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After several decades of failed vitamin D trials, recent successesful clinical trials published since 2024 have demonstrated that high-dose vitamin D therapy is necessary to demonstrate vitamin D’s nonskeletal outcomes in clinical trials. In this review article, we focus on recent randomized controlled trials (RCTs) and large population studies to demonstrate the nonskeletal functions of vitamin D. A recent RCT from France showed that high-dose vitamin D, 100,000 international units every 2 weeks for 24 months significantly reduced disease activity in patients with multiple sclerosis compared to placebo. A Harvard RCT found that vitamin D supplementation over 4 years significantly reduced telomere erosion compared with placebo. A recently published 30-year Finnish population study found that adults with low childhood serum 25-hydroxyvitamin D [25(OH)D] levels had a significantly increased risk of atherosclerotic cardiovascular disease. A recent post hoc analysis of the D2d RCT showed a 62% reduction in the risk of type 2 diabetes among individuals with baseline serum 25(OH)D < 12 ng/mL who received vitamin D for 2.5 years. Another RCT using high-dose vitamin D therapy, 50,000 international units per week for 2 months and then every other week for 10 months or placebo in children and adolescents with type 1 diabetes showed that vitamin D significantly reduced the proinsulin to C-peptide ratio, a marker of β-cell endoplasmic reticulum stress; temporal trends in both A1c and the insulin-dose adjusted A1c, a marker of partial clinical remission; tumor necrosis factor alpha, and significantly slowed the percent change from baseline in the area under the curve of stimulated C-peptide compared to placebo. These recent studies provide incontrovertible evidence that the nonskeletal functions of vitamin D are achieved at elevated 25(OH)D serum concentrations, in contrast to the stipulations of the 2024 Endocrine Society Guidelines on vitamin D, which were based on data from earlier studies that showed none or minimal impact of vitamin D on clinical outcomes.

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High-Dose Vitamin D and Nonskeletal Health

  • 章节

  • 发表日期：

    2026年

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  • Benjamin Udoka Nwosu

摘要

After several decades of failed vitamin D trials, recent successesful clinical trials published since 2024 have demonstrated that high-dose vitamin D therapy is necessary to demonstrate vitamin D’s nonskeletal outcomes in clinical trials. In this review article, we focus on recent randomized controlled trials (RCTs) and large population studies to demonstrate the nonskeletal functions of vitamin D. A recent RCT from France showed that high-dose vitamin D, 100,000 international units every 2 weeks for 24 months significantly reduced disease activity in patients with multiple sclerosis compared to placebo. A Harvard RCT found that vitamin D supplementation over 4 years significantly reduced telomere erosion compared with placebo. A recently published 30-year Finnish population study found that adults with low childhood serum 25-hydroxyvitamin D [25(OH)D] levels had a significantly increased risk of atherosclerotic cardiovascular disease. A recent post hoc analysis of the D2d RCT showed a 62% reduction in the risk of type 2 diabetes among individuals with baseline serum 25(OH)D < 12 ng/mL who received vitamin D for 2.5 years. Another RCT using high-dose vitamin D therapy, 50,000 international units per week for 2 months and then every other week for 10 months or placebo in children and adolescents with type 1 diabetes showed that vitamin D significantly reduced the proinsulin to C-peptide ratio, a marker of β-cell endoplasmic reticulum stress; temporal trends in both A1c and the insulin-dose adjusted A1c, a marker of partial clinical remission; tumor necrosis factor alpha, and significantly slowed the percent change from baseline in the area under the curve of stimulated C-peptide compared to placebo. These recent studies provide incontrovertible evidence that the nonskeletal functions of vitamin D are achieved at elevated 25(OH)D serum concentrations, in contrast to the stipulations of the 2024 Endocrine Society Guidelines on vitamin D, which were based on data from earlier studies that showed none or minimal impact of vitamin D on clinical outcomes.