Multiple Health Benefits of Chocolate, Red Wine, and Apples When Consumed in the Right Amounts

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Summary: Optimal intake of B-type procyanidins, a class of polyphenols found in apples, cocoa and red wine, is linked to metabolic and the hormesis of hemodynamic responses.

Source: Shibaura Institute of Technology

B-type procyanidins, made of catechin oligomers, are a class of polyphenols found abundantly in foods such as cocoa, apples, grape seeds, and red wine.

Several studies have established the benefits of these micronutrients in reducing the risk of cardiovascular diseases and strokes. B-type procyanidins are also successful in controlling hypertension, dyslipidemia, and glucose intolerance.

Studies prove the physiological benefits of its intake on the central nervous system (CNS), namely an improvement of cognitive functions.

These physiological changes follow a pattern of hormesis—a phenomenon in which peak benefits of a substance are achieved at moderate doses, and gradually diminish at lower and higher doses.

The dose-response relationship of most bioactive compounds follows a monotonic pattern, in which a higher dose shows a greater response. However, in some exceptional cases a U-shaped dose-response curve has been observed.

This U-shaped curve means hormesis – an adaptive response, in which a low dose of a normally harmful compound causes resistance in the body to its higher doses. This means that exposure to low levels of a harmful trigger can induce the activation of stress-resistant pathways, leading to greater repair and regeneration capabilities.

In case of B-type procyanidins, several in vitro studies support its hormetic effects, but these results have not been proven in vivo.

To address this knowledge gap, researchers from Shibaura Institute of Technology (SIT), Japan, led by Professor Naomi Osakabe of the Department of Bioscience and Engineering, examined the data from intervention trials that examined hormetic responses of B-type procyanidin intake to support

The team, consisting of Taiki Fushimi and Yasuyuki Fujii from the Graduate School of Engineering and Science (SIT), also performed in vivo experiments to understand possible connections between B-type procyanidin hormetic responses and CNS neurotransmitter receptor activation.

Her article was made available online on June 15, 2022 and was published in volume 9 of Frontiers of Nutrition on September 7, 2022.

The researchers noted that a single oral administration of an optimal dose of cocoa flavanol temporarily increased blood pressure and heart rate in rats. But the hemodynamics did not change when the dose was increased or decreased. Administration of B-type procyanidin monomer and various oligomers produced similar results.

According to Professor Osakabe, “These results are consistent with those of intervention studies after a single intake of food rich in B-type procyanidin, and support the U-shaped dose-response theory, or hormesis, of polyphenols.”

To observe whether the sympathetic nervous system (CNS) is involved in the hemodynamic changes caused by B-type procyanidins, the team administered adrenaline blockers in test rats.

This successfully reduced the temporary increase in heart rate caused by the optimal dose of cocoa flavanol. Another type of blocker-a1-blocker-inhibited the transient increase in blood pressure.

This suggested that the SNS, which controls the action of adrenaline blockers, is responsible for the hemodynamic and metabolic changes caused by a single oral dose of B-type procyanidin.

This suggested that the SNS, which controls the action of adrenaline blockers, is responsible for the hemodynamic and metabolic changes caused by a single oral dose of B-type procyanidin. Image is in the public domain

The researchers then established why optimal doses, and not high doses, are responsible for the thermogenic and metabolic responses. They combined a high dose of cocoa flavanol and yohimbine (an α2-blocker) and noted a temporary but distinct increase in blood pressure in test animals. Similar observations were made using B-type procyanidin oligomer and yohimbine.

Professor Osakabe thinks, “Since α2-blockers are associated with the down-regulation of the SNS, the reduced metabolic and thermogenic outputs at a high dose of B-type procyanidins seen in our study may have caused α2 auto-receptor activation. Thus, SNS deactivation is caused by a high dose of B-type procyanidins.

Previous studies have proven the role of the gut-brain axis in controlling hormetic stress-related responses. The activation of the hypothalamus-pituitary-adrenal (HPA) as a result of optimal stress has a strong influence on memory, cognition and stress tolerance.

This article highlights how HPA activation occurs after a single dose of B-type procyanidin, suggesting that stimulation with an oral dose of B-type procyanidin may be a stressor for mammals and cause SNS activation.

Hormesis and its triggering biochemical pathways provide protection against various pathological and aging processes, improving our overall health and making us resistant to future stress.

Although the exact relationship between B-type procyanidins and the CNS needs more research, the health benefits of B-type procyanidin-rich foods remain undisputed.

Financing information
This study was supported by JSPS KAKENHI (Grant Number: 19H04036).

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Writer: Wang Yu
Source: Shibaura Institute of Technology
Contact: Wang Yu – Shibaura Institute of Technology
Image: The image is in the public domain

Original research: Free access.
“Hormetic response to B-type procyanidin ingestion involves stress-related neuromodulation via the gut-brain axis: preclinical and clinical observations” by Taiki Fushimi et al. Frontiers in Nutrition


Hormetic response to B-type procyanidin ingestion involves stress-related neuromodulation via the gut-brain axis: preclinical and clinical observations

B-type procyanidins, a series of catechin oligomers, are among the most commonly absorbed polyphenols in the human diet.

Results of meta-analyses have suggested that intake of B-type procyanidins reduces the risk of cardiovascular disease.

Another recent focus has been on the effects of B-type procyanidins on central nervous system (CNS) function.

Although long-term B-type procyanidin ingestion is linked to health benefits, a single oral intake has been reported to cause physiological changes in circulation, metabolism, and the CNS.

Extensive analyzes of previous reports indicate an optimal mid-range dose for the hemodynamic effects of B-type procyanidins, with null responses at lower or higher doses, suggesting hormesis.

Indeed, polyphenols, including B-type procyanidins, elicit hormetic responses in vitro, but animal and clinical studies are limited. However, hormesis of hemodynamic and metabolic responses to B-type procyanidins was recently confirmed in animal studies, and our work has linked these effects to the CNS.

Here we evaluate the hormetic response elicited by B-type procyanidins, recontextualizing the results of intervention trials. In addition, we discuss the possibility that this hormetic response to B-type procyanidins occurs via CNS neurotransmitter receptors.

We have verified the direction of future research for B-type procyanidins in this review.

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