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As a someone who is deeply interested in understanding the secrets of healthy aging, I want to share a fascinating topic that has been at the center of my focus since I became interested in the mind-gut connection: the incredible potential of dietary polyphenols.

If you didn’t already know, polyphenols are plant-derived compounds, abundant in foods like berries, tea and cocoa, and are showing great promise in the fight against heart disease, cognitive decline and neurodegenerative diseases. Even more intriguing is their intimate relationship with the gut microbiome, which plays a pivotal role in determining how these compounds benefit our health.

While doing my MS in Human Nutrition at Columbia University, I was co-author of a key review article on the potential of dietary polyphenols for protection of cognitive decline. At the same time, I focused my thesis on the polyphenol flavanol and its protective effects on cognitive function. More on this later…

What Are Polyphenols, and Why Should We Care?

Polyphenols are natural compounds found in plant-based foods, where they act as a defense mechanism against various environmental threats, including droughts, UV lights and pests.

Emphasizing the importance of these molecules for the wellbeing of most plants, there are currently thought to be approximately 8000 different polyphenols. When we consume them, these compounds seem to do similar things for us that they do for plants.

They protect against oxidative stress, inflammation and vascular dysfunction—three key factors in the development of age-related diseases like Alzheimer’s and Parkinson’s disease and of heart disease.

Among polyphenols, flavonoids like flavan-3-ols, anthocyanins and quercetin are particularly fascinating.

Flavan-3-ols, found in cocoa beans and tea, and what I focused my thesis research on, have been shown to improve memory and enhance blood flow to key brain regions involved in cognitive function, in particular, the hippocampus.

Anthocyanins, the compounds that give berries their dark blue and black colors, support vascular health and have been linked to improved memory and mental clarity.

Meanwhile, quercetin, abundant in onions and apples, works as a powerful anti-inflammatory agent, interacting with the flavanols and anthocyanins to protect the brain and cardiovascular system from damage and dysfunction.

The Gut Microbiome: Polyphenols’ Essential Partner

Here’s where things get even more interesting. The benefits of polyphenols don’t happen in isolation—they rely on the gut microbiome to unlock their full potential.

When you eat a polyphenol-rich food, only a small percentage of the compounds are absorbed directly in the small intestine, generally less than 5%. When the benefits of polyphenol consumption were originally endorsed and promoted by the FDA, studies appeared in the literature showing that very little of these compounds could be detected in the blood after oral consumption, and their health benefits as antioxidants could no longer be promoted. This failure led to a rapid loss of interest by companies to offer polyphenols in the form of supplements.

What the FDA and companies involved in polyphenol promotion didn’t know at the time was the fact that the molecular structure of polyphenols prevented them from being absorbed in the small intestine, and that the great majority had to travel to the end of the small intestine and colon, where gut microbes would feed on them and metabolize them into absorbable bioactive forms. These smaller molecules can then enter the bloodstream and exert their beneficial effects throughout the body and the brain.

Equally surprising was the realization that these smaller molecules no longer had the antioxidant effects of the parent compound, and that their health beneficial effects were generally NOT related to their antioxidant properties. This is largely why we (my Dad and I) refer to them as polyphenols rather than antioxidants – however, this trend is catching on and we’ve seen a steady increase in referring to them as polyphenols.

This interplay between polyphenols and the microbiome is nothing short of extraordinary. Certain microbes, like Akkermansia muciniphila and Bifidobacterium, thrive on polyphenols and, in turn, produce metabolites that reinforce the gut barrier, reduce inflammation and even protect brain cells. It’s a two-way relationship: polyphenols nourish beneficial microbes, and these microbes enhance the bioavailability and effectiveness of polyphenols.

Real Benefits, Backed by Science

Through my research, I’ve been fortunate to witness how powerful this synergy can be. For example, diets rich in cocoa flavanols have been shown to improve memory, especially in older adults, by enhancing blood flow to the dentate gyrus (within the hippocampus)—a key brain region for learning and memory.

Anthocyanins from blueberries have been linked to improvements in verbal fluency, short-term memory and even visual-spatial skills. And quercetin, with its anti-inflammatory properties, not only supports heart health but also shows promise in slowing cognitive decline.

What’s truly inspiring is the potential for these compounds to work preventatively. By incorporating polyphenol-rich foods into our daily diets, we may reduce the risk of age-related diseases before they take hold. This proactive approach aligns with the growing understanding that nutrition is one of the most powerful tools we have for preserving brain health.

The Future of Polyphenols and Gut Health

As much as we’ve learned, we’re still just scratching the surface of how polyphenols and the gut microbiome interact. The diversity of our gut microbes varies from person to person, which may explain why some people experience more profound benefits from polyphenol-rich diets than others.

In large controlled clinical trials with flavanol supplementation over multiple years, it was found that individuals with suboptimal levels of flavanol metabolites, indicating poor intake of polyphenol containing foods, had the greatest benefit from taking the flavanol supplement. Understanding these individual differences will be key to optimizing dietary recommendations in the future.

I’m excited about the potential of future research to uncover more about this incredible relationship between phytochemicals and our health. So much so that I’m building a nutrition company that has these special little molecules front of mind (more on this at the end of this post). As we deepen our understanding, we can better harness the power of polyphenols to promote brain health, longevity and cognitive resilience.

A Call to Action

I encourage you to think about the role nutrition plays in your daily life and long-term health. Polyphenols aren’t just about fighting disease—they’re about enhancing vitality, clarity and quality of life.

Incorporating more foods like berries, green tea and pomegranates into your diet is a simple yet profound step you can take today. You may be thinking that every piece of dark chocolate is healthy because of the flavanols in cocoa beans which are the raw product of chocolate, then, right? The truth is it depends on how processed the chocolate is. Unless the manufacturer is adding flavanols back into the chocolate (unlikely) or has a unique processing technique which doesn’t remove all of the flavanols (equally unlikely), most dark chocolate is devoid of these beneficial compounds (sorry!).

As we continue to explore the science, I’m optimistic that the future will bring even more ways to individually tailor these natural compounds for maximum benefit.

Mayer Nutrition

If you are interested in learning more about polyphenols and their effect on the brain-gut-microbiome system, I am in the process of building a business that will both educate and offer research-substantiated, environmentally-sustainable products to supercharge your health. You can sign up for updates at www.mayernutrition.com and follow us on Instagram @mayernutrition – we have our sights set to launch in Spring of 2025.