For the first time, researchers at Fred Hutchinson Cancer Research Center have found that weight loss, in combination with vitamin D supplementation, has a greater effect on reducing chronic inflammation than weight loss alone. Chronic inflammation is known to contribute to the development and progression of several diseases, including some cancers.
Results of the randomized, controlled clinical trial — which involved more than 200 overweight, postmenopausal women who had insufficient levels of vitamin D at the beginning of the study — are published online ahead of the July print issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
“We know from our previous studies that by losing weight, people can reduce their overall levels of inflammation, and there is some evidence suggesting that taking vitamin D supplements can have a similar effect if one has insufficient levels of the nutrient,” said lead and corresponding author Catherine Duggan, Ph.D., a principal staff scientist in the Public Health Sciences Division at Fred Hutch. However, it has not been known whether combining the two — weight loss and vitamin D — would further boost this effect. “It’s the first study to test whether adding vitamin D augments the considerable effect of weight loss on inflammatory biomarkers,” she said.
To explore this question, Duggan and colleagues recruited 218 healthy, overweight older women who had lower-than-recommended levels of vitamin D (less than 32 ng/mL). The women then took part in a 12-month diet and exercise program (including 45 minutes of moderate-to-vigorous exercise five days a week). Half of the study participants were randomly selected to receive 2,000 IU of vitamin D daily for the duration of the year-long trial, and the other half received an identical-appearing placebo, or dummy vitamin. Biomarkers of inflammation were measured at the beginning and end of the study. The researchers then compared changes in these levels between the two groups.
At the end of the study, all of the participants had reduced levels of inflammation, regardless of whether they took vitamin D, “which highlights the importance of weight loss in reducing inflammation,” Duggan said. However, those who saw the most significant decline in markers of inflammation were those who took vitamin D and lost 5 to 10 percent of their baseline weight. These study participants had a 37 percent reduction in a pro-inflammatory cytokine called interleukin-6, or IL-6, as compared to those in the placebo group, who saw a 17.2 percent reduction in IL-6. The researchers found similar results among women in the vitamin D group who lost more than 10 percent of their starting weight. While IL-6 has normal functions in the body, elevated levels are associated with an increased risk of developing certain cancers and diabetes and may be implicated as a cause of depression, Duggan said.
“We were quite surprised to see that vitamin D had an effect on an inflammation biomarker only among women who lost at least 5 percent of their baseline weight,” Duggan said. “That suggests vitamin D can augment the effect of weight loss on inflammation.”
Vitamin D is a steroid hormone that has multiple functions beyond its widely recognized role in regulating calcium levels and bone metabolism. Vitamin D receptors are found in more than 30 cell types and the research focus around this nutrient recently has shifted from bone health to vitamin D’s effect on cancer, cardiovascular health and weight loss, among other health issues.
Inflammation occurs when the body is exposed to pathogens, such as bacteria or viruses, which puts the immune system in overdrive until the “attack” ceases and the inflammatory response abates. Overweight or obese people, however, exist in a state of chronic inflammation. This sustained upregulation of the inflammatory response occurs because fat tissue continually produces cytokines, molecules that are usually only present for a short time, while the body is fighting infection, for example.
“It is thought that this state of chronic inflammation is pro-tumorigenic, that is, it encourages the growth of cancer cells,” she said. There is also some evidence that increased body mass “dilutes” vitamin D, possibly by sequestering it in fat tissue.
“Weight loss reduces inflammation, and thus represents another mechanism for reducing cancer risk,” Duggan said. “If ensuring that vitamin D levels are replete, or at an optimum level, can decrease inflammation over and above that of weight loss alone, that can be an important addition to the tools people can use to reduce their cancer risk.”
Duggan encourages women to speak to their health care providers about measuring their levels of vitamin D to determine the most appropriate dosage.
The Breast Cancer Research Foundation, Susan G. Komen for the Cure, National Institutes of Health, Seattle Cancer Consortium Breast Cancer Specialized Program in Research Excellence, Fred Hutchinson/University of Washington Cancer Consortium and Safeway Foundation funded the research.
Editor’s note: To obtain a copy of the Cancer Prevention Research paper, “Effect of vitamin D3 supplementation in combination with weight loss on inflammatory biomarkers in postmenopausal women: a randomized controlled trial,” or to arrange an interview with corresponding author Catherine Duggan, please contact: Kristen Woodward in Fred Hutch media relations, email@example.com or 206-667-5095.
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At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first and largest cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit fredhutch.org or follow Fred Hutch on Facebook, Twitter or YouTube.
This news release describes a randomized, controlled clinical trial designed to learn whether adding vitamin D supplements to substantial weight loss regimens would have a synergistic effect in reducing inflammatory chemicals in the bodies of overweight, older women with levels of vitamin D considered too low. The study, published in Cancer Prevention Research, has potential relevance for cancer prevention because inflammatory cytokines have been implicated in the genesis and progression of some cancers, as well as heart disease and other disorders. The release offers substantial details about the design, metrics and outcomes of the clinical trial and does a pretty good job of defining the possible reasons for the effects of chronic inflammation and weight loss on cancer development. It goes to some lengths to narrowly define the results and avoid overstatement. That said, the release ends on a sour note by encouraging readers to talk to their doctors about vitamin D testing — a recommendation not consistent with U.S. Preventive Services Task Force guidelines and which is not supported by this research. Readers might also have been better informed if the release had offered more context regarding the many conflicting and sometimes confusing studies that have previously looked for links among vitamin D, inflammatory responses, diet, overweight, sun exposure and cancer.
News releases that include the words “diet,” “overweight,” “vitamin,” and “cancer” are almost narrative nuclear events, often guaranteeing an explosion of coverage, souped up vitamin sales pitches, and lots of negative fallout whose half-life seems forever. Cancer remains the second biggest killer disease overall of Americans, and some experts believe that it will soon push heart disease and stroke out of first place. Thus cancer prevention is a deservedly hot topic, and it is no surprise that Americans are eager for information about ways to limit their risk. News releases that describe research on these topics have enormous power to inform and misinform.
There was no mention of the potential costs of screening women for vitamin D levels (as encouraged in the release in a statement from the principal investigator) or the cost of supplementation.
The release does a good job of comparing data and providing explanations for the measurements used. We’ll award a Satisfactory for that precision, but as noted below under “Evidence,” there was no explicit caution regarding the fact that measurements of interleukin-6 (IL-6) are only surrogates for the effects of weight loss and vitamin D on clinical outcomes related to inflammation (e.g. cancer diagnoses). IL-6 levels dropped in both the placebo and vitamin D arms, and it’s not clear whether the statistically significant additional decline in IL-6 observed in the vitamin D group is clinically important.
Because some of the participants were vitamin D-deficient and the dose of vitamin D provided was modest (2000 IU/d), this was a tough call. But supplementation is often so misunderstood, overhyped and oversold that some statement cautioning readers to pay attention to the specifics of this study and not apply its recommendations to everyone seems prudent.
For the most part, the release provides a cautious and accurate description of what appears to be a well-conducted clinical trial in a well-defined population. For example, it notes that weight loss and vitamin D lowered inflammation LINKED to cancer — not that these things reduced cancer risk itself (something this study couldn’t establish). But as noted above, we would have appreciated an explicit acknowledgment that IL-6 is a surrogate marker for the clinical outcomes that people care about. And more importantly, we’re concerned about the closing comment that women should talk to their doctors about measuring their vitamin D levels to determine the most appropriate dose. The problem is there is no evidence supporting screening or treating to a level — and certainly not from this study. The US Preventive Services Task Force has concluded that evidence is insufficient to recommend routine vitamin D screening and the IOM has said that while there are data supporting the benefits of vitamin D supplementation with bone health and fall prevention, there is no evidence supporting benefits for cancer. While testing may be warranted in those with signs or symptoms of clinical deficiency, the statement made here implies that everyone should be tested so that an appropriate dose of vitamin D can be selected. That goes beyond the available evidence.
It’s hard to argue that overweight, vitamin deficiency, chronic inflammation and cancer are not real threats, so no mongering apparent here.
Funding sources are well documented.
The study didn’t discuss alternative preventive measures or genetic causes of increased cancer risks. But this is such a broad and expansive topic that we don’t think the release should have been expected to address those myriad issues. We’ll rate this Not Applicable.
Primary care physicians and other health providers are well positioned to monitor blood levels of vitamin D, along with dietary and exercise regimens. The news release makes that clear, albeit indirectly. As noted above, we think the release goes too far in suggesting that people ask their doctors about having their vitamin D levels checked. But we’ve already docked points for that, so we’ll award a Satisfactory rating here.
The release makes a case for this being the first clinical trial of its kind; although it’s always difficult to make that statement absolutely, the writer of the release attributes the statement to the study author. As a general rule, it’s probably best to say “believed to be the first.” While the release meets our standard here, we also wish it had delved a bit into the background of previous vitamin D research and the conflicting and confusing messages that research has generated. Without that context, the typical reader might wrongly jump to the conclusion, based on the wording of the lede and other parts of the release, that this study of vitamin D supplementation — because it was a controlled clinical trial — has somehow settled the important questions about the role of vitamin D and inflammation in cancer risk. The debate remains alive and well.