Vitamin D and the gut microbiome: the activation question

Vitamin D helps regulate calcium and phosphate in the body to maintain our bones, teeth, and muscles. Nowadays, studies confirm the beneficial effects of Vitamin D on the bowel, heart, skin, cell overgrowth, and blood sugar [1,2].

Vitamin D and the maintenance of immune defences are also correlated [3]. Current research found that over 80% of 200 COVID-19 patients in Spain had Vitamin D deficiency [4]. Further limited studies and meta-analyses have observed that Vitamin D seems to reduce symptoms of COVID-19 as compared to standard care [5]. However, more substantial data is needed to support its impact on decreasing mortality rates in hospitalised patients.

We now know that there is evidence to support the benefits of Vitamin D in the body. Still, the research community debates its ability to contribute to the management of various diseases. In particular, one study concluded that Vitamin D supplementation may not improve the bone strength of older adults in the US [6]. Another clinical trial concluded that Vitamin D supplementation may not play a role in preventing cancer and cardiovascular disease in ageing adults [7].

These mixed findings on the benefits of Vitamin D have been a mystery to scientists, until now. Researchers at the University of California (UC) San Diego recently revealed a possible explanation for this discrepancy and a new understanding of Vitamin D bioavailability [8].

The Inactive Form of Vitamin D

Like any other substance, Vitamin D comes in several forms. Typically, researchers determine Vitamin D levels in the body by conducting standard blood tests, which only detect an inactive form of Vitamin D stored in the body called 25 hydroxyvitamin D or 25(OH)D.

The body benefits from Vitamin D only when the inactive precursor is metabolised into its active form, 1,25 dihydroxyvitamin D or 1,25(OH)D. So no matter the amount of sun exposure or supplementation you take in, you only gain the benefits once activation of Vitamin D occurs in the body.

UC San Diego researchers have suggested that the Vitamin D paradox, where studies failed to establish a correlation between Vitamin D supplementation, blood inactive Vitamin D status, and positive health outcomes, might be due to scientists measuring in the blood 25(OH)D, the inactive form of Vitamin D, rather than its active form 1,25(OH)D.

Gut Microbiome and Vitamin D Link

In addition, UC San Diego researchers found a consistent association between 1,25(OH)D levels, the active form of Vitamin D, and the diversity and number of bacteria in the gut microbiome. In contrast, 25(OH)D, the precursor form of the vitamin, had a weak correlation with "friendly" gut bacteria. The link between active Vitamin D levels and the gut microbiome outweighed other factors investigated in the study, such as antibiotic use, ethnic background, and even location.

Butyrate and Vitamin D Metabolism

The study also pointed out that participants with the highest levels of active Vitamin D had the greatest abundance of gut bacteria that produce butyrate. This short-chain fatty acid results from bacteria feeding on fibre and has been studied in relation to potential benefits in supporting the gut lining, maintaining the gut microbiome, and further supporting a competent immune system [9].

Researchers believe that butyrate-producing gut bacteria, rather than high quantities of inactive Vitamin D, control Vitamin D activation, which could explain these seemingly contradicting findings.

Contrary to prior logic, participants living in sunnier places did not have significantly higher levels of active Vitamin D than other participants, despite synthesising high amounts of inactive Vitamin D through the skin. Researchers believe that butyrate-producing gut bacteria, rather than high quantities of inactive Vitamin D, control Vitamin D activation, which could explain these seemingly contradictory findings.

Moreover, there is increasing evidence that the microbiome and immune system are interconnected and that active Vitamin D and butyrate may play extensive roles in this dynamic [10].

All of this points to butyrate helping our body transform the inactive precursor into the active form of Vitamin D, allowing us to reap all the benefits for optimal well-being.

Bottom line

Vitamin D supplementation and sunlight appear to be insufficient for optimal Vitamin D bioavailability and turnover. We need to encourage our bodies through gut microbial diversity, including butyrate-producing bacteria, to directly influence Vitamin D metabolism into its active form. Consequently, supplementing Vitamin D with butyrate may help us obtain the full benefits of Vitamin D while maintaining a favourable gut microbiome to support immunity and overall well-being.