Higher serum vitamin D levels may lower risks of death, CVD in psoriasis patients

Individuals with psoriasis may benefit from an increased level of serum 25-hydroxivitamin D (25[OH]D), which has shown an association with a reduced risk of overall mortality and cardiovascular disease (CVD) in a recent study.

"The inverse associations were nonlinear, reaching a plateau at a level of 50 nmol/L,” the investigators said. “Notably, psoriasis patients with high levels of serum 25(OH)D (ie, ≥50 nmol/L) did not seem to have excess risk of mortality and CVD outcomes, compared with their psoriasis-free counterparts.”

A total of 8,947 patients with psoriasis and 178,937 controls had been identified at baseline in the UK Biobank cohort for this study. The investigators prospectively collected serum 25(OH)D levels at the time of recruitment. They examined the relationship between serum 25(OH)D levels and the risks of overall mortality and CVD using multivariable-adjusted Cox proportional hazards regression models.

Patients with psoriasis with the highest level of serum 25(OH)D (≥50 nmol/L) showed reduced risks for overall mortality (hazard ratio [HR], 0.54; p<0.05) and incident CVD (HR, 0.78; p<0.05) compared with those with the lowest level of serum 25(OH)D (<25 nmol/L). [J Am Acad Dermatol 2025;93:678-688]

Likewise, psoriasis patients with serum 25(OH)D ≥50 nmol/L showed no increased risks of mortality and CVD incidence relative to matched controls.

“These findings highlight the importance of maintaining an adequate vitamin D level in the prevention of mortality and CVD among individuals with psoriasis,” the investigators said. 

Mechanisms

It remains unclear how vitamin D helps attenuate the risks of mortality and CVD among individuals with psoriasis, but previous studies suggest potential contributions of a complex involvement of inflammatory responses, impaired glucose metabolism, obesity-related pathways, and renin-angiotensin-aldosterone pathways. [Eur J Epidemiol 2023;38:957-971; Nat Rev Nephrol 2013;9:337-347]

“Patients with psoriasis demonstrate often an activation of immune and inflammatory responses, dysregulated lipid and glucose metabolism, insulin resistance, and obesity,” the investigators said. [Curr Obes Rep 2020;9:165-178; Front Immunol 2023;14:1174998; J Am Acad Dermatol 2015;72:599-605]

In experimental studies, vitamin D improves inflammatory responses by modulating the Toll-like receptor 4-Nuclear Factor kappa-light-chain-enhancer of activated B cells (TLR-4/NF-κB) signalling cascade, which reduces the synthesis and release of proinflammatory factors. [Hepatology 2012;55:1103-1111]

“This is in line with our finding that inflammation factors, including C-reactive protein, white blood cell count, and systemic immune-inflammation index, partly accounted for the associations,” the investigators said. 

Previous in vitro and in vivo studies also found that vitamin D deficiency or vitamin D receptor knockout could disrupt glucose absorption and metabolism and might negatively affect the activity of pancreatic beta cells and decrease insulin secretion. [Science 1980;209:823-825; FASEB J 2003;17:509-511; J Biol Chem 2012;287:42324-42332; Curr Diab Rep 2015;15:76]

“Concordantly, our mediation analysis revealed that 4.4 percent of inverse association between vitamin D and overall mortality among patients with psoriasis was mediated by HbA1c,” the investigators said. 

The current study was limited by the lack of information on psoriasis subtypes.