Oral supplementation with 25(OH)D3 versus vitamin D3: Effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity

To test the effect of 25(OH)D3 (HyD) compared to vitamin D3 on serum 25‐hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ± 3.9 ng/mL (mean ± SD) and a mean age of 61.5 ± 7.2 years were randomized to either 20 µg of HyD or 20 µg (800 IU) of vitamin D3 per day in a double‐blind manner. We measured on 14 visits over 4 months, 25(OH)D serum levels, blood pressure, and seven markers of innate immunity (eotaxin, interleukin [IL]‐8, IL‐12, interferon gamma‐induced protein 10 kDa [IP‐10], monocyte chemotactic protein‐1 [MCP‐1], macrophage inflammatory protein beta [MIP‐1β], and “Regulated upon Activation, Normal T‐cell Expressed, and Secreted” [RANTES]). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit‐to‐stand) was assessed. All analyses were adjusted for baseline measurement, age, and body mass index. Mean 25(OH)D levels increased to 69.5 ng/mL in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/mL with a slow increase in the vitamin D3 group. Women on HyD compared with vitamin D3 had a 2.8‐fold increased odds of maintained or improved lower extremity function (odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.18–6.58), and a 5.7‐mmHg decrease in systolic blood pressure (p = 0.0002). Both types of vitamin D contributed to a decrease in five out of seven markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL‐12, MCP‐1, and MIP‐1 β. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 µg) of HyD per day resulted in a safe, immediate, and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure, and innate immune response compared with vitamin D3. © 2012 American Society for Bone and Mineral Research

[1]  C. Gordon,et al.  Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. , 2011, The Journal of clinical endocrinology and metabolism.

[2]  Daniel Keeton,et al.  Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. , 2011, American journal of hypertension.

[3]  C. Carlberg,et al.  Mechanism of 1α,25-dihydroxyvitamin D(3)-dependent repression of interleukin-12B. , 2011, Biochimica et biophysica acta.

[4]  T. Casale,et al.  The role of vitamin D in asthma. , 2010, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[5]  P. Lips,et al.  14th Vitamin D Workshop consensus on vitamin D nutritional guidelines , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[6]  H. Bischoff-Ferrari,et al.  Multi-step immunofluorescent analysis of vitamin D receptor loci and myosin heavy chain isoforms in human skeletal muscle , 2010, Journal of Molecular Histology.

[7]  J. M. Burton,et al.  A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis , 2010, Neurology.

[8]  R. Jorde,et al.  No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. , 2010, Cytokine.

[9]  S. Boonen,et al.  IOF position statement: vitamin D recommendations for older adults , 2010, Osteoporosis International.

[10]  H. DeLuca,et al.  Identification of a highly specific and versatile vitamin D receptor antibody. , 2010, Archives of biochemistry and biophysics.

[11]  D. Kamen,et al.  Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity , 2010, Journal of Molecular Medicine.

[12]  W. Willett,et al.  Benefit–risk assessment of vitamin D supplementation , 2010, Osteoporosis International.

[13]  J B Wong,et al.  Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials , 2009, BMJ : British Medical Journal.

[14]  D. Rao,et al.  Osteomalacia with bone marrow fibrosis due to severe vitamin D deficiency after a gastrointestinal bypass operation for severe obesity. , 2009, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[15]  J. Brehm,et al.  Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. , 2009, American journal of respiratory and critical care medicine.

[16]  G. Nijpels,et al.  25-Hydroxyvitamin D is not Associated with Carotid Intima-Media Thickness in Older Men and Women , 2009, Calcified Tissue International.

[17]  E John Orav,et al.  Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. , 2009, Archives of internal medicine.

[18]  H. Minne,et al.  Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals , 2009, Osteoporosis International.

[19]  A. Howie,et al.  Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation. , 2008, Kidney international.

[20]  O. Soldin,et al.  IMMULITE 2000 age and sex-specific reference intervals for alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and intact parathyroid hormone. , 2008, Clinical biochemistry.

[21]  W. Willett,et al.  Vitamin D and Health: Perspectives From Mice and Man , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  P. Vanhoutte,et al.  Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. , 2008, American journal of physiology. Heart and circulatory physiology.

[23]  Stefan Pilz,et al.  Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. , 2008, Archives of internal medicine.

[24]  R. Panettieri,et al.  Vitamin D and glucocorticoids differentially modulate chemokine expression in human airway smooth muscle cells , 2008, British journal of pharmacology.

[25]  E. Rimm,et al.  25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. , 2008, Archives of internal medicine.

[26]  R. Heaney,et al.  Pharmacokinetics of a single, large dose of cholecalciferol. , 2008, The American journal of clinical nutrition.

[27]  M. Visser,et al.  Vitamin D deficiency as a risk factor for osteoporotic fractures. , 2008, Bone.

[28]  E. Giovannucci Epidemiological Evidence for Vitamin D and Colorectal Cancer , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  Edward Giovannucci,et al.  Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension , 2007, Hypertension.

[30]  R. Simpson,et al.  Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse , 2007, The Journal of Steroid Biochemistry and Molecular Biology.

[31]  Jorge Yao,et al.  1 a , 25-dihydroxyvitamin D 3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis , 2006 .

[32]  J. Pease Asthma, allergy and chemokines. , 2006, Current drug targets.

[33]  F. Hu,et al.  Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. , 2004, The American journal of clinical nutrition.

[34]  Guilin Qiao,et al.  Vitamin D: a negative endocrine regulator of the renin–angiotensin system and blood pressure , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[35]  D. Felsenberg,et al.  Performance evaluation of automated assays for β-CrossLaps, N-MID-Osteocalcin and intact parathyroidhormone (BIOROSE Multicenter Study) , 2004, Clinical chemistry and laboratory medicine.

[36]  F. Gudat,et al.  Vitamin D Receptor Expression in Human Muscle Tissue Decreases With Age , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  S. Kato,et al.  Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. , 2003, Endocrinology.

[38]  R. Kumar,et al.  Vitamin D and its analogs as regulators of immune activation and antigen presentation. , 2003, Annual review of nutrition.

[39]  R. Lew,et al.  Effects of Vitamin D and Calcium Supplementation on Falls: A Randomized Controlled Trial , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[40]  遠藤 逸朗 Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors , 2003 .

[41]  Shu Q. Liu,et al.  1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system , 2002 .

[42]  Shu Q. Liu,et al.  1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. , 2002, The Journal of clinical investigation.

[43]  H. Minne,et al.  Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. , 2001, The Journal of clinical endocrinology and metabolism.

[44]  A. Arbelo,et al.  The effect of 25-dihydroxyvitamin D on the bone mineral metabolism of elderly women with hip fracture. , 2000, Rheumatology.

[45]  W. Ambrosius,et al.  Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. , 2000, The Journal of clinical endocrinology and metabolism.

[46]  Jennifer R. Harrington,et al.  The Role of MCP‐1 in Atherosclerosis , 2000, Stem cells.

[47]  Arya M. Sharma,et al.  Ultraviolet B and blood pressure , 1998, The Lancet.

[48]  R. Heaney,et al.  Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men , 1998, Osteoporosis International.

[49]  R. Behringer,et al.  Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein , 1997, Nature.

[50]  J. Rufilanchas,et al.  Calcitonin, Etidronate, and Calcidiol Treatment in Bone Loss after Cardiac Transplantation , 1997, Calcified Tissue International.

[51]  Z. Gaciong,et al.  Efficiency of preventive treatment of glucocorticoid-induced osteoporosis with 25-hydroxyvitamin D3 and calcium in kidney transplant patients. , 1996, Transplantation proceedings.

[52]  R. Francis,et al.  Calcium malabsorption in the elderly: the effect of treatment with oral 25‐hydroxyvitamin D3 , 1983, European journal of clinical investigation.

[53]  S. Teitelbaum,et al.  Altered mineral metabolism in glucocorticoid-induced osteopenia. Effect of 25-hydroxyvitamin D administration. , 1979, The Journal of clinical investigation.

[54]  B. Saltin,et al.  Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium. , 1979, Clinical science.

[55]  J. Haddad,et al.  COMPARISON OF ORAL 25-HYDROXYCHOLECALCIFEROL, VITAMIN D, AND ULTRAVIOLET LIGHT AS DETERMINANTS OF CIRCULATING 25-HYDROXYVITAMIN D , 1977, The Lancet.

[56]  G. Schott,et al.  MUSCLE WEAKNESS IN OSTEOMALACIA , 1976, The Lancet.

[57]  J. Haddad,et al.  Acute administration of 25-hydroxycholecalciferol in man. , 1976, The Journal of clinical endocrinology and metabolism.

[58]  T. Stamp Intestinal absorption of 25-hydroxycholecalciferol. , 1974, Lancet.