Nevin Manimala Statistics

The effect of vitamin D supplementation on hypothyroidism in the randomized controlled D-Health Trial

Thyroid. 2023 Sep 12. doi: 10.1089/thy.2023.0317. Online ahead of print.


BACKGROUND: Hypothyroidism is common, and in iodine-sufficient areas 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 via 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 (IQR 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; 95% CI 0.58-1.06) but not in males (overall HR 1.06; 95% 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.

PMID:37698908 | DOI:10.1089/thy.2023.0317

By Nevin Manimala

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