Vitamin D Status is the Important Variable (Biomarker) NOT Treatment Assignment in a RCT

A paper entitled “Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis” was recently published in Lancet. The authors identified 51 randomized control trials (RCT) with high- and low-dose vitamin D supplementation. They concluded:


Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines.


Full disclosure, because of Nature’s paywall Nature PaywallI have not read the paper in detail. However, it is my strongly held position that meta-analyses which only evaluate nutrient supplementation miss the point. It is clearly established that essential nutrients, e.g. vitamins, EPA+DHA, lutein, zeaxanthin, iron, etc, provide benefit when nutrient status is insufficient to support normal cell structure and function.

Food fortification is known to improve nutritional status, help prevent deficiency diseases and save lives. This fact isn’t based on dietary intake data. It is based on status measurements and health outcomes, e.g. effect of mandatory folic acid fortification of flour in incidence of neural tube defects.

So, with input from Dr William B Grant (@wbgrant2), here is evidence (4 examples) that it is vitamin D status, i.e. 25(OH)D3 concentrations, which is correlated with outcome and needs to be measured NOT whether an individual is randomized to a supplement or placebo arm of a RCT.

1.blood vitamin D and risks of falls or fractures

2.Serum vit D and bone mineral density


Maternal 25(OH)D3 status and Gestational Age (weeks

Serum vit D and breast cancer


Serum vit D and overall mortality

4. Serum vit D and cancer risk



About Michael McBurney

Personal Blog | Nutrition scientist with broad interests, including social media and the impact of open access journals on science publishing | Self-employed freelancer
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