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Association Between Serum Zinc Levels and Recurrent Aphthous Stomatitis
TAKE-HOME MESSAGE
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This meta-analysis examined the potential association between serum zinc levels and recurrent aphthous stomatitis (RAS). A total of 19 studies contributed 1079 cases and 965 controls, finding that serum zinc levels were significantly lower in RAS cases than in controls. Subgroup analyses found this to be true for all included population groups, but especially so in the Chinese population, with trial sequential analysis confirming the reliability of these results. The authors suggested that evaluation of serum zinc levels should be considered in diagnosis, management, and prevention of RAS.
- While the etiopathogenesis of RAS is still unclear, nutritional deficiency (vitamins B12, B2, D, and folic acid) has been implicated as one possible causative factor. This meta-analysis highlights the potential implication of low serum zinc levels, suggesting that further controlled studies are needed to evaluate the preventive and/or therapeutic effect of zinc supplements on RAS.
– Tapan N. Koticha, BDS, MDS
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVES
The present meta-analysis sought to investigate the potential association between zinc levels and recurrent aphthous stomatitis (RAS).
METHODS
A comprehensive search of online databases (PubMed, Scopus, Web of Science, and China National Knowledge Infrastructure (CNKI)) was conducted to identify all English and Chinese studies published up to August 2020. All case-control studies that assessed plasma/serum zinc levels were eligible for inclusion. Data were analyzed using Comprehensive Meta-Analysis software version 2.2.046 (Biostat, Englewood, NJ, USA). Trial sequential analysis (TSA) was conducted with the trial sequential analysis program.
RESULTS
Nineteen case-control studies, involving 1079 RAS cases and 965 controls, were included in the meta-analysis. The pooled results of 19 studies showed that zinc level was significantly lower in RAS patients than in healthy controls (weighted difference in means = - 21.092, 95% CI - 26.695 to - 15.490, I2 = 95.375%, P < 0.001). Upon subgroup analysis by geographic distribution of the sample (Chinese vs. others), the association remained significant in each individual subgroup, although the association was more pronounced among Chinese populations. TSA indicated that the current studies surpassed the required information size, confirming that the differences were reliable.
CONCLUSION
The results suggest a significant association between low serum zinc levels and the occurrence of RAS. Although TSA confirmed a solid conclusion, conducting large-scale studies with the highest standards of quality is encouraged.
CLINICAL RELEVANCE
Determining zinc levels should be considered in diagnosis, management, and prevention of RAS.
Additional Info
Association Between Serum Zinc Levels and Recurrent Aphthous Stomatitis: A Meta-Analysis With Trial Sequential Analysis
Clin Oral Investig 2021 Feb 01;25(2)407-415, SA Al-Maweri, E Halboub, HM Al-Sharani, A Shamala, A Al-Kamel, M Al-Wesabi, A Albashari, A Al-Sharani, S AbdulrabFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Clinical Dentistry
This systematic review and meta-analysis resulted from a broad screen (English and Chinese literature) of case–control studies that evaluated serum zinc levels and recurrent aphthous stomatitis (RAS) of any type. A total of 19 studies encompassing 2044 participants (1079 RAS; 965 control) met inclusion/exclusion criteria. Nearly 70% (13/19) of these studies were based in China, representing approximately 79% of the participants (1614/2044). The remaining studies were from Turkey, India, Iran, and Poland. The study was, overall, well done with reasonable inclusion/exclusion criteria, quality of evidence assessed and reported for each study, and reasonable statistical handling, including assessment of heterogeneity within the population with a “random effects model” and applying trial sequential analysis (which establishes a minimum threshold for a reasonable population size to be included in the meta-analysis, similar to a sample size calculation/power analysis for a randomized controlled trial). As different methods for serum zinc concentration [Zn] were used in individual studies, the mean differences from each study were used for downstream statistical comparison as opposed to the raw values. The weighted difference in mean Zn was approximately 21 mcg/dL (±5.6 with 95% CI), being lower in RAS patients compared with controls. Heterogeneity was high: 95.375%. The authors suggested a significant association between decreased Zn and RAS.
Relevant facts to aid interpretation of these findings are:
From my perspective, measuring serum zinc in patients has very limited value in the context of RAS diagnosis or management. The forest plot in Figure 2 of this study is compelling, demonstrating that serum zinc levels were consistently lower in the RAS population. However, causality cannot be established, particularly as factors thought to promote RAS (inflammation, stress) should also directly or indirectly lower serum zinc levels. Most importantly, normal serum zinc usually has a range of approximately 50 mcg/dL, and this study does not allow for calculation of any positive predictive value. With that said, zinc supplementation is safe and there is generally no harm in advising patients to consider taking a multivitamin. RAS has been associated with other vitamin and nutrient deficiencies as well, and clearly discussing this with patients could maximize any placebo effect.