Pure cocoa

Cardiometabolic Impact of Encapsulated Cocoa Powder and Pure Cocoa Ingredients Supplementation: A Comparative Placebo‐Controlled RCT in Adults

Type of study: rct

Number of citations: 0

Year: 2025

Authors: Janina Weigant, Anuschka Afchar, Meike Barzen, L. Dicks, B. Zimmermann, Matthias Schmid, L. Weinhold, Birgit Stoffel-Wagner, Jörg Ellinger, Peter Stehle, S. Ellinger

Journal: Molecular Nutrition & Food Research

Journal ranking: Q1

Key takeaways: Daily intake of flavanol-rich cocoa or pure cocoa ingredients does not significantly influence vascular function and lipid profiles in healthy adults.

Abstract: ABSTRACT Consuming cocoa rich in flavan‐3‐ols (particularly epicatechin [EC]) may reduce vascular stiffness and blood pressure (BP) and improve serum lipid profiles. Because interventional studies on pure EC exhibited inconclusive results, the role of other cocoa ingredients such as methylxanthines (MX) on vascular health was assumed. This study aimed to systematically compare the effects of flavanol‐rich cocoa and its major components EC and MX on vascular function and serum lipid levels. In a randomized controlled trial (RCT), 75 healthy young adults ingested capsules containing either (i) flavanol‐rich cocoa powder, (ii) EC, (iii) MX, (iv) EC + MX, or (v) placebo (n = 15 per group) daily for 4 weeks. Capsules provided equal amounts of EC and/or MX as the cocoa capsules. Pulse wave velocity (PWV), BP, endothelin‐1, and lipids were investigated before and after intervention. No group‐specific statistically significant differences in aortic PWV (p = 0.410) or any other parameters (p ≥ 0.05) were observed between before and after the intervention. Daily intake of neither flavanol‐rich cocoa nor pure cocoa ingredients influenced vascular function and lipid profiles in healthy adults. Consequently, RCTs involving subjects with increased cardiometabolic risk may clarify the effects of EC and MX as cocoa components on cardiovascular health parameters. Trial Registration: URL: https://drks.de/search/en/trial. Unique identifier: DRKS00022056

Cocoa, Blood Pressure, and Vascular Function

Type of study:

Number of citations: 106

Year: 2017

Authors: Valeria Ludovici, Jens Barthelmes, M. Nägele, F. Enseleit, C. Ferri, A. Flammer, F. Ruschitzka, I. Sudano

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: Cocoa and chocolate consumption can reduce blood pressure and improve vascular function, potentially reducing the risk of cardiovascular diseases.

Abstract: Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

Cocoa and Cardiovascular Health

Type of study: literature review

Number of citations: 409

Year: 2009

Authors: R. Corti, A. Flammer, N. Hollenberg, T. Lüscher

Journal: Circulation

Journal ranking: Q1

Key takeaways: Cocoa may have beneficial effects on blood pressure, insulin resistance, and vascular and platelet function, potentially through activation of nitric oxide and antioxidant and antiinflammatory effects.

Abstract: Epidemiological data demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease and stroke. Among many ingredients, cocoa might be an important mediator. Indeed, recent research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert its benefits on cardiovascular health have been proposed, including activation of nitric oxide and antioxidant and antiinflammatory effects. This review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption.

Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial

Type of study: rct

Number of citations: 11

Year: 2022

Authors: H. Sesso, J. Manson, A. Aragaki, P. Rist, L. Johnson, G. Friedenberg, T. Copeland, Allison Clar, S. Mora, M. V. Moorthy, A. Sarkissian, William R Carrick, G. Anderson, H. Sesso, Susanne Rautiainen Lagerstrom, S. Bassuk, Lu-Xuan Wang, A. Hazra, Heike Gibson, M. LeBoff, O. Okereke, Deirdre K. Tobias, N. Cook, P. Chandler, W. Christen, Jasmah Hanna, Denise D’Agostino, M. Vinayagamoorthy, Eunjung Kim, Martin Van Denburgh, G. Kotler, Chunying Li, V. Bubes, Douglas C Smith, E. C. Pereira, Melvyn Okeke, Elise Roche, D. Bates, Claire Ridge, Alexandra Phillips, Brielle Salvo, Anna S Wilson, Leah Hall, Jimaldy Baez, Young-Hwan Sim, Hayara Cardoso, Gabriel Senor, Connor Rudnicki, Hanh Huynh, V. Nguyen, Nicholas Terrell, Beth A Holman, J. Walter, L. Johnson, Amy Casarella, J. O'connell, L. Djoussé, D. K. Tobias, Zareen M. Farukhi, Xuehong Zhang, K. Breen, George V Menjin Jr, Rolando Rodriguez, Shamikhah Curry, Leah Arsenault, Olubunmi Solano, Alison Weinberg, Jennifer Coates, Matthew Kilroe, Lincoln Zernicke, Katelyn Hasson, Karen Matthew, C. Pfeffer, J. Duszlak, Vincent Guzman, J. Falcon, A. Romero, Henry Kupets, F. Cortez, James C LeSuer, Andrea L. Hrbek, Eileen Bowes, P. Quinn, Megan Mele, G. Anderson, L. Johnson, L. Tinker, A. Aragaki, M. Herndon, S. L. Mann, M. Pettinger, Rebecca P. Hunt, Bill Carrick, Kate Szyperski, Lori Proulx-Burns, Elizabeth Burrows, M. Limacher, J. Hsia, G. Asaithambi, Muhib M. Khan, N. Nagaraja, Lenore C. Ocava, Jana Wold, Brian Silver, S. Connelly, Gretchen Van Lom, Cris Garvida, Kathy Hightower, Patricia Spaulding, W. Lin, Jane Schoenberg, Patti Olee, Lawrence S. Cohen, T. Colton, I. Henderson, S. Hulley, A. Lichtenstein, E. Passamani, R. Silliman, N. Wenger, S. Ludlam, H. Schroeter, Michel Faré, Javier Ottawani, C. Kwik-Uribe, Cassandra Arnaiz, A. Costanza, J. Greene, P. Hennessey, S. Vadlamani, Mallik Karmsetty, Paul Martini, Jan-Willem van Klinken, Alpa Shah, Lori Stern

Journal: The American Journal of Clinical Nutrition

Journal ranking: Q1

Key takeaways: Cocoa extract supplementation did not significantly reduce total cardiovascular events in older adults, but reduced cardiovascular death by 27%.

Abstract: ABSTRACT Background Cocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested. Objectives We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. Methods We conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (–)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. Results During a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. Conclusions Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.

Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials.

Type of study: meta-analysis

Number of citations: 591

Year: 2012

Authors: L. Hooper, C. Kay, A. Abdelhamid, P. Kroon, J. Cohn, E. Rimm, A. Cassidy

Journal: The American journal of clinical nutrition

Journal ranking: Q1

Key takeaways: Chocolate or cocoa may improve flow-mediated dilatation and have promising effects on insulin and HOMA-IR, but larger, longer-duration, and independently funded trials are needed to confirm these potential benefits.

Abstract: BACKGROUND There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). OBJECTIVE The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. DESIGN We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. RESULTS We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. CONCLUSIONS We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.

Effects of Cocoa Consumption on Cardiometabolic Risk Markers: Meta-Analysis of Randomized Controlled Trials

Type of study: meta-analysis

Number of citations: 1

Year: 2024

Authors: Tainah O P Arisi, Diego Silveira da Silva, Elana Stein, C. Weschenfelder, Patrícia Caetano de Oliveira, Aline Marcadenti, A. Lehnen, Gustavo Waclawovsky

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Cocoa consumption has protective effects on major cardiometabolic risk markers, potentially reducing cardiovascular risk.

Abstract: Background: We conducted a systematic review and meta-analysis to examine the effect of dietary intake of cocoa on anthropometric measurements, lipid and glycemic profiles, and blood pressure levels in adults, with and without comorbidities. Methods: The databases used were MEDLINE (PubMed), EMBASE, Web of Science, Cochrane, LILACS, and SciELO. The eligible studies were randomized clinical trials (RCTs) involving adults undergoing cocoa consumption (cocoa extract or ≥70% cocoa dark chocolate) for ≥4 weeks that evaluated at least one of the following markers: body weight, body mass index (BMI), waist/abdominal circumference, total cholesterol, LDL-c, triglycerides, HDL-c, blood glucose, glycated hemoglobin (HbA1c), and systolic and diastolic blood pressure (SBP/DBP). Results: Thirty-one studies were included, totaling 1986 participants. Cocoa consumption showed no effects on body weight, BMI, waist circumference, triglycerides, HDL-c and HbA1c. Yet, there was a reduction in total cholesterol (−8.35 mg/dL, 95% CI −14.01; −2.69 mg/dL), LDL-c (−9.47 mg/dL, 95% CI −13.75; −5.20 mg/dL), fasting blood glucose (−4.91 mg/dL, 95% CI −8.29; −1.52 mg/dL), SBP (−2.52 mmHg, 95% CI −4.17; −0.88 mmHg), and DBP (−1.58 mmHg, 95% CI −2.54; −0.62 mmHg). Conclusions: The consumption of cocoa showed protective effects on major cardiometabolic risk markers that have a clinical impact in terms of cardiovascular risk reduction.

Effects of bioactive constituents in functional cocoa products on cardiovascular health in humans.

Type of study: non-rct experimental

Number of citations: 63

Year: 2015

Authors: B. Sarriá, Sara Martínez-López, José Luis Sierra-Cinos, L. García‐Diz, L. Goya, R. Mateos, L. Bravo

Journal: Food chemistry

Journal ranking: Q1

Key takeaways: Cocoa products rich in dietary fiber, flavanols, and methylxanthines improve cardiovascular health by increasing HDL-cholesterol, reducing glucose, and IL-1 levels.

The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease.

Type of study:

Number of citations: 159

Year: 2006

Authors: M. Engler, M. Engler

Journal: Nutrition reviews

Journal ranking: Q1

Key takeaways: Cocoa and chocolate are rich sources of flavonoid-rich compounds with beneficial cardiovascular properties, including antioxidant activity, vasodilation, blood pressure reduction, platelet inhibition, and decreased inflammation.

Abstract: Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.

Cardioprotective effects of cocoa: clinical evidence from randomized clinical intervention trials in humans.

Type of study: literature review

Number of citations: 85

Year: 2013

Authors: S. Arranz, P. Valderas-Martínez, G. Chiva-Blanch, R. Casas, M. Urpi-Sardà, R. Lamuela-Raventós, R. Estruch

Journal: Molecular nutrition & food research

Journal ranking: Q1

Key takeaways: Cocoa and cocoa products contain flavonoids that may reduce cardiovascular risk factors by reducing oxidative stress, inhibiting platelet aggregation, and maintaining normal blood flow.

Abstract: Cocoa is an important source of polyphenols, which comprise 12-18% of its total dry weight. The major phenolic compounds in cocoa and cocoa products are mainly flavonoids such as epicatechin, catechin, and proanthocyanidins. These products contain higher amounts of flavonoids than other polyphenol-rich foods. However, the bioavailability of these compounds depends on other food constituents and their interactions with the food matrix. Many epidemiological and clinical intervention trials have concluded that the ingestion of flavonoids reduces the risk factors of developing cardiovascular disease. This review summarizes the new findings regarding the effects of cocoa and chocolate consumption on cardiovascular risk factors. The mechanisms involved in the cardioprotective effects of cocoa flavonoids include reduction of oxidative stress, inhibition of low-density lipoproteins oxidation and platelet aggregation, vasodilatation of blood vessels, inhibition of the adherence of monocytes to vascular endothelium, promotion of fibrinolysis, and immunomodulatory and anti-inflammatory activity. Scientific evidence supports a cause and effect relationship between consumption of cocoa flavonoids and the maintenance of normal endothelium-dependent vasodilation, which contributes to normal blood flow. However, larger randomized trials are required to definitively establish the impact of cocoa and cocoa products consumption on hard cardiovascular outcomes.

Effect of cocoa on blood pressure.

Type of study: meta-analysis

Number of citations: 66

Year: 2017

Authors: K. Ried, Peter Fakler, N. Stocks

Journal: The Cochrane database of systematic reviews

Journal ranking: Q1

Key takeaways: Flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.

Abstract: BACKGROUND High blood pressure is an important risk factor for cardiovascular disease, contributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular-related deaths in Western populations. Epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Here we update previous meta-analyses on the effect of cocoa on blood pressure. OBJECTIVES To assess the effects on blood pressure of chocolate or cocoa products versus low-flavanol products or placebo in adults with or without hypertension when consumed for two weeks or longer. SEARCH METHODS This is an updated version of the review initially published in 2012. In this updated version, we searched the following electronic databases from inception to November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and Embase. We also searched international trial registries, and the reference lists of review articles and included trials. SELECTION CRITERIA Randomised controlled trials (RCTs) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the risks of bias in each trial. We conducted random-effects meta-analyses on the included studies using Review Manager 5. We explored heterogeneity with subgroup analyses by baseline blood pressure, flavanol content of control group, blinding, age and duration. Sensitivity analyses explored the influence of unusual study design. MAIN RESULTS Thirty-five trials (including 40 treatment comparisons) met the inclusion criteria. Of these, we added 17 trials (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the previous version of this updated review.Trials provided participants with 30 to 1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. The control group received either a flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment comparisons; 259 mg, 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration (mean nine weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804 participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (-2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772 participants.Baseline blood pressure may play a role in the effect of cocoa on blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people (n = 9 treatment comparisons, 401 participants), and tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340 participants), there was no significant difference in normotensive people (n = 23 treatment comparisons, 1063 participants); however, the test for subgroup differences was of borderline significance (P = 0.08; I2 = 60%), requiring further research to confirm the findings.Subgroup meta-analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials, albeit statistically not significant. Further research is needed to confirm whether participant expectation may influence blood pressure results. Subgroup analysis by type of control (flavanol-free versus low-flavanol control) did not reveal a significant difference.Whether the age of participants plays a role in the effect of cocoa on blood pressure, with younger participants responding with greater blood pressure reduction, needs to be further investigated.Sensitivity analysis excluding trials with authors employed by trials sponsoring industry (33 trials, 1482 participants) revealed a small reduction in effect size, indicating some reporting bias.Due to the remaining heterogeneity, which we could not explain in terms of blinding, flavanol content of the control groups, age of participants, or study duration, we downgraded the quality of the evidence from high to moderate.Results of subgroup analyses should be interpreted with caution and need to be confirmed or refuted in trials using direct randomised comparisons.Generally, cocoa products were highly tolerable, with adverse effects including gastrointestinal complaints and nausea being reported by 1% of participants in the active cocoa intervention group and 0.4% of participants in the control groups (moderate-quality evidence). AUTHORS' CONCLUSIONS This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.These findings are limited by the heterogeneity between trials, which could not be explained by prespecified subgroup analyses, including blinding, flavanol content of the control groups, age of participants, or study duration. However, baseline blood pressure may play a role in the effect of cocoa on blood pressure; subgroup analysis of trials with (pre)hypertensive participants revealed a greater blood pressure-reducing effect of cocoa compared to normotensive participants with borderline significance.Long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals

Type of study: rct

Number of citations: 112

Year: 2015

Authors: D. Grassi, G. Desideri, S. Necozione, P. di Giosia, R. Barnabei, L. Allegaert, H. Bernaert, C. Ferri

Journal: Journal of Hypertension

Journal ranking: Q1

Key takeaways: Cocoa consumption dose-dependently improves flow-mediated dilation, decreases arterial stiffness, and lowers blood pressure, making it a potential tool in cardiovascular prevention.

Abstract: Background: Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose–response effects. Objectives: We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. Design: According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Results: Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P < 0.0001). Compared with the control, even 80 mg cocoa flavonoids per day increased FMD (P < 0.0001). Cocoa dose-dependently decreased PWV (P < 0.0001). Cocoa intake decreased office blood pressure (BP) (SBP: −4.8 ± 1.03 mmHg, P < 0.0001; DBP: −3.03 ± 1.07 mmHg, P = 0.0011). With respect to control, cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment <0.05)]. Compared with the control, significant changes were observed for all doses of flavonoids (ET-1; P < 0.05). Conclusion: Our study showed for the first time that cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies.

Type of study: meta-analysis

Number of citations: 231

Year: 2011

Authors: M. Shrime, Scott R. Bauer, Anna McDonald, N. Chowdhury, C. Coltart, E. Ding

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Flavonoid-rich cocoa consumption significantly improves blood pressure, insulin resistance, lipid profiles, and flow-mediated vascular dilation in short-term studies.

Abstract: A growing body of evidence suggests that the consumption of foods rich in polyphenolic compounds, particularly cocoa, may have cardioprotective effects. No review, however, has yet examined the effect of flavonoid-rich cocoa (FRC) on all major cardiovascular risk factors or has examined potential dose-response relationships for these effects. A systematic review and meta-analysis of randomized, controlled trials was performed to evaluate the effect of FRC on cardiovascular risk factors and to assess a dose-response relationship. Inclusion and exclusion criteria as well as dependent and independent variables were determined a priori. Data were collected for: blood pressure, pulse, total cholesterol, HDL cholesterol, LDL cholesterol, TG, BMI, C-reactive protein, flow-mediated vascular dilation (FMD), fasting glucose, fasting insulin, serum isoprostane, and insulin sensitivity/resistance indices. Twenty-four papers, with 1106 participants, met the criteria for final analysis. In response to FRC consumption, systolic blood pressure decreased by 1.63 mm Hg (P = 0.033), LDL cholesterol decreased by 0.077 mmol/L (P = 0.038), and HDL cholesterol increased by 0.046 mmol/L (P = 0.037), whereas total cholesterol, TG, and C-reactive protein remained the same. Moreover, insulin resistance decreased (HOMA-IR: -0.94 points; P < 0.001), whereas FMD increased (1.53%; P < 0.001). A nonlinear dose-response relationship was found between FRC and FMD (P = 0.004), with maximum effect observed at a flavonoid dose of 500 mg/d; a similar relationship may exist with HDL cholesterol levels (P = 0.06). FRC consumption significantly improves blood pressure, insulin resistance, lipid profiles, and FMD. These short-term benefits warrant larger long-term investigations into the cardioprotective role of FRC.

Cocoa, blood pressure, and cardiovascular health.

Type of study:

Number of citations: 39

Year: 2015

Authors: C. Ferri, G. Desideri, L. Ferri, Ilenia Proietti, Stefania Di Agostino, Letizia Martella, Francesca Mai, P. di Giosia, D. Grassi

Journal: Journal of agricultural and food chemistry

Journal ranking: Q1

Key takeaways: Cocoa-rich products may reduce the risk of cardiovascular disease due to their high content in flavanols, which may lower blood pressure and protect against cardiovascular events and strokes.

Abstract: High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and "nutraceutical " viewpoints.

Cardioprotective Mechanisms of Cocoa

Type of study: literature review

Number of citations: 10

Year: 2019

Authors: K. Zięba, M. Makarewicz-Wujec, M. Kozłowska-Wojciechowska

Journal: Journal of the American College of Nutrition

Journal ranking: Q2

Key takeaways: Cocoa consumption, especially dark chocolate with high flavonoid content, may help diminish cardiovascular risk due to beneficial effects on platelet aggregation, blood pressure, dyslipidemia, glycemia, and antioxidant and anti-inflammatory activity.

Abstract: Abstract Cardiovascular diseases are the main cause of deaths in highly developed countries. Dietetic interventions that involve recommendations for consumption of products with a confirmed health-improving action are an important aspect of prevention of cardiovascular diseases. Cocoa is an alimentary product with significant cardioprotective potential due to its high content of bioactive compounds. The aim of the present study was to review the most recent literature concerning the effectiveness and mechanisms of action of compounds contained in cocoa with regard to selected cardiovascular risk factors and cardiometabolic markers. Study results indicate that cocoa consumption, especially in the form of dark chocolate with high flavonoid content, may be a good strategy to diminish cardiovascular risk due to its beneficial effect on platelet aggregation, decreasing blood pressure, diminishing dyslipidemia, and decreasing blood plasma glucose concentration. Many studies have shown that cocoa-derived flavonoids have antioxidant and anti-inflammatory activity and also play a significant role in preventing insulin resistance. However, in order to completely confirm the potential cardiovascular benefits, it is necessary to conduct larger and longer studies, also with regard to potential dangers associated with long-term consumption of large amounts of flavonoids and determination of a safe and effective dose. Key teaching points Cocoa consumption may be a good strategy in diminishing cardiovascular risk. Beneficial effects on platelet aggregation, blood pressure, dyslipidemia, glycemia, as well as antioxidant and anti-inflammatory activity are observed. There is a need to conduct larger and longer studies to determine a safe and effective dose of cocoa flavonoids.

THE INFLUENCE OF COCOA ON THE CARDIOVASCULAR SYSTEM

Type of study:

Number of citations: 0

Year: 2019

Authors: Inesa Jahić, Amra Bašić, M. Šabanović

Journal:

Journal ranking: brak

Key takeaways: Cocoa and chocolate have numerous positive effects on cardiovascular diseases due to their high content of flavonoids, including antioxidant, anti-inflammatory, and antithrombotic effects.

Abstract: Cocoa contains a range of chemicals that can interact with cells and tissue components, providing protection against the development and improvement of pathological conditions. The most important effects of cocoa and chocolate are related to cardiovascular disease. Due to the high content of flavonoids, it has numerous positive effects on cardiovascular diseases, including: antioxidant, anti-inflammatory, antithrombotic effects, and possibly increased HDL, lowering blood pressure and improving endothelial function. The beneficial effects of cocoa are most likely a consequence of reducing oxidative stress and increasing the bioavailability of nitric oxide. Although many positive effects of chocolate on the cardiovascular system have been proven, precautions in its use are mandatory.

Chocolate and Prevention of Cardiovascular Disease: A Systematic Review

Type of study: systematic review

Number of citations: 268

Year: 2006

Authors: Eric L Ding, Susan M Hutfless, Xin Ding, S. Girotra

Journal: Nutrition & Metabolism

Journal ranking: Q1

Key takeaways: Chocolate's flavonoid content may reduce the risk of cardiovascular mortality, while stearic acid may be neutral and stearic acid may be cholesterol-neutral.

Abstract: Consumption of chocolate has been often hypothesized to reduce the risk of cardiovascular disease (CVD) due to chocolate's high levels of stearic acid and antioxidant flavonoids. However, debate still lingers regarding the true long term beneficial cardiovascular effects of chocolate overall.We reviewed English-language MEDLINE publications from 1966 through January 2005 for experimental, observational, and clinical studies of relations between cocoa, cacao, chocolate, stearic acid, flavonoids (including flavonols, flavanols, catechins, epicatechins, and procynadins) and the risk of cardiovascular disease (coronary heart disease (CHD), stroke). A total of 136 publications were selected based on relevance, and quality of design and methods. An updated meta-analysis of flavonoid intake and CHD mortality was also conducted.The body of short-term randomized feeding trials suggests cocoa and chocolate may exert beneficial effects on cardiovascular risk via effects on lowering blood pressure, anti-inflammation, anti-platelet function, higher HDL, decreased LDL oxidation. Additionally, a large body of trials of stearic acid suggests it is indeed cholesterol-neutral. However, epidemiologic studies of serum and dietary stearic acid are inconclusive due to many methodologic limitations. Meanwhile, the large body of prospective studies of flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality. Our updated meta-analysis indicates that intake of flavonoids may lower risk of CHD mortality, RR = 0.81 (95% CI: 0.71-0.92) comparing highest and lowest tertiles.Multiple lines of evidence from laboratory experiments and randomized trials suggest stearic acid may be neutral, while flavonoids are likely protective against CHD mortality. The highest priority now is to conduct larger randomized trials to definitively investigate the impact of chocolate consumption on long-term cardiovascular outcomes.

Effects of cocoa consumption on cardiometabolic risk markers: Protocol for a systematic review and meta-analysis of randomized controlled trials

Type of study: meta-analysis

Number of citations: 1

Year: 2024

Authors: Tainah O P Arisi, Diego Silveira da Silva, Elana Stein, C. Weschenfelder, Patrícia Caetano de Oliveira, A. Marcadenti, A. Lehnen, Gustavo Waclawovsky

Journal: PLOS ONE

Journal ranking: Q1

Key takeaways: Cocoa consumption may have beneficial effects on cardiometabolic risk markers, but the appropriate quantities and timing of consumption need further investigation.

Abstract: Background Cardiometabolic diseases cover a spectrum of interrelated conditions linked to metabolic dysfunctions and/or cardiovascular disorders, including systemic arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. Cocoa is a rich source of dietary polyphenols and has been associated with cardiovascular health benefits. However, beneficial effects of cocoa consumption and appropriate quantities in decreasing cardiometabolic risk factors have yet to be established. Therefore, we will conduct a systematic review and meta-analysis to examine the effects of cocoa consumption on cardiometabolic risk markers (total cholesterol, HDL, LDL, triglycerides, blood glucose, glycated hemoglobin, waist circumference, abdominal circumference, body mass index, systolic blood pressure and diastolic blood pressure) in adults with or without established cardiovascular risk factors. Methods Our review will include all randomized controlled trials published in English, Portuguese and Spanish with no date of publication restrictions evaluating the effects of cocoa consumption on cardiometabolic risk markers selected from the databases MEDLINE (PubMed), LILACS, Cochrane, EMBASE, Web of Science and SciELO, and gray literature. Eligible studies must involve adults (age ≥18y), and the consumption of cocoa or dark chocolate (≥ 70% cocoa), include a control group and evaluate blood pressure, anthropometric measurements, and lipid or glycemic profiles. We will use risk-of-bias 2 (RoB2) tool to assess the risk of bias and the GRADE system to assess the strength of evidence. Statistical analyses will be performed using RStudio for Windows and R package meta. Discussion This meta-analysis will summarize existing evidence on the effects of cocoa consumption on cardiometabolic health in adults. Better understanding the effects of cocoa consumption on anthropometric measurements, blood pressure, and lipid and glycemic profiles can provide valuable insights for health professionals to improve dietary recommendations regarding appropriate quantities. Trial registration Systematic Review Registration: PROSPERO CRD42023484490.

New light on changes in the number and function of blood platelets stimulated by cocoa and its products

Type of study: systematic review

Number of citations: 2

Year: 2024

Authors: Beata Olas

Journal: Frontiers in Pharmacology

Journal ranking: Q1

Key takeaways: Cocoa consumption, especially dark chocolate, has anti-platelet activity and may play a significant role in cardioprotection, reducing cardiovascular risk.

Abstract: Hyperactivation of blood platelets, one of the causes of heart attack, and other cardiovascular diseases (CVDs), is influenced by various dietary components, including phenolic compounds from vegetables, fruits, teas, wines, cocoa and its products, including chocolate. The present paper sheds new light on the effect of cocoa and its products, especially dark chocolate, on the number and function of blood platelets, and the anti-platelet activity of their constituent phenolic compounds. A review was performed of papers identified in various electronic databases, including PubMed, Science Direct, Scopus, Web of Knowledge, and Google Scholar, with the aim of determining whether their anti-platelet activity may serve as part of a sweet strategy in countering CVDs. Various studies demonstrate that cocoa consumption, especially in the form of dark chocolate, with a high flavanol concentration, has anti-platelet activity and may play a significant role in cardioprotection; they also note that cocoa consumption may be a good strategy in diminishing cardiovascular risk, including hyperactivation of blood platelets.

Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies.

Type of study: rct

Number of citations: 93

Year: 2017

Authors: R. Sansone, Javier I. Ottaviani, A. Rodriguez-Mateos, Y. Heinen, Dorina Noske, J. Spencer, A. Crozier, M. Merx, M. Kelm, H. Schroeter, C. Heiss

Journal: The American journal of clinical nutrition

Journal ranking: Q1

Key takeaways: Cocoa flavanols and methylxanthines interact to enhance the beneficial cardiovascular effects of cocoa flavanols, such as increased flow-mediated vasodilation and decreased blood pressure.

Abstract: BACKGROUND Cocoa flavanol intake, especially that of (-)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function. OBJECTIVE We sought to determine whether an interaction between cocoa flavanols and methylxanthines exists that influences cocoa flavanol-dependent vascular effects. DESIGN Test drinks that contained various amounts of cocoa flavanols (0-820 mg) and methylxanthines (0-220 mg), either together or individually, were consumed by healthy volunteers (n = 47) in 4 different clinical studies-3 with a randomized, double-masked crossover design and 1 with 4 parallel crossover studies. Vascular status was assessed by measuring flow-mediated vasodilation (FMD), brachial pulse wave velocity (bPWV), circulating angiogenic cells (CACs), and blood pressure before and 2 h after the ingestion of test drinks. RESULTS Although cocoa flavanol intake increased FMD 2 h after intake, the consumption of cocoa flavanols with methylxanthines resulted in a greater enhancement of FMD. Methylxanthine intake alone did not result in statistically significant changes in FMD. Cocoa flavanol ingestion alone decreased bPWV and diastolic blood pressure and increased CACs. Each of these changes was more pronounced when cocoa flavanols and methylxanthines were ingested together. It is important to note that the area under the curve of the plasma concentration of (-)-epicatechin metabolites over time was higher after the co-ingestion of cocoa flavanols and methylxanthines than after the intake of cocoa flavanols alone. Similar results were obtained when pure (-)-epicatechin and the methylxanthines theobromine and caffeine were consumed together. CONCLUSION A substantial interaction between cocoa flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concentration of (-)-epicatechin metabolites that coincides with enhanced vascular effects commonly ascribed to cocoa flavanol intake. This trial was registered at clinicaltrials.gov as NCT02149238.

Effects of Cocoa-Rich Chocolate on Blood Pressure, Cardiovascular Risk Factors, and Arterial Stiffness in Postmenopausal Women: A Randomized Clinical Trial

Type of study: rct

Number of citations: 17

Year: 2020

Authors: Irene A. Garcia-Yu, L. García‐Ortiz, M. Gomez-Marcos, E. Rodríguez-Sánchez, C. Agudo-Conde, J. González-Sánchez, J. Maderuelo-Fernández, J. Recio-Rodríguez

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Daily intake of 10g of cocoa-rich chocolate provides little improvement in cardiovascular health and does not cause adverse effects in postmenopausal women over the long term.

Abstract: This study aimed to evaluate the effects of the intake of 10 g of cocoa-rich chocolate on blood pressure, other cardiovascular risk factors, and vascular structure and function in postmenopausal women. A total of 140 postmenopausal women participated in this randomized and controlled parallel clinical trial. For six months, the intervention group (IG; n = 73) consumed daily 10 g of chocolate (99% cocoa) added to their usual food intake, whereas the control group (CG; n = 67) did not receive any intervention. Blood pressure, pulse pressure (PP), cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), augmentation index, and laboratory variables were measured at baseline and six months. ANCOVA analyses adjusted for baseline values revealed no significant differences for systolic blood pressure (−1.45 mm Hg; 95% confidence interval (CI): −4.79, 1.88; p = 0.391) or baPWV (0.18 m/s; 95% CI: −0.14, 0.50; p = 0.263) between groups. A decrease in PP was observed in the IG compared to the CG (−2.05 mm Hg; 95% CI: −4.08, −0.02; p = 0.048). The rest of the vascular structure and function parameters and other measured variables remained unchanged. The daily intake of 10 g of cocoa-rich chocolate seems to provide little improvement to cardiovascular health, but neither does it cause any adverse effects on the parameters evaluated in postmenopausal women in the long term.

Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial

Type of study: rct

Number of citations: 46

Year: 2022

Authors: Laura D. Baker, J. Manson, S. Rapp, H. Sesso, S. Gaussoin, S. Shumaker, M. Espeland

Journal: Alzheimer's & Dementia

Journal ranking: Q1

Key takeaways: Cocoa extract and a multivitamin-mineral supplement may improve cognition in older women and men when taken together.

Abstract: Dietary supplements are touted for cognitive protection, but supporting evidence is mixed. COSMOS‐Mind tested whether daily administration of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin‐mineral (MVM) versus placebo improved cognition in older women and men.

The neuroprotective effects of cocoa flavanol and its influence on cognitive performance.

Type of study: literature review

Number of citations: 222

Year: 2013

Authors: A. Nehlig

Journal: British journal of clinical pharmacology

Journal ranking: Q1

Key takeaways: Cocoa flavanols, particularly epicatechin, improve cognitive performance, brain health, and reduce the risk of Alzheimer's disease and stroke.

Abstract: Cocoa powder and chocolate contain numerous substances among which there is a quite large percentage of antioxidant molecules, mainly flavonoids, most abundantly found in the form of epicatechin. These substances display several beneficial actions on the brain. They enter the brain and induce widespread stimulation of brain perfusion. They also provoke angiogenesis, neurogenesis and changes in neuron morphology, mainly in regions involved in learning and memory. Epicatechin improves various aspects of cognition in animals and humans. Chocolate also induces positive effects on mood and is often consumed under emotional stress. In addition, flavonoids preserve cognitive abilities during ageing in rats, lower the risk for developing Alzheimer's disease and decrease the risk of stroke in humans. In addition to their beneficial effects on the vascular system and on cerebral blood flow, flavonoids interact with signalization cascades involving protein and lipid kinases that lead to the inhibition of neuronal death by apoptosis induced by neurotoxicants such as oxygen radicals, and promote neuronal survival and synaptic plasticity. The present review intends to review the data available on the effects of cocoa and chocolate on brain health and cognitive abilities.

Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease

Type of study:

Number of citations: 72

Year: 2018

Authors: S. Camandola, Natalie Plick, M. Mattson

Journal: Neurochemical Research

Journal ranking: Q1

Key takeaways: Regular consumption of coffee, tea, and dark chocolate (cacao) can promote brain health and reduce the risk of age-related neurodegenerative disorders.

Abstract: Increasing evidence suggests that regular consumption of coffee, tea and dark chocolate (cacao) can promote brain health and may reduce the risk of age-related neurodegenerative disorders. However, the complex array of phytochemicals in coffee and cacao beans and tea leaves has hindered a clear understanding of the component(s) that affect neuronal plasticity and resilience. One class of phytochemicals present in relatively high amounts in coffee, tea and cacao are methylxanthines. Among such methylxanthines, caffeine has been the most widely studied and has clear effects on neuronal network activity, promotes sustained cognitive performance and can protect neurons against dysfunction and death in animal models of stroke, Alzheimer’s disease and Parkinson’s disease. Caffeine’s mechanism of action relies on antagonism of various subclasses of adenosine receptors. Downstream xanthine metabolites, such as theobromine and theophylline, may also contribute to the beneficial effects of coffee, tea and cacao on brain health.

Effect of Cocoa and Cocoa Products on Cognitive Performance in Young Adults

Type of study: systematic review

Number of citations: 40

Year: 2020

Authors: M. Martín, L. Goya, S. de Pascual-Teresa

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Cocoa and cocoa products positively impact cognitive function and neuroplasticity in young adults, with both acute and chronic intake showing beneficial effects.

Abstract: Increasing evidence support a beneficial role of cocoa and cocoa products on human cognition, particularly in aging populations and patients at risk. However, thorough reviews on the efficacy of cocoa on brain processes in young adults do not exist precisely due to the limited number of studies in the matter. Thus, the aim of this study was to summarize the findings on the acute and chronic effects of cocoa administration on cognitive functions and brain health in young adults. Web of Science and PubMed databases were used to search for relevant trials. Human randomized controlled studies were selected according to PRISMA guidelines. Eleven intervention studies that involved a total of 366 participants investigating the role of cocoa on cognitive performance in children and young adults (average age ≤25 years old) were finally selected. Findings from individual studies confirm that acute and chronic cocoa intake have a positive effect on several cognitive outcomes. After acute consumption, these beneficial effects seem to be accompanied with an increase in cerebral blood flow or cerebral blood oxygenation. After chronic intake of cocoa flavanols in young adults, a better cognitive performance was found together with increased levels of neurotrophins. This systematic review further supports the beneficial effect of cocoa flavanols on cognitive function and neuroplasticity and indicates that such benefits are possible in early adulthood.

Chocolate and Cocoa-Derived Biomolecules for Brain Cognition during Ageing

Type of study: systematic review

Number of citations: 11

Year: 2022

Authors: Corinna Zeli, M. Lombardo, M. Storz, Morena Ottaviani, Gianluca Rizzo

Journal: Antioxidants

Journal ranking: Q1

Key takeaways: Cocoa and cocoa-derived biomolecules show potential in managing cognitive decline in the elderly, but their molecular mechanisms remain unresolved.

Abstract: Cognitive decline is a common problem in older individuals, often exacerbated by neurocognitive conditions, such as vascular dementia and Alzheimer’s disease, which heavily affect people’s lives and exert a substantial toll on healthcare systems. Currently, no cure is available, and commonly used treatments are aimed at limiting the progressive loss of cognitive functions. The absence of effective pharmacological treatments for the cognitive decline has led to the search for lifestyle interventions, such as diet and the use of nutraceuticals that can prevent and limit the loss of cognition. Cocoa and chocolate are foods derived from cocoa beans, commonly used in the population and with good acceptability. The purpose of this review was to collect current experimental evidence regarding the neuroprotective effect of chocolate and cocoa (or derived molecules) in the elderly. From a systematic review of the literature, 9 observational studies and 10 interventional studies were selected, suggesting that the biomolecules contained in cocoa may offer promising tools for managing cognitive decline, if provided in adequate dosages and duration of treatment. However, the molecular mechanisms of cocoa action on the central nervous system are not completely understood.

Chocolate and the brain: Neurobiological impact of cocoa flavanols on cognition and behavior

Type of study: literature review

Number of citations: 157

Year: 2013

Authors: A. Sokolov, M. Pavlova, S. Klosterhalfen, P. Enck

Journal: Neuroscience & Biobehavioral Reviews

Journal ranking: Q1

Key takeaways: Cocoa flavanols may have neuroprotective effects, promoting neurogenesis, neuronal function, and brain connectivity, with potential benefits for neurocognition and behavior in aging, dementia, and stroke.

Exploring the Nutritional Composition and Bioactive Compounds in Different Cocoa Powders

Type of study:

Number of citations: 19

Year: 2023

Authors: María del Carmen Razola-Díaz, María José Aznar-Ramos, V. Verardo, S. Melgar-Locatelli, E. Castilla-Ortega, Celia Rodríguez-Pérez

Journal: Antioxidants

Journal ranking: Q1

Key takeaways: Non-alkalized cocoa powders, particularly from Peru, have higher bioactive compounds and antioxidant activity, making them promising candidates for potential brain plasticity and cognitive function benefits.

Abstract: Cocoa, the main derivative of the seeds of Theobroma cacao L., has been recognized to have several effects on human health including antioxidant and neuro- and cardio-protective effects, among others. These effects have been attributed mainly to its bioactive compounds. In this context, the aim of this work is to evaluate the nutritional composition, bioactive compounds (i.e., phenolic compounds, procyanidins and methylxanthines) and the antioxidant activity of seven different cocoas (alkalized and non-alkalized) from different origins (Peru, Venezuela, Ivory Coast, Dominican Republic, and West Africa). It represents the first stage of a larger project aiming to find high polyphenol cocoa-based nutritional strategies and related biomarkers that may potentiate brain plasticity and cognitive function. Cocoa powders were extracted by ultrasound-assisted technology, and the total phenolic content (TPC) was measured by Folin–Ciocalteu. Methylxanthines (caffeine and theobromine) and procyanidin contents were determined by HPLC-FLD-DAD, and the antioxidant activity was assessed through DPPH, ABTS and FRAP assays. Non-alkalized cocoas showed higher phenolic and procyanidin contents and higher antioxidant activity compared to the alkalized ones. A strongly significant (p < 0.05) positive correlation between the antioxidant activity and the TPC, especially with the total procyanidin content, but not with methylxanthines was found. In conclusion, the non-alkalized cocoas, especially the one from Peru, were the best candidates in terms of bioactive compounds. The cocoa from Peru had a TPC of 57.4 ± 14.4 mg of gallic acid equivalent/g d.w., 28,575.06 ± 62.37 µg of catechin equivalents/g d.w., and 39.15 ± 2.12 mg/g of methylxanthines. Further studies should be undertaken to evaluate its effect on brain plasticity and cognitive function.

Diet enriched with high-phenolic cocoa potentiates hippocampal brain-derived neurotrophic factor expression and neurogenesis in healthy adult micewith subtle effects on memory.

Type of study:

Number of citations: 3

Year: 2024

Authors: S. Melgar-Locatelli, M. C. Mañas‐Padilla, A. Castro-Zavala, Patricia Rivera, María Del Carmen Razola-Díaz, Francisco J Monje, Celia Rodríguez-Pérez, E. Castilla-Ortega

Journal: Food & function

Journal ranking: Q1

Key takeaways: A high-phenolic cocoa diet enhances object recognition memory and increases adult hippocampal neurogenesis in healthy adult mice, with minimal effects on exploratory behavior and anxiety-like behavior.

Abstract: Cocoa is widely known for its health benefits, but its neurocognitive impact remains underexplored. This preclinical study aimed to investigate the effects of cocoa and cocoa polyphenols on hippocampal neuroplasticity, cognitive function and emotional behavior. Seventy young-adult C57BL/6JRj male and female mice were fed either a standard diet (CTR) or a diet enriched with 10% high-phenolic content cocoa (HPC) or low-phenolic content cocoa (LPC) for at least four weeks. In a first experiment, behavioral tests assessing exploratory behavior, emotional responses and hippocampal-dependent memory were conducted four weeks into the diet, followed by animal sacrifice a week later. Adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex were evaluated using immunohistochemistry and western blot. In a different experiment, hippocampal synaptic response, long-term potentiation and presynaptic-dependent short-term plasticity were studied by electrophysiology. Cocoa-enriched diets had minimal effects on exploratory activity and anxiety-like behavior, except for reduced locomotion in the LPC group. Only the HPC diet enhanced object recognition memory, while place recognition memory and spatial navigation remained unaffected. The HPC diet also increased adult hippocampal neurogenesis, boosting the proliferation, survival and number of young adult-born neurons. However, both cocoa-enriched diets increased immobility in the forced swimming test and hippocampal BDNF expression. Hippocampal electrophysiology revealed no alterations in neuroplasticity among diets. The results were mostly unaffected by sex. Overall, the HPC diet demonstrated greater potential regarding cognitive and neuroplastic benefits, suggesting a key role of cocoa flavanols in dietary interventions aimed at enhancing brain health.

Effects of Cocoa-Derived Polyphenols on Cognitive Function in Humans. Systematic Review and Analysis of Methodological Aspects

Type of study: systematic review

Number of citations: 33

Year: 2020

Authors: P. K. Barrera-Reyes, J. Lara, Melissa Gonzalez-Soto, M. Tejero

Journal: Plant Foods for Human Nutrition

Journal ranking: Q2

Key takeaways: Cocoa-derived polyphenols show a positive effect on memory and executive function, but the evidence is diverse and future studies should address methodological issues.

Abstract: The effects of cocoa-derived polyphenols on cognitive functions have been analyzed through numerous studies using different interventions (doses, vehicles, time frame, cognition tests, and characteristics of participants) which may hamper the interpretation and comparison of findings across investigations. Thus, a systematic review was conducted to analyze the effects of cocoa-derived polyphenols intake on human cognition and discuss the methodological aspects that may contribute to the heterogeneity of findings. Randomized clinical trials evaluating the effect of cocoa polyphenols on cognitive function in healthy subjects were selected according to selection criteria. Twelve studies were selected. Quality was assessed according to the Cochrane risk for bias tool. The most common risk for bias was the lack of information about the sequence generation process. Effects on cognitive function were observed after consumption of 50 mg/day of (−)-epicatechin and in studies using a component-matched placebo and cocoa as the polyphenol vehicle given to healthy adults (18–50 years). Memory (n = 5) and executive function (n = 4) showed the most significant effects with medium and large effect sizes after intake of intermediate doses of cocoa flavanols (500–750 mg/day). Overall, this set of studies suggest a positive effect of cocoa polyphenols on memory and executive function. However, the available evidence is very diverse and future studies may address the identified sources of variation to strengthen current evidence on this promising field.

Exploring cocoa properties: is theobromine a cognitive modulator?

Type of study: literature review

Number of citations: 40

Year: 2019

Authors: I. Cova, V. Leta, C. Mariani, L. Pantoni, S. Pomati

Journal: Psychopharmacology

Journal ranking: Q1

Key takeaways: Theobromine, a component of cocoa, has a reduced and delayed nootropic effect compared to caffeine, but may have potential neuroprotective effects through reducing A amyloid pathology in Alzheimer's disease patients' brains.

Abstract: Nutritional qualities of cocoa have been acknowledged by several authors; a particular focus has been placed on its high content of flavanols, known for their excellent antioxidant properties and subsequent protective effect on cardio- and cerebrovascular systems as well as for neuromodulatory and neuroprotective actions. Other active components of cocoa are methylxanthines (caffeine and theobromine). Whereas the effects of caffeine are extensively researched, the same is not the case for theobromine; this review summarizes evidence on the effect of theobromine on cognitive functions. Considering animal studies, it can be asserted that acute exposition to theobromine has a reduced and delayed nootropic effect with respect to caffeine, whereas both animal and human studies suggested a potential neuroprotective action of long-term assumption of theobromine through a reduction of Aβ amyloid pathology, which is commonly observed in Alzheimer’s disease patients’ brains. Hence, the conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.

The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial

Type of study: rct

Number of citations: 110

Year: 2015

Authors: D. Lamport, Deepa Pal, C. Moutsiana, D. Field, C. Williams, J. Spencer, L. Butler

Journal: Psychopharmacology

Journal ranking: Q1

Key takeaways: A single dose of flavanol-rich cocoa improves regional cerebral perfusion in older adults, potentially benefiting cognitive performance through increased neuronal function.

Abstract: There has recently been increasing interest in the potential of flavanols, plant-derived compounds found in foods such as fruit and vegetables, to ameliorate age-related cognitive decline. Research suggests that cocoa flavanols improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects. These effects may be mediated by increased cerebral blood flow (CBF), thus, stimulating neuronal function.The present study employed arterial spin labelling functional magnetic resonance imaging to explore the effect of a single acute dose of cocoa flavanols on regional CBF.CBF was measured pre- and post-consumption of low (23 mg) or high (494 mg) 330 ml equicaloric flavanol drinks matched for caffeine, theobromine, taste and appearance according to a randomized counterbalanced crossover double-blind design in eight males and ten females, aged 50-65 years. Changes in perfusion from pre- to post-consumption were calculated as a function of each drink.Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe.Consumption of cocoa flavanol improves regional cerebral perfusion in older adults. This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance.

Cacao Polyphenol-Rich Dark Chocolate Intake Contributes to Efficient Brain Activity during Cognitive Tasks: A Randomized, Single-Blinded, Crossover, and Dose-Comparison fMRI Study

Type of study: rct

Number of citations: 5

Year: 2023

Authors: Akihiro Sasaki, Eriko Kawai, Kyosuke Watanabe, Emi Yamano, Chisato Oba, Kentaro Nakamura, M. Natsume, K. Mizuno, Yasuyoshi Watanabe

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Cacao polyphenol-enriched dark chocolate intake improves brain function during cognitive tasks by reducing the effort of brain activity.

Abstract: Cacao polyphenol-enriched dark chocolate may have beneficial effects on human health, such as facilitating maintaining good performance in long-lasting cognitive tasks. This study examined the effects of dark chocolate intake on improving brain function during cognitive tasks using functional magnetic resonance imaging (fMRI). In this randomized, single-blinded, crossover, and dose-comparison study, 26 healthy middle-aged participants ingested dark chocolate (25 g) either with a low concentration (LC) (211.7 mg) or a high concentration (HC) (635 mg) of cacao polyphenols. Thereafter, their brain activities were analyzed during continuous and effortful cognitive tasks relevant to executive functioning using fMRI in two consecutive 15 min sessions (25 and 50 min after ingestion). We observed significant interaction effects between chocolate consumption and brain activity measurement sessions in the left dorsolateral prefrontal cortex and left inferior parietal lobule. After HC chocolate ingestion, these areas showed lower brain activity in the second session than in the first session; however, these areas showed higher activity in the second session after LC chocolate ingestion. These results suggest that cacao polyphenol-enriched dark chocolate enhances the efficient use of cognitive resources by reducing the effort of brain activity.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial.

Type of study: rct

Number of citations: 8

Year: 2023

Authors: Chirag M. Vyas, J. Manson, H. Sesso, P. Rist, Alison Weinberg, Eunjung Kim, M. V. Moorthy, Nancy R. Cook, Olivia I. Okereke

Journal: The American journal of clinical nutrition

Journal ranking: Q1

Key takeaways: Daily cocoa extract supplementation showed no overall benefits for global or domain-specific cognitive function in older adults over 2 years.

Effects of chocolate on cognitive function in healthy adults: A systematic review and meta‐analysis on clinical trials

Type of study: meta-analysis

Number of citations: 3

Year: 2023

Authors: Zainab Shateri, Akram Kooshki, Razieh Hormozi, S. Hosseini, Reihaneh Mousavi, E. Foroumandi

Journal: Phytotherapy Research

Journal ranking: Q1

Key takeaways: Daily cocoa consumption may improve cognitive performance in learning, memory, and attention for young adults in the short and medium term.

Abstract: Cognitive function is defined as performance in objective tasks that need conscious mind effort. It has been shown that consuming foods rich in flavanols causes neurobiological effects and improves learning, memory, and global cognitive function. This study aimed to investigate the impact of chronic chocolate consumption on cognitive function in healthy adults based on published trials. The PICO strategy was applied to examine the research question in this study. Researchers searched the Web of Science, Science Direct, Pubmed, Scopus, Cochrane Library, and Google Scholar databases. Related articles of randomized controlled trials that evaluated the chronic effect of chocolate on cognitive function were selected (all published from their inception to February 2021). The difference in means of the last and first measurements was the main effect measure between the control and intervention groups. For quantitative data synthesis, weighted mean difference (WMD) and 95% confidence interval (CI) were performed in the random effect model. Of the initial 340 articles identified, seven trials met the eligibility criteria. Chronic chocolate intake significantly reduced executive function time (WMD: −11.77, 95% CI: −22.49, −1.05, p = 0.03) of the participants. Further, the language and executive function (WMD: 6.38, 95% CI: 5.97, 6.80, p < 0.001) was raised by 6.38 times after the intervention with chocolate. We could not perform subgroup analysis due to insufficient trials and significant heterogeneity in some studies. It is concluded that daily consumption of cocoa may provide short and middle‐term effects on young adults and make them better cognitive performance in learning, memory, and attention.

Dietary Cocoa Flavanols Do Not Alter Brain Excitability in Young Healthy Adults

Type of study: rct

Number of citations: 0

Year: 2024

Authors: Raphael Hamel, Rebecca Oyler, Evie Harms, Rosamond Bailey, Catarina Rendeiro, Ned Jenkinson

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Dietary cocoa flavanols do not significantly alter brain excitability in young healthy adults, but may predominantly affect cerebral endothelium functions.

Abstract: The ingestion of dietary cocoa flavanols acutely alters functions of the cerebral endothelium, but whether the effects of flavanols permeate beyond this to alter other brain functions remains unclear. Based on converging evidence, this work tested the hypothesis that cocoa flavanols would alter brain excitability in young healthy adults. In a randomised, cross-over, double-blinded, placebo-controlled design, transcranial magnetic stimulation was used to assess corticospinal and intracortical excitability before as well as 1 and 2 h post-ingestion of a beverage containing either high (695 mg flavanols, 150 mg (−)-epicatechin) or low levels (5 mg flavanols, 0 mg (−)-epicatechin) of cocoa flavanols. In addition to this acute intervention, the effects of a short-term chronic intervention where the same cocoa flavanol doses were ingested once a day for 5 consecutive days were also investigated. For both the acute and chronic interventions, the results revealed no robust alteration in corticospinal or intracortical excitability. One possibility is that cocoa flavanols yield no net effect on brain excitability, but predominantly alter functions of the cerebral endothelium in young healthy adults. Future studies should increase intervention durations to maximize the acute and chronic accumulation of flavanols in the brain, and further investigate if cocoa flavanols would be more effective at altering brain excitability in older adults and clinical populations than in younger adults.

Effects of chocolate on cognitive function and mood: a systematic review.

Type of study: systematic review

Number of citations: 106

Year: 2013

Authors: A. Scholey, L. Owen

Journal: Nutrition reviews

Journal ranking: Q1

Key takeaways: Chocolate can improve mood and enhance cognitive function, with cocoa flavanols and methylxanthine showing clear cognitive enhancement effects.

Abstract: A systematic review was conducted to evaluate whether chocolate or its constituents were capable of influencing cognitive function and/or mood. Studies investigating potentially psychoactive fractions of chocolate were also included. Eight studies (in six articles) met the inclusion criteria for assessment of chocolate or its components on mood, of which five showed either an improvement in mood state or an attenuation of negative mood. Regarding cognitive function, eight studies (in six articles) met the criteria for inclusion, of which three revealed clear evidence of cognitive enhancement (following cocoa flavanols and methylxanthine). Two studies failed to demonstrate behavioral benefits but did identify significant alterations in brain activation patterns. It is unclear whether the effects of chocolate on mood are due to the orosensory characteristics of chocolate or to the pharmacological actions of chocolate constituents. Two studies have reported acute cognitive effects of supplementation with cocoa polyphenols. Further exploration of the effect of chocolate on cognitive facilitation is recommended, along with substantiation of functional brain changes associated with the components of cocoa.

Effects of cocoa-rich chocolate on cognitive performance in postmenopausal women. A randomised clinical trial

Type of study: rct

Number of citations: 8

Year: 2020

Authors: Irene A. Garcia-Yu, L. García‐Ortiz, M. Gomez-Marcos, E. Rodríguez-Sánchez, S. Mora-Simón, J. Maderuelo-Fernández, J. Recio-Rodríguez

Journal: Nutritional Neuroscience

Journal ranking: Q1

Key takeaways: Adding 10g of cocoa-rich (99%) chocolate to the habitual diet slightly improves cognitive flexibility and processing speed in postmenopausal women, but does not affect attention, verbal memory, phonological fluency, or working memory.

Abstract: ABSTRACT Objectives The aim of this research was to evaluate the effects of adding 10 g of cocoa-rich chocolate (99%) to the habitual diet on cognitive performance in postmenopausal women. Methods Following a randomised controlled parallel clinical trial, a total of 140 postmenopausal women aged 50–64 were recruited. The intervention group (n = 73) consumed daily 10 g of chocolate (99% cocoa) in addition to their usual food intake for 6 months, whereas the control group (n = 67) did not receive any intervention. Attention and executive functions, verbal memory, working memory, phonological fluency, category fluency and clinical variables were assessed at baseline and 6 months. Results Trail Making Test B execution time showed a decreased of −12.08 s (95% CI: −23.99, −0.18; p = 0.047) in the intervention group compared to the control group, after adjusting for age, educational level, time elapsed from the beginning of menopause and daily energy consumption (Cohen’s d = −0.343). Attention, immediate or delayed verbal memory, phonological or category fluency, and working memory remained unchanged. Conclusions The consumption of cocoa-rich (99%) chocolate in addition to the habitual diet could be related to a slight improvement in cognitive performance regarding cognitive flexibility and processing speed in postmenopausal women, with no changes in the rest of the cognitive performance variables evaluated.Trial registration: This clinical trial has been registered at clinicaltrials.gov as NCT03492983.

Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial.

Type of study: rct

Number of citations: 31

Year: 2021

Authors: Ji-Hee Shin, Chong-Su Kim, Lina Cha, Sojeong Kim, Seokoh Lee, S. Chae, Woo Young Chun, Dong-Mi Shin

Journal: The Journal of nutritional biochemistry

Journal ranking: Q1

Key takeaways: Daily consumption of 85% cocoa dark chocolate improves mood and reduces negative emotions, potentially through its prebiotic effects on gut microbiota.

Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline

Type of study: non-rct observational study

Number of citations: 54

Year: 2016

Authors: Afonso Moreira, M. J. Diógenes, A. de Mendonça, N. Lunet, H. Barros

Journal: Journal of Alzheimer's Disease

Journal ranking: Q1

Key takeaways: Regular long-term chocolate consumption is associated with a lower risk of cognitive decline in elderly individuals with an average daily caffeine consumption lower than 75 mg.

Abstract: Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38–0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31–0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans.

The effects of cocoa on the immune system

Type of study:

Number of citations: 52

Year: 2013

Authors: F. Pérez-Cano, M. Massot-Cladera, À. Franch, C. Castellote, M. Castell

Journal: Frontiers in Pharmacology

Journal ranking: Q1

Key takeaways: Cocoa consumption may improve immune system function by modulating T cell functions, potentially inhibiting IgE synthesis, and modulating gut-associated lymphoid tissue function.

Abstract: Cocoa is a food relatively rich in polyphenols, which makes it a potent antioxidant. Due to its activity as an antioxidant, as well as through other mechanisms, cocoa consumption has been reported to be beneficial for cardiovascular health, brain functions, and cancer prevention. Furthermore, cocoa influences the immune system, in particular the inflammatory innate response and the systemic and intestinal adaptive immune response. Preclinical studies have demonstrated that a cocoa-enriched diet modifies T cell functions that conduce to a modulation of the synthesis of systemic and gut antibodies. In this regard, it seems that a cocoa diet in rats produces changes in the lymphocyte composition of secondary lymphoid tissues and the cytokines secreted by T cells. These results suggest that it is possible that cocoa could inhibit the function of T helper type 2 cells, and in line with this, the preventive effect of cocoa on IgE synthesis in a rat allergy model has been reported, which opens up new perspectives when considering the beneficial effects of cocoa compounds. On the other hand, cocoa intake modifies the functionality of gut-associated lymphoid tissue by means of modulating IgA secretion and intestinal microbiota. The mechanisms involved in these influences are discussed here. Further research may elucidate the cocoa compounds involved in such an effect and also the possible medical approaches to these repercussions.

Cocoa: antioxidant and immunomodulator

Type of study:

Number of citations: 132

Year: 2009

Authors: E. Ramiro-Puig, M. Castell

Journal: British Journal of Nutrition

Journal ranking: Q1

Key takeaways: Cocoa has antioxidant properties and may have an immunomodulating effect on immune cells, promoting the T helper 1 response and increasing intestinal T lymphocyte count in young rats.

Abstract: Cocoa, a product consumed since 600 BC, is now a subject of increasing interest because of its antioxidant properties, which are mainly attributed to the content of flavonoids such as ( − )-epicatechin, catechin and procyanidins. Moreover, recent findings suggest a regulatory effect of cocoa on the immune cells implicated in innate and acquired immunity. Cocoa exerts regulatory activity on the secretion of inflammatory mediators from macrophages and other leucocytes in vitro. In addition, emerging data from in vivo studies support an immunomodulating effect. Long-term cocoa intake in rats affects both intestinal and systemic immune function. Studies in this line suggest that high-dose cocoa intake in young rats favours the T helper 1 (Th1) response and increases intestinal γδ T lymphocyte count, whereas the antibody-secreting response decreases. The mechanisms involved in this activity are uncertain; nonetheless, because redox-sensitive pathways control immune cell function, the action of cocoa flavonoids on modulating cell signalling and gene expression deserves investigation.

Cocoa as immunomodulatory agent: an update

Type of study: literature review

Number of citations: 5

Year: 2023

Authors: Maria Atanassova, M. Martorell, F. Sharopov, L. Atanassov, Pradeep Kumar, Javad Sharifi‐Rad, Silvia Tejada-Gavela, Marcello Iriti, R. Pezzani, E. Varoni

Journal: Natural Product Research

Journal ranking: Q2

Key takeaways: Cocoa and chocolate consumption has been shown to impact the immune system, acting as an anti-inflammatory, antioxidant, and immunomodulatory agent, with potential health benefits.

Abstract: Abstract Cocoa is rich in polyphenols, mainly flavonoids, which correlate with several health benefits mediated by their antioxidant, anti-inflammatory and immunomodulatory properties. Cocoa and chocolate consumption have been reported to impact the regulation of the immune system, both in preclinical studies and in human trials. The mechanisms for immunomodulation can involve different effects of cocoa polyphenols on the immune system, acting as anti-inflammatory, antioxidant and anti-allergic agents, as well as the direct influence of cocoa on innate and acquired immunity, with cytokines production and activation of both lymphocyte-dependent and -independent pathways. Cocoa intake has been also correlated to changes in gut microbiota ecology and composition, also affecting the intestinal immune system. This review summarises the updates of the last two decades on cocoa as immunomodulatory agent and explores the health-related benefits of cocoa and chocolate intake. Graphical Abstract

Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

Type of study: non-rct in vitro

Number of citations: 56

Year: 2017

Authors: L. Dugo, Maria Giovanna Belluomo, C. Fanali, M. Russo, F. Cacciola, M. Maccarrone, A. Sardanelli

Journal: Oxidative Medicine and Cellular Longevity

Journal ranking: Q1

Key takeaways: Cocoa polyphenolic extract suppresses inflammation and promotes anti-inflammatory M2 polarization in macrophages, potentially benefiting human health.

Abstract: Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

Come to the dark side - A review on the health-beneficial and disease-alleviating effects of cocoa-rich dark chocolate.

Type of study: literature review

Number of citations: 0

Year: 2025

Authors: Heike Muth, S. Bereswill, M. Heimesaat

Journal: European journal of microbiology & immunology

Journal ranking: Q2

Key takeaways: Cocoa-rich dark chocolate may have anti-inflammatory effects, potentially improving various diseases and enhancing gut function, but may worsen acne symptoms.

Abstract: Cocoa that is abundant in dark chocolate is known for its anti-inflammatory effects that are mainly due to biologically active ingredients like polyphenols and methylxanthines. We here provide a comprehensive literature survey of both, in vitro and in vivo studies including clinical trials summarizing recent evidence on the immune-modulatory effects exerted by application of cocoa-rich dark chocolate or distinct cocoa-derived molecules. The survey revealed that dark chocolate and its derivatives could effectively dampen pro-inflammatory including oxidative stress responses in vascular diseases including atherosclerosis, hypertension, and decompression sickness, metabolic morbidities such as obesity and type 2 diabetes mellitus, celiac disease, chronic kidney diseases, and polycystic ovary syndrome, enhance gut epithelial barrier function, and modulate pain sensations. On the other hand, dark chocolate consumption intake was found to worsen acne symptoms. In conclusion, dietary supplementation with dark chocolate with high contents of biologically active polyphenols and methylxanthines might be promising adjunct immune-modulatory treatment options of distinct acute as well as chronic inflammatory morbidities that need to be evaluated in more detail in future in vivo including clinical studies.

Cocoa Diet and Antibody Immune Response in Preclinical Studies

Type of study:

Number of citations: 18

Year: 2017

Authors: Mariona Camps-Bossacoma, M. Massot-Cladera, M. Abril-Gil, À. Franch, F. Pérez-Cano, M. Castell

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: A cocoa-enriched diet can modify immune system function and potentially prevent antibody-induced immune diseases.

Abstract: The ability of cocoa to interact with the immune system in vitro and in vivo has been described. In the latter context, a cocoa-enriched diet in healthy rats was able to modify the immune system’s functionality. This fact could be observed in the composition and functionality of lymphoid tissues, such as the thymus, spleen, and lymph nodes. Consequently, immune effector mechanisms, such as antibody synthesis, were modified. A cocoa-enriched diet in young rats was able to attenuate the serum levels of immunoglobulin (Ig) G, IgM, and IgA and also the intestinal IgM and IgA secretion. Moreover, in immunized rats, the intake of cocoa decreased specific IgG1, IgG2a, IgG2c, and IgM concentrations in serum. This immune-regulator potential was then tested in disease models in which antibodies play a pathogenic role. A cocoa-enriched diet was able to partially prevent the synthesis of autoantibodies in a model of autoimmune arthritis in rats and was also able to protect against IgE and T helper 2-related antibody synthesis in two rat models of allergy. Likewise, a cocoa-enriched diet prevented an oral sensitization process in young rats. In this review, we will focus on the influence of cocoa on the acquired branch of the immune function. Therefore, we will focus on how a cocoa diet influences lymphocyte function both in the systemic and intestinal immune system. Likewise, its potential role in preventing some antibody-induced immune diseases is also included. Although further studies must characterize the particular cocoa components responsible for such effects and nutritional studies in humans need to be carried out, cocoa has potential as a nutraceutical agent in some hypersensitivity status.

Theobromine Is Responsible for the Effects of Cocoa on the Antibody Immune Status of Rats.

Type of study: non-rct experimental

Number of citations: 21

Year: 2018

Authors: Mariona Camps-Bossacoma, F. Pérez-Cano, À. Franch, M. Castell

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Cocoa's theobromine plays an immunoregulatory role, affecting antibody concentrations and lymphoid tissue lymphocyte composition in young healthy rats after a single week of feeding.

Abstract: Background A 10% cocoa-enriched diet influences immune system functionality including the prevention of the antibody response and the induction of lower immunoglobulin (Ig) concentrations. However, neither cocoa polyphenols nor cocoa fiber can totally explain these immunoregulatory properties. Objectives This study aimed to establish the influence of cocoa theobromine in systemic and intestinal Ig concentrations and to determine the effect of cocoa or theobromine feeding on lymphoid tissue lymphocyte composition. Methods Three-week-old female Lewis rats were fed either a standard diet (AIN-93M; RF group), a 10% cocoa diet (CC group), or a 0.25% theobromine diet (the same amount provided by the cocoa diet; TB group) in 2 separate experiments that lasted 19 (experiment 1) or 8 (experiment 2) d. Serum IgG, IgM, IgA, and intestinal secretory IgA (sIgA) concentrations were determined. In addition, at the end of experiment 2, thymus, mesenteric lymph node (MLN), and spleen lymphocyte populations were analyzed. Results Both CC and TB groups in experiments 1 and 2 showed similar serum IgG, IgM, and IgA and intestinal sIgA concentrations, which were lower than those in the RF group (46-98% lower in experiment 1 and 23-91% lower in experiment 2; P < 0.05). In addition, in experiment 2, the cocoa and theobromine diets similarly changed the thymocyte composition by increasing CD4-CD8- (+133%) and CD4+CD8- (+53%) proportions (P < 0.01), changed the MLN composition by decreasing the percentage of T-helper (Th) lymphocytes (-3%) (P = 0.015), and changed the spleen composition by increasing the proportion of Th lymphocytes (+9%) (P < 0.001) after 1 wk of diet treatment. Conclusions The theobromine in cocoa plays an immunoregulatory role that is responsible for cocoa's influence on both systemic and intestinal antibody concentrations and also for modifying lymphoid tissue lymphocyte composition in young healthy Lewis rats. The majority of these changes are observed after a single week of being fed a diet containing 0.25% theobromine.

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.

Type of study: meta-analysis

Number of citations: 1

Year: 2024

Authors: Mehrdad Behzadi, Mohammad Vesal Bideshki, Maryam Ahmadi-Khorram, Meysam Zarezadeh, Alireza Hatami

Journal: Complementary therapies in medicine

Journal ranking: Q1

Key takeaways: Dark chocolate/cocoa consumption may have anti-inflammatory and antioxidant properties, but results in this context are inconsistent.

Cell surface ATP synthase-released H+ and ATP play key roles in cocoa butter intake-mediated regulation of gut immunity through releases of cytokines in rat

Type of study: non-rct experimental

Number of citations: 0

Year: 2023

Authors: Nariaki Arai, Ryou Kajihara, Mieko Takasaka, Kei Amari, Norika Kuneshita, Daisuke Maejima, T. Watanabe-Asaka, M. Hayashi, Yumiko Yokoyama, M. Kaidoh, Y. Kawai, T. Ohhashi

Journal: Pflügers Archiv - European Journal of Physiology

Journal ranking: Q1

Key takeaways: Cocoa butter intake regulates gut immunity through the release and transport of IL-1, IL-6, and IL-10 into mesenteric lymph vessels, with H+ and ATP released from cell surface ATP synthase playing key roles in this process.

Abstract: Proper food intake is important for maintaining good health in humans. Chocolate is known to exert anti-inflammatory effects; however, the mechanisms remain unclear. In this study, we aimed to investigate the effects of cocoa butter intake on gut immunity in rats and rabbits. Cocoa butter intake increased the lymph flow, cell density, and IL-1β, IL-6 and IL-10 levels in mesenteric lymph. Clodronate, a macrophage depletion compound, significantly enhanced the release of all cytokines. The immunoreactivities of macrophage markers CD68 and F4/80 in the jejunal villi were significantly decreased with clodronate. Piceatannol, a selective cell surface ATP synthase inhibitor significantly reduced the cocoa butter intake-mediated releases of IL-1β, IL-6 and IL-10. The immunoreactivities of cell surface ATP synthase were observed in rat jejunal villi. Shear stress stimulation on the myofibroblast cells isolated from rat jejunum released ATP and carbon dioxide depended with H^+ release. In rabbit in vivo experiments, cocoa butter intake increased the concentrations of ATP and H^+ in the portal vein. The in vitro experiments with isolated cells of rat jejunal lamina propria the pH of 3.0 and 5.0 in the medium released significantly IL-1β and IL-6. ATP selectively released IL-10. These findings suggest that cocoa butter intake regulates the gut immunity through the release and transport of IL-1β, IL-6, and IL-10 into mesenteric lymph vessels in a negative feedback system. In addition, the H^+ and ATP released from cell surface ATP synthase in jejunal villi play key roles in the cocoa butter intake–mediated regulation of gut immunity.

Protective Effect of a Cocoa-Enriched Diet on Oxidative Stress Induced by Intensive Acute Exercise in Rats

Type of study: non-rct experimental

Number of citations: 2

Year: 2022

Authors: Patricia Ruiz-Iglesias, M. Massot-Cladera, M. J. Rodríguez-Lagunas, À. Franch, Mariona Camps-Bossacoma, F. Pérez-Cano, M. Castell

Journal: Antioxidants

Journal ranking: Q1

Key takeaways: A cocoa-enriched diet can prevent excessive oxidative stress from intensive exercise, but it does not prevent immune function impairment due to exercise.

Abstract: Intensive acute exercise can induce oxidative stress, leading to muscle damage and immune function impairment. Cocoa diet could prevent this oxidative stress and its consequences on immunity. Our aim was to assess the effect of a cocoa-enriched diet on the reactive oxygen species (ROS) production by peritoneal macrophages, blood immunoglobulin (Ig) levels, leukocyte counts, and the physical performance of rats submitted to an intensive acute exercise, as well as to elucidate the involvement of cocoa fiber in such effects. For this purpose, Wistar rats were fed either a standard diet, i.e., a diet containing 10% cocoa (C10), or a diet containing 5% cocoa fiber (CF) for 25 days. Then, half of the rats of each diet ran on a treadmill until exhaustion, and 16 h later, the samples were obtained. Both C10 and CF diets significantly prevented the increase in ROS production. However, neither the cocoa diet or the cocoa fiber-enriched diet prevented the decrease in serum IgG induced by acute exercise. Therefore, although the cocoa-enriched diet was able to prevent the excessive oxidative stress induced by intensive exercise, this was not enough to avoid the immune function impairment due to exercise.

Anti-influenza virus effects of cocoa.

Type of study: rct

Number of citations: 34

Year: 2016

Authors: M. Kamei, H. Nishimura, Toshio Takahashi, N. Takahashi, Koichi Inokuchi, T. Mato, Kazuo Takahashi

Journal: Journal of the science of food and agriculture

Journal ranking: Q1

Key takeaways: Drinking cocoa activates natural immunity and enhances vaccination-induced immune response, providing stronger protection against influenza virus infection and disease onset.

Abstract: BACKGROUND Cocoa contains biologically active ingredients that have broad-spectrum antimicrobial activity, which includes an inhibitory effect on influenza virus infection. RESULTS A cocoa extract (CE) was prepared by treating defatted cocoa powder with boiling water. The extract demonstrated dose-dependent inhibition of infection in Madin-Darby canine kidney (MDCK) cells infected with human influenza virus A (H1N1, H3N2), human influenza virus B and avian influenza viruses (H5N1, H5N9). CE inhibited viral adsorption to MDCK cells. Animal experiments showed that CE significantly improved survival in mice after intra-nasal administration of a lethal dose of influenza virus. In human intervention trials, participants were allocated to two groups, one in which the participants ingested cocoa for 3 weeks before and after vaccination against A(H1N1)pdm2009 influenza virus and another in which the participants did not ingest cocoa. Neutralizing antibody titers against A(H1N1)pdm2009 influenza virus increased significantly in both groups; however, the extent of the increase was not significantly different between the two groups. Although natural killer cell activity was also elevated in both groups, the increase was more substantial in the cocoa intake group. CONCLUSION Drinking cocoa activates natural immunity and enhances vaccination-induced immune response, providing stronger protection against influenza virus infection and disease onset.

Influence of a cocoa-enriched diet on specific immune response in ovalbumin-sensitized rats.

Type of study: non-rct experimental

Number of citations: 47

Year: 2009

Authors: T. Pérez-Berezo, E. Ramiro-Puig, F. Pérez-Cano, C. Castellote, Joan Permanyer, À. Franch, M. Castell

Journal: Molecular nutrition & food research

Journal ranking: Q1

Key takeaways: Cocoa-enriched diets can reduce antibody synthesis in adult rats, potentially due to specific down-regulation of the Th2 immune response.

Abstract: Previous studies in young rats have reported the impact of 3 weeks of high cocoa intake on healthy immune status. The present article describes the effects of a longer-term cocoa-enriched diet (9 weeks) on the specific immune response to ovalbumin (OVA) in adult Wistar rats. At 4 weeks after immunization, control rats produced anti-OVA antibodies, which, according their amount and isotype, were arranged as follows: IgG1 > IgG2a > IgM > IgG2b > IgG2c. Both cocoa diets studied (4% and 10%) down-modulated OVA-specific antibody levels of IgG1 (main subclass associated with the Th2 immune response in rats), IgG2a, IgG2c and IgM isotypes. Conversely, cocoa-fed rats presented equal or higher levels of anti-OVA IgG2b antibodies (subclass linked to the Th1 response). Spleen and lymph node cells from OVA-immunized control and cocoa-fed animals proliferated similarly under OVA stimulation. However, spleen cells from cocoa-fed animals showed decreased interleukin-4 secretion (main Th2 cytokine), and lymph node cells from the same rats displayed higher interferon-gamma secretion (main Th1 cytokine). These changes were accompanied by a reduction in the number of anti-OVA IgG-secreting cells in spleen. In conclusion, cocoa diets induced attenuation of antibody synthesis that may be attributable to specific down-regulation of the Th2 immune response.

A Cocoa Diet Can Partially Attenuate the Alterations in Microbiota and Mucosal Immunity Induced by a Single Session of Intensive Exercise in Rats

Type of study: non-rct experimental

Number of citations: 10

Year: 2022

Authors: Patricia Ruiz-Iglesias, M. Massot-Cladera, M. J. Rodríguez-Lagunas, À. Franch, Mariona Camps-Bossacoma, M. Castell, F. Pérez-Cano

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: A cocoa-enriched diet can partially attenuate the alterations in gut microbiota and mucosal immunity caused by intense exercise in rats, partially due to its fiber content.

Abstract: Background Following intensive sports events, a higher rate of upper respiratory tract infections and the appearance of gastrointestinal symptomatology have been reported. We aimed to evaluate the effect of a cocoa-enriched diet on the cecal microbiota and mucosal immune system of rats submitted to high-intensity acute exercise, as well as to elucidate the involvement of cocoa fiber in such effects. Methods Wistar rats were fed either a standard diet, a diet containing 10% cocoa providing 5% fiber and a diet containing only 5% cocoa fiber. After 25 days, half of the rats of each diet performed an exhaustion running test. Sixteen hours later, samples were obtained to assess, among others, the cecal microbiota and short chain fatty acids (SCFAs) composition, mesenteric lymph nodes (MLNs) and Peyer’s patches (PPs) lymphocyte composition, and immunoglobulin (Ig) content in salivary glands. Results The intake of cocoa, partially due to its fiber content, improved the SCFA production, prevented some changes in PPs and in MLNs lymphocyte composition and also decreased the production of proinflammatory cytokines. Cocoa diet, contrary to cocoa fiber, did not prevent the lower salivary IgM induced by exercise. Conclusion A cocoa dietary intake can partially attenuate the alterations in microbiota and mucosal immunity induced by a single session of intensive exercise.

Cocoa Polyphenols and Gut Microbiota Interplay: Bioavailability, Prebiotic Effect, and Impact on Human Health

Type of study:

Number of citations: 126

Year: 2020

Authors: Vincenzo Sorrenti, Sawan Ali, Laura Mancin, S. Davinelli, A. Paoli, G. Scapagnini

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Cocoa polyphenols interact bidirectionally with gut microbiota, promoting gut health and reducing the risk of various diseases by modulating gut microbial composition and promoting beneficial bacteria growth.

Abstract: Cocoa and its products are rich sources of polyphenols such as flavanols. These compounds exert antioxidant and anti-inflammatory activities, accountable for cocoa health-promoting effects. However, cocoa polyphenols are poorly absorbed in the intestine, and most of them cannot reach the systemic circulation in their natural forms. Instead, their secondary bioactive metabolites are bioavailable, enter the circulation, reach the target organs, and exhibit their activities. In fact, once reaching the intestine, cocoa polyphenols interact bidirectionally with the gut microbiota. These compounds can modulate the composition of the gut microbiota exerting prebiotic mechanisms. They enhance the growth of beneficial gut bacteria, such as Lactobacillus and Bifidobacterium, while reducing the number of pathogenic ones, such as Clostridium perfringens. On the other hand, bioactive cocoa metabolites can enhance gut health, displaying anti-inflammatory activities, positively affecting immunity, and reducing the risk of various diseases. This review aims to summarize the available knowledge of the bidirectional interaction between cocoa polyphenols and gut microbiota with their various health outcomes.

Effect of a cocoa-enriched diet on immune response and anaphylaxis in a food allergy model in Brown Norway rats.

Type of study:

Number of citations: 32

Year: 2016

Authors: M. Abril-Gil, F. Pérez-Cano, À. Franch, M. Castell

Journal: The Journal of nutritional biochemistry

Journal ranking: Q1

Key takeaways: A cocoa-enriched diet in rats shows a protective effect against food allergy and partially against anaphylaxis, acting on intestinal and systemic immune functions.

Cocoa and Dark Chocolate Polyphenols: From Biology to Clinical Applications

Type of study:

Number of citations: 121

Year: 2017

Authors: Thea Magrone, M. Russo, E. Jirillo

Journal: Frontiers in Immunology

Journal ranking: Q1

Key takeaways: Cocoa and dark chocolate polyphenols exhibit antioxidant, anti-inflammatory, and cardioprotective effects, with potential benefits for individuals with various diseases and aging populations.

Abstract: It is well known that cocoa and dark chocolate possess polyphenols as major constituents whose dietary consumption has been associated to beneficial effects. In fact, cocoa and dark chocolate polyphenols exert antioxidant and anti-inflammatory activities switching on some important signaling pathways such as toll-like receptor 4/nuclear factor κB/signal transducer and activator of transcription. In particular, cocoa polyphenols induce release of nitric oxide (NO) through activation of endothelial NO synthase which, in turn, accounts for vasodilation and cardioprotective effects. In the light of the above described properties, a number of clinical trials based on the consumption of cocoa and dark chocolate have been conducted in healthy subjects as well as in different categories of patients, such as those affected by cardiovascular, neurological, intestinal, and metabolic pathologies. Even if data are not always concordant, modifications of biomarkers of disease are frequently associated to improvement of clinical manifestations. Quite interestingly, following cocoa and dark chocolate ingestion, cocoa polyphenols also modulate intestinal microbiota, thus leading to the growth of bacteria that trigger a tolerogenic anti-inflammatory pathway in the host. Finally, many evidences encourage the consumption of cocoa and dark chocolate by aged people for the recovery of the neurovascular unit.

Relationship between Cocoa Intake and Healthy Status: A Pilot Study in University Students

Type of study: non-rct observational study

Number of citations: 19

Year: 2019

Authors: M. J. Rodríguez-Lagunas, F. Vicente, P. Pereira, M. Castell, F. Pérez-Cano

Journal: Molecules

Journal ranking: Q1

Key takeaways: Moderate cocoa consumption is associated with lower allergy prevalence and chronic disease frequency in university students.

Abstract: Due to its polyphenol content, cocoa’s potential health effects are attracting much attention, showing, among other things, cardioprotective, anti-inflammatory, anti-obesity, and neuroprotective actions. However, there is very limited information regarding the effect of cocoa on human immunity. This study aimed to establish the relationship between cocoa consumption and health status, focusing on physical activity habits and allergy prevalence in young people. For this, a sample of 270 university students was recruited to complete a food frequency questionnaire, the International Physical Activity Questionnaire (IPAQ), and a lifestyle and health status questionnaire. The results were analysed by classifying the participants into tertiles defined according to their cocoa consumption: low (LC), moderate (MC), and high (HC) consumers. The consumption of cocoa inversely correlated with physical activity and the MC group had significantly less chronic disease frequency than the LC group. The percentage of allergic people in the MC and HC groups was lower than that in the LC group and, moreover, the cocoa intake, especially moderate consumption, was also associated with a lower presence of allergic symptoms. Thus, from these results a positive effect of cocoa intake on allergy can be suggested in the young population.

Cocoa modulatory effect on rat faecal microbiota and colonic crosstalk.

Type of study:

Number of citations: 124

Year: 2012

Authors: M. Massot-Cladera, T. Pérez-Berezo, À. Franch, M. Castell, F. Pérez-Cano

Journal: Archives of biochemistry and biophysics

Journal ranking: Q1

Key takeaways: A cocoa-enriched diet in rats alters gut microbiota growth and alters the TLR pattern, potentially impacting the intestinal immune system.

Cocoa-enriched diets modulate intestinal and systemic humoral immune response in young adult rats.

Type of study: non-rct experimental

Number of citations: 45

Year: 2011

Authors: T. Pérez-Berezo, À. Franch, S. Ramos‐Romero, C. Castellote, F. Pérez-Cano, M. Castell

Journal: Molecular nutrition & food research

Journal ranking: Q1

Key takeaways: A 5% or higher cocoa diet has a downregulatory effect on systemic and intestinal humoral immune response in adult rats.

Abstract: SCOPE Previous studies have shown that a highly enriched cocoa diet affects both intestinal and systemic immune function in young rats. The aim of this study was to elucidate whether diets containing lower amounts of cocoa could also influence the systemic and intestinal humoral immune response. METHODS AND RESULTS Fecal and serum samples were collected during the study and, at the end, intestinal washes were obtained and mesenteric lymph nodes and small-intestine walls were excised for gene expression assessment. IgA, IgM, IgG1, IgG2a, IgG2b and IgG2c concentrations were quantified in serum whereas S-IgA and S-IgM were determined in feces and intestinal washes. Animals receiving 5 and 10% cocoa for 3 wk showed no age-related increase in serum IgG1 and IgG2a concentrations, and IgG2a values were significantly lower than those in reference animals. Serum IgM was also decreased by the 10% cocoa diet. The 5 and 10% cocoa diets dramatically reduced intestinal S-IgA concentration and modified the expression of several genes involved in IgA synthesis. A diet containing 2% cocoa had no effect on most of the studied variables. CONCLUSION The results demonstrate the downregulatory effect of a 5% or higher cocoa diet on the systemic and intestinal humoral immune response in adult rats.

Effect of roasting conditions on cocoa bioactivity and gut microbiota modulation.

Type of study: non-rct in vitro

Number of citations: 16

Year: 2021

Authors: Lida Yaneth Maldonado-Mateus, S. Pérez-Burillo, Alberto Lerma-Aguilera, D. Hinojosa-Nogueira, Sonia Ruíz-Pérez, M. Gosalbes, M. P. Francino, J. Rufián‐Henares, Silvia Pastoriza de la Cueva

Journal: Food & function

Journal ranking: Q1

Key takeaways: Roasting cocoa decreases antioxidant capacity and alters gut microbiota composition, with unroasted cocoa favoring acetate and propionate production and roasted cocoa favoring butyrate production.

Abstract: Cocoa is a highly consumed food with beneficial effects on human health. Cocoa roasting has an important influence on its sensory and nutritional characteristics; therefore, roasting could also play a role in cocoa bioactivity. Thus, the aim of this paper is to unravel the effect of cocoa roasting conditions on its antioxidant capacity and modifications of gut microbiota after in vitro digestion-fermentation. HMF and furfural, chemical markers of non-enzymatic browning, were analyzed in unroasted and roasted cocoa powder at different temperatures, as well as different chocolates. The antioxidant capacity decreased with roasting, most probably due to the loss of phenolic compounds during heating. In the case of the evaluated chocolates, the antioxidant capacity was 2-3 times higher in the fermented fraction. On the other hand, HMF and furfural content increased during roasting due to increasing temperatures. Moreover, unroasted and roasted cocoa powder have different effects on gut microbial communities. Roasted cocoa favored butyrate production, whereas unroasted cocoa favored acetate and propionate production in a significant manner. In addition, unroasted and roasted cocoa produced significantly different gut microbial communities in terms of composition. Although many bacteria were affected, Veillonella and Faecalibacterium were some of the most discriminant ones; whereas the former is a propionate producer, the latter is a butyrate producer that has also been linked to positive effects on the inflammatory health of the gut and the immune system. Therefore, unroasted and roasted cocoa (regardless of the roasting temperature) promote different bacteria and a different SCFA production.