Overlooked Link Between Vitamin D and GI Health

 Vitamin D is a fat-soluble vitamin long associated with bone health, but emerging evidence is revealing that it has a broader role, particularly in gut health. Both animal and human studies have linked low vitamin D levels with a variety of gastrointestinal (GI) diseases, including inflammatory bowel disease (IBD), diverticulitis, colon cancer, and liver disease. 

Such results are concerning, given the high rates of vitamin D deficiency observed globally. In the United States, there are notable prevalence disparities in vitamin D deficiency, where the overall rate is estimated to be 42%, with the highest rate in the African American population (82%), followed by the Hispanic population (63%). 

This article reviews the implications of vitamin D levels on GI health and highlights the importance for practitioners to make appropriate assessments and, where needed, design optimal interventions. 

Biologic Effects on the Gut

Vitamin D is synthesized in the skin following sun exposure and is then transported to the liver and kidneys for transformation into its biologically active form. Although dietary intake and supplementation contribute to vitamin D status, sunlight remains the primary source. 

Vitamin D deficiency has been implicated in altering the gut microbiome composition, compromising intestinal mucosal barrier integrity, and predisposing individuals to various intestinal pathologies. 

In the intestines, vitamin D binds to vitamin D receptors present in immune cells, which play a crucial role in immune function. Vitamin D affects the gene function responsible for modulating inflammation; cell proliferation; and the development, progression, and migration/metastasis of neoplasia. Vitamin D receptors also exert regulatory control, via signal transduction pathways, over the intestinal microbiome in both healthy and disease states. 

Studies have found that vitamin D supplementation can improve the diversity and stability of the fecal microbiome. 

Diverticulitis

Diverticulitis is a common disease, accounting for over 200,000 hospitalizations annually in the United States, but its pathophysiology is not well established. 

Higher prediagnostic vitamin D levels are associated with a significant reduction in the risk for diverticulitis. Seasonal variations in sun exposure may play a role, as evidence suggests that those residing in low-ultraviolet-light areas have higher rates of diverticulitis, diverticular abscess, and colectomy, as compared with those in high-ultraviolet-light areas. 

Colon Cancer

A recent review paper highlighted the significant relationship between vitamin D levels and colorectal cancer (CRC). 

Low levels were associated with an increased risk for/incidence of CRC as well as a poorer prognosis, whereas higher levels may confer a protective role. The latter effect has been attributed in part to the sirtuin family of proteins, particularly sirtuin 1, that play a critical role in DNA repair. 

National cohort studies have consistently shown a reduced risk for CRC with adequate dietary ingestion of vitamin D. 

IBD

Given the association between vitamin D and inflammation, it presents a logical risk factor for IBD. 

Vitamin D deficiency is common in IBD, affecting approximately 45% of patients with ulcerative colitis and 35%-100% of patients with Crohn’s disease. 

Data suggest that vitamin D deficiency is not uniformly a consequence of active IBD but most likely also contributes to disease pathogenesis. Potential mechanisms include microbial changes, inflammatory/cytokine upregulation, compromised mucosal integrity, and impaired immune function, all of which can result from low serum levels of vitamin D. Clinically, low vitamin D levels are linked to greater disease activity and risks for surgery, poor treatment response, and higher relapse rates. 

A 2023 Cochrane review found fewer clinical relapses with vitamin D supplementation, although there were no overall differences in clinical response or quality-of-life endpoints due to limited evidence quality. 

Liver Disease

The data for vitamin D insufficiency are strongest in regard to its correlation with liver disease. 

Such deficiencies are particularly prevalent among patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially in metabolically impaired individuals. Findings suggest that vitamin D supplementation may offer potential as an antifibrotic and antilipogenic agent.

Dose and Supplementation

Most experts define a vitamin D level of < 50 nmol/L as indicating a risk for insufficiency and of < 30 nmol/L as indicating a risk for deficiency. However, it should be noted that the recent recommendations from the Endocrine Society do not suggest specific levels to define vitamin D insufficiency and deficiency.

There are two main dietary forms of vitamin D: D2, which is primarily found in plants and fungi, and D3, which is animal-derived. Although both contribute to overall vitamin D levels, the latter is significantly more effective in raising serum levels. Testing for the biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), is recommended to more accurately identify deficiency.

Although dietary intake of vitamin D-rich foods remains a cornerstone recommendation, supplementation may be required in patients whose levels remain inadequate despite these efforts, or among those considered to be at particularly high risk. 

Evidence supports daily supplementation with up to 2000 international units (IU), preferably with vitamin D3, to prevent and/or treat vitamin D deficiency. 

According to large randomized controlled trials, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily supplementation with 2000 IU can be considered a simple, effective, and safe dosage to prevent and/or treat vitamin D deficiency in the general adult population. 

The most recent recommendations from the Endocrine Society, however, do not recommend empiric supplements and/or routine screening, except in certain populations, such as for those with osteoporosis, malabsorption, or high-risk diabetes; for those aged ≥ 75 years; or for children and adolescents aged 1-18 years. 

Bottom Line

Vitamin D deficiency is extraordinarily common and nearly absolute among certain ethnic or high-risk populations. 

Although the latest guidelines from the Endocrine Society recommend against routine supplementation, they do not specifically address its use in populations with, or at risk for, GI diseases. 

Given the strong association between low vitamin D levels and inflammatory and/or neoplastic disease, as well as the extraordinarily low risk profile of supplementation, practitioners should consider targeted testing or empiric treatment as part of their GI disease management and risk-reduction strategies.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. 

https://www.medscape.com/viewarticle/overlooked-link-between-vitamin-d-and-gi-health-2025a1000bki