This article is part of our May 2020 special issue. Download the full issue here.
Charoenngam N, Shirvani A, Kalajian TA, Song A, Holick MF. The effect of various doses of oral vitamin D3 supplementation on gut microbiota in healthy adults: a randomized, double-blinded, dose-response study. Anticancer Res. 2020;40(1):551-556.
This randomized, double-blinded, dose-response study investigated the effects of vitamin D3 supplementation on gut microbiota.
Twenty adults with low vitamin D status (defined as serum 25-hydroxyvitamin D [25(OH)D] of less than 30 ng/mL).
Study Medication and Dosage
Participants received either 600, 4,000, or 10,000 IU per day of oral vitamin D3.
Researchers collected stool samples at baseline and 8 weeks to identify gut microbiota using 16S rRNA gene amplification and sequencing.
Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (P<0.05). After the intervention, data analysis showed a dose-dependent increase in relative abundance of Bacteroides, with a significant difference between the 600 IU group and the 10,000 IU group (P=0.027), and Parabacteroides, with a significant difference between the 600 IU group and the 4,000 IU group (P=0.039). Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria.
Vitamin D3 supplementation was linked to a dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity. This is not the first time D3 supplementation has been connected with shifts in gut microbiota. A number of studies have monitored gut microbiota with varying findings.
A November 2019 paper by Naderpoor et al reported results of their randomized clinical trial giving vitamin D to 26 vitamin D–deficient, overweight people and the impact this had on their fecal microbiota.1 This study defined vitamin D deficiency as ≤50 nmol/L (equivalent to 20 ng/mL) in contrast to Charoenngam’s 30 ng/mL line. Naderpoor’s participants received a 100,000 IU loading dose followed by 4,000 IU daily for 16 weeks. Vitamin D supplementation in this earlier trial increased abundance of gut microbiota of the genus Lachnospira. After supplementation, participants whose vitamin D blood levels increased to greater than 75 nmol/L had a higher abundance of genus Coprococcus and lower abundance of genus Ruminococcus compared to those whose vitamin D levels remained below 50 nmol/L.
Nevertheless, there is something intriguing about the idea that exposing one’s abdomen to the sun might change gut microbiota.
We also have data from a 2015 study by Cantarel et al that examined vitamin D supplementation (5,000 IU per day) for 90 days in women (n=70) with multiple sclerosis (MS) and 8 healthy controls. Fecal microbiome testing showed decreased abundance of genus Ruminococcus and increased Akkermansia and Faecalibacterium in this small group. The MS patients not on the drug glatiramer treatment showed an increase in Coprococcus, Akkermansia, and Faecalibacterium after vitamin D supplementation.2
Do we know what these various findings mean? There is some consensus that vitamin D supplements alter the gut microbiome. These various studies do not suggest a consistency in these alterations, though some do agree that Akkermansia increases. In recent years, Akkermansia muciniphila has received favorable attention, and many consider increased numbers of it beneficial. Akkermansia exerts control on basal metabolism and immunity.3 Thus, seeing an increased abundance would be considered a good thing, especially in the overweight or obese people in Naderpoor’s study.
Reading in Charoenngam et al that “Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (P<0.05)” perked up my antennae. It is the bacteria Porphyromonas gingivalis that have been isolated from Alzheimer’s disease brains, and this finding is the basis of an intriguing theory that this neurodegenerative condition is triggered by chronic reactions to these bacteria.4 While not widely accepted as causative yet, the idea that vitamin D is associated with decreases in Porphyromonas populations has a certain appeal.
Somewhere we should mention that several papers suggest that ultraviolet light exposure will alter the gut microbiome, and the effects differ from vitamin D supplementation. Again, the changes vary between studies.5,6 Nevertheless, there is something intriguing about the idea that exposing one’s abdomen to the sun might change gut microbiota.
Although we prefer to consider data from human studies, there is one mouse study on vitamin D supplementation that should be mentioned in this discussion.
In a July 2018 paper, Ghaly et al describe a study in which they gave high-dose vitamin D to mice treated with dextran sodium sulfate to trigger colitis. The mice receiving the highest doses of vitamin D (10,000 IU/kg) experienced the most severe colitis.7 The problem with reading studies done with mice is that we don’t know how to extrapolate results to humans, and this situation is a good example. Still, it wouldn’t hurt to have this study in the back of our minds when supplementing with vitamin D in high doses until we are certain that some people will not have a similar response.
The other thing that wouldn’t hurt is to adopt the view that part of the mechanism of action of vitamin D may be in shifting the gut microbiome rather than systemic biochemical effects on cells within the body. This won’t be the first time we have to step into this paradigm. We’ve already had to adjust our understanding of metformin’s mechanism.8
- Naderpoor N, Mousa A, Fernanda Gomez Arango L, Barrett HL, Dekker Nitert M, de Courten B. Effect of vitamin D supplementation on faecal microbiota: a randomised clinical trial. Nutrients. 2019;11(12):pii: E2888.
- Cantarel BL, Waubant E, Chehoud C, et al. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015;63:729-734.
- Xu Y, Wang N, Tan HY, Li S, Zhang C, Feng Y. Function of Akkermansia muciniphila in obesity: interactions with lipid metabolism, immune response and gut systems. Front Microbiol. 2020;11:219.
- Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333.
- Ghaly S, Kaakoush NO, Hart PH. Effects of UVR exposure on the gut microbiota of mice and humans. Photochem Photobiol Sci. 2020;19(1):20-28.
- Ghaly S, Kaakoush NO, Lloyd F, et al. Ultraviolet irradiation of skin alters the faecal microbiome independently of vitamin D in mice. Nutrients. 2018;10(8):pii: E1069.
- Ghaly S, Kaakoush NO, Lloyd F, et al. High dose vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis. Sci Rep. 2018;8(1):11511.
- Zhang W, Xu JH, Yu T, Chen QK. Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice. Biomed Pharmacother. 2019;118:109131.