TY - JOUR
T1 - The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial
AU - Waterhouse, Mary
AU - Pham, Hai
AU - Rahman, Sabbir T.
AU - Baxter, Catherine
AU - Duarte Romero, Briony
AU - Armstrong, Bruce K.
AU - Ebeling, Peter R.
AU - English, Dallas R.
AU - Hartel, Gunter
AU - van der Pols, Jolieke C.
AU - Venn, Alison J.
AU - Webb, Penelope M.
AU - Whiteman, David C.
AU - McLeod, Donald S.A.
AU - Neale, Rachel E.
N1 - Funding Information:
M.W., H.P., S.T.R., C.B., B.D.R., B.K.A., D.R.E., G.H., J.C.v.d.P., A.J.V., D.C.W., and D.S.A.M. have nothing to disclose. P.R.E. received grants and other from Amgen, other from Sanofi, grants and other from Novartis, grants from Eli-Lilly, and grants from Alexion. P.M.W. received funding from Astra Zeneca for an unrelated study of ovarian cancer. R.E.N. received funding from Viatris for an unrelated study of pancreatic cancer.
Funding Information:
The D-Health Trial is funded by National Health and Medical Research Council (NHMRC) project grants (APP1046681; APP1120682). The vitamin D assays were performed at the University of Western Australia, supported by infrastructure funding from the Western Australian State Government in partnership with the Australian Federal Government, through Bioplatforms Australia and the National Collaborative Research Infrastructure Strategy (NCRIS). M.W., H.P., S.T.R., C.B., B.D.R., B.K.A., D.R.E., G.H., J.C.v.d.P., and A.J.V. received no funding. P.R.E. received NHMRC fellowship (GNT1197958). P.M.W. received NHMRC fellowship (GNT1173346). D.C.W. received NHMRC fellowship (GNT1156072). D.S.A.M. was supported by a Metro North Clinician Research Fellowship and the Queensland Advancing Clinical Research Fellowship. R.E.N. was supported by an NHMRC fellowship (GNT1060183).
Publisher Copyright:
Copyright 2023, Mary Ann Liebert, Inc., publishers.
PY - 2023/11
Y1 - 2023/11
N2 - Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial (n = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.
AB - Background: Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism. Methods: We analyzed data from the D-Health Trial (n = 21,315), a randomized double-blind placebo-controlled trial of 60,000 international units per month of supplemental vitamin D3 among Australians aged 60 years and over. Hypothyroidism, a tertiary outcome of the D-Health Trial, was defined by treatment with levothyroxine, ascertained through linkage with the Australian Pharmaceutical Benefits Scheme. The outcome was time to first prescription of levothyroxine. We began follow-up at 12 months after randomization; people who had died or who had been dispensed levothyroxine during the first year were excluded. Flexible parametric survival models were used to assess the effect of vitamin D supplementation on hypothyroidism, overall and within strata defined by age, sex, body mass index, and predicted baseline vitamin D status. Results: We included 17,851 participants in the main analysis (vitamin D = 8939; placebo = 8912). During a median follow-up of 4.1 years (interquartile range 4.1-4.1), 293 participants developed hypothyroidism (vitamin D = 138 [1.5%]; placebo = 155 [1.7%]). Vitamin D supplementation did not significantly reduce the incidence of hypothyroidism (overall hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.71-1.12). There was some suggestion of an effect in females (overall HR 0.78; CI 0.58-1.06) but not in males (overall HR 1.06; CI 0.74-1.50; p interaction 0.20). Conclusions: Vitamin D supplementation did not reduce the incidence of hypothyroidism overall; however, the possible beneficial effect observed in females warrants further investigation. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000743763.
KW - hypothyroidism
KW - randomized controlled trial
KW - vitamin D supplementation
UR - http://www.scopus.com/inward/record.url?scp=85174607931&partnerID=8YFLogxK
U2 - 10.1089/thy.2023.0317
DO - 10.1089/thy.2023.0317
M3 - Article
C2 - 37698908
AN - SCOPUS:85174607931
SN - 1050-7256
VL - 33
SP - 1302
EP - 1310
JO - Thyroid
JF - Thyroid
IS - 11
ER -
