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The efficacy of vitamin D supplementation for irritable bowel syndrome: narrow scope and GRADE miss-interpretation


We read the article by Haung et al. that pooled the effects of vitamin D on irritable bowel syndrome symptoms and associated quality of life. However, the current review suffers from some methodological errors: inadequate search strategy; the grading of recommendations assessment, development, and evaluation (GRADE) miss-assessment; and miss-interpretation. Accordingly, addressing the emphasized limitations will lead to more robust findings and conclusions.

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Dear Editor,

We read with great interest the recent review by Haung et al. [1] on the efficacy of vitamin D on the severity of symptoms and the quality of life in irritable bowel disease (IBS) patients currently published in your prestigious journal. Although we praised the authors’ efforts, we were concerned by some methodological issues.

First, the narrow and defective search strategy did not cover all the possibly includable studies that meet their inclusion criteria. The authors included four studies with 335 participants. While we searched the same databases with the same search terms until January 2022, as mentioned by the authors. However, our search yielded three more eligible studies [2,3,4] with 351 participants that should have been included in the current analysis. Including the missed eligible studies can significantly change the summary effect estimates of the outcomes of interest. To clarify, a recently published systematic review and meta-analysis that included the previously mentioned missed studies yielded different findings regarding the IBS severity scoring system (IBS-SSS) [5]. Another review that also included the missed article yielded consistent IBS-SSS findings [6]; however, its results have been under debate due to statistical concerns [7]. In addition, the narrow search strategy that leads to missing multiple key publications in the pooled analysis is a serious limitation of systematic reviews that have been previously emphasized [8, 9].

Second, the authors assessed the quality of evidence following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) [10]. However, we suspect a miss-assessment of the certainty of evidence. On one hand, the authors assessed IBS-SSS and IBS total score (IBS-TS) as “very low” quality of evidence downgrading it in three domains (inconsistency – imprecision – publication bias) assessed as “serious” in all of them. On the other hand, the authors assessed IBS quality of life (IBS-Qol) as “low” quality of evidence while downgrading it in four domains (risk of bias - inconsistency – imprecision – publication bias) assessed as “serious” in all of them, as demonstrated in (table 2) [1]. Surprisingly, IBS-Qol was downgraded more times than IBS-SSS and IBS-TS, but IBS-Qol’s certainty of the evidence was higher, which is contradictory with GRADE guidelines [10]. Also, the authors have not clarified the rationales for the downgrading of each domain.

Moreover, the authors failed to incorporate the certainty of evidence yielded by the GRADE approach to their conclusion. To clarify, the authors stated that vitamin D is effective for improving both the IBS-SSS and (IBS-Qol), but the certainty of the evidence of IBS-SSS was reported by the authors as “very low”, while the authors reported the certainty of the evidence of IBS-Qol as “low”. According to Chap. 15 of the Cochrane Handbook for Systematic Reviews of Interventions and the interpretation guidelines of the GRADE system [11, 12], “very low” and “low” rating implies that the evidence is very uncertain about the intervention effect and intervention may cause an effect, respectively. Hence, drawing a strong conclusion about the efficacy of vitamin D on IBS based on this weak evidence is questionable.

Altogether, the current review is undermined by the following methodological issues: narrow inadequate search strategy and GRADE system miss-assessment and miss-interpretation. The correction of the previously mentioned issues may lead to significant variations in the conclusions based on the current pooled analysis. Therefore, the findings and conclusions of the current review should be cautiously considered.

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  1. Huang H, Lu L, Chen Y, Zeng Y, Xu C. The efficacy of vitamin D supplementation for irritable bowel syndrome: a systematic review with meta-analysis. Nutr J. 2022;21:1–11 BioMed Central. Available from: Cited 2022 May 7.

    Article  Google Scholar 

  2. Zeid W, Ezzeldeen E, Khattab M, Ahmed S, Abdo M. Effect of vitamin D3 (cholecalciferol) supplementation on gastrointestinal symptoms in patients with irritable bowel syndrome attending El-Mahsama Family Practice Center, Ismailia, Egypt: a randomized clinical trial. Al-Azhar Int Med J. 2020;0:0.

    Article  Google Scholar 

  3. Williams CE, Williams EA, Corfe BM. Vitamin D supplementation in people with IBS has no effect on symptom severity and quality of life: results of a randomised controlled trial. Eur J Nutr. 2022;61:299–308. Springer Berlin Heidelberg.

    Article  CAS  Google Scholar 

  4. Jalili M, Vahedi H, Poustchi H, Hekmatdoost A. Effects of vitamin D supplementation in patients with irritable bowel syndrome: a randomized, double-blind, placebo-controlled clinical trial. Int J Prev Med. 2019;10:16.

    Article  Google Scholar 

  5. Abuelazm M, Muhammad S, Gamal M, Labieb F, Amin MA, Abdelazeem B, et al. The effect of vitamin D supplementation on the severity of symptoms and the quality of life in irritable bowel syndrome patients: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2022;14.

  6. Chong RIH, Yaow CYL, Loh CYL, Teoh SE, Masuda Y, Ng WK, et al. Vitamin D supplementation for irritable bowel syndrome: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2022; John Wiley & Sons, Ltd. Available from: Cited 2022 Apr 17.

  7. Abuelazm M, Abdelazeem B. Vitamin D supplementation for irritable bowel syndrome: concerns about the meta-analysis. J Gastroenterol Hepatol. 2022;37:1402–3.

    Article  CAS  Google Scholar 

  8. Pan A, Hu FB. Question about a recent meta-analysis of low-calorie sweeteners and body weight. Am J Clin Nutr. 2014;100:1604 Oxford Academic. Available from: Cited 2022 May 8.

    Article  CAS  Google Scholar 

  9. Parastouei K, Rostami H. Comment on “Pistachios and cardiometabolic risk factors: a systematic review and meta-analysis of randomized controlled clinical trials”. Complement Ther Med. 2021;70:102717 Churchill Livingstone.

  10. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94 Elsevier. Available from: Cited 2022 May 8.

    Article  Google Scholar 

  11. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. Cochrane handbook for systematic reviews of interventions. Cochrane Handb Syst Rev Interv. 2019:1–694.

  12. Santesso N, Glenton C, Dahm P, Garner P, Akl EA, Alper B, et al. GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions. J Clin Epidemiol. 2020;119:126–35 Pergamon.

    Article  Google Scholar 

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by M.A. and B.A. The first draft of the manuscript was written by M.A. and B.A. All authors read and approved the final manuscript.

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Correspondence to Mohamed Abuelazm.

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Abuelazm, M., Abdelazeem, B. The efficacy of vitamin D supplementation for irritable bowel syndrome: narrow scope and GRADE miss-interpretation. Nutr J 22, 8 (2023).

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