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.

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This meta-analysis found DC/cocoa intake has beneficial effects on the systemic oxidative status by reducing MDA and increasing NO.

Introduction

This systematic review and dose-response meta-analysis provides a comprehensive overview of the controlled trials (CTs) examining the effects of dark chocolate (DC)/cocoa on oxidative stress and inflammation biomarkers in adults.

Methods

Databases including PubMed, Web of Science, and Scopus, were searched for relevant studies through April 2024. The method was conducted according to PRISMA guidelines. Studies were selected on the following inclusion criteria:

• Results from controlled trials (CTs)
• Interventions using DC or cocoa with duration of at least two weeks
• Adult participants (18 ≤ years old)
• Studies assessing 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.

Based on the random-effects model, weighted mean differences (WMDs), standard mean differences (SMDs) and 95 % confidence intervals (CIs) were calculated. Sensitivity, sub-group, meta-regression and dose-response analyses were also conducted.

Results

• Thirty-three eligible CTs with 1379 participants were included.
• Trials were conducted on participants with cardiovascular disease (CVD), overweight and obesity, T2DM, hemodialysis, cancer, metabolic syndrome, HIV, and hypercholesterolemia.
• 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 < 0.001).
• No significant effects on the other outcomes were found.
• Greater anti-inflammatory effects occurred at higher flavonoid doses (>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.

Conclusion

DC/cocoa may improve systemic oxidative status and inflammation in adults. However, further studies should be performed to determine its benefits.

Limitations

• The main limitation was the heterogeneity of enrolled studies.
• Differences in duration of trials ranged from 2-12 weeks and type of cocoa supplementation, as well as the preparation method used, content and compositions.
• Age, gender, pharmaceuticals management, genetic and population lifestyle variation, may have influenced the results and should be considered when interpreting them.

• While, anti-inflammatory effects were observed in the higher dosages (> 450 mg/d) and shorter duration (≤ 4 weeks), the number of studies were not enough to draw conclusions and the certainty of evidence was not high for most outcomes.

• Future studies should assess the side effects/toxicity of cocoa and its products in high dosages.
• More high-quality future trials with appropriate design (considering randomisation, blinding assessment and independent testing for purity and potency) and larger sample sizes are needed to indicate the effect of DC/ cocoa on inflammation and oxidative stress.