Trending Clinical Topic: Vitamin D Benefits

Ryan Syrek


February 24, 2023

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The potential benefits of vitamin D are the subject of frequent investigations. New studies have explored whether supplementation can prevent diabetes, reduce suicide attempts, and lower melanoma risk. Promising results helped drive interest in this week's top trending clinical topic. In findings published in early February, researchers detailed the impact of vitamin D among patients with prediabetes (see Infographic).

Researchers found no difference in the rate ratios for adverse events (kidney stones, 1.17 [95% CI, 0.69-1.99]; hypercalcemia, 2.34 [95% CI, 0.83-6.66]; hypercalciuria, 1.65 [95% CI, 0.83-3.28]; death, 0.85 [95% CI, 0.31-2.36]) between participants who received vitamin D and those who received placebo. The authors acknowledged that the absolute risk reduction number is small (3.3%), and they confirmed that intensive lifestyle changes and metformin remain more effective interventions. However, they noted that "extrapolating to the more than 374 million adults worldwide who have prediabetes suggests that inexpensive vitamin D supplementation could delay the development of diabetes in more than 10 million people."

The authors also suggest that the optimal level of vitamin D in the blood needed to reduce diabetes risk may be higher than previously thought. "[T]he blood 25-hydroxyvitamin D level needed to optimally reduce diabetes risk may be near and possibly above the range of 125 to 150 nmol/L (50 to 60 ng/mL) that the 2011 Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D provided as the range corresponding to the tolerable upper intake level (UL) of 4000 IU/d for vitamin D," the authors said.

An accompanying editorial urges caution regarding dosing. Those authors note that "Vitamin D supplementation of 10 to 20 mcg (400 to 800 IU) daily can be applied safely at the population level to prevent skeletal, and possibly nonskeletal, disease. Very-high-dose vitamin D therapy might prevent type 2 diabetes in some patients but may also cause harm."

In other encouraging news, supplementation nearly halved the rates of suicide and intentional self-harm among US veterans with vitamin D deficiency. Effects were even stronger among Black veterans. A retrospective cohort study reviewed records for 1.3 million veterans and found 490,885 veterans who received vitamin D3 (cholecalciferol) and 169,241 who received vitamin D2 (ergocalciferol). Those patients were compared one-on-one with veterans of similar demographics and medical histories who didn't receive supplementation.

Unadjusted suicide attempt/intentional self-harm rates were 0.27% for those taking vitamin D2 vs 0.52% for those not taking the supplement. For vitamin D3, the rates were 0.20% vs 0.36%, respectively. Vitamin D2 supplementation was associated with a 48.8% reduction in suicide/self-harm risks. Vitamin D3 was associated with a 44.8% reduction. Risk reductions were similar between men and women; however, supplementation had a greater effect in Black veterans (57.9% reduction for vitamin D2, 63.8% for vitamin D3) vs White veterans (46.3% for vitamin D2, 38.7%, for vitamin D3). These findings only applied to those with insufficient vitamin D levels. Among those with levels ≥ 40 ng/mL, no significant overall or dose-response associations with suicide/self-harm attempt risk were seen.

Vitamin D may also help lower melanoma risk. A Finnish study found that individuals who regularly take supplements are significantly less likely to have malignant melanoma or skin cancers of any type. The study involved nearly 500 individuals. Regular vitamin D users had a significant 55% reduction in melanoma diagnosis. Occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types. However, senior author Ilkka T. Harvima, MD, PhD, warned there are limitations to the study. Despite controlling for several possible confounding factors, "it is still possible that some other, yet unidentified or untested, factors can still confound the present result," he said.

An important caveat from a separate study: Response to vitamin D supplementation may be blunted in patients who are overweight or have obesity. A new post hoc analysis examined the large-scale Vitamin D and Omega-3 Trial (VITAL). VITAL found no benefits overall associated with vitamin D supplementation (2000 IU/d) for 5 years in terms of cancer or major cardiovascular disease outcomes. However, prespecified secondary analyses according to body weight showed that patients with a healthy weight (BMI < 25) did have significant benefits compared with placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower). Among leading theories as to why higher BMI would be linked to reduced benefits of vitamin D supplementation is that because vitamin D is a fat-soluble vitamin, increased adiposity and fat storage capacity associated with higher BMI results in greater removal of the vitamin from circulation.

From diabetes to suicide and skin cancer, the potential for interventions involving vitamin D supplementation remains promising. Even with caveats and concerns, such as possible reduced efficacy in persons with greater body weight, the promise of these recent findings resulted in this week's top trending clinical topic.

Take a quiz about vitamin D.


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