medwireNews: Vitamin D supplementation is associated with a reduced risk for metastatic or fatal cancer, but the benefit appears to be largely restricted to people with normal BMI, shows an analysis of VITAL study data.
Paulette Chandler (Harvard Medical School, Boston, Massachusetts, USA) and co-investigators explain that VITAL was set up to investigate the benefits of vitamin D3 (cholecalciferol, 2000 IU/day) and marine omega-3 fatty acid (1 g/day) supplementation in men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline.
During a median 5.3 years of treatment, 1617 (6.3%) of the 25,871 participants were diagnosed with an invasive cancer, most commonly of the prostate, breast, or lung.
The primary data analysis showed no significant difference in overall cancer incidence by treatment arm but suggested that vitamin D supplementation may lower the risk for advanced (metastatic or fatal) cancer, with the effect modified by BMI.
The current secondary analysis investigated this further and indeed revealed that individuals randomly assigned to receive vitamin D had a significant 17% lower risk for advanced cancer than those assigned to receive placebo.
Specifically, the rate of advanced cancer was 1.7% among the 12,927 participants who received vitamin D and 2.1% among the 12,944 who received placebo.
Chandler and co-authors note in JAMA Network Open that the survival curves for the vitamin D and placebo groups began to diverge after 2 years, but there was no association between omega-3 fatty acid supplementation and advanced cancer risk.
When the researchers stratified the participants by BMI, they found a significant 38% reduction in advanced cancer risk with vitamin D versus placebo among those with a normal BMI (<25.0 kg/m2), but there was no significant risk reduction among those who were overweight (BMI 25.0–29.9 kg/m2) or obese (BMI ≥30.0 kg/m2).
Chandler et al say “[t]here was a stepwise decrease in effect size of the association of vitamin D treatment with metastatic cancer and cancer mortality by each higher BMI subgroup.”
They suggest: “A dynamic interplay between adiposity and immunomodulatory or inflammatory mediators may contribute to the differential response to vitamin D3.”
The team oberseved no differences in effect by race or baseline vitamin D level and point out that the results are not due to one particular cancer, “because a broad mix of cancers contributed” to their findings.
They therefore conclude that “vitamin D supplementation may be operating through a general, rather than site-specific, mechanism to reduce the risk of advanced cancer.”
In an accompanying commentary, Lina Zgaga, from the University of Dublin in Ireland, says that the protective effect observed among people with normal BMI but not those who were overweight or obese was “most likely because of the simple volumetric dilution of this fat-soluble vitamin in fat tissue.”
It therefore “seems sensible to wonder whether overweight individuals would benefit from a higher dose of vitamin D,” she suggests.
Zgaga believes that, overall, the findings “support the role of vitamin D in cancer prevention and add substantially to the weight of the evidence in this field.”
She notes, however, that “it is difficult to eliminate the possibility that in some cases carcinogenesis began before the trial commenced; it might be argued that vitamin D affected cancer progression and not necessarily occurrence. Therefore, further investigation is warranted.”
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JAMA Netw Open 2020; 3: e2025850
JAMA Netw Open 2020; 3: e2027176