Habitual Cocoa Intake
Most results support an anti-diabetic effect of cocoa flavonoids by enhancing insulin secretion, improving insulin sensitivity in peripheral tissues, exerting a lipid-lowering effect and preventing the oxidative and inflammatory damages associated to the disease. While it could be suggested that daily consumption of flavanols from cocoa or dark chocolate would constitute a potential preventive tool useful for the nutritional management of T2D, this recommendation should be cautious since most of commercially available soluble cocoa products or chocolates contain low amount of flavanols and are rich in sugar and calories that may aggravate glycaemic control in T2D patients.
The meta-analysis was performed to investigate the effects ofcocoa/chocolate consumption on lipid profile, glycemia, and blood pressure control in diabetic patients. A systematic search of the databases PubMed, Scopus, Web of Science, and Cochran Library was performed up to July 2020. All randomized controlled trials (RCTs) using cocoa/dark chocolate in diabetic patients were included in the study. The search results were limited to English-language publications. Eight RCTs, including 433 participants, were selected for this meta-analysis. Pooled analysis indicated a significant reduction in low-density lipoprotein cholesterol LDL-c levels (WMD: -15.49 mg/dl; 95% CI: -24.56, -6.42, p = .001) and fasting blood sugar (FBS) concentrations (WMD: -6.88 mg/dl; 95% CI: -13.28, -0.48, p = .03) following cocoa/dark chocolate consumption. The analysis of papers included in current study indicates that the consumption of cocoa/dark chocolate reduced the serum fasting blood glucose (FBS) and LDL cholesterol concentrations.
Acute and habitual intake of flavanol-enriched cocoa and/or dark chocolate was reported to increase flow-mediated vasodilator response, thereby effectively lowering blood pressure (BP).9,10 In addition, associations have been reported between habitual cocoa and/or dark-chocolate intake and reduced BP, antioxidant effects, improved blood-lipid profiles, and reduced endothelin (ET)-1 vasoconstrictor activity.10–12 These findings indicate that habitual intake of flavanol-enriched cocoa and/or dark chocolate may have a number of beneficial effects on cardiovascular health. Furthermore, habitual cocoa intake has been shown to reduce central arterial stiffness in healthy young, middle-aged,13 and older adults,10,14 and an association has been found between habitual intake of flavanol-enriched cocoa and improved vascular endothelial function in hypercholesterolemic postmenopausal women.15 Although participants in many previous studies ingested cocoa on a daily basis, daily cocoa intake may be unnecessary to achieve the associated cardiovascular benefits, which range in duration from a few hours to a few days.16–20
To our knowledge, this is the first study to investigate the effects of various cocoa-intake frequencies on arterial stiffness among postmenopausal women. The key finding of this study was that central and peripheral arterial stiffness decreased significantly in both groups after cocoa intake. Since the same dose of cocoa was ingested by each group, although at a different frequency, this indicates that intake frequency does not affect the cocoa-induced changes in arterial stiffness.
Daily consumption of cocoa and/or dark chocolate has a beneficial effect in the prevention of cardiovascular events.24,25 In a previous study, daily consumption of cocoa and dark chocolate over a 4-week period improved vascular function and reduced cardiovascular risk in both healthy and overweight adults.26 In a similar study, cocoa intake for 4 weeks was shown to reduce cardiovascular risk in healthy middle-aged adults, regardless of sex.13 These findings provide evidence that habitual cocoa intake has a beneficial effect on CVD risk factors24 and an inverse association with all-cause mortality and cardiovascular death.12 However, although the beneficial effects of cocoa intake have been reported, the effect of intake frequency on arterial stiffness has remained unclear. In this study, a significant decrease in arterial stiffness among postmenopausal women was observed after 12 weeks of cocoa intake, regardless of intake frequency. This finding suggests that intake frequency has no effect on the cardiovascular-protective actions exerted by cocoa.
Arterial stiffness increases with age, as evidenced by increases in PWV, and arterial stiffness is dramatically increased in postmenopausal compared with premenopausal women.7 Therefore, suppressing increases in arterial stiffness among this population is crucial for health promotion. Daily consumption of cocoa has been shown to be associated with decreases in central arterial stiffness in healthy adults, regardless of age.10,14 However, the findings in the present study among postmenopausal women indicate that consuming cocoa every other day also reduces central and peripheral arterial stiffness. Therefore, cocoa intake exerts beneficial effects regardless of frequency. This finding suggests that regardless of intake frequency, decreases in arterial stiffness may be associated with the dose of cocoa ingested weekly. Higher quantities of regularly ingested cocoa have been reported to be an independent determinant of reduced arterial stiffness,27 which is an effect dependent upon the dose of cocoa flavonoids.10 The participants in the present study consumed cocoa powder that included flavanols, a dose that has been shown to exert antiatherosclerotic effects. Both groups in the present study ingested an equivalent total weekly dose of cocoa flavanols, which suggests that habitual intake of flavanol-rich cocoa exerts positive effects on cardiovascular health in postmenopausal women, regardless of intake frequency. This finding expands upon previous research regarding the effects of habitual cocoa intake on arterial stiffness among postmenopausal women.
Several mechanisms may explain why the frequency of intake does not appear to alter the effects of cocoa on arterial stiffness. Some meta-analyses have proposed that flavanol-enriched cocoa reduces BP,28–30 which is a key determinant of arterial stiffness.31 In addition, ingestion of cocoa flavanols induces vasodilation, which also reduces BP.30 In the present study, BP was effectively reduced in both groups. Furthermore, ingestion of flavanol-enriched cocoa has been shown to be associated with reduced BP and significant improvements in vascular endothelial function.24,29,32 Vascular endothelial cells produce vasoactive substances, such as nitric oxide (NO), which help to regulate arterial stiffness and thus play a key role in the control of vascular tone.33–35 Vascular endothelial function affects large elastic and muscular arterial stiffness.36 Cocoa flavanols have been shown to stimulate NO production in endothelial cells.17,37 Acute intake of dark chocolate improved vascular endothelial function in healthy smokers 2–8 hours after ingestion, and this improvement was higher than baseline at even 24 hours after ingestion, although the difference was not significant.38 Moreover, daily consumption of cocoa and/or dark chocolate is associated with significant increases in basal and peak arterial diameter, as well as improved arterial blood flow through the brachial artery, which helps to reduce peripheral arterial stiffness.26 Increased arterial diameter with greater arterial blood flow has been shown to persist for several hours after the ingestion of flavanol-enriched cocoa.20 Therefore, it is reasonable to assume that acute unfavorable responses, such as increased arterial stiffness in the central and peripheral arterial vascular walls, might be reduced via peripheral artery vasodilation. In fact, consequential changes in vasodilator function may persist for several weeks,39 which can reduce baseline levels of arterial stiffness. This mechanism might help explain reductions in arterial stiffness in the absence of daily cocoa intake, and thereby supports the findings in the present study that cocoa intake twice daily every other day is also beneficial for arterial function. However, it should be noted vascular endothelial function was not measured in this study, which is an important limitation.
Endothelium-derived NO and ET1 play important roles in the regulation of arterial stiffness.40,41 Oral administration of (−)-epicatechin can increase NO production and reduce ET1 concentrations, thereby improving endothelial function.42 In addition, epicatechin can lead to acute improvements in endothelial function by modulating the circulating concentrations of vasoactive NO products and ET1.42 The endothelium regulates vascular tone by balancing the production of vasodilators, such as NO,43 and vasoconstrictors, such as ET1.44 Flavanols help to prevent reactive oxygen species-mediated degradation of NO, as well as blunt vasoconstrictor and proinflammatory responses.11 In the present study, plasma ET1 concentrations decreased in both groups. Decreases in plasma ET1 concentrations caused by flavanol occurred not only with daily cocoa intake but also with twice-daily cocoa intake ingested on an every-other-day basis, which may contribute to reductions in arterial stiffness. However, additional studies are needed to determine the precise mechanisms underlying the effects of intake frequency on arterial stiffness.
The findings in the present study demonstrated significant decreases in FG and TG, and these were consistent with previous observations that consumption of flavanol-enriched cocoa improves FG and TG levels in healthy adults.45,46 However, no effects were observed in regard to TC, HDL-C, or LDL-C. Increases in LDL-C and decreases in HDL-C can lead to the development of CVD.47 Flavanol-rich cocoa has been reported to reduce plasma levels of LDL-C and increase HDL-C serum concentrations in hypercholesterolemic patients.48,49 In this respect, our results differ from previous findings. One possible reason for this difference may be differences in the subjects of the studies. However, as TC, HDL-C, and LDL-C values in this study were within the standard ranges, these values might not have differed from baseline.
This study had several limitations. First, it did not include a sedentary control group who did not actively engage in regular physical exercise. Second, structural changes in the arterial wall that could impact arterial stiffness, such as changes in intima-media thickness, were not assessed.31 Third, the participants in the present study were all healthy postmenopausal women. Therefore, our findings might not be generalizable to older males or patients with CVD. Nevertheless, we believe that the present findings provide some potentially important clinical implications for postmenopausal women.