Vitamin D, Headlines, and Guidelines for Meta-Analysis of Nutrient Studies
According to headlines by USA Today and Bloomberg, people don’t need to be supplementing with vitamin D. It is ‘pointless’ to use vitamin D. This message, based on a meta-analysis of 9 intervention studies by Bolland et al (2014) is irresponsible. Being bundled up to endure the polar vortex, it is difficult to imagine that my skin is exposed to enough sunlight to meet my vitamin D requirement. Especially when experts increased the dietary reference intakes (DRIs) for vitamin D in 2010 and the choices of vitamin D-rich foods are limited.
Bolland and colleagues collated data from randomized controlled trials (RCTs), comparing vitamin D against no vitamin D, involving a myriad of endpoints (myocardial infarctions, stroke, cancer, fractures, etc). The results are boiled down to ‘favors decreased risk with vitamin D’ versus ‘favors increased risk with vitamin D’. The paper fails to follow the 6 rules for meta-analyses for nutrient effects outlined by Dr Robert Heaney below:
1. Individual studies selected must have: a) assessed basal nutrient status of participants, b) intervention must be sufficient to change nutrient status, c) change in nutrient status must e measured and recorded/reported, d) hypothesis to be tested must be that a change in status produces sought-after effect, and e) status of other relevant nutrients must be optimized so that the nutrient being tested is the only nutrition-related factor limiting the response.
2. All included studies must have started from same or similar basal nutrient status
3. All included studies must have same or similar doses.
4. All included studies must have used same chemical form of the nutrient. The food matrix must be the same if food is used as the vehicle for the test nutrient.
5. All included studies must have same co-nutrient status
6. All included studies must have had approximately equal periods of exposure to the altered intake.
The most glaring errors of the paper by Bolland and colleagues are: 1) a failure to consider vitamin D status of the subjects at baseline and 2) a lack of discussion whether the RCTs provided sufficient amounts of vitamin D to alter serum 25(OH)D status. The authors also assume that a statistical analysis suitable for drugs (placebo vs intervention) is adequate. Nutrients are not drugs. Scientists need to remember this point when designing clinical trials and conducting systematic reviews.
Bolland and colleagues conclude there is a benefit of vitamin D supplementation but a risk reduction of ~15% isn’t sufficient to justify using vitamin D supplements. A 15% reduced risk doesn’t seem inconsequential. After all, according to a meta-analysis, statins reduce the risk of all cause mortality in people without established cardiovascular disease by 12%. Nevertheless, medical professions recommend statins to people with certain cardiovascular risk factors. Why is a different standard applied with regards to a vitamin D supplement than a statin prescription?
Vitamin D insufficiency is a worldwide problem. Scientists and journalists have a responsibility to put scientific findings in perspective. For people living in the northern half the world, it is winter. For people living south of the equator, many are working indoors and wearing sunscreen when outdoors. Considering the season, cultural practices, skin color and the limited number of foods rich in vitamin D, supplementation should be encouraged not discouraged.
Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. 2014 Lancet Diabetes Endocrinol doi: 10.1016/S2213-8587
Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RGJ, de Craen AJM, Knopp RH, Nakamura H, Ridker P, van Domburg R, Deckers JW. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trials. 2009 Br Med J doi: 10.1136/bmj.b2376
Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith Jr SC, Watson K, Wilson PWF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart AssociationTask Force on Practical Guidelines 2013 Circ doi: 10.1161/01.cir.0000437738.63853.7a
Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. 2014 Nutr Rev doi: 10.1111/nure.12090