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

Source: Shibaura Institute of Technology

Type B procyanidins, made up of catechin oligomers, are a class of polyphenols found abundantly in foods like cocoa, apples, grape seeds and red wine.

Several studies have established the benefits of these micronutrients in reducing the risk of cardiovascular disease and stroke. Type B procyanidins are also successful in controlling hypertension, dyslipidemia and glucose intolerance.

Studies attest to the physiological benefits of their contribution to the central nervous system (CNS), namely an improvement in cognitive functions.

These physiological changes follow a pattern of hormesis – a phenomenon in which the maximum benefits of a substance are achieved at medium doses, becoming progressively less 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 is observed.

This U-shaped curve signifies hormesis – an adaptive response, in which a low dose of a generally harmful compound induces 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 abilities.

In the case of type B procyanidins, several in vitro studies confirm their hormetic effects, but these results have not been demonstrated live.

To fill this knowledge gap, researchers at the Shibaura Institute of Technology (SIT), Japan, led by Professor Naomi Osakabe of the Department of Biosciences and Engineering, examined data from intervention trials supporting the responses hormetics of procyanidin type B ingestion.

The team, comprising Taiki Fushimi and Yasuyuki Fujii from the Graduate School of Engineering and Science (SIT), also conducted in long live experiments to understand possible links between procyanidin type B hormetic responses and activation of CNS neurotransmitter receptors.

Their article was put online on June 15, 2022 and was published in volume 9 of Nutrition Frontiers 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 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 following a single intake of foods rich in procyanidin type B, and support the U-shaped dose-response theory, or hormesis, of polyphenols.”

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

This was successful in reducing the temporary increase in heart rate induced by the optimal dose of cocoa flavanol. Another type of blocker – an a1 blocker – inhibited the transient increase in blood pressure.

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

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

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

Professor Osakabe surmises: “Since α2 blockers are associated with downregulation of the SNS, the reduced metabolic and thermogenic outputs at a high dose of B-type procyanidins observed in our study may have induced the activation of auto -α2 receptors. Thus, SNS deactivation can be induced 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. Activation of the hypothalamic-pituitary-adrenal (HPA) axis by optimal stress has a strong influence on memory, cognition and stress tolerance.

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

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

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

Funding Information
This study was supported by JSPS KAKENHI (grant number: 19H04036).

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Author: Wang Yu
Source: Shibaura Institute of Technology
Contact: Wang Yu – Shibaura Institute of Technology
Image: Image is in public domain

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


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

Type B procyanidins, a series of catechin oligomers, are among the most ingested polyphenols in the human diet.

The results of meta-analyses have suggested that the consumption of type B procyanidins reduces the risk of cardiovascular disease.

Another recent interest has focused on the effects of type B procyanidins on central nervous system (CNS) function.

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

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

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

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

We checked the direction of future research on type B procyanidins in this review.

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