Nyerovwo Charity Okei, a trailblazing researcher at the University of Camerino’s School of Biosciences and Veterinary Medicine in Italy, says natural food metabolites could revolutionise the treatment of Alzheimer’s disease.
In a field long dominated by high-tech drug trials and genetic engineering, Okei points to a quiet yet powerful shift — one rooted in the humble origins of everyday foods such as green tea, berries, and cocoa.
These natural compounds, she explains, have shown potential in protecting brain cells, reducing inflammation, and slowing cognitive decline.
Her groundbreaking work on polyphenol metabolites – the bioactive compounds gotten from plant-based polyphenols which gets broken down by the gut microbiota, is offering fresh hope for combating Alzheimer’s disease (AD), the world’s most common form of dementia affecting millions.
Okei’s research, detailed in her 2024 publication in the European Journal of Medical and Health Research, uncovers how these metabolites, particularly phenyl-γ-valerolactones (PVLs) derived from flavan-3-ols, could supercharge the brain’s natural “waste disposal” system: the proteasome.
In Alzheimer’s, toxic proteins like beta-amyloid and tau build up due to a dysfunctional proteasome, leading to plaque formation, inflammation, and neurodegeneration.
These PVLs enhance proteasome activity, enabling brain cells to clear misfolded proteins more efficiently, reduce aggregate buildup, and even mitigate cellular stress and inflammation – key drivers of AD pathology.
“This isn’t just about antioxidants; it’s about targeting the root mechanisms of the disease,” Okei explained in an exclusive interview.
Her work demonstrates that PVLs not only boost protein clearance but also exhibit neuroprotective effects, potentially slowing disease progression. “These metabolites cross the blood-brain barrier, reaching where they’re needed most, and they come from natural sources we already consume,” she added.
The findings highlight polyphenols’ therapeutic potential, paving the way for safer, diet-inspired interventions beyond current symptom-managing drugs.
Okei’s journey into this research stems from a deep-seated frustration with the status quo in AD treatment. “Current therapies focus on symptoms, not the underlying damage,” she said. Inspired by the untapped power of nutrition, Okei zeroed in on a critical research gap: while parent polyphenols in foods have been studied, their metabolites – the “real players” circulating in the bloodstream – have been overlooked.
These metabolites, produced via gut metabolism, offer better bioavailability and brain penetration, yet their role in AD remains underexplored.
Her big questions? Can PVLs revive the brain’s cleanup system to eliminate toxic proteins? And could they inspire food-based therapies that target disease mechanisms, not just mask symptoms? Okei’s fascination with diet’s influence on health, coupled with a desire to bridge nutrition science and molecular biology, drove her forward.
“It’s about hope – safer, natural ways to protect the brain, especially when options are limited,” she shared. Her study answers with a resounding yes, opening doors to metabolite-inspired treatments that could transform AD care.
One of the most exciting aspects of Okei’s research is its emphasis on specificity. Not all polyphenol metabolites behave the same; some potently activate the proteasome, while others show minimal impact. This variability, she argues, is a goldmine for precision medicine. “There’s no one-size-fits-all,” Okei noted.
Her vision? Developing therapies – via optimized diets, supplements, or drugs – that deliver the most effective compounds based on an individual’s genetics, metabolism, or disease stage.
Imagine personalized AD strategies: a patient with early-stage buildup gets targeted PVLs to enhance protein clearance, while another with advanced inflammation receives anti-stress variants. “This knowledge moves us from broad support to precisely tuned brain protection,” Okei said.
By understanding these unique effects, her work could lead to bespoke interventions, reducing side effects and boosting efficacy in a disease that affects over 50 million people globally.
The benefits of harnessing polyphenol metabolites are clear: they’re safe, abundant in daily diets, and gentler than synthetic drugs. Okei envisions them as accessible tools for brain health, potentially integrated into preventive lifestyles.
Yet challenges loom large. Bioavailability varies wildly – only select metabolites reach the brain, influenced by genetics, gut microbiome, and metabolism. Achieving therapeutic doses through diet alone is tricky, and individual responses differ. “We need to solve delivery, consistency, and personalization to turn promise into reality,” Okei cautioned.
Still, their low toxicity makes them a compelling alternative in an era of failed drug trials.
Okei is optimistic about technology’s integration into AD research. Omics tools – genomics, proteomics, metabolomics – provide a “big picture” of disease interactions, while AI sifts through vast datasets to uncover patterns and predict pathways.]
“Alzheimer’s is multifaceted; these tools let us map it all,” she said. For instance, AI could identify which PVLs best target the proteasome in specific patients, combining with metabolomics to track brain-reaching compounds. Together, they edge toward personalized medicine, tailoring treatments to biology, risks, and lifestyles – a far cry from one-size-fits-all approaches.
Okei’s next steps are ambitious. She’s prioritizing identification of the most potent metabolites, confirming their brain activity, and testing in transgenic AD mouse models to measure protein reduction and memory improvement. Biomarkers will validate target engagement, with human trials on the horizon.
