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Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care

Posted on: December 28, 2016   by  Dr William Grant


The journal Osteoporosis International published the findings of an exciting new study in which elderly white British inhabitants were given 2000 or 4000 IU/d vitamin D3 or a placebo for a year [Hin, 2016].

The participants averaged 70 years of age and had an average vitamin D level of 20 ng/mL at time of entry. Those taking 2000 IU/d reached an average of 42 ng/mL (107 nmol/L) after a year, while those taking 4000 IU/d reached 55 ng/mL (137 nmol/L). Research shows levels of 40 ng/ml or greater obtain most of the benefits of vitamin D.

Importantly, no significant adverse effects of taking 2000 or 4000 IU/d were found. No participant developed clinical hypercalcaemia (high blood calcium level) or kidney stones. There were more falls and fractures among those taking vitamin D, but the differences were not statistically significant.

In the discussion, reports of harmful effects for vitamin D levels >50 ng/mL (125 nmol/L) were mentioned as reported in observational studies. We suggested that these results may have been due to studies enrolling people who had begun taking vitamin D supplements just prior to enrollment in the study, leading the researchers to place the individuals in the wrong category for vitamin D status[Grant, 2016].

Very few beneficial effects of vitamin D supplementation were found in the study. This result may be due to the small number of participants (102 in each of the three arms), the short duration and the baseline vitamin D level. As shown in Cannell et al. [2015], for clinical trials that administered vitamin D supplementation to participants with baseline 25OHD <20 ng/mL (49 nmol/L), there was a 50% chance of finding a significant reduction in biomarkers of inflammation, while for 25OHD >20 ng/mL, the chance dropped to 26%. This study had a baseline 25OHD of 20 ng/mL, so it may have had about a 35% chance of finding a reduction in inflammation. One plausible explanation for why no benefits from supplementation was observed is that the lower 25OHD concentrations were more likely to be associated with lower baseline vitamin D levels than those with > 20 ng/mL.

The authors noted that the ongoing major vitamin D trials, even in combination, will be unlikely to have sufficient numbers of participants with incident fractures to clearly demonstrate plausible effects on osteoporotic fractures. Since fracture prevention is one of the recognized benefits of vitamin D, their comment does not bode well for expectations that the ongoing trials will find any benefits of vitamin D supplementation. Some of these trials did not obtain baseline vitamin D levels, and most are supplementing with 2000 IU/d vitamin D.


Cannell JJ, Grant WB, Holick MF. Vitamin D and inflammation. Dermatoendocrinol. 2015 Jan 29;6(1):e983401. 

Grant WB, Karras SN, Bischoff-Ferrari HA, Annweiler C, Boucher BJ, Juzeniene A, Garland CF, Holick MF. Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects? Dermato-Endocrinology,  2016;8(1): e1187349.

Hin H, Tomson J, Newman C, Kurien R, Lay M, Cox J, Sayer J, Hill M, Emberson J, Armitage J, Clarke R. Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care. Osteoporos Int. 2016 Dec 16.

1 Response to Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care

  1. allometric24

    It looks as if Vitamin D is not the only player in the sun/skin
    interplay. If the research below is anywhere near correct it could be a major player in the benefits seen from sun exposure.

    .Thieu X. Phan, Barbara Jaruga, Sandeep C. Pingle, Bidhan C. Bandyopadhyay, Gerard P. Ahern. Intrinsic Photosensitivity Enhances Motility of T Lymphocytes. Scientific Reports, 2016; 6: 39479 DOI: 10.1038/srep39479

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