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Association between serum zinc levels and recurrent aphthous stomatitis: a meta-analysis with trial sequential analysis

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Abstract

Objectives

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.

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References

  1. Abdullah MJ (2013) Prevalence of recurrent aphthous ulceration experience in patients attending Piramird dental speciality in Sulaimani City. J Clin Exp Dent 5:e89–e94. https://doi.org/10.4317/jced.51042

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jurge S, Kuffer R, Scully C, Porter SR (2006) Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis 12(1):1–21. https://doi.org/10.1111/j.1601-0825.2005.01143.x

    Article  PubMed  Google Scholar 

  3. Preeti L, Magesh K, Rajkumar K, Karthik R (2011) Recurrent aphthous stomatitis. J Oral Maxillofac Pathol 15(3):252–256. https://doi.org/10.4103/0973-029X.86669

    Article  PubMed  PubMed Central  Google Scholar 

  4. Saikaly SK, Saikaly TS, Saikaly LE (2018) Recurrent aphthous ulceration: a review of potential causes and novel treatments. J Dermatol Treat 29:542–552. https://doi.org/10.1080/09546634.2017.1422079

    Article  Google Scholar 

  5. Tarakji B, Gazal G, Al-Maweri SA, Azzeghaiby SN, Alaizari N (2015) Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners. J Int Oral Health 7(5):74–80

    PubMed  PubMed Central  Google Scholar 

  6. Al-Maweri SA, Halboub E, Ashraf S, Alqutaibi AY, Qaid NM, Yahya K, Alhajj MN (2020) Single application of topical doxycycline in management of recurrent aphthous stomatitis: a systematic review and meta-analysis of the available evidence. BMC Oral Health 20(1):231. https://doi.org/10.1186/s12903-020-01220-5

    Article  PubMed  PubMed Central  Google Scholar 

  7. Aggour RL, Mahmoud SH, Abdelwhab A (2020) Evaluation of the effect of probiotic lozenges in the treatment of recurrent aphthous stomatitis: a randomized, controlled clinical trial. Clin Oral Investig. https://doi.org/10.1007/s00784-020-03527-7

  8. Ruan HH, Li GY, Duan N, Jiang HL, Fu YF, Song YF, Zhou Q, Wang X, Wang WM (2018) Frequencies of abnormal humoral and cellular immune component levels in peripheral blood of patients with recurrent aphthous ulceration. J Dent Sci 13:124–130. https://doi.org/10.1016/j.jds.2017.09.003

    Article  PubMed  Google Scholar 

  9. Al-Maweri SA, Halboub E, Al-Sufyani G, Alqutaibi AY, Shamala A, Alsalhani A (2019) Is vitamin D deficiency a risk factor for recurrent aphthous stomatitis? A systematic review and meta-analysis. Oral Dis 26:1116–1123. https://doi.org/10.1111/odi.13189

    Article  Google Scholar 

  10. Bao ZX, Shi J, Yang XW, Liu LX (2018) Hematinic de fi ciencies in patients with recurrent aphthous stomatitis: variations by gender and age. Med Oral Patol Oral Cir Bucal 23(2):e161–e167. https://doi.org/10.4317/medoral.21885

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mohammad R, Halboub E, Mashlah A, Abou-Hamed H (2013) Levels of salivary IgA in patients with minor recurrent aphthous stomatitis: a matched case-control study. Clin Oral Investig 17(3):975–980. https://doi.org/10.1007/s00784-012-0785-2

    Article  PubMed  Google Scholar 

  12. Bao ZX, Yang XW, Shi J, Liu LX (2016) Serum zinc levels in 368 patients with oral mucosal diseases: a preliminary study. Med Oral Patol Oral Cir Bucal 21(3):e335–e340. https://doi.org/10.4317/medoral.21079

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ozler GS (2014) Zinc deficiency in patients with recurrent aphthous stomatitis: a pilot study. J Laryngol Otol 128(6):531–533. https://doi.org/10.1017/s0022215114001078

    Article  PubMed  Google Scholar 

  14. Ozturk P, Belge Kurutas E, Ataseven A (2013) Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis. J Trace elem Med Biol: Organ Soc Miner Trace Elem (GMS) 27(4):312–316. https://doi.org/10.1016/j.jtemb.2013.04.002

    Article  Google Scholar 

  15. Hassan A, Sada KK, Ketheeswaran S, Dubey AK, Bhat MS (2020) Role of zinc in mucosal health and disease: a review of physiological, biochemical, and molecular processes. Cureus 12(5):e8197. https://doi.org/10.7759/cureus.8197

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gray NA, Dhana A, Stein DJ, Khumalo NP (2019) Zinc and atopic dermatitis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol: JEADV 33(6):1042–1050. https://doi.org/10.1111/jdv.15524

    Article  PubMed  Google Scholar 

  17. Huo J, Liu T, Huan Y, Li F, Wang R (2020) Serum level of antioxidant vitamins and minerals in patients with vitiligo, a systematic review and meta-analysis. J Trace elem Med Biol: Organ Soc Miner Trace Elem (GMS) 62:126570. https://doi.org/10.1016/j.jtemb.2020.126570

    Article  Google Scholar 

  18. Sanna A, Firinu D, Zavattari P, Valera P (2018) Zinc status and autoimmunity: a systematic review and meta-analysis. Nutrients 10(1). https://doi.org/10.3390/nu10010068

  19. Arora PN, Dhillon KS, Rajan SR, Sayal SK, Das AL (2002) Serum zinc levels in cutaneous disorders. Med J Armed Forces India 58(4):304–306. https://doi.org/10.1016/s0377-1237(02)80083-1

    Article  PubMed  Google Scholar 

  20. Khademi H, Shaikhiany J (2008) Comparison of serum zinc levels in recurrent apthous stomatitis patients and normal individuals. Dent Res J 2(2):1–5

    Google Scholar 

  21. Ślebioda Z, Krawiecka E, Szponar E, Dorocka-Bobkowska B (2017) Evaluation of serum zinc levels in patients with recurrent aphthous stomatitis (RAS). BMC Oral Health 17(1):158. https://doi.org/10.1186/s12903-017-0450-x

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tamer F, Avci E (2019) Decreased serum ferritin and vitamin D levels in patients with recurrent aphthous stomatitis. Our Dermatol Online 10:229–233

    Article  Google Scholar 

  23. Tong SQ, Wang X, Zhang B (2018) Study on the relationship between the trace elements, folic acid, vitamin B12 and recurrent oral ulcer. Lab Med Clin Med 15(12):3

    Google Scholar 

  24. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269, w264. https://doi.org/10.7326/0003-4819-151-4-200908180-00135

    Article  PubMed  Google Scholar 

  25. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  26. Wetterslev J, Jakobsen JC, Gluud C (2017) Trial sequential analysis in systematic reviews with meta-analysis. BMC Med Res Methodol 17(1):39. https://doi.org/10.1186/s12874-017-0315-7

    Article  PubMed  PubMed Central  Google Scholar 

  27. Brok J, Thorlund K, Wetterslev J, Gluud C (2009) Apparently conclusive meta-analyses may be inconclusive--Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol 38(1):287–298. https://doi.org/10.1093/ije/dyn188

    Article  PubMed  Google Scholar 

  28. Li G, Ji X, Shi A (2005) Detection and analysis of zinc and T lymphocyte subsets in patients with RAU. Mod Med Health 21(17):2

    Google Scholar 

  29. Cai HX (1995) Discussion on the relationship between recurrent oral ulcers and trace element zinc. Guangdong J Dent Prev Treat 3(02):2

    Google Scholar 

  30. Li JW, Rao X (2016) Study on the relationship between trace elements, immune indicators and recurrent oral ulcers. J Hainan Med Coll 22(7):3

    Google Scholar 

  31. Li WS, Zhu J, Hongfeng G (2010) Lymphocyte transformation rate and serum iron and zinc levels in recurrent aphtha. Heilongjiang Med Sci 33(3):2

    Google Scholar 

  32. Liu WQ, Bai Q, Wang K (1995) Discussion on the relationship between recurrent oral ulcers and serum zinc. Res Trace Elem Health 12(04):1

    Google Scholar 

  33. Liu X, Cheng Y, Deng M, Han Z, Yang G, Tianzhen D (2010) Analysis of hemorrheology and trace elements contents in patients with oral recurrent aphthae ulcer. J Chongqing Med Univ 35(10):3

    Google Scholar 

  34. Ming SJ, Zhang J, Yin J, Song J, Li M (1997) Observation of the relation between serum Zn, body fluid and cell immunity and recurrent oral ulcer. Guangdong Trace Elem Sci 8(4):12–14

    Google Scholar 

  35. Song WG, Qin D, Yang Z, Yang C, Zhangbin B, Wangwei Z, Qu X (2002) Study on serum trace element content and cellular immune function in patients with recurrent oral ulcer. Res Trace Elem Health 19(03):3

    Google Scholar 

  36. Song YL, Feng Y, Ren H, Li X, Du W, Li E (2016) Study on the correlation between serum zinc, selenium, iron content and recurrent oral ulcers. Chin J Clin 44(08):3

    Google Scholar 

  37. Sun SZ, Ling D, Wei F (1994) Detection and analysis of serum trace elements in patients with recurrent aphtha. Stomatology 4(003):171–172

    Google Scholar 

  38. Zhang ZC, Wang H, Chen G, Wu Z, Fang H (2018) A clinical study of the serum content of copper iron and zinc iron in patients with minor recurrent aphthous ulcer. China Med Her 15(6):114–117

    Google Scholar 

  39. Al-Maweri SA, Alaizari N, Alharbi AA, Alotaibi SA, AlQuhal A, Almutairi BF, Alhuthaly S, Almutairi AM (2020) Efficacy of curcumin for recurrent aphthous stomatitis: a systematic review. J Dermatol Treat:1–6. https://doi.org/10.1080/09546634.2020.1819529

  40. Yıldırımyan N, Özalp Ö, Şatır S, Altay MA, Sindel A (2019) Recurrent aphthous stomatitis as a result of zinc deficiency. Oral Health Prev Dentist 17(5):465–468. https://doi.org/10.3290/j.ohpd.a42736

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Oral Medicine and Diagnostic Sciences, AlFarabi Colleges of Dentistry and Nursing, Riyadh, Saudi Arabia

    Sadeq A. Al-Maweri

  2. Department of Oral Medicine, Oral Pathology and Oral Radiology, Faculty of Dentistry, Sana’a University, Sana’a, Yemen

    Sadeq A. Al-Maweri & Esam Halboub

  3. Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jizan, Saudi Arabia

    Esam Halboub

  4. Department of Oral and Maxillofacial Surgery, College of Dentistry, Ibb University, Ibb, Yemen

    Hesham Mohammed Al-Sharani

  5. Department of Maxillofacial Surgery, School of Stomatology, Harbin Medical University, Harbin, China

    Hesham Mohammed Al-Sharani

  6. Department of Preventive and Biomedical Science, Faculty of Dentistry, University of Science and Technology, Sana’a, Yemen

    Anas Shamala, Ahlam Al-Kamel, Mohammed Al-Wesabi & Amani Al-Sharani

  7. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China

    Abdullkhaleg Albashari

  8. Madinat Khalifa Health Center, Primary Health Care Corporation, Doha, Qatar

    Saleem Abdulrab

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  1. Sadeq A. Al-Maweri
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Al-Maweri, S.A., Halboub, E., Al-Sharani, H.M. et al. Association between serum zinc levels and recurrent aphthous stomatitis: a meta-analysis with trial sequential analysis. Clin Oral Invest 25, 407–415 (2021). https://doi.org/10.1007/s00784-020-03704-8

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