Vitamin D supplementation for fracture prevention? A definitive verdict

N Engl J Med 2022 July 28; 387:299-309     DOI: 10.1056/NEJMoa2202106 LINK

Over a third over 60 years of age in the US takes Vitamin D supplements. In Sri Lanka it is increasingly common to see Vit D prescriptions for various disease conditions from back pain to osteoporosis from consultants and primary care doctors.

More than a century ago, nutritional rickets, in infants and children, was noted to be cured by artificial ultraviolet light, irradiation of food, or supplementation with phytosterol. This led to the assumption that Vit D could lead to osteoporosis. Observational studies showed that low Vit D levels were associated with osteoporosis and other health conditions, but RCT evidence was not there for long period of time.

National Academy of Medicine (NAM) report in 2011 published the dietary requirements of 600-800 IU Vit D per day. The NAM report also recommended that large clinical trials of vitamin D be undertaken to determine the role of supplementation for the prevention or treatment of common diseases (REF-1). This resulted in ‘Vitamin D and Omega-3 Trial’ (VITAL) largest, prolific, and most definitive trial to date with a total population of 25,871 U.S. men and women and followed up for more than 5 years (REF-2).

Results of analyses from VITAL published in peer-reviewed journals over the past years have shown that vitamin D supplementation did not prevent cancer or cardiovascular disease, prevent falls, improve cognitive function, reduce atrial fibrillation, change body composition, reduce migraine frequency, improve stroke outcomes, decrease age-related macular degeneration, or reduce knee pain. (REF-3  REF-4 REF-5 REF-6)

This week the NEJM published the latest definitive ancillary study from VITAL (REF-7) 25,871 U.S. men 50 years of age or older and women 55 years of age or older, not selected for vitamin D deficiency, low bone mass, or osteoporosis, were randomly assigned to receive vitamin D3 (2000 IU/day) or placebo and followed for a median duration of approximately 5 years. The primary end points were incident total, non vertebral, and hip fractures. Supplemental vitamin D3 had no significant effect on any primary end point in comparison with placebo. No effect modification was observed according to baseline demographic variables, body-mass index, non trial use of supplemental calcium or vitamin D, or level of serum 25-hydroxyvitamin D. Safety: The incidence of hypercalcemia and kidney stones did not differ substantially between the vitamin D and placebo groups.

Another important factor is measuring serum 25-hydroxyvitamin D levels with the results given classifying vitamin D levels as “insufficiency” (<30 ng per milliliter) and “deficiency” (<20 ng per milliliter), prompting vitamin D supplementation. In this ancillary study and other VITAL studies, no subgroups defined according to baseline 25-hydroxyvitamin D level, even below 20 ng per millilitre, benefited from supplements. Thus, there is no widespread justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level.

The only justification may be in severe Vit D deficiency. Persons living in residential settings with little or no sunlight exposure or malabsorption or those receiving treatments for osteoporosis that might cause hypocalcemia may benefit from vitamin D supplementation.

In Sri Lanka Vit D3 tablet (with calcium) cost varies from Rs 25 – 50 per tablet? These are normally prescribed for months, and years and the cost are exorbitant with little or no benefit to patients.

Bottom line

The fact that Vit. D had no effect on fractures should put to rest any notion of an important benefit of vitamin D alone to prevent fractures in the larger population. Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests, that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life

Ref: Editorial NEJM – VITAL Findings — A Decisive Verdict on Vitamin D Supplementation

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