RA is a chronic autoimmune inflammatory disease that leads to inflammation and joint pain that might affect other organs. Dietary components can affect the severity or improvement of the disease symptoms. Numerous studies have shown that coffee and tea consumption could increase inflammatory markers in these patients. On the other hand, a number of other studies have revealed the protective role of coffee and tea in RA. As a result, we conducted a systematic review and meta-analysis on relevant cohorts to summarize the findings of these studies. The results of our systematic review and meta-analysis of five cohort studies showed a significant association between coffee intake and the risk of RA. We found a similar positive association between decaffeinated coffee intake and the risk of RA. We did not observe significant associations between caffeine, caffeinated coffee and tea intake with the risk of RA.
In the present study, we found that higher coffee intake was associated with an increased risk of RA, which is consistent with the case-control study by Pedersen et al. who found a significant, positive association between coffee intake and the risk of RA 36. The possible mechanism by which coffee may associated with the increased risk of RA is related to the effect of coffee on the level of inflammatory markers. Zampelas et al., in a cohort study, found that IL-6 increased among those drinking more than 4 cups per day (28). However, there are studies that report conflicting results. Some studies have shown that coffee can exert anti-inflammatory and antioxidant effects due to compounds such as caffeine, cafestol, chlorogenic acid and trigonelline 37. This theory has been supported in some observational studies. The Nurses’ Health Study II showed a negative association between coffee consumption and c-reactive protein, interleukin-6, tumor necrosis factor alpha and other inflammatory markers 38.
Another mechanism for significant association between coffee intake and an increased risk of RA may be the lack of controlling for confounding variables such as physical activity, smoking, and other lifestyle-related factors. Studies have shown that people who consume higher amounts of coffee are more likely to be a smoker 39,40. Smoking is a risk factor for increased levels of inflammation and diseases such as RA 41. Our findings revealed that increased caffeine consumption was not related to an increase in risk of RA. Thus, besides caffeine, other chemical ingredients that are used in the growing or preparation of coffee may be responsible for this finding.
With regards to caffeinated coffee, we found no significant association between its intake and the risk of RA. Some studies have demonstrated that people who drank caffeinated coffee had higher levels of IL-6 compared to those consuming no coffee 42,43. On the other hand, Wedick et al., in a clinical trial, have shown that caffeinated coffee can increase adiponectin levels 43,44. Some studies have pointed out that adiponectin can play a pro-inflammatory role in the pathophysiology of autoimmune disease such as RA through stimulating the secretion of inflammatory mediators 45,46.
We also found a positive association between decaffeinated coffee consumption and the risk of RA. The mechanism involved seems to be the method of extracting caffeine from coffee by direct application of industrial solvents including benzene, acetone, ammonium hydroxide, sulfuric acid, ethyl acetate, methylene chloride, chloroform, ether, alcohol, trichloroethylene and carbon tetrachloride 47. Chronic ingestion of solvent residues, even small quantities, could result in connective tissue disorders such as scleroderma, lupus, and RA 48. Additionally, decaffeinated coffee has a smaller antioxidant capacity than regular coffee 49.
In our study, there was no significant relationship between tea consumption and the risk of RA. However, a case-control study in Iran showed an inverse association between tea consumption and the risk of RA 50. Similarly, Jin et al., in a cross-sectional study on RA patients, found an inverse association between high tea consumption (> 750 mL/day) and disease severity in patients with RA 51. A number of studies have also shown that tea consumption could have a beneficial effect on inflammatory factors which is due to catechins and other flavonoids 52,53. The null findings observed in our study may be due to the insufficient prospective cohort studies examining the association between tea intake and the incidence of inflammation and RA. Also, the included studies did not report the risk of RA according to the type of tea. Although the exact role of different types of tea in the pathogenesis of RA remains unknown, some publications have indicated that green tea has an immunomodulatory effect and, thus, can protect against RA 54. Furthermore, Rambod et al., in a case-control study, showed that green tea intake was correlated with a 35% decreased risk of RA 55. On the other hand, there are studies that have indicated that black tea intake was not associated with the level of inflammatory markers 56–58. Given that all types of tea are processed differently, this may lead to changes in chemical ingredients and finally different properties 15.
We did not observe a significant relationship between caffeine intake and the risk of RA. Our finding is in agreement with a previous systematic review on clinical trials indicating that caffeine has no definite role in short-term inflammatory responses and these pathways are not clearly understood 59. However, a cross-sectional study found a statistically significant reduction in disease activity and cytokine levels in systemic lupus erythematosus patients who had higher intakes of caffeine 60. It was shown that caffeine metabolites, such as xanthine and theobromine, have antioxidant activities and decrease hydroxyl radicals 61. Also, it is believed that caffeine has an adenosine antagonist effect and can induce a decrease in cytokine production 62.
The present study has some strengths that should be acknowledged. Unlike previous meta-analyses, we performed a dose-response analysis which has provided more precise results than the highest versus lowest analysis. Also, we assessed the association of different types of coffee (caffeinated vs. decaffeinated) with RA which revealed their different effects on RA. Moreover, the included studies were a cohort with a relatively large sample size which increased the generalizability of the findings and statistical inferences.
In spite of these strengths, this study has some limitations which should be taken into account when interpreting the results. First, our study included a small number of publications that weakened the interpretation of the relationships in the meta-analyses. Second, the results are subject to residual confounding because of the cohort design of the included studies. Third, most of the included studies used a food frequency questionnaire to evaluate dietary intake and, therefore, measurement error and misclassification of the study participants in terms of exposure were inevitable. Finally, the size of the cup of coffee and tea in the entire study was not determined, which could influence the observed associations.