BEST-D Trial: Higher Doses of Vitamin D may be Required for Optimal Osteoporosis Prevention Save

Osteoporosis is a major public health problems and is associated with a high burden of fractures and subsequent increased mortality.

A vast body of evidence implicates chronic vitamin D insufficiency as an important reversible risk factor. Observational studies suggest that the lowest risks of mortality and morbidity are associated with plasma 25(OH)D levels around 90 nmol/L (36 ng/mL). In addition, plasma levels of parathyroid hormone (PTH) are inversely associated with plasma levels of 25(OH)D up to levels of about 70–100 nmol/L.

Various trials and meta-analyses of trials, assessing the effects of equivalent daily doses of 400–800 IU (10–20 μg) of vitamin D on risk of fracture, have reported conflicting results. In addition, compliance with vitamin D supplementation in these trials was rather low.

The BEST-D trial is a double-blind, randomized placebo-controlled, parallel group trial comparing the effects of daily supplementation with either 4000 IU (100 μg) or 2000 IU (50 μg) cholecalciferol (vitamin D3) or placebo for 12 months on biochemical markers of vitamin D status, cardiovascular risk factors and clinical tests of physical function.
About 300 men and women aged 65 years or older were recruited from a single general practice in Banbury, Oxfordshire, UK.

The one year study demonstrated that supplementation with 4000 IU daily vitamin D3 compared with 2000 IU daily was associated with a significantly higher proportion of individuals achieving plasma levels of 25(OH)D >90 nmol/L (88% vs 70%, respectively).

Mean plasma levels of PTH decreased significantly in both active vitamin D groups but were significantly lower in those allocated 4000 IU vitamin D daily compared to 2000 IU at both 6 and 12 months.

The intake of vitamin D at these high doses was well tolerated and was not associated with any adverse clinical events at 1 year. There were no reports of clinical hypercalcaemia or kidney stones.

Supplementation with these high doses of vitamin D had no detectable effects on cardiovascular risk factors or on measures of physical function after 1 year of treatment.

Study results suggest that daily doses of 4000 IU of vitamin D3 may be required to achieve the high plasma levels of 25(OH)D associated with the lowest risks of mortality in the observational studies.

However, additional trials testing the effects of such high doses of vitamin D should be conducted first before making recommendations on vitamin D supplementation for disease prevention in older people.