"Taking a daily multivitamin pill may lower the risk of developing cancer in men, US researchers have claimed," reports the BBC News website.

This news is based on a long-term trial that looked at whether men who took a daily multivitamin supplement had a different risk of developing cancer compared to men who took a dummy pill (placebo) each day.

The researchers found that people taking the multivitamin had an estimated 8% lower risk of developing any major cancer over approximately 11 years. However, when examining the effect of daily vitamin supplements on specific types of cancers, such as prostate or colon cancer, researchers found that there was no statistically significant difference in terms of any single cancer risk. The researchers concluded that taking a daily multivitamin led to a clinically modest but statistically significant reduction in men’s risk of developing cancer.

However, the fact that the findings for individual cancers were not statistically significant means that multivitamins may have no effect, or may actually increase the risk of men developing some types of cancer. This is borne out by previous conflicting evidence on multivitamin supplementation and cancer risk. Based on the results of this study, you shouldn’t rush down to your holistic health store, as relying solely on multivitamins to reduce your cancer risk would be an unwise strategy.

Middle-aged and elderly men would do better to adopt the lifestyle changes known to reduce cancer risk, such as quitting smoking, eating a healthy balanced diet, moderating consumption of alcohol and taking regular exercise.

Read more about preventing cancer.

Where did the story come from?

The study was carried out by researchers from Brigham and Women’s Hospital, Harvard Medical School and Harvard School of Public Health in the US and was funded by the US National Institutes of Health and the BASF Corporation, a chemical company that produces dietary supplements among other products. The vitamins and packaging were provided by BASF Corporation, Pfizer and DSM Nutritional Products Inc. The authors note, however, that no funding organisation was involved in the design, execution or analysis of the study, or in the writing of the paper for publication.

The study was published in the peer-reviewed Journal of the American Medical Association.

BBC News and the Daily Mail covered the story reasonably accurately, highlighting the relatively modest protective effect. The BBC also made clear that there is conflicting evidence. Both report that it is difficult to generalise the results to women or younger men, and mention that the mechanism through which multivitamins may reduce cancer risk is still not known.

The BBC and the Mail’s accurate reporting is in sharp contrast to the Daily Express, which led with the claim “Daily multivitamin pill can dramatically slash the risk of men developing cancer”. An overall relative drop in cancer cases of just 8%, and no effect on cancer-related deaths, is not what most people would describe as “dramatic”.

What kind of research was this?

This was a long-term randomised controlled trial (RCT) that examined the impact of daily multivitamin supplement use on the risk of developing cancer in middle-aged or older men. RCTs have long been considered the gold standard of research design when investigating the impact of a treatment.

This RCT was also double-blind, so neither the researchers nor the participants knew who was taking which pill.

What did the research involve?

The researchers recruited 14,641 male physicians over the age of 50, and randomised them into two main groups, the first to take a daily multivitamin and the second to take a daily dummy pill. It is not clear whether the term ‘physician’ is used in the current British sense to mean doctors who are not surgeons, or in a broader sense to include a range of health professionals.

The study participants were followed up for an average of 11.2 years. Researchers compared the differences between the two groups, in terms of:

rates of specific types of cancer

rate of all types of cancer

risk of dying of cancer

The researchers ensured that each group consisted of people of comparable ages, history of cancer diagnosis and cardiovascular disease to balance known cancer risk factors. They sent out annual questionnaires to determine whether the participants were taking their daily pill as intended. The researchers used medical records and death certificates to collect data regarding cancer diagnosis during the follow-up period.

The researchers analysed the data on an intention-to-treat basis, meaning that all participants who were randomised at the beginning of the study were included in the analysis in their original group, regardless of whether or not they were available for follow-up or maintained treatment as intended.

This is done to prevent bias from influencing the results. The statistical model that was used took into account the participants’ age and other variables related to the study design.

What were the basic results?

Between 1997 and 1999 there were 14,461 male physicians over the age of 50 included in the study, with 7,317 randomised to the multivitamin group and 7,324 to the placebo group. The average age of participants was 64.3 years, and there were 1,312 men with a history of cancer included in the trial.

The researchers followed-up with the participants for an average of 11.2 years. At the end of the trial, outcome data were available for a very high percentage of participants (98.2% to 99.9%). This is an impressive number for this sort of trial – usually many more subjects are lost to follow-up.

The proportion of people taking the pill every day as intended at the end of the trial was similar between the two groups, at 67.5% in the multivitamin group and 67.1% in the placebo group.

Use of multivitamins other than those supplied for the trial was reported by 19.0% of people in the multivitamin group and 19.7% of the placebo group.

Overall, there were 2,669 confirmed cases of cancer during the follow-up period, including 1,373 new cases of prostate cancer and 210 new cases of bowel cancer. There were 2,757 (18.8%) deaths during the trial, of which 859 (5.9%) were due to cancer.

When examining the impact of daily multivitamin use on cancer risk, the researchers found:

there were 17.0 cases of cancer for every 1,000 men in the multivitamin group, and 18.3 cases of cancer for every 1,000 men in the placebo group, representing a reduction of 1.3 cases of new cancer for every 1,000 men aged over 50

there was an 8% reduction in the risk of developing cancer overall in the 11.2-year follow-up in men taking a daily multivitamin compared with dummy pill (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.86 to 0.998, probability [p-value] 0.04)

When examining the impact of daily multivitamin use on the risk of developing specific types of cancer or of dying of cancer, the researchers found:

no significant difference in risk of prostate cancer (HR 0.98, 95% CI 0.88 to 1.09, p-value 0.76)

no significant difference in risk of colorectal cancer (HR 0.89, 95% CI 0.68 to 1.17, p-value 0.39)

no significant difference in risk of lung cancer (HR 0.84, 95% CI 0.61 to 1.14, p-value 0.26)

no significant difference in risk of overall mortality (HR 0.94, 95% CI 0.88 to 1.02, p-value 0.13)

no significant difference in risk of cancer mortality (HR 0.88, 95% CI 0.77 to 1.01, p-value 0.07)

How did the researchers interpret the results?

The researchers concluded that in “middle-aged and older men, a daily multivitamin supplement significantly but modestly reduced the risk of total cancer”. They say that while “the main reason to take multivitamins is to prevent nutritional deficiency, these data provide support for the potential use of multivitamin supplements in the prevention of cancer” in this group.

Conclusion

This large-scale randomised controlled trial provides evidence that daily use of a low-dose multivitamin may help to protect against cancer among men over the age of 50. However, given the design of the trial, these results should not be assumed to apply to women or younger men.

The study has several strengths. It was large (including nearly 15,000 people) and its long-term follow-up period (approximately 11 years) means that there was sufficient time to see results in terms of new cases of cancer. Follow-up data were available for most of the participants, and the treatment adherence rates were similar between the two groups.

There were limitations to the study, however. These include the fact that approximately 19% of both groups reported taking multivitamins as well as the trial supplements. This means that those who were classified as not taking vitamin supplements may have in fact been taking them, which may have influenced the results. The subjects were all physicians, and the authors note that they represent “on average a well nourished population”, so the findings may not be applicable to people who have a poorer nutritional status.

The researchers point out that the content of the multivitamins may have altered over time, and that the vitamin formulation used in the study is no longer for sale. They also say that the biological mechanism that accounts for their results is unknown, and that “an improved understanding of the effects of single versus combined nutrients – at usual levels of dietary intake – on intermediate mechanisms leading to cancer is critically needed”.

There have been many studies into the effectiveness of multivitamins at preventing chronic conditions. The results of these studies have been mixed:

some studies have suggested that there is no benefit to multivitamin supplementation

others conclude that multivitamin use is beneficial

some have found that daily use of high-dose vitamin supplements may in fact be harmful

It should be noted that the types and amounts of vitamin and mineral supplements used in previous studies were not uniform. The researchers report that the current study used a common multivitamin, with supplement levels at the recommended dietary levels. However, this formulation may differ from other studies that use higher doses of single vitamin supplements.

Despite its limitations (which are often unavoidable), this was a large well conducted trial that suggests that a daily multivitamin may offer modest benefits for middle-aged or older men. If you want a more certain way to reduce your risk of cancer, stopping smoking and maintaining a healthy weight are key.

Analysis by Bazian

Edited by NHS Website