The Roles of Vitamin D in Skeletal Muscle: Form, Function, and Metabolism
Endocrine Reviews February 1, 2013 vol. 34 no. 1 33-83
Christian M. Girgis, Roderick J. Clifton-Bligh, Mark W. Hamrick, Michael F. Holick and Jenny E. Gunton
Garvan Institute of Medical Research (C.M.G., J.E.G.) and St. Vincent's Clinical School (J.E.G.), University of New South Wales, Sydney, New South Wales 2010, Australia; Faculty of Medicine (C.M.G., R.J.C.-B., J.E.G.), University of Sydney, Sydney, New South Wales 2052, Australia; The Kolling Institute of Medical Research (R.J.C.-B.) and Royal North Shore Hospital (R.J.C.-B.), Sydney, New South Wales 2065, Australia; Georgia Health Sciences University (M.W.H.), Augusta, Georgia 30912; Boston University Medical Center (M.F.H.), Boston, Massachusetts 02118; and Department of Endocrinology and Diabetes (J.E.G.), Westmead Hospital, Sydney, New South Wales 2145, Australia
Address requests for reprints to: Dr. Christian M. Girgis or Associate Professor Jenny E. Gunton, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales, Australia. E-mail: c.girgis at garvan.org.au or j.gunton at garvan.org.au.
Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of research and one that continues to extend the frontiers of knowledge of vitamin D's broad functional repertoire.
Sections of this impressive review
II. Background Physiology
A. The vitamin D pathway
B. Skeletal muscle physiology
C. Calcium and muscle contraction
D. Calcium and exercise-related glucose uptake
E. Calcium and insulin-stimulated glucose uptake
III. Vitamin D and Muscle: Cell Models
A. VDR in muscle
B. Calcium homeostasis
C. Phosphate homeostasis
D. Proliferation and differentiation
E. Muscle contractile proteins
F. Phospholipid composition
G. Bone-muscle cross talk and vitamin D
H. Cell models and molecular pathways for insulin signaling and diabetes
IV. Vitamin D and Muscle: Studies in Animal Models
A. VDRKO mice
B. Other animal models
C. Animal studies on insulin sensitivity and diabetes
D. Summary: vitamin D and muscle function in animal studies
V. VDR Polymorphisms and Muscle Function
A. FokI polymorphisms
B. BsmI polymorphisms
C. VDR polymorphisms and insulin resistance/type 2 diabetes
VI. Vitamin D and Muscle: Human Studies
B. Myalgia and vitamin D deficiency
D. Drug-related myopathy and vitamin D
E. Falls and vitamin D
F. Muscle strength and physical performance
G. Muscle morphology and electromyography (EMG)
H. Insulin sensitivity and glucose handling VII. Conclusions
TABLE 8. Conclusions and outstanding questions
- Vitamin D exerts rapid and genomic effects in primary muscle cells and cell lines.
These effects relate to intracellular calcium handling,differentiation and contractile protein composition.
- In vivo, it is not clear whether VDR is expressed in adult skeletal muscle.
- Whole-body VDRKO mice and vitamin D-deficient animals display significant defects in muscle function and development.
- In humans, single nucleotide polymorphisms in the gene encoding VDR have been associated with differences in muscle strength.
- Changes in muscle morphology in humans with severe vitamin D deficiency have been reported since the 1970's.
- Proximal myopathy and muscle pain in subjects with severe vitamin D deficiency resolve following vitamin D supplementation.
- Associations between vitamin D deficiency, muscle weakness and falls are confounded by factors including frailty and lower exposure to sunlight.
Clinical parameters of muscle function are not standardized making data aggregation difficult.
- Randomized data suggest that vitamin D supplementation may reduce falls in older individuals but not all studies support this conclusion.
- The recommended dose of vitamin D supplementation and vitamin D targets remain hotly contested issues.
- Does the VDR exist in fully differentiated adult muscle and does it have physiological relevance at this site?
Or rather, as suggested by in vitro studies, is its role predominantly related to the function of immature muscle cells such as in myogenesis?
- Are changes in muscle function and morphology directly related to vitamin D or indirectly to its effects in calcium and mineral homeostasis?
- Does skeletal muscle possess the ability to 1-a-hydroxylate 25D at any stage in its development?
- As suggested by studies on phosphate handling in myocytes, does 25D itself exert direct effects on muscle?
- Is vitamin D deficiency or its reversal an important consideration among those with other muscle disorders such as congenital dystrophies and acquired immune-related myositis?
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See also VitaminDWiki
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- Skeletal muscles helped by vitamin D – Review Feb 2014
- Muscle improved by increasing vitamin D if previously less than 24 ng – June 2013
- Athletes need at least 40 ng of vitamin D – literature review Oct 2012
- MRI of elderly skeletal muscle lacking vitamin D – April 2014
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- Overview Sports and vitamin D which had the following summary of benefits as of Oct 2012
- Faster reaction time
- Far fewer colds/flues during the winter
- Less sore/tired after a workout
- Fewer micro-cracks and broken bones
- Bones which do break heal much more quickly
- Increased VO2 and exercise endurance Feb 2011
- Indoor athletes especially need vitamin D
- Professional indoor athletes are starting to supplement with vitamin D or use vitamin D beds
- Olympic athletes have used UV/vitamin D since the 1930's
- The biggest gain from the use of vitamin D is by those who exercise less than 2 hours per day.
Short url = http://is.gd/dmuscle