Nonskeletal Effects of Vitamin D – Endocrine Society Statement
The Nonskeletal Effects of Vitamin D: An Endocrine Society Scientific Statement
Endocrine Reviews June 1, 2012 vol. 33 no. 3 456-492
Clifford J. Rosen, John S. Adams, Daniel D. Bikle, Dennis M. Black, Marie B. Demay, JoAnn E. Manson, M. Hassan Murad and Christopher S. Kovacs
Tufts University School of Medicine (C.J.R.), Boston, Massachusetts 02111; UCLA-Orthopaedic Hospital Department of Orthopedic Surgery (J.S.A.), University of California, Los Angeles, California 90095; University of California (D.D.B.), San Francisco, California 94121; Department of Epidemiology and Biostatistics (D.M.B.), University of California, San Francisco, California 94143; Endocrine Unit (M.B.D.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Harvard Medical School (J.E.M.), Brigham and Women's Hospital, Boston, Massachusetts 02215; College of Medicine (M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; and Memorial University of Newfoundland (C.S.K.), St. John's, Newfoundland and Labrador, Canada A1B 3V6
Address all correspondence and requests for reprints to: Clifford J. Rosen, M.D., Maine Medical Center Research Institute, 81 Research Drive, Scarborough, Maine 04074-7205. E-mail: crofen@gmail.com.
Significant controversy has emerged over the last decade concerning the effects of vitamin D on skeletal and nonskeletal tissues. The demonstration that the vitamin D receptor is expressed in virtually all cells of the body and the growing body of observational data supporting a relationship of serum 25-hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases have led to widespread utilization of vitamin D supplementation for the prevention and treatment of numerous disorders. In this paper, we review both the basic and clinical aspects of vitamin D in relation to nonskeletal organ systems. We begin by focusing on the molecular aspects of vitamin D, primarily by examining the structure and function of the vitamin D receptor. This is followed by a systematic review according to tissue type of the inherent biological plausibility, the strength of the observational data, and the levels of evidence that support or refute an association between vitamin D levels or supplementation and maternal/child health as well as various disease states. Although observational studies support a strong case for an association between vitamin D and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there remains a paucity of large-scale and long-term randomized clinical trials. Thus, at this time, more studies are needed to definitively conclude that vitamin D can offer preventive and therapeutic benefits across a wide range of physiological states and chronic nonskeletal disorders.
Outline
I. Introduction
II. Distribution, Structure, and Function of the Vitamin D Receptor
A. Background
B. VDR distribution
C. VDR structure
D. Role of coactivators and corepressors
E. Plasticity of the VDRE
F. Nongenomic actions of vitamin D
III. Vitamin D and the Skin
A. Introduction
B. Proliferation, differentiation, barrier function of skin
C. Coactivators and corepressors of vitamin D in skin
D. Hair follicle phenotype, 1,25-(OH)2D independence, molecular interactors, and targets
E. Translational studies and clinical trials of vitamin D and skin
F. Conclusions
IV. Vitamin D and Its Relationship to Obesity and Diabetes Mellitus
A. Introduction
B. Observational studies of the relationship of vitamin D to obesity and the metabolic syndrome
C. Randomized trials of vitamin D in obesity, type 2 diabetes mellitus
D. Conclusions
V. Vitamin D for the Prevention of Falls and Improvement in Quality of Life
A. Introduction
B. Observational studies of vitamin D and falls
C. Randomized trials of vitamin D on falls
D. Effects of vitamin D supplementation on pain and quality of life
E. Conclusions
VI. Vitamin D and Cancer
A. Introduction
B. Total cancer and cancer mortality: research findings
C. Vitamin D and the risk of site-specific cancers
D. Other site-specific cancers
E. Conclusions
VII. Vitamin D and Cardiovascular Disease
A. Introduction
B. Studies of hypertension and lipids
C. Studies of other CVD endpoints
VIII. Vitamin D and Immune Function
A. Introduction
B. Clinical observations and trials
C. Conclusions
IX. Vitamin D, the Placenta, and Maternal/Fetal Health
A. Introduction
B. Biological plausibility
C. Animal data
D. Observational and association studies
E. Randomized interventional trials
F. Conclusions
X. Summary and Future Direction
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