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Review
. 2011 Nov 15;15(10):2779-811.
doi: 10.1089/ars.2010.3697. Epub 2011 Jun 13.

Cocoa and chocolate in human health and disease

David L Katz  1 , Kim Doughty, Ather Ali
Affiliations
Review

Cocoa and chocolate in human health and disease

David L Katz et al. Antioxid Redox Signal. .

Abstract

Cocoa contains more phenolic antioxidants than most foods. Flavonoids, including catechin, epicatechin, and procyanidins predominate in antioxidant activity. The tricyclic structure of the flavonoids determines antioxidant effects that scavenge reactive oxygen species, chelate Fe2+ and Cu+, inhibit enzymes, and upregulate antioxidant defenses. The epicatechin content of cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated through anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-κB. Antioxidant effects of cocoa may directly influence insulin resistance and, in turn, reduce risk for diabetes. Further, cocoa consumption may stimulate changes in redox-sensitive signaling pathways involved in gene expression and the immune response. Cocoa can protect nerves from injury and inflammation, protect the skin from oxidative damage from UV radiation in topical preparations, and have beneficial effects on satiety, cognitive function, and mood. As cocoa is predominantly consumed as energy-dense chocolate, potential detrimental effects of overconsumption exist, including increased risk of weight gain. Overall, research to date suggests that the benefits of moderate cocoa or dark chocolate consumption likely outweigh the risks.

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Figures

FIG. 1.
FIG. 1.
Blood pressure and prevalence of hypertension among island-dwelling and mainland Kuna Indians. Reprinted with permission from Hollenberg (102).
FIG. 2.
FIG. 2.
C15 (C6-C3-C6) Flavonoid basic skeleton with high multifunctional activities including free radical scavenging, metal ion chelating, and enzyme inhibiting.
FIG. 3.
FIG. 3.
Mechanism of antioxidant action of flavonoids (3′, 4′-diOH polyphenols).
FIG. 4.
FIG. 4.
Diagram to show how the downstream effects of cocoa polyphenols might affect the vascular system, with nitric oxide (NO) as the target. Endothelial dysfunction, lipoprotein oxidation, platelet aggregation, and inflammation all increase cardiovascular risk (+), whereas vascular effects of cocoa polyphenols reduce risk (−) from these intermediary factors. Reprinted with permission from Cooper et al. (41). eNOS, endothelial nitric oxide synthase.
FIG. 5.
FIG. 5.
Structures of selected polyphenols and IC50 values for inhibition of NADPH oxidase activity. The noncatechol 4-hydroxyphenyl group of apocynin is a determinant for inhibition of NADPH oxidase by structurally related flavonoids and derivatives of cinnamic acid and silbenes. IC50 is the half-maximal inhibitory concentration, a measure of a compound's effectiveness in inhibiting a biochemical function. IC50 values are dependent on the specific conditions of the assay and cannot simply be translated to in vivo conditions. They permit, however, comparison of structurally related compounds. Reprinted with permission from Schewe et al. (216).
FIG. 6.
FIG. 6.
Inhibition mechanisms of phorbol myristate acetate (PMA)-induced NF-kB activation by cocoa flavanols, including a dimer. The specific steps in the NF-kB activation cascade by which cocoa flavanols can interfere are indicated with an “x.” Reprinted with permission from Selmi et al. (226).
FIG. 7.
FIG. 7.
Kaplan-Meier curves for cumulative event-free survival associated with endothelial function measured as flow-mediated dilatation (FMD) (lowest tertile<2%, highest tertile>6.3%). Log-rank analysis revealed a significant difference between the low and intermediate tertiles (p=0.037). Further analysis revealed a significant difference in event rate between those with the most severe FMD abnormality (tertile 1) and the combined group of second and third tertiles (log-rank p=0.029). When this analysis was restricted to all-cause mortality alone, it remained significant (log-rank p=0.047). Adapted from Fathi et al. (68).
FIG. 8.
FIG. 8.
Acute and sustained effects of flavanol-containing cocoa. At study entry, baseline values for flow-mediated dilation (FMD) were similar in both groups. In the treatment group (squares), FMD was significantly augmented over time. On top of sustained FMD increases, acute improvements were observed at 2 h after ingestion of flavanol-containing cocoa. No significant changes could be observed in the control group (circles). Data are given as mean ± standard deviation. *Indicates significant differences in FMD compared with baseline differences within each group, p < 0.001; #Indicates significant differences in FMD between the control group and the treatment group, p < 0.05. Reprinted with permission from Balzer et al. (17).
FIG. 9.
FIG. 9.
Average flavanol content of natural cocoa powders and cocoa powders undergoing light, medium, or heavy alkalization. Reprinted with permission from Miller et al. (169).
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