supplements; it does not apply to the antioxidants found in food that are consumed as part of a healthy diet.
• These results do not apply to people who have specific deficiencies in these antioxidants.

People take supplements for a wide range of reasons from believing they may be of benefit to treat a certain condition or just to supplement the diet as part of a healthy lifestyle approach. Although this review does provide some evidence of potential harm from taking certain supplements at the doses tested, there may be benefits of lower doses of supplements in certain selected groups. This review will undoubtedly lead to further research and questioning of the role of antioxidant supplements for health.