Vitamin D and the Athlete: Current Perspectives and New Challenges

Abstract

The last decade has seen a dramatic increase in general interest in and research into vitamin D, with many athletes now taking vitamin D supplements as part of their everyday dietary regimen. The most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health in non-athletic individuals. In contrast, data have consistently failed to demonstrate any relationship between serum 25[OH]D and bone health, which may in part be due to the osteogenic stimulus of exercise. Vitamin D may interact with extra-skeletal tissues such as muscle and the immune system to modulate recovery from damaging exercise and infection risk. Given that many athletes now engage in supplementation, often consuming extreme doses of vitamin D, it is important to assess whether excessive vitamin D can be detrimental to health. It has been argued that toxic effects only occur when serum 25[OH]D concentrations are greater than 180 nmol·l^-1, but data from our laboratory have suggested high-dose supplementation could be problematic. Finally, there is a paradoxical relationship between serum 25[OH]D concentration, ethnicity, and markers of bone health: Black athletes often present with low serum 25[OH]D without physiological consequences. One explanation for this could be genetic differences in vitamin D binding protein due to ethnicity, resulting in greater concentrations of bioavailable (or free) vitamin D in some ethnic groups. In the absence of any pathology, screening may be unnecessary and could result in incorrect supplementation. Data must now be re-examined, taking into consideration bioavailable or "free" vitamin D in ethnically diverse groups to enable new thresholds and target concentrations to be established; perhaps, for now, it is time to "set vitamin D free".

Fig. 1

a Dietary vitamin D₃ or exposure of skin to ultraviolet B (UVB) radiation results in circulating vitamin D₃ (cholecalciferol). This metabolite is hydroxylated in the liver at carbon 25 to form the metabolite 25[OH]D, a biologically inactive compound with the longest half-life of the vitamin D metabolites. 25[OH]D circulates bound to vitamin D-binding protein (VDBP; 85–90%), whereas a smaller fraction circulates freely in serum (10–15%). 25[OH]D is transported to the kidney or target tissues expressing 1α-hydroxylase, where it is hydroxylated further at carbon 1 to form 1α,25[OH]D₂D₃, the biologically active vitamin D metabolite. At the target tissue, 1α,25[OH]D₂D₃ binds to the vitamin D receptor (VDR) and subsequently forms a heterodimer with retinoid X receptor (RXR), forming a transcriptional complex that recruits co-activators and repressors to vitamin D response elements to activate and repress the gene. b The most common vitamin D metabolites and their sites of production. c The US Institute of Medicine (IoM) guidelines for the classification of vitamin D status. mRNA messenger RNA

Fig. 2

Known and predicted vitamin D receptor (VDR) protein interactions in Homo sapiens. The figure demonstrates numerous signaling pathways in which the VDR is involved. Each node (sphere) represents all the proteins produced by a single protein-coding gene locus. Lines connecting nodes represent the type of interaction, defined in the key. Note that interactions do not necessarily mean a physical interaction between proteins. Interactions were limited to no more than 20 interactions. The minimum known interaction score was set at 0.150 (http://string-db.org)

Fig. 3

Schematic representation of demographic (blue) and pathological (red) factors that may influence the cardiovascular adaptation to exercise [133]

Fig. 4

Schematic representation of the vitamin D-binding protein (VDBP) domain structure. The 458 amino acid sequence of human VDBP with the three structural domains and known functional regions is indicated. Domain I: amino acids 1–191; domain II: 192–378; domain III: 379–458; vitamin D binding: 35–49; C5a chemotactic cofactor: 130–149; G-actin binding: 373–403. The domain and functional regions are drawn approximately to scale. The N-terminus refers to the start of a protein or polypeptide terminated by an amino acid with a free amine group (–NH₂). By convention, peptide sequences are written N-terminus to C-terminus [127]

Fig. 5

Vitamin D supplementation decision tree for use with athletes