Obesity blunts benefits of vitamin D supplements

3 minute read

A new study explores the association between BMI and vitamin D metabolism.

Higher doses of vitamin D may be required to elicit similar health benefits in overweight individuals to those seen in individuals of a normal weight, researchers have found.

The finding comes from the latest analysis of data collected in the VITamin D and OmegA-3 TriaL (VITAL) study, conducted throughout the US by researchers from the Brigham and Women’s Hospital in Boston, Massachusetts.

“This study sheds light on why we’re seeing 30-40 percent reductions in cancer deaths, autoimmune diseases and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D,” VITAL principal investigator and senior author of the new study, Professor JoAnn Mason, said in a statement.

Previous findings from the VITAL study suggest that, compared to placebo, vitamin D supplementation lowers cancer incidence and mortality and protects against autoimmune disease but fails to prevent bone fractures in healthy adults.

The new study, published in JAMA Network Open, focused on a cohort of participants from the VITAL study, delving deeper into an earlier finding that vitamin D supplementation was associated with positive effects on several health outcomes, but only in individuals that fell into the normal weight category (a BMI between 18.5 and 24.9).

Based on these findings, researchers were specifically interested in whether someone’s BMI could modify their vitamin D metabolism, as any disruptions to this process could limit the potential benefits of ongoing vitamin D supplementation.

About 16,500 participants from the original trial had relevant biomarkers (including free vitamin D and total 25-hydroxyvitamin D (25-OHD) assayed before vitamin D supplementation commenced. Of these, 2700 provided a follow-up blood sample two years later.

At baseline, total 25-OHD levels were lower for overweight (mean 31ng/ml), obese class I (29ng/ml) and obese class II (28ng/ml) participants compared to normal weight participants (32ng/ml),  after accounting for relevant factors that could influence serum vitamin D levels including age, diabetes status and ethnicity.

After two years of supplementation, participants who received vitamin D displayed increased serum 25-OHD levels (mean increase of 12ng/ml) compared to the placebo group, which displayed little change (decrease of 1ng/ml). Similar increases were observed for total 25-OHD and 25-OHD3 (a metabolite of 25-OHD).

However, the average increase in total 25-OHD for normal weight individuals (14ng/ml) was higher than the associated increase observed in overweight (13ng/ml), obese class I (11ng/ml), and obese class II (10ng/ml) participants.

Multiple mechanisms could underlie the association between higher BMI and the reduced increase in total 25-OHD levels, the researchers wrote.

One theory posits that the increased adipose tissue in obese individuals removes (and subsequently stores) a greater amount of vitamin D. Another theory proposes obesity leads to hepatic dysfunction, which impairs vitamin D metabolism.

In a statement, the researchers concluded that “these nuances make it clear that there’s more to the vitamin D story”, but acknowledged further mechanistic research was required to determine the true cause of the association.  

JAMA Network Open 2023, 17 January

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