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Why does vitamin D supplementation not work as well for everybody? Image credit: Xvision/Getty Images.
  • People with obesity are more likely to have a vitamin D deficiency.
  • Trials designed to determine whether or not vitamin D supplementation has a beneficial effect have repeatedly reported inconclusive results.
  • Secondary analysis of one of the largest trials to date — the VITAL study — into the effect of vitamin D supplementation showed different levels of beneficial effects for people with different body mass indexes (BMIs).
  • The study team has now shown that vitamin D supplementation is less effective at correcting deficiencies in people with obesity than in people with a BMI below 25.

As many as 40% of Europeans have a vitamin D deficiency, with people with dark skin more likely to be affected. Another group more likely to be affected by vitamin D deficiency are people with obesity.

The scale and type of impact of this are unknown, but vitamin D deficiency has been blamed for rising rates of type 1 and type 2 diabetes, multiple sclerosis, and various autoimmune conditions.

This deficiency has also been linked to cancer risk and poorer cancer treatment outcomes. Obesity is also a risk factor for many of these conditions.

Increasingly, research has shown that supplementation with vitamin D in people with obesity, defined as having a BMI over 30, does not correct the deficiency as effectively as it does in people with a BMI under 25.

Dr. Linia Patel, consultant dietitian, sports nutritionist, and British Dietetic Association spokesperson, told Medical News Today in an interview that her own research on a cohort of 2,842 individuals under 40 in the United Kingdom showed that vitamin D deficiency was associated with higher BMI and waist circumference.

BMI is a measurement that infers overall adiposity, or body fat, and the waist measurement infers the amount of visceral fat an individual may have in their abdomen.

“We’ve got two issues going on,” said Dr. Patel. “We have seen that […] people […] who are obese have lower vitamin D, starting off. And then even when you supplement them, their levels of vitamin D don’t go as high as people having ‘normal weight.’ So that’s one issue.”

“If you are having a higher BMI, you are more at risk of cardiometabolic risk factors, and what’s fantastic for me, as a public health dietitian, is [that] if we supplement people with vitamin D, we reduce that risk,” she told us.

The issue was that vitamin D supplementation advice is “one size fits all,” with little consideration given to different populations, she said.

The potential role vitamin D deficiency can play in increasing the risk of developing different conditions is controversial, with many trials and studies reporting inconclusive results.

It is also possible that the trials were asking the wrong questions in the first place, said Dr. Patel.

“A lot of other research that has been done into vitamin D hasn’t looked specifically at the right question. So you can see that the research is conflicting in this area. And a lot of research actually shows that vitamin D supplementation doesn’t make a difference, but some shows then that vitamin D supplementation does make a difference in reducing your risk factors.”

– Dr. Linia Patel

“And I think the papers that showed that it doesn’t make a difference, are perhaps not using a high enough dose, and perhaps not asking the right questions in terms of what, in fact, are we looking at? Are we looking at when people die? Are we looking at their risk of diseases? So I think we just need more specific and good quality research in this area,” she added.

The VITAL study sought to determine the effects of vitamin D and omega-3 supplementation on cancer and cardiovascular events in a cohort of 25,871 adults in the United States.

The initial results from the trial were published in the New England Journal of Medicine in 2019 and showed that while vitamin D supplementation did not reduce the risk of cancer, cardiovascular disease, or bone fractures in the cohort, the risk of cancer-related death was reduced with supplementation.

However, further analysis of the results told a different story when stratified by BMI. For people who had a BMI under 25, vitamin D supplementation was associated with a 24% lower cancer incidence, 42% lower cancer mortality, and 22% lower incidence of autoimmune disease compared to placebo.

This effect did not occur in people with overweight or obesity, which led the researchers to carry out a further analysis to quantify the difference in the impact of vitamin D supplementation on people with different BMIs. The results of this research appear in JAMA.

Researchers looked at the vitamin D levels of 16,515 participants before and after supplementation, as well as their BMI.

This paper shows that those with a BMI below 25 were less likely to have a vitamin D deficiency in the first place, and more likely to see their vitamin D deficiency corrected with vitamin D supplementation than those with a BMI over 30.

The authors proposed that this difference could be due to the difference in the activity of the parathyroid hormone, which can stimulate vitamin D production in the kidneys when a person has low levels, in people with a higher BMI.

In people with a BMI under 25 researchers expect that there is an inverse relationship between vitamin D levels and parathyroid hormone levels, but the level at which vitamin D supplementation can lower parathyroid hormone levels is likely to be higher in people in obesity than in people without.

Prof. JoAnn Mason, professor of medicine at Harvard Medical School, and principal investigator of the VITAL trial told MNT that “[t]he parathyroid hormone didn’t come down, […] it didn’t reduce as much in response to supplementation in those with higher BMI.”

Next, the team wants to investigate whether or not the dosage of vitamin D makes any difference to people at different BMIs as well as looking at the gene expression that occurs in people when they are given vitamin D supplementation.

Prof. Mason added: “We really believe that more attention [should] be given to body mass index, and to adiposity as a factor in modifying the effects or possibly blunting the effects of vitamin D supplementation. Because if you don’t take that into account, you can actually misinterpret the vitamin D trial.”