You may been approached by concerned patients in the last few months asking whether they should stop taking their vitamins because of something worrying they have seen in the news. Their concerns are likely to be related to the mainstream media coverage of a recent press release by the University of Colorado Cancer Center investigator Time Byers MD, following a forum at the American Association of Cancer Research (AACR) Annuel Meeting 2015.
In the said press release, Byers suggests that while dietary supplements may be advertised to promote health, there is research showing that over-the-counter supplements may actually increase cancer risk if taken in excess of the recommended dose.[1]
“We are not sure why this is happening at the molecular level but evidence shows that people who take more dietary supplements than needed tend to have a higher risk of developing cancer,” said Byers.
The line of research, which started 20 years ago when it was noted that people who ate more fruit and vegetables were less likely to have cancer, lead researchers to investigate if taking extra vitamins and minerals would reduce cancer risk even further.
“When we first tested dietary supplements in animal models we found that the results were promising,” said Byers. “Eventually we were able to move on to human populations. We studied thousands of patients for ten years who were taking dietary supplements and placebos.”
However, the results were not what they expected. “We found that the supplements were actually not beneficial for their health. In fact, some people actually got more cancer while on the vitamins,” according to the University of Colorado press release.
One trial exploring the effects of betacarotene supplements showed that taking more than the recommended dose increased the risk for developing both lung cancer and heart disease by 20%. Folic acid, which was thought to help reduce the number of polyps in the colon, actually increased the number in another trial.
“At the end of the day we have discovered that taking extra vitamins and minerals do more harm than good,” said Byers.
In contrast to the above comments, Byers then goes on to state: “This is not to say that people need to be afraid of taking vitamins and minerals. If taken at the correct dosage, multivitamins can actually be good for you. But there is no substitute for good nutritional food.”
Whilst Byers certainly makes some valid points, such as not everybody needs to take extra vitamins at all times and that consumption of nutrients at high doses – sometimes many times over the recommended daily intake – may have adverse effects on health outcomes, there are several facts that have been left out in the University of Colorado press release that deserve a mention.
Firstly, the data presented at the recent conference is taken from a 2012 review published in the Journal of the National Cancer Institute that focused on antioxidants, folic acid, vitamin D and calcium.[2] A note has since been added to the original press release disclosing the data source, along with the comment “Many recent news reports stemming from this news release present incomplete data.”
Also omitted is any mention of the Physicians’ Health Study (PHS) II.
Physicians’ Health Study II
The PHS II – which was published after the 2012 review and therefore available to Byers et al at the time of the 2015 conference – is a large-scale, randomised, double-blind, placebo-controlled trial investigating the long-term effects of a common multivitamin and mineral supplement (Centrum Silver) on the risk of total and site-specific cancer events among men.[3]
The researchers followed more than 14,600 middle-aged and older men for over a decade. It was found that the daily multivitamin supplement significantly reduced the risk of cancer by 8% during a mean of 11 years of treatment and follow up compared to placebo.
While this figure is considered modest, an estimated 128,000 new cases of cancer will be diagnosed in Australia this year, with that number set to rise to 150,000 by 2020.[4] If the statistics of the PHS II translate to women as well, it would mean that at least 10,240 Australians could be spared the angst of a cancer diagnosis this year alone simply by taking a daily low-dose multivitamin.
Moreover, the PHS II participants represented a well-nourished population for whom the effect of a daily multivitamin on cancer outcomes may be less applicable to those of a poorer nutritional status.
In early 2011, a multiethnic cohort study of more than 182,000 participants found no evidence to indicate that multivitamin use is associated with risk of cancer, overall or at major sites, including lung, colorectal, prostate and breast, nor cardiovascular disease or overall risk of death.[5]
What about the betacarotene and folic acid?
Sure, Byers presents some scary statistics. But why doesn’t he mention that the participants of the betacarotene study were smokers, ex-smokers and workers exposed to asbestos?
Due to their molecular structure, carotenoids as a class are particularly vulnerable to free radical attack. Betacarotene acts as a scavenger of nitrogen oxides in cigarette smoke leading to production of carotene oxidation products that, if not effectively neutralised by other antioxidants, particularly tocopherol and ascorbate, may initiate cell damage that could lead to neoplasm.[6]
In contrast, the PHS found no significant influence on molecular markers of lung carcinogenesis among healthy male physicians (smokers and non-smokers) following 50mg of betacarotene supplementation on alternate days for 12 years.[7]
A prospective cohort study of almost 89,000 women suggest a substantially reduced risk for colon cancer with long-term use of multivitamins.[8] This effect is thought to be related to the folic acid content in the supplement. Moreover, higher intake of folate and methionine, regular use of multivitamins containing folate and avoidance of moderate to heavy alcohol consumption may diminish the excess risk of colon cancer associated with family history of the condition.[9]
Supplement use and disease markers – the more the better?
A study from the US has shown that long-term multiple dietary supplement users who consume a broad array of vitamin/mineral, botanical and condition-specific supplements on a daily basis are more likely to have optimal concentrations of chronic disease-related biomarkers.[10]
Supplements found to be most frequently consumed include a multivitamin/mineral, B complex, vitamin C, carotenoids, vitamin E, calcium with vitamin D, omega-3 fatty acids, flavonoids, lecithin, alfalfa, coenzyme Q10 with resveratrol, glucosamine and a herbal immune supplement. The majority of women also consumed gamma linolenic acid (GLA) and probiotics, whereas men also consumed zinc, garlic, saw palmetto and a soy protein supplement.
After adjustment for potential confounding variables, multiple supplement use was associated with more favourable concentrations of serum homocysteine, C-reactive protein (CRP), HDL cholesterol and triglycerides, as well as lower risk of hypertension and diabetes. In addition, those taking multiple supplements were four times more likely to describe their health as “very good” or “excellent” compared to non-users.
Multivitamin use has also been linked to a younger biological age in women.[11]
Take-home points for patients
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References
- Sundem G. Dietary supplements shown to increase cancer risk. University of Colorado Cancer Center 2015. Viewed 20 May 2015, http://www.coloradocancerblogs.org/dietary-supplements-shown-to-increase...
- Martinez ME, Jacobs ET, Baron JA, et al. Dietary supplements and cancer prevention: balancing potential benefits against proven harms. J Natl Cancer Inst 2012;104:732-739. [Full text]
- Gaziano MJ, Sesso HD, Christen WG, et al. Multivitamins in the prevention of cancer in men: the physicians’ health study II randomized controlled trial. JAMA 2012;308(18):1871-1880. [Full text]
- Facts and figures: cancer in Australia. Cancer Council Australia 2015. Viewed 22 May 2015, http://www.cancer.org.au/about-cancer/what-is-cancer/facts-and-figures.h...
- Park SY, Murphy SP, Wilkens LR, et al. Multivitamin use and the risk of mortality and cancer incidence: the multiethnic cohort study. Am J Epidemiol 2011;173(8):906-914. [Full text]
- Patrick L. Beta-carotene: the controversy continues. Altern Med Rev 2000;5(6):530-545. [PDF]
- Liu C, Wang XD, Mucci L, et al. Modulation of lung molecular biomarkers by beta-carotene in the Physicians’ Health Study. Cancer 2009;115(5):1049-1058. [Full text]
- Giovannucci E, Sampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 1998;129(7):517-524. [Abstract]
- Fuchs CS, Willett WC, Colditz GA, et al. The influence of folate and multivitamin use on the familial risk of colon cancer in women. Cancer Epidemiol Biomarkers Prev 2002;11(3):227-234. [Full text]
- Block G, Jensen CD, Norkus EP, et al. Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study. Nutr J 2007;6:30. [Full text]
- Xu Q, Parks CG, DeRoo LA, et al. Multivitamin use and telomere length in women. Am J Clin Nutr 2009;89(6):1857-1863. [Full text]
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