“More supplementation is not better”: Vitamin D studies reveal role of gut in micronutrient uptake

02 Dec 2020 --- Two studies have revealed more about the relationship between vitamin D and the gut. One investigation pinpointed the section of the intestine where vitamin D regulates calcium, while the other found that gut microbiome diversity is linked to the body’s ability to transform vitamin D into its active, usable form in older men.

The researchers of the latter study, based at the University of California San Diego, also found that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D.

The study, published in Nature Communications, also revealed a new understanding of vitamin D and how it's typically measured.

“It seems like it doesn’t matter how much vitamin D you get through sunlight or supplementation, nor how much your body can store,” explains Deborah Kado, senior author on the study who is also director of the Osteoporosis Clinic at UC San Diego Health. 

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

“We often find in medicine that more is not necessarily better,” chimes in Robert Thomas, co-first author on the study and fellow in the Division of Endocrinology at UC San Diego School of Medicine. 

Vitamin D’s link to health
Vitamin D is a hormone that is important for bone health and immunity, with low levels of it being linked to a higher risk for cancer, heart disease and worse COVID-19 outcomes, write the study authors. 

Yet the largest randomized clinical trial to date, with more than 25,000 adults, previously concluded that taking vitamin D supplements has no effect on health outcomes, including heart disease, cancer or even bone health. Researchers found no correlation between where study participants lived in the US and their active vitamin D levels. 

“Our study suggests that might be because these studies measured only the precursor form of vitamin D, rather than the active hormone,” says Kado. 

The new study measured all forms of vitamin D in the participants’ blood serum: the precursor, active hormone and the breakdown product. 

“Measures of vitamin D formation and breakdown may be better indicators of underlying health issues [than measures of the precursor alone],” says Kado.

These measures may also give better insight into who might best respond to vitamin D supplementation, she notes.

Metabolizing D
Vitamin D can take several different forms, but standard blood tests detect only one, an inactive precursor that can be stored by the body.  

To use vitamin D, the body must metabolize the precursor into an active form.

“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,” Kado notes. 

Sun is not everything
The team analyzed stool and blood samples contributed by 567 men participating in Osteoporotic Fractures in Men Study Research Group.  

The participants lived in six cities around the US, their mean age was 84 and most reported being in good or excellent health. 

As expected, men who lived in sunny San Diego, California, got the most sun, while also exhibiting the highest levels of the precursor form of vitamin D.

However, the team unexpectedly found no correlations between where men lived and their levels of active vitamin D hormone.

Certain strains play a role
In addition to discovering a link between active vitamin D and overall microbiome diversity, the researchers also noted that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D. 

Most of those 12 bacteria produce butyrate, a beneficial fatty acid that helps maintain gut lining health.

According to the team, more studies are needed to better understand the part bacteria play in vitamin D metabolism, and to determine whether intervening at the microbiome level could be used to augment current treatments to improve bone and possibly other health outcomes.

Vitamin D’s role in calcium
In other developments, a Rutgers study has discovered that vitamin D regulates calcium in a section of the intestine that previously was thought not to have played a key role. 

The findings have important implications on how bowel disease, including ulcerative colitis and Crohn’s disease, may disrupt calcium regulation.

The study, published in the journal Molecular and Cellular Biology, highlights the importance of the distal segments of the intestine – including the colon – in vitamin D regulation of calcium and bone calcification. 

Previously, this regulation was thought to only occur in the proximal intestine, the first section of the intestine immediately beyond the stomach.

From the study, researchers also learned that a transporter of manganese – an essential element that plays a role in many cellular processes – was one of the genes most induced by vitamin D in both the proximal and distal intestine.

By Missy Green