{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:45:48Z","timestamp":1761677148040,"version":"3.40.5"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Education, Malaysia","doi-asserted-by":"crossref","award":["FRGS\/1\/2014\/SKK10\/IMU\/03\/1"],"award-info":[{"award-number":["FRGS\/1\/2014\/SKK10\/IMU\/03\/1"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>While vitamin D inadequacy occurs worldwide, there is a lack of consensus internationally on the optimum plasma levels of 25(OH)D to maximally suppress the level of parathyroid hormone toward reducing bone loss. This study aimed to investigate the response of intact parathyroid hormone (iPTH) to vitamin D3 supplementation among Malaysian women of reproductive age in a randomised double-blind placebo-control trial [NMRR-15-479-25680]. A total of 106 women who fulfilled the study inclusion criteria were randomly assigned to receive daily one of these three supplement doses (i) 600 IU vitamin D3 + 500 mg calcium; (ii) 1200 IU vitamin D3 + 500 mg calcium; or (iii) 4000 IU vitamin D3 + 500 mg calcium. The placebo group received daily 500 mg calcium. The outcome examined was change in plasma iPTH concentration in response to daily vitamin D3 supplementation for 16 weeks. Fasting blood sample was obtained at baseline and post-supplementation. A total of 78 subjects (73.6%) completed the intervention. None of the supplementation groups brought about any detectable suppression of iPTH concentration post-supplementation. Vitamin D3 supplementation resulted in overall increase in plasma 25(OH)D levels, but only the 4000 IU\/day group showed a significant dose effect post-supplementation (mean 49.7 \u00b1 26.5 nmol\/L) compared to placebo (29.3 \u00b1 13.3 nmol\/L). The lack of iPTH suppression is attributed to high prevalence of vitamin D insufficiency at baseline and the supplementation regimen was inadequate to raise the 25(OH)D level to cause PTH suppression. Inadequate calcium intake of the participants was also a likely contributing factor to the result. As prolonged vitamin D insufficiency and hypocalcaemia could lead to a compensatory rise in PTH resulting in accelerated bone loss, as well as posing increasing risks of non-skeletal morbidities, further clinical trials with an adequately powered sample size should be undertaken over an appropriate study duration to verify the results obtained in this study.<\/jats:p>","DOI":"10.1371\/journal.pone.0276506","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T18:45:30Z","timestamp":1668105930000},"page":"e0276506","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Plasma parathyroid hormone response to vitamin D3 supplementation among women of reproductive age: A randomized double-blind placebo-control trial"],"prefix":"10.1371","volume":"17","author":[{"given":"Megan Chong Hueh","family":"Zan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa Leong En","family":"Ying","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-1501","authenticated-orcid":true,"given":"Loke Seng","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khor Geok","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"pone.0276506.ref001","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jsbmb.2012.11.018","article-title":"Nutritional rickets around the world","volume":"136","author":"A. Prentice","year":"2013","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"7","key":"pone.0276506.ref002","doi-asserted-by":"crossref","first-page":"e0180512","DOI":"10.1371\/journal.pone.0180512","article-title":"Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data","volume":"12","author":"L Rejnmark","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"pone.0276506.ref003","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/nutrit\/nuz037","article-title":"Effect of vitamin D supplementation on serum lipid profiles: a systematic review and meta-analysis","volume":"77","author":"DT Dibaba","year":"2019","journal-title":"Nutr Rev."},{"issue":"16","key":"pone.0276506.ref004","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1001\/jama.2020.2642","article-title":"Health Outcomes With Vitamin D Supplementation","volume":"323","author":"WB Grant","year":"2020","journal-title":"JAMA"},{"key":"pone.0276506.ref005","article-title":"Vitamin D supplementation after the menopause","author":"FR P\u00e9rez-L\u00f3pez","year":"2020","journal-title":"Therapeutic Advances in Endocrinology and Metabolism"},{"issue":"1","key":"pone.0276506.ref006","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/ajcn\/65.1.67","article-title":"Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women","volume":"65","author":"B Dawson-Hughes","year":"1997","journal-title":"Am J Clin Nutr"},{"issue":"1","key":"pone.0276506.ref007","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/ajcn\/84.1.18","article-title":"Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes","volume":"84","author":"HA Bischoff-Ferrari","year":"2006","journal-title":"Am J Clin Nutr"},{"issue":"1","key":"pone.0276506.ref008","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/nyas.13968","article-title":"Global prevalence and disease burden of vitamin D deficiency: a roadmap for action in low- and middle-income countries","volume":"1430","author":"DE Roth","year":"2018","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"pone.0276506.ref009","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3945\/jn.109.116681","article-title":"Three-phase model harmonizes estimates of the maximal suppression of parathyroid hormone by 25-hydroxyvitamin D in persons 65 years of age and older","volume":"140","author":"RA Durazo-Arvizu","year":"2010","journal-title":"J Nutr"},{"issue":"3","key":"pone.0276506.ref010","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1093\/ajcn\/84.3.602","article-title":"Optimal vitamin D status and serum parathyroid hormone concentrations in African American women","volume":"84","author":"JF Aloia","year":"2006","journal-title":"The American Journal of Clinical Nutrition"},{"issue":"3","key":"pone.0276506.ref011","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1210\/jcem.86.3.7327","article-title":"A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial","volume":"86","author":"P Lips","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"issue":"13","key":"pone.0276506.ref012","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1111\/jcmm.15330","article-title":"Seasonal variation and correlation analysis of vitamin D and parathyroid hormone in Hangzhou, Southeast China","volume":"24","author":"M Shen","year":"2020","journal-title":"J Cell Mol Med"},{"issue":"1","key":"pone.0276506.ref013","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00198-015-3219-6","article-title":"Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults","volume":"27","author":"JM Olmos","year":"2016","journal-title":"Osteoporos Int"},{"issue":"6","key":"pone.0276506.ref014","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1017\/S0007114507844382","article-title":"Very high rates of vitamin D insufficiency in women of child-bearing age living in Beijing and Hong Kong","volume":"99","author":"J Woo","year":"2008","journal-title":"Br J Nutr"},{"issue":"1","key":"pone.0276506.ref015","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00198-010-1207-4","article-title":"Vitamin D status and parathyroid hormone in a urban population in Vietnam","volume":"22","author":"LT Ho-Pham","year":"2011","journal-title":"Osteoporos Int."},{"issue":"1","key":"pone.0276506.ref016","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4161\/derm.24054","article-title":"Vitamin D status and sun exposure in southeast Asia","volume":"5","author":"H Nimitphong","year":"2013","journal-title":"Dermatoendocrinol"},{"issue":"8","key":"pone.0276506.ref017","doi-asserted-by":"crossref","first-page":"e585","DOI":"10.1097\/MD.0000000000000585","article-title":"The high prevalence of hypovitaminosis D in China: a multicenter vitamin D status survey","volume":"94","author":"S Yu","year":"2015","journal-title":"Medicine (Baltimore)"},{"volume-title":"A Report of The Technical Working Group on Nutritional Guidelines","year":"2017","author":"National Coordinating Committee on Food and Nutrition (NCCFN)","key":"pone.0276506.ref018"},{"volume-title":"Dietary reference intakes for calcium and vitamin D.","year":"2011","author":"Institute of Medicine","key":"pone.0276506.ref019"},{"issue":"3","key":"pone.0276506.ref020","first-page":"388","article-title":"Diet, nutritional knowledge and health status of urban middle-aged Malaysian women","volume":"15","author":"LW Pon","year":"2006","journal-title":"Asia Pac J Clin Nutr"},{"issue":"3","key":"pone.0276506.ref021","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/sj.ejcn.1602696","article-title":"Vitamin D status and its association with parathyroid hormone concentrations in women of child-bearing age living in Jakarta and Kuala Lumpur","volume":"62","author":"TJ Green","year":"2008","journal-title":"Eur J Clin Nutr"},{"issue":"2","key":"pone.0276506.ref022","first-page":"191","article-title":"Calcium and Vitamin D status of Kelantanese Malay women from low income family: A population-based study","volume":"2","author":"M Hawa","year":"2013","journal-title":"Journal of Aging Research & Clinical Practice"},{"issue":"2","key":"pone.0276506.ref023","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1530\/EC-18-0432","article-title":"Vitamin D testing and treatment: a narrative review of current evidence","volume":"8","author":"S Pilz","year":"2019","journal-title":"Endocr Connect."},{"volume-title":"Report of a WHO Consultation on Obesity","year":"1998","author":"World Health Organization","key":"pone.0276506.ref024"},{"volume-title":"Nutrient composition of Malaysian foods","year":"1997","author":"ES Tee","key":"pone.0276506.ref025"},{"volume-title":"Dietary Guidelines 2003 for Adult Singaporeans (18\u201365 Years)","year":"2003","author":"Health Promotion Board","key":"pone.0276506.ref026"},{"key":"pone.0276506.ref027","first-page":"179","article-title":"Development and Validation of a Food Frequency Questionnaire for Vitamin D intake among Urban Pregnant Women in Malaysia","volume":"21","author":"MI Zaleha","year":"2015","journal-title":"Malaysian Journal of Nutrition"},{"issue":"3","key":"pone.0276506.ref028","first-page":"391","article-title":"Effects of sun exposure on 25(OH) vitamin D concentration in urban and rural women in Malaysia","volume":"22","author":"M Nurbazlin","year":"2013","journal-title":"Asia Pac J Clin Nutr"},{"volume-title":"Dietary Reference Intakes for Calcium and Vitamin D.","year":"2010","author":"Institute of Medicine","key":"pone.0276506.ref029"},{"issue":"3","key":"pone.0276506.ref030","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4103\/2229-3485.184823","article-title":"Common pitfalls in statistical analysis: Intention-to-treat versus per-protocol analysis","volume":"7","author":"P Ranganathan","year":"2016","journal-title":"Perspect Clin Res"},{"key":"pone.0276506.ref031","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4103\/2229-3485.83221","article-title":"Intention-to-treat concept: A review","volume":"2","author":"SK Gupta","year":"2011","journal-title":"Perspect Clin Res"},{"issue":"6","key":"pone.0276506.ref032","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.5811\/westjem.2017.8.35985","article-title":"Understanding the Intention-to-treat Principle in Randomized Controlled Trials","volume":"18","author":"CE McCoy","year":"2017","journal-title":"West J Emerg Med."},{"issue":"13","key":"pone.0276506.ref033","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1111\/1471-0528.15199","article-title":"Randomised controlled trials\u2014the gold standard for effectiveness research: Study design: randomised controlled trials","volume":"125","author":"E Hariton","year":"2018","journal-title":"BJOG."},{"issue":"5","key":"pone.0276506.ref034","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1007\/s00198-015-3475-5","article-title":"Establishment of a normal reference value of parathyroid hormone in a large healthy Chinese population and evaluation of its relation to bone turnover and bone mineral density","volume":"27","author":"M Li","year":"2016","journal-title":"Osteoporos Int"},{"issue":"12","key":"pone.0276506.ref035","doi-asserted-by":"crossref","first-page":"e10417","DOI":"10.1002\/jbm4.10417","article-title":"Controversies in Vitamin D: A Statement From the Third International Conference","volume":"4","author":"A Giustina","year":"2020","journal-title":"JBMR Plus10"},{"issue":"5","key":"pone.0276506.ref036","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1093\/advances\/nmab051","article-title":"Vitamin D: Nutrition Information Brief","volume":"12","author":"SJ Whiting","year":"2021","journal-title":"Adv Nutr"},{"volume-title":"Dietary Reference Intakes for Calcium and Vitamin D","year":"2011","author":"Institute of Medicine (US)","key":"pone.0276506.ref037"},{"issue":"8","key":"pone.0276506.ref038","first-page":"466","article-title":"Comparative analysis of nutritional guidelines for vitamin D","volume":"13","author":"R. Bouillon","year":"2017","journal-title":"Nat Rev Endocrinol.Epub 2017 Apr 7"},{"key":"pone.0276506.ref039","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1186\/1471-2458-11-735","article-title":"High prevalence of vitamin D insufficiency and its association with obesity and metabolic syndrome among Malay adults in Kuala Lumpur, Malaysia","volume":"11","author":"FM Moy","year":"2011","journal-title":"BMC Public Health"},{"key":"pone.0276506.ref040","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12889-016-2924-1","article-title":"Vitamin D level and its association with adiposity among multi-ethnic adults in Kuala Lumpur, Malaysia: a cross sectional study","volume":"16","author":"IS Shafinaz","year":"2016","journal-title":"BMC Public Health"},{"issue":"2","key":"pone.0276506.ref041","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ecl.2010.02.008","article-title":"Low vitamin D status: definition, prevalence, consequences, and correction","volume":"39","author":"N Binkley","year":"2010","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"10","key":"pone.0276506.ref042","doi-asserted-by":"crossref","first-page":"e110476","DOI":"10.1371\/journal.pone.0110476","article-title":"Effect of Vitamin D Supplementation on Cardiometabolic Risks and Health-Related Quality of Life among Urban Premenopausal Women in a Tropical Country\u2013A Randomized Controlled Trial","volume":"9","author":"M Ramly","year":"2014","journal-title":"PLoS ONE"},{"issue":"13","key":"pone.0276506.ref043","first-page":"1555","article-title":"Vitamin D Status and Correlation with Glucose and Lipid Metabolism in Gansu Province, China","volume":"7","author":"K Yang","year":"2020","journal-title":"Diabetes MetabSyndrObes"},{"issue":"3","key":"pone.0276506.ref044","doi-asserted-by":"crossref","first-page":"103","DOI":"10.33176\/AACB-20-00006","article-title":"Vitamin D Metabolism and Guidelines for Vitamin D Supplementation","volume":"41","author":"I. Ramasamy","year":"2020","journal-title":"Clin Biochem Rev"},{"issue":"6","key":"pone.0276506.ref045","doi-asserted-by":"crossref","first-page":"e0129017","DOI":"10.1371\/journal.pone.0129017","article-title":"Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes\u2014A Double-Blind, Randomized Controlled Trial","volume":"10","author":"TP Yeow","year":"2015","journal-title":"PLoS One"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T16:20:37Z","timestamp":1701361237000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276506"}},"subtitle":[],"editor":[{"given":"Maret G.","family":"Traber","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,11,10]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0276506","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,11,10]]}}}