title: A dose-response study of vitamin D3 supplementation in healthy Chinese: a 5-arm randomized, placebo-controlled trial.
abstract: OBJECTIVE
  To determine the dose-response of vitamin D3 supplementation on serum 25-hydroxyvitamin D [25(OH)D] among Chinese adults.
  
  
  METHODS
  In this 5-arm, randomized, double-blinded controlled trial, 76 healthy participants were assigned to orally administrate 0, 400, 800, 1200 or 2000 IU/d of vitamin D3 for 16 weeks. Serum 25(OH)D, parathyroid hormone, calcium, biomarkers of liver and renal function were measured at multiple time points.
  
  
  RESULTS
  The mean (SD) serum 25(OH)D at baseline was 31.6 (8.7) nmol/L, and the dose-response relationship was curvilinear with a plateau around 6 weeks for all doses. At week 16, 25(OH)D was increased by 6.0 (6.5), 21.7 (15.8), 26.3 (12.6), 32.0 (12.8) and 36.3 (26.0) nmol/L for 0, 400, 800, 1200 and 2000 IU/d (all P ≤ 0.002), corresponding to approximately 19, 53, 67, 77 and 80 % of reversion of vitamin D deficiency, respectively. Daily intake of 800 IU vitamin D3 reached a targeted 25(OH)D ≥ 30 nmol/L in at least 97.5 % of Chinese, but not a targeted 25(OH)D ≥ 50 nmol/L even with 2000 IU/d. Change of 25(OH)D was inversely associated with change of PTH concentration (r = -0.39, P < 0.001) after controlling for age and sex. No between-group differences were observed in terms of the change in serum calcium, alanine transaminase, aspartate aminotransferase, gamma-glutamyltransferase and creatinine (P ≥ 0.22).
  
  
  CONCLUSIONS
  Supplementation with 400, 800, 1200 or 2000 IU/d vitamin D could improve the vitamin D deficiency with various degrees. Whether 2000 IU/d vitamin D3 would generate a better result without side effect requires more studies with larger samples in future.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Pang
authors.initials: P
authors.lastname: Yao
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Huadong Hospital, Fudan University, Shanghai, China.
authors.forename: Xiafei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Ye
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: He
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China.
authors.forename: Huaixing
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai, 200031, China. xlin@sibs.ac.cn.|State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China. xlin@sibs.ac.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044466:Asian People; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000097:blood; D003404:Creatinine / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D012959:Socioeconomic Factors; D014808:Vitamin D Deficiency / Q000097:blood; D055105:Waist Circumference; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Dose–response; Safety; Serum 25-hydroxyvitamin D; Vitamin D3 supplementation