PerspectiveIn the Journals

Combined weight loss, vitamin D reduces inflammation in cancer

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June 30, 2015

Weight loss combined with vitamin D supplementation has a greater effect on reducing chronic inflammation than weight loss alone in postmenopausal women, according to research in Cancer Prevention Research.

In a prospective, double blind analysis of a broad set of inflammatory markers during a 1-year period, researchers found that participants who lost 5% to 10% of their body weight and took vitamin D supplements saw the greatest reduction in interleukin-6 when compared with women assigned a weight-loss regimen and placebo.

“Weight loss has a significant impact on levels of inflammatory biomarkers,” Catherine Duggan, PhD, director of collaborative data services at Fred Hutchinson Cancer Research Center in Seattle, told Endocrine Today. “This study demonstrates that vitamin D supplementation appears to have an effect on levels of IL-6 over and above that of weight loss alone.”

Catherine Duggan

Catherine Duggan

Duggan and colleagues analyzed data from 218 postmenopausal women with overweight or obesity aged 50 to 75 years and levels of serum 25-hydroxyvitamin D between 10 ng/mL and 32 ng/mL (mean age, 59.6 years; mean BMI, 32.4 kg/m²; 86.2% white). Researchers randomly assigned 109 women to 12 months of 2,000 IU per day of vitamin D supplementation plus a lifestyle-based weight-loss program with a goal of 10% weight loss; 109 women in the control arm were randomly assigned a daily placebo and the same lifestyle-based weight-loss program.

Researchers measured serum levels of tumor necrosis factor-alpha (TNF-a), IL-6, IL-1 beta, IL-8 and IL-10, as well as BMI and total body and trunk fat measured by DXA. Researchers stratified mean changes in serum levels by study arm; participants also were stratified by degree of weight loss (< 5%; 5% to 10%; and > 10% of baseline weight lost) and compared with participants who gained weight or experienced no change in weight.

Researchers found that participants in the vitamin D arm who lost 5% to 10% of their baseline body weight reduced IL-6 levels by 37.3%; participants who experienced weight loss in the placebo arm reduced IL-6 levels by 17.2% (P = .004). Researchers found similar results among participants who lost more than 10% of their baseline body weight.

Researchers saw no effects on TNF-a, IL-10, IL-8, the composite score, adiponectin or leptin when stratified by weight loss.

“Overweight individuals should be encouraged to lose weight in order to reduce long-term effects of chronic inflammation, which has been linked to a number of adverse clinical outcomes,” Duggan said. “They should also speak to their doctor about testing their vitamin D levels and supplementing with appropriate levels of vitamin D where necessary.”

Further studies examining the relationship between weight loss, vitamin D supplementation and inflammation are needed, she said.

“As a first step, these results need to be verified in other studies, and effects examined among other racial/ethnic groups, and in men,” Duggan said. by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

itj+ Perspective

JoAnn E. Manson

JoAnn E. Manson

A role of vitamin D supplementation in modulation of systemic inflammation is biologically plausible, but these study results are far from conclusive. The researchers found no overall effect of vitamin D supplementation combined with weight loss, compared with weight loss alone, on the inflammatory cytokines and adipokines that they set out to study. The significant findings were limited to one subgroup — those who lost 5% to 10% of their weight — and to only one of seven different biomarkers — interleukin-6. This leads to a “multiple comparison” problem.  Although the results are promising, there wasn’t a prespecified hypothesis related to one subgroup or one specific biomarker. Residual confounding by the amount of weight loss in that subgroup, which might have differed between those who were randomly assigned to vitamin D and those assigned to placebo, cannot be ruled out and may have contributed to the lower IL-6 levels.

I agree with the researchers that there’s a need for additional research on vitamin D supplementation and inflammation, but clinical enthusiasm for high-dose vitamin D supplementation is outpacing the evidence. Overall, the randomized trials of vitamin D supplementation have shown inconsistent and inconclusive effects on non-skeletal outcomes. We are conducting a large-scale nation-wide trial of vitamin D supplementation (VITAL) in almost 26,000 participants looking at prevention of cancer and cardiovascular disease. Those results should be available in late 2017.  The VITAL trial, together with several other large-scale randomized studies being done worldwide, will provide answers about the balance of benefits and risks of moderate-to-high dose vitamin D supplementation. Although an effect of vitamin D supplementation on inflammatory cytokines would be an intriguing finding, it’s unknown whether this will translate into a reduced risk for clinical events, such as cancer, CVD and diabetes, which are being assessed in ongoing trials.

JoAnn E. Manson, MD, DrPH, FACE
Chief, Division of Preventive Medicine
Brigham and Women's Hospital
Professor, Harvard Medical School

Disclosure: Manson reports no relevant financial disclosures.