Effect of dark chocolate/ cocoa consumption on oxidative stress and inflammation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of controlled trials

Background: Oxidative stress and inflammation play critical roles in the pathogenesis of many chronic diseases. Dark chocolate (DC)/cocoa, as a rich source of polyphenols like flavonoids, has anti-inflammatory and antioxidant properties that may confer health benefits, but findings in this context are inconsistent. Objective: This systematic review and dose-response meta-analysis aimed to provide a comprehensive overview of the controlled trials (CTs) that have examined the effects of DC/cocoa on oxidative stress and inflammation biomarkers in adults. Search methods: Databases including PubMed, Web of Science, and Scopus, were searched for relevant studies through April 2024. selection criteria: Studies assessed C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), nitric oxide (NO), P-selectin, E-selectin and thiobarbituric acid reactive substances (TBARS) in adults were included. Data analysis: Based on the random-effects model, we calculated WMDs, SMDs and 95 % confidence intervals (CIs). Sensitivity, sub-group, meta-regression and dose-response analyses were also conducted. Results: Thirty-three eligible CTs with 1379 participants were included. All studies reported the intervention types (cocoa powder, beverages and chocolate bars) and dosage. However, sixteen studies didn’t do/report testing for purity and potency by independent groups. Also, none of the studies mentioned the risk of contamination with heavy metals. Another limitation was the lack of blinding assessment in studies. DC/cocoa significantly reduced MDA (SMD: −0.69, 95 %CI: −1.17, −0.2, p = 0.005) and increased NO levels (SMD: 2.43, 95 %CI: 1.11,3.75, p 450 mg/day) and for shorter durations (≤4 weeks) in the non-healthy participants. Non-linear dose-response relationships between cocoa dosage and CRP level and also between flavonoid dosage and IL-6 level were observed. Based on the GRADE evaluation, just CRP and MDA results were considered as high certainty evidence and the other outcomes results were categorized as very low to moderate certainty. Conclusions: DC/cocoa may improve systemic oxidative status and inflammation in adults. However, further studies should be performed to determine its benefits.