Article - Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials.

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Take home message

Existing evidence on dietary polyphenols shows potential benefit for reducing RA disease activity and improving associated inflammatory and oxidative stress markers.
However, the number of RCTs on dietary polyphenols and RA is limited and the trial size is small and subject to bias. Therefore, interpretation of these results needs to be made with caution.

Evidence category

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

Summary review

Introduction

The aim of this systematic review and meta-analysis of RCTs was to evaluate the impact of dietary polyphenols on markers and symptoms of rheumatoid arthritis (RA).

Methods

This systematic review and meta-analysis was conducted according to PRISMA guidelines and is registered with PROSPERO.
RCTs examining patients with a diagnosis of RA, with a treatment arm looking at dietary polyphenols, were included.
47 RCTs were included in the final analysis, involving 15 dietary polyphenols and 3,503 participants.
Outcome measures included disease activity scores, serum inflammatory markers, and oxidative stress markers.

Results

Meta-analysis was possible for total glucosides of Paeony (23 RCTs), tea polyphenols (2 RCTs), crocus sativus L. extract (2 RCTs) and curcumin (5 RCTs).
Total glucosides of paeony. The following markers were lower in the treatment arm compared to controls: disease activity score in 28 joints (DAS28) [WMD=-0.92 95%CI (-1.52, -0.31), P=0.003]; C-reactive protein (CRP) [SMD=-1.32 95%CI (-1.81, -0.83), P<0.00001]; erythrocyte sedimentation rate (ESR) [WMD=6.44 95%CI (=9.24, -3.63), P<0.00001]; and rheumatoid factor (RF) [SMD=-2.01 965%CI (-3.01, -1.01) P,0.0001].
Tea polyphenols: The following markers were lower in the treatment arm compared to controls: DAS28 [WMD=-1.76 95%CI (-2.71, -0.81), P=0.0003]; and CRP [WMD=-1.83 95%CI (-3.08, -0.59), P=0.004].
Crocus sativus L. extract. No statistical significance was found for the following markers: DAS28 [WMD=–0.48 95%CI (-1.31, 0.35), P=0.26]; ESR [WMD=-4.01 95%CI (-11. 80, 3.78), P=0.31].
Curcumin. The following markers were lower in the treatment arm compared to controls: DAS28 [WMD=- 1.10 95%CI (-1.67, -0.53), P=0.0002]; CRP [WMD=-0.35 95%CI (-0.55, -0.15), P=0.0005]; ESR [WMD=-54.67 95%CI (-88.32, -21.02), P=0.001]; and RF [WMD=-51.30 95%CI (-60.59, -42.01), P<0.00001].
Whilst statistically significant results were reported for other polyphenols, these were based on single, small trials and are therefore not summarised in this expert review.

Conclusion

Dietary polyphenols appear to reduce RA disease activity, lower inflammation and improve oxidative stress markers, however further research is needed.

Clinical practice applications

Whilst the outcomes of this research are based on a small number of studies with a high risk of bias, healthcare practitioners working with RA patients can use the results to encourage intake of a broad range of dietary polyphenols from foods as one strategy to reduce inflammation and RA disease activity.
Supplementation with total glucosides of Paeony, tea polyphenols, crocus sativus L. extract and curcumin at therapeutic doses could be considered as part of a protocol when working with RA patients.

Considerations for future research

Larger clinical trials of polyphenols and RA, with both single and multiple phenolic compounds, are required to further knowledge in this area.

Abstract

OBJECTIVE

To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA).

METHODS

CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software.

RESULTS

A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events.

CONCLUSION

Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.