Vitamin D deficiency is associated with cancer, cardiovascular disease, and osteoporosis, but clinical trials of vitamin D supplements have yielded mixed results. A new study that found links between the active form of the vitamin and gut bacteria may help explain why.

Vitamin D is essential for strong immunity and maintaining healthy bones and teeth.

Several studies have found that low levels of vitamin D in the blood correlate with a wide range of illnesses, including cancer, cardiovascular disease, diabetes, and osteoporosis.

A few studies have even hinted that low vitamin D levels are associated with severe COVID-19, although the research is inconclusive.

Despite these associations, evidence for the benefits of widespread vitamin D supplementation to prevent disease in otherwise healthy people has been mixed.

For example, a large clinical trial found no evidence that a vitamin D supplement prevented cardiovascular disease and cancer in older adults. Another trial found no evidence that taking a supplement improved bone health.

This apparent lack of health benefits from widespread vitamin D supplementation has baffled medical researchers.

Stores of inactive vitamin D

When healthcare professionals and medical researchers want to determine an individual’s vitamin D status, they measure serum levels of the inactive precursor, because this reflects how much vitamin D the body stores.

However, the crucial factor may be how the vitamin is metabolized rather than how much of it is stored.

When measuring how much active vitamin D older males had in their blood, the UC San Diego researchers found that its levels correlated with the diversity of the community of bacteria living in their gut, or gut microbiome.

Levels of active vitamin D also correlated with the number of “friendly” bacteria in their gut.

By contrast, there was not a strong association between the inactive, precursor form of the vitamin and bacterial diversity or friendly bacteria.

“We were surprised to find that microbiome diversity — the variety of bacteria types in a person’s gut — was closely associated with active vitamin D but not the precursor form,” says senior author of the study Dr. Deborah Kado, director of the Osteoporosis Clinic at UC San Diego Health.

“Greater gut microbiome diversity is thought to be associated with better health in general,” she adds.

Sunlight exposure

The correlation between microbial diversity and active vitamin D remained even after adjusting for factors known to determine microbial diversity. These included the participants’ age, where in the United States they lived, their ethnic background, and their antibiotic use.

In fact, the participants’ levels of active vitamin D correlated much more strongly with microbiome diversity than any of these other factors.

This is particularly remarkable given that people who live in sunnier places, such as California, are able to synthesize more of their own vitamin D through the action of ultraviolet light on their skin.

“It seems like it does not matter how much vitamin D you get through sunlight or supplementation, nor how much your body can store.”

– Dr. Deborah Kado

“It matters how well your body is able to metabolize that into active vitamin D, and maybe that is what clinical trials need to measure in order to get a more accurate picture of the vitamin’s role in health,” Dr. Kado explains.

The researchers say more studies are needed to investigate the role of bacteria in vitamin D metabolism. They speculate that changing patients’ microbiota could augment existing treatments for improving bone density, and possibly other health outcomes.

The authors stress that their study was unable to determine whether high levels of active vitamin D allow butyrate-producing bacteria to thrive or whether these bacteria promote the conversion of the vitamin to its active form.

By the same token, the study could not prove that having a more diverse gut microbiome leads to better vitamin D metabolism. It only found an association between the two.

Another limitation of the study was that the participants were predominantly older white males.

In addition, around 75% of them reported that they were taking some form of vitamin D supplement. Only 7% of all the participants met the standard definition of vitamin D deficiency.

Medical reference: Medical News Today