S1 Fig. People with food allergies or certain medical xrthritis Polyphenols and arthritis need to avoid certain polyphenol-rich foods, however. For each leg, a dose of μg i. Exp Ther Med 6 1 —

Polyphenols and arthritis -

Figure 3 Efficacy indicators of Total glucosides of paeony A DAS28; B ACR20; C ACR50; D ACR A total of 17 RCTs reported CRP. A total of 16 RCTs reported ESR. A total of 10 RCTs reported RF. Only 3 RCTs reported IL Only Yu et al. Figure 4 Inflammatory parameters of Total glucosides of paeony A CRP; B ESR; C RF; D IL A total of 15 RCTs reported adverse events.

Only 2 RCTs reported tea polyphenols in the treatment of RA, efficacy indicators, inflammatory parameters and adverse event outcomes were reported, so a meta-analysis was performed.

Both 2 RCTs reported DAS Only Alghadir et al. Both 2 RCTs reported CRP. Mirtaheri et al. Alghadir et al. Yang et al. They found that DAS28, ESR, CRP, IL-6 was lower after Puerarin intervention. They also found no significant difference in adverse event rates between the two groups. Kometani et al.

They found that RA symptoms improved 3 out of 9 patients after the patients drank the Hesperidin-containing beverage, compared with only 1 improvement in 10 patients in the control group.

Only 2 RCTs reported Crocus sativus L. extract in the treatment of RA, efficacy indicators, inflammatory parameters, oxidative stress markers and adverse event outcomes were reported, so a meta-analysis was performed. Only Hamidi et al. They found that the CRP decreased after Crocus sativus L. extract intervention.

Both 2 RCTs reported ESR. Adverse events were not reported in either RCTs, probably because they did not monitor for adverse events. Only Aryaeian et al.

They found that DAS29 was reduced after the ginger intervention compared to the control group. Regarding inflammatory parameters, they found that peroxidase-activated proliferative receptor PPAR -γ gene expression was significantly increased in the ginger group and the control group, but there was no significant difference between the two groups Only Shishehbor et al.

They found that DAS28 decreased, the number of tender and swollen joints decreased, and serum CRP and TNF-α levels were significantly reduced after the cinnamon extract intervention However, no difference in ESR between the two groups was observed. Only Helli et al.

They found that compared with the placebo group, after sesamin intervention, the joint pain was relieved, the number of tender joints was reduced, and the serum hs-CRP, TNF-α and cyclooxysynthase COX -2 levels were significantly reduced 65 , Only 2 RCTs reported Cranberry extract in the treatment of RA.

Thimóteo et al. Fatel et al. Only 2 RCTs reported olive oil and 1 RCTs reported olive extracts in the treatment of RA. Hekmatpou et al. Berbert et al. Bitler et al. A total of 5 RCTs reported curcumin in the treatment of RA, efficacy indicators, inflammatory parameters and adverse event outcomes were reported, so a meta-analysis was performed.

Four 4 RCTs reported DAS Three 3 RCTs reported CRP. Five 5 RCTs reported ESR. Two 2 RCTs reported RF. Figure 11 Inflammatory parameters of curcumin A CRP; B ESR; C RF.

Three 3 RCTs reported adverse events. The number of RCTs for total glucosides of paeony and curcumin exceeded 4, so a subgroup analysis was performed according to the duration and dosage Tables 2 , 3. Total glucosides of paeony: The difference from the results above is that although the summary results of DAS28 were statistically significant, subgroup analysis showed no statistical difference in DAS28 at each time point.

In addition, for RF, patients receiving total glucosides of paeony twice a day had lower RF than controls, while patients receiving total glucosides of paeony three times a day had similar RF to controls. And after subgroup analysis of time. At 8 weeks of curcumin treatment, the ESR and CRP of the experimental group were not statistically different from those of the control group, and the statistical difference only appeared at 12 weeks.

The sensitivity analysis was performed for total glucosides of paeony and curcumin Figure The sensitivity analysis showed that no matter which RCTs were removed, it had little effect on the overall results, suggesting that the results were stable. Figure 13 Sensitivity Analysis results A adverse events of total glucosides of paeony; B CRP of total glucosides of paeony; C DAS28 of total glucosides of paeony; D ESR of total glucosides of paeony; E RF of total glucosides of paeony; F CRP of curcumin; G DAS28 of curcumin; H ESR of curcumin; I RF of curcumin.

The publication bias was performed for total glucosides of paeony and curcumin Figure Figure 14 Publication bias results A adverse events of total glucosides of paeony; B CRP of total glucosides of paeony; C DAS28 of total glucosides of paeony; D ESR of total glucosides of paeony; E RF of total glucosides of paeony; F CRP of curcumin; G DAS28 of curcumin; H ESR of curcumin; I RF of curcumin.

Figure 15 Meta-regression Results of the duration of intervention A adverse events of total glucosides of paeony; B CRP of total glucosides of paeony; C DAS28 of total glucosides of paeony; D ESR of total glucosides of paeony; E RF of total glucosides of paeony; F CRP of curcumin; G DAS28 of curcumin; H ESR of curcumin.

Figure 16 Meta-regression Results of dose A adverse events of total glucosides of paeony; B CRP of total glucosides of paeony; C DAS28 of total glucosides of paeony; D ESR of total glucosides of paeony; E RF of total glucosides of paeony; F CRP of curcumin; G DAS28 of curcumin; H ESR of curcumin; I RF of curcumin.

The evidence quality of total glucosides of paeony and curcumin was assessed by GRADE pro CDT Tables 4 , 5. The recommended rating for all results is low to very low. Punica granatum L. is rich in vitamins, minerals, organic acids, proteins 79 , and also rich in phenolic and flavonoid active ingredients.

Pomegranate peel polyphenols mainly include gallic tannin, ellagitannin, ellagic acid, chlorogenic acid, gallic acid, catechin, epicatechin, anthocyanin, ferulic acid and quercetin 80 , Studies have shown that pomegranate has been consumed as a medicinal plant for thousands of years and has various properties such as anti-inflammatory, antioxidant, anti-cancer, anti-diabetic, anti-hyperlipidemic, anti-hypertensive and cardiovascular protection 82 , In addition, animal 84 and human 85 , 86 studies did not report any serious adverse outcomes following pomegranate consumption.

Animal studies have shown that ethanolic extract of pomegranate peel can significantly increase paw withdrawal latency and reduce adverse histological changes and arthritis scores 87 , and reduce serum RF, MDA, IL-1β and TNFα. Karwasra et al. reported that Pomegranate extract can significantly inhibit hind paw swelling and bone destruction, and reduce complications such as erythema, improve joint inflammation, synovial hyperplasia, inflammatory cell infiltration, periarticular bone resorption, bone erosion and joint space narrowing In vitro studies indicated that pomegranate seed oil and fermented pomegranate juice extract can inhibit COX and lipoxygenase involved in triggering the inflammatory cascade The main fatty acid punicic acid in pomegranate seed oil inhibits prostaglandin biosynthesis 90 and inhibits neutrophil activation and lipid peroxidation outcomes In addition to the inhibitory effect of pomegranate on eicosanoid production, pomegranate also exerts its anti-inflammatory effect by inhibiting the pMAPK pathway and the transcription factor NF-κB 89 — Extracts of phenolic compounds present in pomegranate peel are potential scavengers of diphenylpicrylhydrazine DPPH free radicals.

This may be because the phenolic substances in the peel extract have strong proton-donating ability and can agglomerate with hydroxyl groups to stabilize free radicals 92 , Morvaridzadeh et al.

demonstrated that pomegranate juice caused a non-significant increase in TAC and paraoxonase and a non-significant decrease in MDA concentration in humans The limitation of this systematic review is that it contains only 1 RCT, and they found that compared with placebo, pomegranate extract reduced DAS28 scores, improved joint swelling and tenderness, decreased ESR levels, and increased GPx concentrations.

Quercetin is a flavonoid commonly found in fruits and vegetables such as onions, apples, beans and various berries It has anti-inflammatory, anti-angiogenic, anti-cancer, hepatoprotective, cardiovascular, anti-aging, and neuroprotective potentials 96 — In a large number of preclinical or clinical studies, quercetin has also been shown to have a certain effect on RA 30 , In terms of bone protection, quercetin can modulate mTOR, ERK, IκB-α and AMPK signaling pathways and inhibit the expression of receptor activator of NF-κB ligand RANKL in FLS 30 — It can also inhibit the activation of MAPKs ERK, p38, JNK and NF-κB signaling pathway to inhibit the expression of MMP-1 and MMP-3 in FLS — Only two RCTs reported quercetin in the treatment of RA.

Because meta-analyses could not be combined, the results need to be interpreted with caution. Resveratrol is a natural polyphenolic antioxidant that is abundantly present in a variety of plants, especially red grape skins, and has pharmacological properties, including antioxidants, reactive oxygen species with scavenging, anticancer, and anti-inflammatory effects — Previous studies have shown that resveratrol has beneficial effects on the occurrence and development of RA — Resveratrol acts directly on mitochondrial production of ROS.

Its ROS scavenging potential may be driven by the dissociative junction of leaked electrons from the respiratory chain — Several studies have reported that resveratrol can reduce the activity of COX-1, COX-2, and reduce the expression of potent inflammatory parameters such as prostaglandins and leukotrienes , In addition, resveratrol reduced TNF-α and IL-1β levels in rats with adjuvant arthritis Cheon et al.

demonstrated that resveratrol supplementation significantly reduced inflammation, pannus formation, and cartilage damage in mice with collagen-induced arthritis, and reduced bone destruction In this systematic review, only 1 RCT reported resveratrol in the treatment of RA.

More RCTs are needed for further research in the future Garlic is a functional food that has been used worldwide for thousands of years. It is rich in bioactive compounds including allicin, ajoene, s-allyl cysteine, s-methyl cysteine, diallyl disulfide DADS , diallyl sulfide DAS , alliin, amino acids, polysaccharides and different polyphenols — The main phenolic compounds are β-resorcinol, gallic acid, pyrogallol, quercetin, rutin and protocatechuic acid Garlic improves immune system function by stimulating certain cell types, such as macrophages and lymphocytes, and reduces cytokine secretion The anti-inflammatory effects of allicin and DAS have been demonstrated in several studies , Garlic-derived compounds can reduce serum TNF-α, IL-6 and CRP levels by inhibiting cell signaling pathways, including COX-2 and inhibit NF-κB activation , In addition, scientific studies have reported the analgesic and anti-fatigue effects of garlic — The antioxidant properties of garlic may help reduce pain in patients with rheumatoid arthritis For example, garlic supplements can relieve pain in patients with knee osteoarthritis OA — Hussain and Salalah showed that mg of garlic capsules per day for 8 weeks significantly reduced TNF-α concentrations in patients with knee OA Only one RCT reported Garlic extract in the treatment of RA.

Total glucosides of paeony are extracted from the dried roots of Paeonia lactiflora , including paeoniflorin, hydroxypaeoniflorin, paeoniflorin, paeoniflorin, and benzoylpaeoniflorin Total glucosides of paeony have a wide range of anti-inflammatory and immunomodulatory effects, and have been widely used in the treatment of autoimmune diseases, including RA, systemic lupus erythematosus SLE , psoriasis, allergic contact dermatitis, etc.

In terms of intervening in RA, total glucosides of paeony regulate the function and activation of immune cells in RA, reduce the production of inflammatory mediators, and restore abnormal signaling pathways , Total Paeoniflorin can balance immune cell subsets such as macrophage-like synoviocytes, fibroblast-like synoviocytes, etc.

in experimental arthritis FLS , — This meta-analysis showed that total glucosides of paeony may improve the clinical manifestations of RA decrease DAS28, ACR20 and ACR70 and inhibit inflammatory reduce CRP, ESR, RF, IL-6 and TNF-α.

Meanwhile, the addition of total glucosides of paeony may reduce the incidence of adverse events. Tea polyphenols such as catechins, etc. are the most abundant in tea , Therapeutic benefits of green tea have been seen in neurodegenerative, inflammatory, cardiovascular, and various cancers , Catechins have demonstrated their anti-inflammatory effects in many studies related to pathological conditions in which inflammation is a core driver Extensive in vitro studies have shown that catechins have promising applications in the treatment of RA, with differential modulation of cartilage, bone, and synovial fibroblast activity In cartilage, catechins have been found to inhibit IL-1β-induced inducible NOS iNOS and COX-2 expression by inhibiting IκBα phosphorylation and proteasomal degradation , Catechin also inhibits IL-1β-induced phosphorylation of c-Jun, thereby preventing activating protein 1 AP-1 from binding to DNA Akhtar and Haqqi found that when IL-1β was inhibited, IL-6, IL-8 and TNF-α were also down-regulated due to the inhibition of NF-κB An early study suggests that prophylactic consumption of green tea may help improve inflammation and reduce cartilage destruction associated with different forms of arthritis In bone biology, catechins are thought to reduce the amount of osteoclast formation by reducing osteoblast differentiation Catechin blocks the receptor activator of RANKL-mediated activation of JNK and NF-κB pathways to inhibit the expression of the transcription factor NFATc1 required for osteoclast differentiation In regulating apoptosis, catechin treatment selectively downregulated Mcl-1 anti-apoptotic protein expression, thereby increasing the sensitivity of synovial fibroblasts to apoptosis Studies have also shown that catechins can reduce the production of MMP-1, MMP-2 and MMP-3 by RA synovial fibroblasts to prevent further cartilage and bone destruction , Therefore, although tea and tea polyphenols can neutralize the inflammatory effects of IL-1β and IL-6, they also effectively utilize TNF-α to play its basic function of regulating the uncontrolled proliferation of activated synovial fibroblasts to improve the functional status of arthritis joints.

This meta-analysis showed that tea polyphenols may improve the clinical manifestations of RA decrease DAS28, ACR20 and ACR70 and inhibit inflammatory reduce CRP and ESR. Meanwhile, the addition of total glucosides of paeony may not increase the incidence of adverse events.

Puerarin exists in the roots of the genus Pueraria common name Pueraria , which is isolated from Pueraria and other species — Numerous health benefits have been attributed to puerarin, namely antioxidant , anti-inflammatory , neuroprotective , liver protection , anticancer , antidiabetic , cardioprotective and anti-atherosclerotic effect In terms of bone protection, puerarin is an effective compound that inhibits bone resorption and improves bone structure.

It can stimulate osteoblast differentiation and inhibit osteoclastogenesis at the same time , Puerarin can stimulate bone formation and regulate bone metabolism by inhibiting bone resorption The anti-atherosclerotic properties of puerarin also include inhibition of lipopolysaccharide or ovalbumin-induced inflammation — , protection of endothelial cells from damage induced by oxidized LDL or Aß40, and reduction of lipid accumulation in vessel walls — The vasoprotective effect of puerarin inhibits vascular smooth muscle cells and protects against ischemia and reperfusion injury — This systematic review showed that puerarin may decrease DAS28, ESR, CRP, IL Hesperidin is a flavonoid that is abundant in citrus fruits.

Hesperidin has many biological functions, including antioxidant, anti-inflammatory, antiviral, and anticancer activities Ahmad et al.

Therefore, the use of hesperidin may help reduce the severity of RA disease. Umar et al. found that hesperidin may inhibit collagen-induced arthritis by inhibiting free radical load and reducing neutrophil activation and infiltration Qi et al.

Liu et al. Li et al. found the therapeutic effect of hesperetin on adjuvant arthritis in rats by inhibiting the JAK2-STAT3 signaling pathway Hesperidin also promotes the anti-inflammatory and analgesic activities of Siegesbeckia pubescens makino by inhibiting COX-2 expression and inflammatory cell infiltration This systematic review showed that hesperidin may improve RA symptoms.

Crocus sativus L. extract is well known in herbal medicine and has attracted the attention of researchers for its properties, especially its anti-inflammatory and proliferative abilities in bone and cartilage destructive diseases , Among these bioactive components, there are four recognized components that may be associated with the therapeutic potential of saffron, including crocin, saffron flavonoids, saffron aldehyde, and saffron , Recent studies have revealed other therapeutic and pharmacological activities of saffron — , such as neuroprotection, neurogenetics, antidepressant, antiapoptotic, antioxidant, and anti-inflammatory.

One study found that crocin modulates serum levels of enzymatic and non-enzymatic inflammatory cytokines, including MMP, MMP-3, MMP-9, HAases, TNF-α, IL-1β, NF-κB, IL -6, COX-2 and PGE2 and ROS media Crocin also increased levels of GSH, SOD, CAT and GST.

In addition, inhibition of the exoglycosidase cathepsin-D and tartrate-resistant acid phosphatase in the bone near the joint by crocin protects bone resorption Rasol et al.

found that TNF-α and IL-1β levels were decreased and SOD and GR activities were increased after crocin intervention Hu et al. found that paw swelling and ankle diameter were significantly reduced in crocin-treated rats. Histological analysis also showed reduced inflammation in joints and other organs, such as the spleen.

In addition, TNF-α and TGF-β1 levels were decreased in synovial tissue In a similar study, Liu et al. found that MMP-1, MMP-3, and MMP protein expression levels were decreased in RA rats after crocin intervention showed similar results, suggesting that crocin had a positive effect on RA-induced rats In an in vitro study, Li et al.

Wang et al. However, this meta-analysis showed that the efficacy of Crocus sativus L. extract may not be significantly different from the control group. Ginger has been cultivated in China and other countries around the world since ancient times as a source of medicinal plants for spice and therapeutic benefits The main components of ginger are 6-shogaol, ginger oil terpene, water fennel, camphor terpene, gingerol, eucalyptus, etc.

Evidence suggests that consuming ginger may help relieve joint pain associated with RA Kiuchi et al. discovered the potential of ginger to inhibit the synthesis of prostaglandins, which are key to inflammation.

Further research found that ginger exhibits anti-inflammatory activity by inhibiting the biosynthesis of prostaglandins and leukotrienes Ribel-Madsen et al.

observed the analgesic and anti-inflammatory effects of 6-gingerol Ojewole observed potential analgesic and anti-inflammatory activity of ginger, which can be used to reduce pain and inflammation caused by arthritis Srivastava et al. observed the antiarthritic activity of ginger in patients who independently experienced RA, OA and muscle discomfort The beneficial effect of ginger on reducing RA-related pain may be due to the inhibition of prostaglandin and leukotriene biosynthesis van Breemen et al.

found that gingerol, 8-shogaol, and shogaol strongly inhibited COX 2, thereby significantly reducing inflammation In addition, ginger can inhibit the biosynthesis of leukotrienes by inhibiting 5-lipoxygenase Nurtjahja-Tjendraputra et al.

also demonstrated the inhibitory effect of ginger on COX-1 activity One study found that components of ginger significantly inhibited the release of pro-inflammatory cytokines IL, TNF-α and IL-1 β and pro-inflammatory chemokines in LPS-induced macrophages This systematic review showed that Ginger extract may decrease DAS Cinnamon, one of the most commonly used spices in the world and one of the oldest herbal medicines used to treat certain diseases and inflammations, has been used to treat RA in China for nearly years Cinnamon can modulate immune system function by modulating anti-inflammatory and pro-inflammatory gene expression — Cinnamaldehyde is the main active component of cinnamon, and its anti-inflammatory effect has been observed in several studies — Several other flavonoids, including anti-inflammatory hesperidin and quercetin, have also been extracted from cinnamon , Scientific evidence suggests that cinnamon extract can be used to modulate the immune system, as well as prevent and treat inflammation The beneficial effects of cinnamon extract and its polyphenols on reducing serum levels of TNF-α, CRP and IL-6, as well as improving clinical symptoms and antioxidant activity have been reported in animal models In vitro experiments also demonstrated the beneficial effects of cinnamon polyphenols in improving immune responses by modulating the expression of pro- and anti-inflammatory cytokine genes , In experimental arthritis studies, cinnamaldehyde in cinnamon significantly inhibits joint disease in experimentally arthritic animals.

Cinnamaldehyde can not only significantly reduce the IL-6 content of inflammatory mediator TNF-α in peripheral mononuclear cells of RA patients , but also inhibit the release of IL-1β and matrix MMP from synovial fibroblasts in arthritis patients Cinnamaldehyde can significantly reduce the levels of TNF-α, IL-6 and IL-1β in the peripheral blood of collagen-induced arthritic rats, and significantly increase the content of the anti-inflammatory factor IL, exerting a systemic anti-inflammatory effect This systematic review showed that Ginger extract may decrease DAS28, the number of tender and swollen joints, and serum CRP and TNF-α levels.

Sesame is an important traditional health food that has been used in Asian countries for thousands of years to improve nutritional status and prevent various diseases Sesame seeds contain high amounts of oil and protein, as well as various lignans such as sesamin , Several studies have shown that sesamin one of the most abundant lignans in sesame has various physiological functions, including antioxidant, antihypertensive, anti-obesity and hypolipidemic effects — The anti-inflammatory properties of sesame compounds have been reported in rat models The results of another study showed that sesamin inhibited lipopolysaccharide-induced inflammation by inhibiting p38 mitogen-activated protein kinase and NF-kB, which are the major pathways regulating cytokine production.

Based on this result, sesamin may also prevent cartilage degeneration in other joint diseases such as RA , This systematic review showed that sesamin may improve the joint pain, decrease the number of tender joints, and decrease serum hs-CRP, TNF-α and COX-2 levels.

Cranberry Vaccinium macrocarpon juice has strong antioxidant activity, mainly containing polyphenolic compounds such as flavonols myricetin and quercetin , anthocyanins and procyanidins Clinical studies have shown that cranberry juice has beneficial effects on biomarkers of cardiovascular disease risk , Several intervention studies have found that cranberry has beneficial effects on biomarkers of oxidative stress, dyslipidemia, and inflammation in healthy people , and in patients with type 2 diabetes and metabolic syndrome Studies have found that quercetin flavonol , which is abundant in cranberry, can lead to a significant down-regulation of the nuclear factor kappa B NF-κB pathway Additionally, resveratrol has been shown to be another abundant polyphenol in cranberries.

NF-κB regulates the expression of many pro-inflammatory genes, including adhesion molecules, IL-6, and TNF-α. Other components present in cranberries, such as proanthocyanidins, anthocyanins, hydroxycinnamic acid, and acetylsalicylic acid, inhibit NF-κB activation This systematic review showed that Cranberry extract may decrease DAS28, and serum ESR and CRP.

The current study found that olive oil contains high amounts of polyphenolic compounds. Numerous studies have found polyphenolic extracts of olive oil as antioxidants to prevent and treat cardiovascular disease and prevent certain types of cancer, as well as reduce the incidence of coronary heart disease and stroke — Furthermore, it has been shown to inhibit IL-1β-induced MMP, TNF-α and IL-6 production in the SW human synovial fibroblast cell line Polyphenol extracts also down-regulated COX-2 and mPGE-1 induced by IL-1β.

In addition, it inhibits MAPK phosphorylation and NF-κB activation , This systematic review showed that Olive oil may decrease DAS28, relieve joint pain and decrease the number of painful joints and the number of swollen joints.

The study also found that a Mediterranean diet centered on olive oil can reduce the risk of autoimmune diseases such as RA , , which is strong evidence in the treatment of RA. Curcumin, a yellow pigment and active component of turmeric Curcuma longa , is one of the well-known natural compounds with a wide range of pharmacological activities and potential immunomodulatory properties , Curcumin has a high ability to modulate inflammation in RA by suppressing pro-inflammatory immune cell populations and suppressing the production of immune-inflammatory cytokines and chemokines , Studies have found that curcumin can significantly block the expression of IL-6 in FLS stimulated by IL-1β in RA patients Curcumin can also reduce the protein expression levels of IL-6, IL-8, MCP-1, MMP-1 and MMP-3 in FLS of RA patients Several studies on animal models of RA also confirmed this finding.

Curcumin can reduce the production of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6 and MCP-1 — These two cells play a key role in the pathogenesis of RA by producing key pro-inflammatory cytokines including TNF-α, IFN-γ, IL, IL and IL and are responsible for joint and bone destruction , In addition, curcumin has a strong ability to induce regulatory T cell Treg differentiation and inhibit TH1- and THmediated inflammatory responses This meta-analysis showed that curcumin may decrease DAS28, CRP, ESR and RF.

Dietary polyphenols are currently widely used as alternative therapies, and preclinical and clinical studies have demonstrated their efficacy in the treatment of RA. In addition to the 15 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 in this study, there are many other polyphenols in the world.

The reason why this study did not include other polyphenols is that this study is about the systematic review and meta-analysis of RCTs, so these animal experiments were not included.

In order to further provide future researchers with reference information for dietary polyphenols in the treatment of RA, we summarized dietary polyphenols with potential medicinal value. Dietary polyphenols derived from dietary fruits, vegetables and natural herbs for anti-rheumatic activity in the treatment of RA include Stilbenes, Phenolic acids, Flavonoids, etc.

Among them, phenolic acids such as benzoic acid and cinnamic acid Hydroxybenzoic acids including gallotannins and ellagitannins also exhibit anti-RA effects Natural flavonoids also exhibit strong anti-RA activity, such as anthocyanins, flavanols catechins, epigallocatechin gallate , flavonoids luteolin, apigenin , flavanones naringenin , flavonols quercetin and kaempferol , isoflavones genistein, daidzein and glycitein , Some herbs have also been shown to exhibit prominent anti-RA activity, including Adhatoda vasica Nees pyrroloquinazoline , Ajuga bracteosa wall Withaferin-A, Ajugarin-I , Aconitum carmechaeli Debeaux aconitine, benzoylmethasone , Barleria prionitis triterpenoids , pine pinitol At present, the most studied pathways are immune inflammation-related signaling pathways to reduce bone and joint damage, such as NFKB signaling pathways, TLR signaling pathways, TNF signaling pathways, etc.

The strengths of this research are that compared with previous studies, this study included the results of a meta-analysis and included more RCTs 48 RCTs were included in this study and involved 15 dietary polyphenols: Cinnamon extract, Cranberry extract, Crocus sativus L.

Sensitivity analysis, publication bias assessment, meta-regression, and quality of evidence ratings were also performed in this meta-analysis. The limitations of this research are that: 1 There is obvious heterogeneity in outcomes.

According to meta-regression, part of the heterogeneity of total glucosides of paeony and curcumin may come from drug dosage and intervention time. The remaining heterogeneity may be due to the selection of the population, the choice of dietary polyphenol preparations for treatment of dietary polyphenols, and information biases during data collection.

The authors of some RCTs are funded or employed by drug manufacturers, which may introduce bias. Through the systematic review and meta-analysis of this study, it can be found that the research on the efficacy and mechanism of various dietary polyphenols in relieving RA has made significant progress.

Among them, curcumin and total glucosides of paeony have improved the treatment of rheumatoid arthritis. Symptoms, inhibition of inflammation and other outcome indicators. In general, dietary polyphenols can be used as an effective anti-inflammatory drug in the adjuvant treatment of RA, and can be used for daily dietary supplementation with relatively good safety.

However, there are still some knowledge gaps in current clinical research and basic research, which need to be addressed in future research. In terms of basic research, most previous studies have cultured a single phenolic compound or a mixture of multiple phenolic compounds with synovial cells, lacking pharmacokinetic studies targeting dietary polyphenols in animal studies.

This situation is even more lacking in clinical studies, and few clinical studies have explored the pharmacokinetics of dietary polyphenols in RA patients such as, absorption and metabolism of polyphenols, and interactions with gut microbiota. For example, in previous studies, most studies using animal or cell culture models focused on the biological activity of polyphenols themselves.

Moreover, few studies have focused on the microbial metabolism of polyphenols. In particular, the current study — showed that the α-diversity and β-diversity of gut microbiota in RA patients were significantly lower than those in healthy people.

Among them, Bacteroidetes and Shiga toxoid-producing Escherichia coli were more abundant in RA patients, in contrast, Lactobacillus, Ravivibacterium isoprawizia, Enterobacter and Stinkbacter were less abundant in the RA group.

More studies have found that the intestinal flora can affect the development of RA by regulating immune molecules including immune cells such as regulatory B cells and CD4 T helper T cells, etc. Therefore, research on the interaction between dietary polyphenols and gut microbiota of RA disease is the main direction of future basic and clinical research.

In addition, most dietary polyphenols are degraded by gut flora in the colon due to poor polyphenol absorption. The biological activity of dietary polyphenols may be partially attributed to microbial metabolites. The exact role or biological activity of microbial metabolites should be focused on in future studies.

Dietary polyphenols are a group of biologically active phytochemicals with a wide range of sources, diverse structures, low toxicity, and good biological activity.

In terms of curative effect in the treatment of RA, it is mainly attributed to the immuno-inflammation modulating activity of dietary polyphenols, which provides a new option for the comprehensive management strategy of RA, and dietary polyphenols also alleviate the adverse reactions of DMARDs.

Since these dietary polyphenols are ubiquitously present in the diet, medication adherence may be better in RA patients. Meanwhile, studies have found that some dietary polyphenols can reduce the side effects of glucocorticoids such as bone destruction, drug resistance, etc.

Therefore, the current preliminary preclinical data on dietary polyphenols indicate that polyphenols have great potential in the treatment of RA, and the dietary types that have been carried out RCTs are mainly Cinnamon extract, Cranberry extract, Crocus sativus L.

In addition, there are many dietary polyphenols such as rutin, chlorogenic acid, anthocyanins, luteolin, lignans, etc. Dietary polyphenols have multi-target effects on signaling pathways in RA, so it is important to further explore the pharmacological mechanism of these dietary polyphenols, which will also provide the molecular structure core of lead compounds or new drugs for RA drug development.

Based on this systematic review and meta-analysis, we look forward to clinicians and patients using dietary polyphenols as adjunctive therapy or in combination with other current DMARDs in a comprehensive management strategy for RA.

In addition, since some polyphenols are mainly derived from herbs, it is necessary in clinical practice to study the pharmacokinetic results of the interaction of herbs as a multi-component drug not only polyphenols with DMARDs to prevent potential adverse drug reactions. Some polyphenol active substances have been formulated into new delivery systems to improve solubility, permeability and enhance the therapeutic effect in preclinical studies due to problems such as absorption.

In the future, it is necessary to explore the efficacy and safety of this new type of administration. Although the number of RCTs on dietary polyphenols is limited, existing evidence shows their potential benefits, mainly increasing DAS28, reducing CRP and ESR, and improving oxidative stress, etc.

However, given the small number of patients recruited, the study designs varied widely between RCTs and the characteristics of RA patients varied; it is difficult to immediately extrapolate these results to RA patients in general.

More RCTs are needed in the future to determine the efficacy and safety of dietary polyphenols. Further inquiries can be directed to the corresponding author. ZL, WaX, QH and WeX are responsible for the study concept and design.

ZL, WX, QH, WeX, HW, HL, HG, YC, MY, XY, LZ, KY, YD, ZH are responsible for the data collection, data analysis and interpretation; ZL, WaX and KY drafted the paper; ZH and WeX supervised the study; all authors participated in the analysis and interpretation of data and approved the final paper.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun doi: PubMed Abstract CrossRef Full Text Google Scholar. Radu AF, Bungau SG. Management of rheumatoid arthritis: An overview. Cells 10 11 Sparks JA. Rheumatoid arthritis.

Ann Intern Med 1 :ITC1—ITC Cush JJ. Rheumatoid arthritis: Early diagnosis and treatment. Med Clin North Am 2 — Dai Y, Wang W, Yu Y, Hu S. Rheumatoid arthritis-associated interstitial lung disease: an overview of epidemiology, pathogenesis and management.

Clin Rheumatol 40 4 — Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA, et al. Global, regional and national burden of rheumatoid arthritis a systematic analysis of the global burden of disease study Ann Rheum Dis 78 11 — Zhao J, Guo S, Schrodi SJ, He D.

Molecular and cellular heterogeneity in rheumatoid arthritis: Mechanisms and clinical implications. Front Immunol Wang GY, Zhang SL, Wang XR, Feng M, Li C, An Y, et al. Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

Clin Rheumatol 34 2 — van Vollenhoven RF. Sex differences in rheumatoid arthritis: more than meets the eye. BMC Med Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet — Dong Y, Cao W, Cao J. Treatment of rheumatoid arthritis by phototherapy: advances and perspectives.

Nanoscale 13 35 — Kerschbaumer A, Sepriano A, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, et al. Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the update of the EULAR recommendations for management of rheumatoid arthritis.

Ann Rheum Dis 79 6 — Nagy G, Roodenrijs NMT, Welsing PM, Kedves M, Hamar A, van der Goes MC, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 80 1 —5. Maity S, Wairkar S. Dietary polyphenols for management of rheumatoid arthritis: Pharmacotherapy and novel delivery systems.

Phytother Res 36 6 — Tresserra-Rimbau A. Dietary polyphenols and human health. Nutrients 12 9 Zeng L, Yang T, Yang K, Yu G, Li J, Xiang W, et al. Efficacy and safety of curcumin and curcuma longa extract in the treatment of arthritis: A systematic review and meta-analysis of randomized controlled trial.

Cao H, Ou J, Chen L, Zhang Y, Szkudelski T, Delmas D, et al. Dietary polyphenols and type 2 diabetes: Human study and clinical trial. Crit Rev Food Sci Nutr 59 20 —9.

Luca SV, Macovei I, Bujor A, Miron A, Skalicka-Woźniak K, Aprotosoaie AC, et al. Bioactivity of dietary polyphenols: The role of metabolites.

Crit Rev Food Sci Nutr 60 4 — Yabas M, Orhan C, Er B, Tuzcu M, Durmus AS, Ozercan IH, et al. A next generation formulation of curcumin ameliorates experimentally induced osteoarthritis in rats via regulation of inflammatory mediators.

Shakoor H, Feehan J, Apostolopoulos V, Platat C, Al Dhaheri AS, Ali HI, et al. Immunomodulatory effects of dietary polyphenols. Nutrients 13 3 Lu J, Zheng Y, Yang J, Zhang J, Cao W, Chen X, et al. Resveratrol alleviates inflammatory injury and enhances the apoptosis of fibroblast-like synoviocytes via mitochondrial dysfunction and ER stress in rats with adjuvant arthritis.

Mol Med Rep 20 1 — Page MJ, McKenzie JE, Bossuyt PM, outron I, Hoffmann TC, Mulrow CD, et al. The PRISMA statement: an updated guideline for reporting systematic reviews. BMJ CrossRef Full Text Google Scholar. Deeks JJ, Higgins JP, Altman DG. Chapter Special topics in statistics. In: Higgins JP, Green S, editors.

Cochrane handbook for systematic reviews of interventions. UK: The Cochrane Collaboration Google Scholar. Chapter 8: assessing risk of bias in included studies.

In: Higgins JP Green S, editor. Cochrane handbook or systematic reviews of interventions version 6. Chapter 9: Analyzing data and undertaking meta-analyses.

GRADEpro GDT. GRADEpro guideline development tool. Australia: McMaster University Ghavipour M, Sotoudeh G, Tavakoli E, Mowla K, Hasanzadeh J, Mazloom Z. Pomegranate extract alleviates disease activity and some blood biomarkers of inflammation and oxidative stress in rheumatoid arthritis patients.

Eur J Clin Nutr 71 1 —6. Javadi F, Ahmadzadeh A, Eghtesadi S, Aryaeian N, Zabihiyeganeh M, Rahimi Foroushani A, et al. The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: A double-blind, randomized controlled trial.

J Am Coll Nutr 36 1 :9— Javadi F, Eghtesadi S, Ahmadzadeh A, Aryaeian N, Zabihiyeganeh M, Foroushani AR, et al. The effect of quercetin on plasma oxidative status, c-reactive protein and blood pressure in women with rheumatoid arthritis.

Int J Prev Med 5 3 — PubMed Abstract Google Scholar. Bae SC, Jung WJ, Lee EJ, Yu R, Sung MK. Effects of antioxidant supplements intervention on the level of plasma inflammatory molecules and disease severity of rheumatoid arthritis patients.

J Am Coll Nutr 28 1 — Khojah HM, Ahmed S, Abdel-Rahman MS, Elhakeim EH. Resveratrol as an effective adjuvant therapy in the management of rheumatoid arthritis: a clinical study. Clin Rheumatol 37 8 — Moosavian SP, Paknahad Z, Habibagahi Z. A randomized, double-blind, placebo-controlled clinical trial, evaluating the garlic supplement effects on some serum biomarkers of oxidative stress, and quality of life in women with rheumatoid arthritis.

Int J Clin Pract 74 7 :e Moosavian SP, Paknahad Z, Habibagahi Z, Maracy M. The effects of garlic Allium sativum supplementation on inflammatory biomarkers, fatigue, and clinical symptoms in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled trial.

Phytother Res 34 11 — Yan Z, Xianming W, Lan X, Yapei X, Dongfeng C. Clinical observation of total glucosides of paeonia lactiflora combined with hydroxychloroquine sulfate tablets in the treatment of T2DM complicated with rheumatoid arthritis.

Med Theory Pract 34 23 — Ding B, Li Y, Lu S. Observation of curative effect of total glucosides of paeony and tripterygiumwilfordii in the treatment of rheumatoid arthritis and its effects on inflammatory factors and quality of life.

China Sci Technol Tradit Chin Med 28 05 — Wu T, Chen F, Tang Z, Liu L. Effects of total glucosides of paeony on inflammatory indexes in patients with rheumatoid arthritis. Hebei Med 27 04 — Ju Y, Li R, Guo D, Feng X. Study on the effect of total glucosides of paeony on liver function protection and treatment of rheumatoid arthritis.

Modern Chin Doctor 57 30 —7. Zheng H, Wang W, Wang Z, Tao X, Yu J, Zhang W, et al. Efficacy evaluation of total glucosides of paeony combined with methotrexate and hydroxychloroquine in maintenance treatment of rheumatoid arthritis.

Zhejiang J Integrated Tradit Chin Western Med 28 11 —6. Yu H, Peng J, Ye X. Efficacy and safety of leflunomide and total glucosides of paeony combined with methotrexate in the treatment of rheumatoid arthritis.

China Med Innovation 15 27 :8— Yu W, Xu J, Liang Y, Li M, Sha H. Clinical observation of total glucosides of paeonia lactiflora combined with methotrexate and leflunomide in the treatment of rheumatoid arthritis. Sichuan Med 39 01 —5.

Chen Z, Liu Q, Liu J, Jiang X, Xue Y. Observation on the effect of total glucosides of paeonia lactiflora combined with methotrexate in the treatment of refractory rheumatoid arthritis. Chin J Pract Diagnosis Treat 31 07 — Han L, Gujanet Khan B, Bayan A, Shi R, Bahar Guli L, Wei R.

Leflunomide combined with total glucosides of paeonia lactiflora in the treatment of elderly efficacy of rheumatoid arthritis and its influence on ESR, CRP and RF. Chin J Hosp Pharm 36 07 — Efficacy observation of leflunomide tablets combined with total glucosides of paeonia lactiflora in the treatment of rheumatoid arthritis.

Clin Med Pract 24 05 —5. Zheng H, Xiao Y. Clinical observation of total glucosides of paeony and methotrexate in the treatment of senile rheumatoid arthritis. China J Basic Med Tradit Chin Med 19 12 —8.

Zheng H, Jun H, Yang Y. Effects of total glucosides of paeony on blood lipids in patients with rheumatoid arthritis. Chin J Basic Med Tradit Chin Med 20 06 —4. Li X, Chen M, Wang H.

J Anhui Univ Tradit Chin Med 30 03 —8. Yu J, Zhang H. A clinical study on total glucosides of paeony and leflunomide in the treatment of active rheumatoid arthritis.

Chin Med Forum 25 04 :9— Shang G, Liu J. Efficacy observation of combined use of methotrexate and total glucosides of paeony in the treatment of rheumatoid arthritis. J Clin Rational Drugs 2 04 :1—2.

Wang X, Liu W. China J Tradit Chin Med 07 —7. Fan Y, Li G. Study on total glucosides of paeony combined with lower dose of methotrexate in the treatment of senile-onset rheumatoid arthritis.

J Modern Integr Med 11 —2. Shi L, Yang D. Clinical observation of total glucosides of paeonia lactiflora combined with methotrexate in the treatment of rheumatoid arthritis.

Hubei J Tradit Chin Med 03 —6. Zhang L, Zhou Y, Liu W. Clinical observation of total glucosides of paeonia lactiflora combined with tripterygium wilfordiipolyglycosides in the treatment of rheumatoid arthritis with enhanced efficacy and reduced toxicity.

Tianjin Tradit Chin Med 22 03 —8. Zhao Y, Liu Y. Clinical observation of leflunomide and total glucosides of paeony in the treatment of rheumatoid arthritis.

China J Integr Med 4 —7. Du J, Dong B. Comparison of the clinical efficacy of methotrexate alone and combined with total glucosides of paeony in the treatment of rheumatoid arthritis. China J Integr Med 25 6 —2.

Chen Z, Li XP, Li ZJ, Xu L, Li XM. Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis. Int Immunopharmacol 15 3 —7.

Xiang N, Li XM, Zhang MJ, Zhao DB, Zhu P, Zuo XX, et al. Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritis.

Int Immunopharmacol 28 1 —7. Mirtaheri E, Khabbazi A, Nazemiyeh H, Ebrahimi AA, Hajalilou M, Shakibay Novin Z, et al. Stachys schtschegleevii tea, matrix metalloproteinase, and disease severity in female rheumatoid arthritis patients: a randomized controlled clinical trial.

Clin Rheumatol 41 4 — Alghadir AH, Gabr SA, Al-Eisa ES. Green tea and exercise interventions as nondrug remedies in geriatric patients with rheumatoid arthritis.

J Phys Ther Sci 28 10 —9. Yang M, Luo Y, Liu T, Zhong X, Yan J, Huang Q, et al. The effect of puerarin on carotid intima-media thickness in patients with active rheumatoid arthritis: ARandomized controlled trial.

Clin Ther 40 10 — Kometani T, Fukuda T, Kakuma T, Kawaguchi K, Tamura W, Kumazawa Y, et al. Effects of alpha-glucosylhesperidin, a bioactive food material, on collagen-induced arthritis in mice and rheumatoid arthritis in humans. Immunopharmacol Immunotoxicol 30 1 — Sahebari M, Heidari H, Nabavi S, Khodashahi M, Rezaieyazdi Z, Dadgarmoghaddam M, et al.

A double-blind placebo-controlled randomized trial of oral saffron in the treatment of rheumatoid arthritis. Avicenna J Phytomed 11 4 — Hamidi Z, Aryaeian N, Abolghasemi J, Shirani F, Hadidi M, Fallah S, et al. The effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Phytother Res 34 7 —8. Aryaeian N, Shahram F, Mahmoudi M, Tavakoli H, Yousefi B, Arablou T, et al. The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active rheumatoid arthritis.

Gene — Shishehbor F, Rezaeyan Safar M, Rajaei E, Haghighizadeh MH. Cinnamon consumption improves clinical symptoms and inflammatory markers in women with rheumatoid arthritis. J Am Coll Nutr , 1—6.

Helli B, Shahi MM, Mowla K, Jalali MT, Haghighian HK. A randomized, triple-blind, placebo-controlled clinical trial, evaluating the sesamin supplement effects on proteolytic enzymes, inflammatory markers, and clinical indices in women with rheumatoid arthritis. Phytother Res 33 9 —8.

Helli B, Mowla K, Mohammadshahi M, Jalali MT. Effect of sesamin supplementation on cardiovascular risk factors in women with rheumatoid arthritis. J Am Coll Nutr 35 4 —7. Thimóteo NSB, Iryioda TMV, Alfieri DF, Rego BEF, Scavuzzi BM, Fatel E, et al. Cranberry juice decreases disease activity in women with rheumatoid arthritis.

Nutrition —7. Fatel ECS, Rosa FT, Alfieri DF, Flauzino T, Scavuzzi BM, Lozovoy MAB, et al. Beneficial effects of fish oil and cranberry juice on disease activity and inflammatory biomarkers in people with rheumatoid arthritis.

Nutrition Hekmatpou D, Mortaji S, Rezaei M, Shaikhi M. The effectiveness of olive oil in controlling morning inflammatory pain of phalanges and knees among women with rheumatoid arthritis: A randomized clinical trial. Rehabil Nurs 45 2 — Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I.

Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 21 2 —6. Bitler CM, Matt K, Irving M, Hook G, Crea R.

Olive extract supplement decreases pain and improves daily activities in adults with osteoarthritis and decreases plasma homocysteine in those with rheumatoid arthritis. Nutr Res 27 8 —7. Amalraj A, Varma K, Jacob J, Divya C, Kunnumakkara AB, Stohs SJ, et al. A novel highly bioavailable curcumin formulation improves symptoms and diagnostic indicators in rheumatoid arthritis patients: A randomized, double-blind, placebo-controlled, two-dose, three-arm, and parallel-group study.

J Med Food 20 10 — Pourhabibi-Zarandi F, Rafraf M, Zayeni H, Asghari-Jafarabadi M, Ebrahimi AA. Fruit Basics All fruits have health benefits, but some have more disease-fighting properties than others.

Berries, for example are among some of the best fruits for arthritis. They are loaded with antioxidants, such ascorbic acid a form of vitamin C and anthocyanins and carotenoids, which give berries their deep color. These compounds also help rid the body of free radicals that promote inflammation and help prevent heart disease and certain cancers.

Whatever your favorite fruit, try to choose seasonal, locally grown produce says Mitzi Dulan, a Kansas City-based dietitian and team sports nutritionist for the Kansas City Royals.

Aim for five or more servings a day of fruit to your diet, which can help manage weight since most are low in calories. The fruits below boast some of the best benefits for people with arthritis and related conditions.

Tart cherries Tart cherries get their dark red color and many of their powerful anti-inflammatory and antioxidant benefits from the flavonoid anthocyanin.

Some researchers compare the anti-inflammatory properties of cherries to non-steroidal anti-inflammatory drugs NSAIDs. Studies, which often use the concentrated juice of Montmorency cherries, have found tart cherries may relieve joint pain in people with osteoarthritis OA and lower the risk of flares in those with gout.

In addition, recent studies suggest tart cherries may improve the quality and duration of sleep. Strawberries Strawberries are naturally low in sugar and have more vitamin C per serving than an orange. Vitamin C can lower risk for gout, high blood pressure and cholesterol problems.

Research has also shown that women who ate 16 or more strawberries a week had lower C-reactive protein CRP , a measure of body-wide inflammation linked to arthritis flares and heart disease. As with cherries, scientists suspect it is anthocyanin, along with other phytochemicals, that gives strawberries their anti-inflammatory and antioxidant health benefits.

Strawberries are also a good source of folic acid, which the arthritis medication methotrexate can deplete. People taking methotrexate often need folic acid supplements to help prevent side effects, but eating strawberries is still beneficial.

Red Raspberries Like strawberries, these berries are among the highest in vitamin C and anthocyanin. Animal studies have shown extracts from the fruit reduce inflammation and OA symptoms.

Avocado The rich, creamy texture of this fruit comes in part from its high concentration of anti-inflammatory monounsaturated fat. Avocados are also rich in the carotenoid lutein. Unlike most fruits, avocados are a good source of vitamin E, a micronutrient with anti-inflammatory effects.

Diets high in these compounds are linked to decreased risk of the joint damage seen in early OA.

Xnd diseases Aryhritis are a group of BCAA and muscle growth arthriti characterized by inflammation Lentils for hormonal balance functional disability. There is evidence suggesting that Polyphenolx consumption of polyphenols Polyphhenols therapeutic effects capable of relieving RD arthritix. To synthesize data from randomized BCAA and muscle growth trials on administration of polyphenols and their effects on RD activity. A systematic search was conducted in the databases PubMed MedlineLILACS BVSIBECS BVSCUMED BVSBINACIS BVSEMBASE, Web of Science and Cochrane Library and in the grey literature. The present study followed a PRISMA-P checklist. In total, articles were considered potentially eligible, of which 33 were then subjected to complete reading. Out of these, 17 randomized controlled trials articles were selected to form the final sample. RELIEVE RHEUMATIC DISEASES Used in herbal medicine as Polyphenoks natural anti-inflammatory to Arthrtis relieve joint arthriits. Concentrated formula composed of Nutrition for competitive runners BCAA and muscle growth Boswellia serrata. Helps relieve joint pain associated with arthritisrheumatismosteoarthritisrheumatoid arthritisetc. Improve physical performance and provide better recovery after physical effort. An antioxidant that helps fight against oxidation in the body protects cells from oxidative stress.