Food For Thought: Plant-Based Polyphenols From Coffee, Cacao, Red Wine, and Mushrooms Protect Brain Health in Older Adults

‘We are what we eat’ is a well-known adage that certainly rings true regarding brain health. Just as some foods can protect cognitive function, others we consume damage or deteriorate an aging brain. In a field known as neuronutrition, scientists are uncovering how what we choose to eat — and what we avoid — can dramatically alter the brain’s health and how it functions with age.

One group of brain-boosting molecules making a name for themselves in the neuronutrition field are polyphenols. Found in various plant foods, polyphenols act as antioxidants and protect the brain from excess inflammation and oxidative stress — the accumulation of harmful compounds that damage cells, proteins, and DNA. In a recent study, a Barcelona-based research team identifies compounds created during the metabolism of polyphenol-rich foods and how they affect the brain — both positively and negatively. With this research, González-Domínguez and colleagues spotlight certain foods that protect cognition in a 12-year study combining two sets of older adults — with coffee, cacao, mushrooms, and red wine leading the brain-boosting pack of polyphenols. 

Uncovering Metabolite Mysteries

Researchers know that certain foods correlate with better brain health, like omega-3 fatty acids, leafy green vegetables, and antioxidant-rich foods — especially when looked at in a lab setting. However, when studying actual humans in real life, the data is often inconsistent. This is partly because most human studies rely on food intake surveys, which ask the participant to recall foods they recently ate. This method is unsurprisingly prone to reporting errors, as many people can barely remember what they consumed this morning — let alone last year.

An alternative to food intake surveys is studying metabolites — small molecules produced in the body when cells convert food into energy. With this method, researchers can more easily determine how much of a particular food or food group someone has been consuming based on the levels of metabolites found in their blood. 

However, it’s not always that simple, as the bacteria in our guts play a prominent role in this process. Many metabolites found in the participant’s blood were microbial-derived compounds, meaning that the gut microbiome converted the “parent polyphenol” (the one found in the food itself) into an entirely new metabolite. This could suggest that a healthy and diverse microbiome is needed to synthesize these metabolites.

Good News For Chocolate and Coffee Lovers

In this study of over 800 French adults, the research team identified many metabolites related to stronger cognitive health. Over the 12-year study, people with higher metabolite markers from cocoa, coffee, mushrooms, and red wine had a reduced risk of developing cognitive problems by 25%, 43%, 10%, and 30%, respectively. 

The prominent polyphenol in cacao (or cocoa) is theobromine, with its microbiota-derived metabolite known as 3-methylxanthine. Chocolate consumption is beneficial to brain health, as theobromine can cross the highly selective blood-brain barrier, increasing blood flow and influencing neuron activity. While this is good news for chocolate lovers, keep in mind that milk chocolate or ‘candy’-type chocolate won’t contain significant amounts of theobromine — when it comes to the brain-boosting benefits, the darker (and more bitter), the better.

Coffee intake exhibited the strongest link to better cognitive health, as measured by the metabolite 2-furoylglycine. However, overall caffeine consumption produced contradictory results, as people who had greater circulating caffeine metabolites were 88% more likely to develop poor cognition over the 12 years. The researchers suggest that these contradictions may arise from person-to-person differences in metabolizing caffeine. Still, more research is needed to understand this ​​coffee-caffeine paradox better. 

Dish Up the Mushroom Sauce and Red Wine

Many studies have exhibited the health benefits of resveratrol — the main antioxidant in red grapes and wine — and this one adds to the evidence that moderate red wine intake may benefit brain health. However, similar to the coffee-caffeine contradiction, the data also shows that while people with markers of red wine consumption showed better cognition, those with high amounts of total alcohol intake were at much higher risk of poor cognitive health. This solidifies that resveratrol, and not another component of alcohol, is why wine benefits the brain. 

Lastly, eating mushrooms led to a modest yet significant boost to cognition. Previous research has found that the primary polyphenol in mushrooms, ergothioneine, is linked to neural protection in the brain. But, blood ergothioneine levels tend to decline with age, which may be restored by loading up on mushrooms and possibly boosting brain function at the same time.  

To recap the mouthful of metabolites just mentioned: 

• Theobromine (found in cacao or cocoa): Crosses the blood-brain barrier to increase blood flow and support neuron activity.

• 3-methylxanthine: The gut microbiota-derived metabolite of theobromine.

• 2-furoylglycine (found in coffee): Exhibits the strongest link to better cognitive health.

• Resveratrol (found in red grapes and wine): A potent antioxidant that fights oxidative stress and supports cognitive function.

• Ergothioneine (found in mushrooms): This polyphenol is associated with neural protection, but its levels decline in the body with age.

The Bad News

The metabolomics analysis also found some compounds or foods detrimental to brain health. In addition to the previously mentioned caffeine and total alcohol intake, consumption of artificial sweeteners was also linked to poor cognition. Specifically, metabolites of saccharin (found in Sweet’N Low) and acesulfame-K (found in many diet sodas and processed foods) increased the risk of poor cognitive function by 26% and 12%, respectively. 

While previous research with animals has found artificial sweetener consumption to impair cognition and alter neuronal activity, long-term research with humans has not been conclusive. As the authors state in their paper, “This is, to our knowledge, the first time that this hypothesis linking artificial sweeteners with [poor cognitive health] is corroborated from a long-term perspective, and also validated in two separate sample sets.”

Lastly, high amounts of the metabolite proline betaine — found in citrus fruits — surprisingly showed a detrimental effect on brain health. However, the researchers speculate that this association may be due to a higher intake of commercial fruit juices (which are high in added sugar and lack fiber) rather than consuming whole citrus fruit itself. Another study adds credence to their speculation, showing that the proline betaine metabolite is more correlated with citrus juice intake than the whole citrus fruit.

Bring on the Brain Food 

This study adds to the evidence that the certain polyphenols found in plant foods — and their subsequently derived metabolites from the gut microbiome — are beneficial to brain health. It’s even better that the most significant benefits to cognition came from foods and drinks that most people thoroughly enjoy, like chocolate, red wine, and coffee. As the lead author of the study, professor Cristina Andrés-Lacueva, concludes, "A higher intake of fruits, vegetables, and plant-based foods provides polyphenols and other bioactive compounds that could help reduce the risk of [poor cognitive function] due to aging.”

One area of future research to explore is how the gut microbiota plays a role in creating some of these beneficial (or harmful) metabolites, including identifying the bacteria involved in the processes. For now, loading up on polyphenol-rich plant foods and (moderately) consuming red wine, coffee, and cacao-rich chocolate appears to be a safe — and tasty — bet.

References:

Erbaş O, Erdoğan MA, Khalilnezhad A, et al. Evaluation of long-term effects of artificial sweeteners on rat brain: a biochemical, behavioral, and histological study. J Biochem Mol Toxicol. 2018;32(6):e22053. doi:10.1002/jbt.22053

González-Domínguez R, Castellano-Escuder P, Carmona F, et al. Food and Microbiota Metabolites in Older Subjects: A 12-Year Prospective Study. Mol Nutr Food Res. 2021;65(23):e2100606. doi:10.1002/mnfr.202100606

Low DY, Lefèvre-Arbogast S, González-Domínguez R, et al. Diet-Related Metabolites Associated with [Cognition] Revealed by Untargeted Metabolomics in a Prospective Cohort. Mol Nutr Food Res. 2019;63(18):e1900177. doi:10.1002/mnfr.201900177