Growing Evidence on Vitamin D and Its Physiological Functions

In 1922, Alfred Hess, MD, discovered that children with rickets improved when exposed to direct sunlight, and by the 1960s, vitamin D was linked directly to muscle weakness.

Presently, it’s widely known that vitamin D isn’t a vitamin at all; rather, it’s the steroid hormone calcitriol. Receptors to calcitriol are distributed widely throughout human tissues, including vascular smooth muscle, endothelium, and cardiomyocytes.

As many countries report high rates of vitamin D deficiency, there is increasing interest in vitamin D’s physiological functions. Thus, researchers from several Australian institutions have jointly published a review covering the hormone’s actions based on observational studies, meta-analyses, clinical trials and basic research.

The authors began their research with a focus on vitamin D and muscle function in the elderly, as vitamin D deficiency is clearly associated with muscle weakness, falls, and sarcopenia. They reviewed randomized clinical trials that support vitamin D’s role in fall prevention among older or institutionalized patients. However, the evidence was conflicting in many areas, as the Institute of Medicine (IOM) recommends serum 25-hydroxyvitamin D (25OHD) levels >50 nmol/L, while the Endocrine Society recommends 25OHD levels >75 nmol/L.

The researchers then examined vitamin D in younger populations, including its role in athletics — where more work is needed to determine if vitamin D improves performance — and muscle metabolic function, specifically insulin sensitivity. They noted that vitamin D deficiency is associated with insulin resistance, though adiposity and sedentary, indoor living confounded most findings. While vitamin D deficiency is associated with myalgia, supplementation to alleviate myalgia in deficient subjects has not been shown to improve the condition.

The investigation of vitamin D and its physiological roles is a dynamic field. Several common allelic variants in the gene encoding of the vitamin D receptor have been identified and can be used to predict differences in bone density, accounting for up to 75% of the total genetic effect on bone density in healthy individuals. Hopefully, expanded testing and guidelines that can be applied in real-world situations will become available within the next few years.