Vitamin D for preventing cancer: evidence and health beliefs

  • By: Bernd Richter
  • On: June 24, 2014, 11:00
thumbnail image: Vitamin D for preventing cancer: evidence and health beliefs

Good communication between patients and physicians is essential but not easy. Physicians need to understand and appreciate (and implement in their management plans) patients' values, preferences, and health beliefs. Health beliefs do not appear from nowhere but are influenced by cultural, psychological and social factors, and by parties with vested interests.

Food in particular is so much intertwined with life that food-related health beliefs seem almost unshakable. Vitamins are a good example. Decades after the discovery of various vitamins and their associated deficiencies many people endorse the idea that vitamin intake is good, and the more, the better. Scientific societies defined amounts of vitamin intake per day, usually covered by regular meals. The composition of our food without doubt affects our health and the body is very efficient in extracting and discarding just the right amount of essential elements. Somehow, beliefs crept in (or were installed) judging our way of life as dangerous, circling around junk food, couch potatoism, smoking, and drinking, so that good things like vitamins had to be 'supplemented'.

It took a landmark study published in 1994 to cast serious doubts on the idea of widespread vitamin supplementation. Epidemiologic studies had suggested that vitamin E and beta-carotene were associated with a reduced risk of lung cancer, but the surprising results of a big Finnish study were that men who had received beta-carotene were more likely to die from lung cancer.[1] Related doubts have recently arisen about the proclaimed healthy effects of antioxidants, another panacea for almost any disease.[2]

Time passed, memories faded, and another vitamin hype arrived, this time vitamin D, a fat-soluble vitamin that helps the body absorb calcium and phosphorus and plays an important role in the immune system. Vitamin D3 (cholecalciferol) is usually synthesised in the skin after sun exposure with subsequent conversion into calcidiol in the liver and calcitriol, the biologically active form of vitamin D, in the kidneys. Vitamin D may be obtained from dietary sources or supplements as vitamin D3 or vitamin D2 (ergocalficerol). There is a debate about whether sufficient doses can be obtained through diet alone. The exact amount needed is hard to define and depends on factors like age, body weight, and where people live. Vitamin D status can be determined by the measurement of serum 25-hydroxyvitamin D, although optimal vitamin D levels are controversial.[3]

Two recent Cochrane Reviews by Bjelakovic and colleagues have addressed hot topics in vitamin D supplementation. The first review, from January 2014, analysed 38 randomised controlled trials (RCTs) with 76,627 participants in high-income countries and showed that vitamin D3 reduced all-cause mortality in adults (mostly elderly and mostly women).[4] About 150 people had to be treated over five years to prevent one additional death. However, combination with calcium increased the risk of renal stone formation.

A new Cochrane Review investigates whether vitamin D supplementation prevents cancer in adults.[5] Most of the included RCTs evaluated vitamin D3, again mainly in elderly women from high-income countries. Analysis of the 14 studies of vitamin D3 (49,891 participants; five to seven years' follow-up) showed no decrease or increase in cancer occurrence. The same results applied to participants with vitamin D status below 20 ng/mL (defined as vitamin D deficiency) and those with higher vitamin D status at entry. However, cancer mortality was lower following vitamin D3 supplementation (RR 0.88; 95% CI 0.78 to 0.98; P = 0.02), although the overall quality of the evidence was low. To explore these data further, the authors did trial sequential analysis, a statistical technique for cumulative meta-analyses to avoid random errors, similar to interim analyses for RCTs.[6] The required information size, that is the least number of participants needed in a well-powered single trial, to achieve a 10% relative risk reduction, which one could denote as a clinically relevant effect, was 110,556 participants, and was thus not reached.

Where do we go from here, and how about health beliefs? Advocates of vitamin D supplementation could be tempted to jump on the results proclaiming positive effects, neglecting the quality and uncertainty of the available data. On the other side, a recent umbrella review, analysing 107 systematic reviews and 161 meta-analyses of the associations of vitamin D with diverse outcomes, confirmed the non-existence of convincing evidence of a clear effect of vitamin D on any outcome.[7] Summing up, the vitamin D story is another good example how difficult it is to adequately analyse and critically appraise scientific data. We all have to live with probabilities instead of certainties of the results of medical research, and this has to be openly and sufficiently communicated during any patient-doctor encounter to optimise shared decision making. A sensitive perception of patients' health beliefs is an important aspect of this process, helping to reduce the often diverging conceptions patients and doctors have about the cause and nature of disease.

Bernd Richter

Professor of Clinical Epidemiology, Institute of General Practice, University Hospital Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany; Co-ordinating Editor, Cochrane Metabolic and Endocrine Disorders Group richterb@uni-duesseldorf.de

How to cite: Richter B. Vitamin D for preventing cancer: evidence and health beliefs [editorial]. Cochrane Database of Systematic Reviews 2014;(6):ED000085.

References

1. The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England Journal of Medicine 1994;330(15):1029-35. dx.doi.org/10.1056/NEJM199404143301501

2. Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO. Antioxidants accelerate lung cancer progression in mice. Science Translational Medicine 2014;6(221):221ra15. dx.doi.org/10.1126/scitranslmed.3007653

3. Hilger J, Friedel A, Herr R, Rausch T, Roos F, Wahl DA, et al. A systematic review of vitamin D status in populations worldwide. British Journal of Nutrition 2014;111(1):23-45. dx.doi.org/10.1017/S0007114513001840

4. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database of Systematic Reviews 2014;(1):CD007470. dx.doi.org/10.1002/14651858.CD007470.pub3

5. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Krstic G, Wetterslev J, et al. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database of Systematic Reviews 2014;(6):CD007469. dx.doi.org/10.1002/14651858.CD007469.pub2

6. Copenhagen Trial Unit. Trial sequential analysis. www.ctu.dk/tsa (accessed 25 May 2014).

7. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 2014;348:g2035. dx.doi.org/10.1136/bmj.g2035

Competing interests: The author has completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request) and declares no interests.

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Keywords:

The Cochrane Library - Independent high-quality evidence for health care decision making

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