Genes may play a role in vitamin D deficiency
10 June 2010
Gene variants may indicate a risk of having low levels of vitamin D, suggests a new study.
01 September 2013
Daniel J. Owens and Graeme L. Close, Liverpool John Moores University, Research Institute for Sport and Exercise Science, Liverpool, United Kingdom
“The importance of sunlight for physical performance has been known for centuries. Indeed ancient Greek Olympians were encouraged to train under the sunrays presumably due to the benefits to physical health described by the Greek physician Antyllus. However, only in recent times and with the development of scientific principles has the data pointed our understanding of the beneficial effects of sunlight exposure for muscle health, and potentially athletic performance, to vitamin D. It is now apparent that its effects may be explained by the vitamin’s regulation of genomic and non-genomic cellular pathways inside skeletal muscle tissue (1). This field of research is however in its infancy; and given the complexity of cell signaling and control of gene expression, which vitamin D appears to mediate, there are many questions yet to be answered.
Epidemiological data indicates poor vitamin D status is widespread around the globe, even in sun-rich environments. The classification of vitamin D deficiency is a highly debated topic, with much disparity as to what serum 25-hydroxyvitamin D (or 25[OH]D) concentrations constitute a deficiency, what is ‘optimal’ and what is a safe concentration. If we consider the US Institute of Medicine’s guidelines for vitamin D status classification, deficiency is defined as concentrations below 30 nmol/L. However, such recommendations are considered by many to be too conservative with some authors suggesting that 100–250 nmol/L is the optimal level for human health (2). Observational studies indicate that vitamin D deficiency (below 30 nmol/L) and inadequacy (below 50 nmol/L) – as defined by the US Institute of Medicine – are prevalent in athletes (3–12). Furthermore, these observations appear to be irrespective of competition standard and geographic location. Such findings are likely attributable to a predominantly sun-shy lifestyle in developed countries, few foods containing vitamin D, severe cloud cover at northerly latitudes, sub-optimal solar zenith for cutaneous vitamin D synthesis during winter months and covering the majority of one’s skin with clothing.
There appear to be a number of ways in which vitamin D affects cellular processes that may potentially impact cellular physiology. It is generally accepted that these processes fall into two main categories: 1) genomic effects mediated by interaction of 25(OH)D with the vitamin D receptor (VDR) and 2) non-genomic effects mediated by numerous transmembrane signaling pathways initiated by 25(OH)D. Available evidence suggests that the impact that vitamin D may have on muscle fibers (myotubes) and subsequently muscle function, may be more dependent on rapid non-genomic mechanisms than alterations in gene expression mediated by the VDR (13) and indeed it is currently unknown whether the vitamin D receptor exists in fully differentiated muscles as recent investigations have failed to identify the receptor. One major mechanism mediated by 25(OH)D that may impact upon muscle function is its role in calcium homeostasis (14). As calcium is essential for interaction of actin and myosin, it is paramount that intracellular calcium concentra-tions remain within the physiological range for normal muscle contraction. A further mechanism by which vitamin D may mediate the function of muscle, has been provided by investigations demonstrating a role for 25(OH)D in phosphate uptake of skeletal muscle tissue (14). Like calcium, phosphate is a key substrate for muscle contraction involved in cross bridge cycling. There is also evidence to suggest that vitamin D may directly influence contractile components of skeletal muscle tissue.
Emerging data suggests that adequate vitamin D concentration is important for skeletal muscle regeneration following damage. In vitro experiments and animal studies have shown that expression of the VDR gene is increased significantly following injury in skeletal muscle tissue (15). In addition, 25(OH)D3 induced the synthesis of factors related to the generation of new muscle tissue (16). Moreover, recent data suggests that 25(OH)D seems to stimulate the proliferation and differentiation of muscle cells and the formation of new blood vessels (angiogenesis), a key process in tissue development and repair (17).
Taken together, the evidence described above suggests a firm link between vitamin D and the function and health of skeletal muscle tissue. However in order to fully establish this link, we must consider if such data translates into whole muscle/whole body physical performance. Such data is lacking in young healthy and particularly ‘athletic’ populations. There is however data from elderly populations that directly suggest that poor vitamin D status is associated with poorer physical performance and that this may be attributed to aberrant muscle function, muscular disease (myopathy) and in some cases muscle loss (atrophy) (18–22). Recent well-controlled and designed studies suggest vitamin D may have a role in moderating the age related decline in muscle function (23-28).
Oral supplementation with vitamin D3 is an effective method for elevating serum 25(OH)D concentrations responding in a dose dependent fashion (29). Furthermore, it should be noted that D3 is more effective than D2 in elevating and maintaining serum 25(OH)D concentrations (30) particularly during the winter months. Trials in young healthy and active cohorts reveal deficiency is reversible with oral supplementation (31). The data provided thus far demonstrate the positive effects of supplementing with high doses of vitamin D, but toxicity from vitamin D supplementation must also be considered when supplementing with vitamin D. The US Institute of Medicine has set the ‘no observed effects level’ (NOAEL) for vitamin D intake at 4,000 IU per day (32). However, in review of scientific literature it is apparent that no side effects have been reported at daily doses of 10,000 IU a day (33). It is clear that vitamin D deficiency is treatable with oral supplemen-tation as evidenced by the data provided. However, further work is warranted to establish the effect of varying vitamin D concentrations on muscle function, from a functional and molecular perspective.”
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10 June 2010
Gene variants may indicate a risk of having low levels of vitamin D, suggests a new study.
5 July 2010
Insufficient levels of vitamin D may increase the risk of metabolic syndrome by about 40% in seniors, suggests a new Dutch study.
20 April 2012
Regular supplementation with vitamin B12 may improve arterial function and reduce atherosclerosis risk for vegetarians, suggests a new Chinese study.