Individuals with a higher BMI showed a weakened response to vitamin D supplementation, which could explain disparities in outcomes such as cancer, diabetes, and autoimmune diseases.
Researchers from Brigham and Women’s Hospital, a member of the Mass General Brigham healthcare system, have uncovered new evidence suggesting that how vitamin D metabolizes may vary in individuals with a high Body Mass Index (BMI). The findings, published in JAMA Network Open, come from a reanalysis of data from the VITAL trial, a nationwide clinical study led by Brigham researchers that explored the impact of vitamin D and marine omega-3 supplements on reducing the risk of cancer, heart disease, and stroke.
“The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25,” said first author Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham’s Division of Preventive Medicine. “There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI.”
Vitamin D is an essential nutrient involved in many biological processes, most notably helping our body absorb minerals, such as calcium and magnesium. While some of the vitamin D we need is made in the body from sunlight, vitamin D deficiencies are often treated with supplementation. Evidence from laboratory studies, epidemiologic research, and clinical research has also suggested that vitamin D may play a role in the incidence and progression of cancer and cardiovascular disease, and it was this evidence that prompted the original VITAL trial.
The VITAL trial was a randomized, double-blind, placebo-controlled trial in 25,871 U.S. participants, which included men over the age of 50 and women over the age of 55. All participants were free of cancer and cardiovascular disease at the time of enrollment. While the trial found little benefit of vitamin D supplementation for preventing cancer, heart attack, or stroke in the overall cohort, there was a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. Other studies suggest similar results for type 2 diabetes.
The new study aimed to investigate this correlation. The researchers analyzed data from 16,515 participants from the original trial who provided blood samples at baseline (before randomization to vitamin D), as well as 2,742 with a follow-up blood sample taken after two years. The researchers measured the levels of total and free vitamin D, as well as many other novel biomarkers for vitamin D, such as its metabolites, calcium, and parathyroid hormone, which helps the body utilize vitamin D.
“Most studies like this focus on the total vitamin D blood level,” said senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham and principal investigator of VITAL. “The fact that we were able to look at this expanded profile of vitamin D metabolites and novel biomarkers gave us unique insights into vitamin D availability and activity, and whether vitamin D metabolism might be disrupted in some people but not in others.”
The researchers found that vitamin D supplementation increased most of the biomarkers associated with vitamin D metabolism in people, regardless of their weight. However, these increases were significantly smaller in people with elevated BMIs.
“We observed striking differences after two years, indicating a blunted response to vitamin D supplementation with higher BMI,” Tobias said. “This may have implications clinically and potentially explain some of the observed differences in the effectiveness of vitamin D supplementation by obesity status.”
“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,” said Manson. “These nuances make it clear that there’s more to the vitamin D story.”
The authors conclude that the VITAL findings are a call to action for the research community to continue exploring the potential benefits of vitamin D supplementation for preventing cancer and other diseases and to take BMI into account when evaluating the supplement’s health impacts.
Reference: “Association of Body Weight With Response to Vitamin D Supplementation and Metabolism” by Deirdre K. Tobias, ScD, Heike Luttmann-Gibson, Ph.D., Samia Mora, MD, MHS, Jacqueline Danik, MD, DrPH, Vadim Bubes, Ph.D., Trisha Copeland, MS, RD, Meryl S. LeBoff, MD, Nancy R. Cook, ScD, I-Min Lee, MD, ScD, Julie E. Buring, Sc and JoAnn E. Manson, MD, DrPH, 17 January 2023, JAMA Network Open.
Co-author Julie Buring reported that her spouse was on the scientific advisory board of Pharmavite, which provided vitamin D and placebo. Additional disclosures can be found in the JAMA Network Open publication.
The Vitamin D and Omega-3 Trial was supported by the National Center for Complementary and Integrative Health and, during the intervention phase, was supported by grants from the National Cancer Institute; National Heart, Lung, and Blood Institute; Office of Dietary Supplements; National Institute of Neurological Disorders and Stroke; and the National Center for Complementary and Integrative Health. The ancillary studies are supported by grants from multiple institutes, including the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Mental Health; and others. Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma of Norway, and BASF (Omacor fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs. Quest Diagnostics measured serum 25-hydroxyvitamin D, parathyroid hormone, and other biomarkers at no cost to the study. Dr. LeBoff reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The study doesn’t make it clear whether increased Vitamin D for larger people would be helpful or not. Larger and fatter people need larger doses of drugs to get the same effect. This has been known for some time, yet doctors largely ignore it, choosing or forced to follow guidelines for average people, which is odd since obesity is extremely common these days, yet everything from sugary soda to prepackaged meals is based around high sugar and salt content, which makes it all worse.
Meanwhile, groups of people demonize artificial sweeteners despite literally ZERO REAL SCIENTIFIC STUDIES showing anything particularly harmful from them (very slight increase in cancer rate in a couple of them using amounts per day most people don’t come close to). Then there was the saccharin study that proved that rats and humans aren’t the same, despite most studies implying they react in the same exact way. They fed these rats 5x-10x their own body weight in saccharin and were surprised when there was a problem (If one drinks too much water it can kill even so dosing is important and unlike aspartame, saccharin is excreted when you pee). Further studies eventually proved that NO AMOUNT of saccharin in humans had the same effect as it did in rats. Saccharin does NOT cause cancer in humans. Sucralose showed 0% chance of increased cancer in humans. Aspartame showed a tiny percentage when taking in huge quantities (not enough to worry about compared to getting fat or diabetes from endless sugary drinks because let’s face it, most people don’t like plain water).
We need strategies that people will actually follow, not things like “eat less” or eat mostly veggies you hate. People won’t follow that advice. Other advice like low-fat diets or even margarine substituted for butter proved more fatal than the things they were fighting. Many food studies are also flawed because they rely on people’s memories for questionnaires. A recent thorough study debunked the notion that red meat is worse for you than say chicken or pork. The results were due to such study flaws.
It’s the same reason one day coffee is bad for you and another day it’s great for you and then bad and then great again. People tend to find (and try to prove) what they’re looking for (bias) and this leads to no end of media-carried “studies prove” stories that end up being mostly nonsense in the end.
That doesn’t mean this study is wrong, of course, but it does warrant caution to trust one finding without more detailed analysis.
Are there any vitamins that would help in weight gain and maintain
My husband needs to gain weight he is very boney and weak !