Article - Association between serum vitamin D level and Graves' disease: a systematic review and meta-analysis.

Plain Language Summary

Graves’ disease (GD) is an autoimmune disorder that leads to hyperthyroidism and is characterised by the overproduction of thyroid hormones. Recent studies have suggested a potential link between vitamin D (VD) levels and autoimmune thyroid diseases, including GD. The primary aim of this study was to systematically review and analyse the association between serum VD levels and GD, assessing whether low VD levels are linked to the disease’s prevalence or severity. This research is a systematic review and meta-analysis, incorporating data from multiple observational studies that examined the relationship between serum VD levels and GD. Results showed that: - patients with GD had significantly lower serum VD levels compared to healthy controls. - a higher prevalence of VD deficiency was observed in patients with GD. - lower VD levels were associated with increased disease activity scores in GD patients. Authors concluded that low VD levels may increase the risk of GD. Larger and more comprehensive clinical research is needed to determine if VD insufficiency contributes to the onset of GD and whether VD supplementation is a viable treatment strategy for GD.

Expert Review

Reviewer: Chloe Steele

13th Feb 2025

Conflict of interest

None

Take home message

Low vitamin D levels may be a risk factor for the development of GD.
However, causation needs to be determined before vitamin D can be used as a therapy for individuals with GD.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

Graves’ Disease (GD) is an autoimmune disorder that results in an increase in the production of thyroid hormones (TH) and subsequent hyperthyroidism.
If left untreated it can result in poor health outcomes and death.
However, treatment can result in hypothyroidism.
GD has been associated with low vitamin D levels. However, previous meta-analyses have used low quality papers and the association is uncertain.
This study aimed to use high-quality peer-reviewed articles to determine the relationship between GD and vitamin D.

Methods

This was a systematic review and meta-analysis of 12 cohort and case-control studies.
Studies had to include a GD group and a control group for comparison.
All studies that weren’t deemed high quality were excluded.
Studies were published between 1980 and 2020 and were mostly from China, with publications from India, USA, Sweden, Japan, Germany, and Belgium.

Results

The results showed that individuals with GD had low levels of vitamin D (SMD = − 0.66; 95% CI: −1.05, − 0.27; p = 0.001).

• There was high heterogeneity amongst the studies and this was attributed to different methods of measuring vitamin D levels, geographic location, and age.

Interestingly, individuals with GD from North America did not have lower vitamin D levels, whereas those from Europe (SMD = 0.69; 95% CI: −1.30, − 0.07) and Asia (SMD = 0.75; 95% CI: −1.27, − 0.23) did.

Conclusion

It was concluded that low serum vitamin D levels are a risk factor for GD.

Clinical practice applications

Practitioners may like to consider investigating vitamin D levels in individuals with GD.
Those with low levels may like to consider supplementation, safe sun exposure or increasing dietary intake through oily fish, eggs, and mushrooms. However it should be acknowledged that sun exposure is challenging during the winter months in the northern hemisphere and only low levels of vitamin D are found in foods. It is therefore likely that supplementation would be more effective.

Considerations for future research

Future studies should focus on the effects of vitamin D supplementation on individuals with GD.

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Abstract

OBJECTIVE

This meta-analysis aims to analyze the relationship between serum vitamin D (VD) levels and Graves' disease (GD).

METHODS

We conducted a search for publications on VD and GD in the English language. Our search encompassed databases such as PubMed, Embase, Web of Science, and the Cochrane Library, covering publications available through August 2023. A meta-analysis was performed using Cochrane RevMan 5.4 software. The standardized mean difference (SMD) and 95% confidence interval (CI) were used for outcome calculation. We used R software to test for publication bias.

RESULTS

Twelve studies were selected, comprising 937 (22.4%) cases with GD and 3254 (77.6%) controls. The overall meta-analysis revealed that patients with GD are significantly more likely to have low VD levels (SMD = - 0.66; 95% CI: -1.05, - 0.27; p = 0.001) than those in the control group. Egger's test results indicated no publication bias (p = 0.0791). These studies exhibited a high degree of heterogeneity (chi-square = 205.86, p < 0.00001; I = 95%). Subgroup analysis was conducted based on assay method, geographic location, and mean age of the case group to explore the heterogeneity sources. Assay methods and geographic locations were identified as potential heterogeneity sources. Based on the mean age, there were no statistically significant differences found in the subgroup analysis of the included studies.

CONCLUSION

There is promising evidence that low serum VD levels may increase the risk of GD. Further rigorous and long-term trials are needed to explore the role of VD in the onset and treatment of GD.