Findings supported by previous research
The trial results are consistent with those of prior large studies and meta-analyses of older adults with a low prevalence of vitamin D deficiency showing that vitamin D3 supplementation, regardless of whether taken daily or monthly, is not likely to have an effect on all-cause mortality.
In the US VITAL trial, recently published in the New England Journal of Medicine, among 25,871 participants administered 2,000 IU/day of vitamin D3 for a median of 5.3 years, there was no reduction in all-cause mortality.
The ViDA trial of 5,110 older adults in New Zealand, published in 2019 in the Journal of Endocrinological Investigation, also showed monthly vitamin D3 supplementation of 100,000 IU for a median of 3.3 years was not associated with a benefit in people who were not deficient.
“In total, the results from the large trials and meta-analyses suggest that routine supplementation of older adults in populations with a low prevalence of vitamin D deficiency is unlikely to reduce the rate of all-cause mortality,” Dr. Neale and colleagues concluded.
Longer-term supplementation beneficial?
The population was limited to older adults and the study had a relatively short follow-up period, which Dr. Neale noted was necessary for pragmatic reasons.
“Our primary outcome was all-cause mortality, so to have sufficient deaths we either needed to study older adults or a much larger sample of younger adults,” she explained.
“However, we felt that [the former] ... had biological justification, as there is evidence that vitamin D plays a role later in the course of a number of diseases, with potential impacts on mortality.”
She noted that recent studies evaluating genetically predicted concentrations of serum 25(OH)D have further shown no link between those levels and all-cause mortality, stroke, or coronary heart disease.
“This confirms the statement that vitamin D is unlikely to be beneficial in people who are not vitamin D deficient, irrespective of whether supplementation occurs over the short or longer term,” Dr. Neale said.
The source of vitamin D, itself, is another consideration, with ongoing speculation of differences in benefits between dietary or supplementation sources versus sunlight exposure.
“Exposure to ultraviolet radiation, for which serum 25(OH)D concentration is a good marker, might confer benefits not mediated by vitamin D,” Dr. Neale and coauthors noted.
They added that the results in the older Australian population “cannot be generalized to populations with a higher prevalence of vitamin D deficiency, or with a greater proportion of people not of White ancestry, than the study population.”
Ten-year mortality rates from the D-Health trial are expected to be reported in the future.
Strategies still needed to address vitamin D deficiency
Further commenting on the findings, Dr. Schoenmakers underscored that “vitamin D deficiency is very common worldwide, [and] more should be done to develop strategies to address the needs of those groups and populations that are at risk of the consequences of vitamin D deficiency.”
That said, the D-Health study is important in helping to distinguish when supplementation may – and may not – be of benefit, she noted.
“This and other research in the past 15 years have contributed to our understanding [of] what the ranges of vitamin D status are [in which] health consequences may be anticipated.”
The D-Health Trial was funded by the National Health and Medical Research Council. Dr. Neale and Dr. Schoenmakers have reported no relevant financial relationships.
version of this article first appeared on Medscape.com.