Prebiotic Type Spotlight: Polyphenols

Each edition of GPA’s Prebiotic Spotlight focuses on a specific prebiotic type to raise awareness around the prebiotic itself, its sources, any notable and/or recent research, and how it is used in the marketplace. This edition’s spotlight is on polyphenols. 

Overview 

Polyphenols are a broad class of plant-based organic compounds characterized by one or more phenolic rings with hydroxyl groups in their chemical structure (Lippolis et al., 2023). Based on their structural features, polyphenols are categorized into two main groups: flavonoids and non-flavonoids. Flavonoids include subcategories such as flavonols, flavononols, flavones, flavanols, flavanones, anthocyanidins, and isoflavonoids, while non-flavonoids comprise phenolic acid, stilbenes, coumarins, lignans, and tannins (Lackner et al., 2024).  

Polyphenols occur naturally in plant-based foods and serve as a protective mechanism against biotic and abiotic stress for the plant and have strong colouring properties that attract beneficial organisms (Meiners et al., 2024). In humans, the consumption of polyphenol-rich foods has been associated with beneficial gut microbiota modulation and related health benefits (Lackner et al., 2024). 

Due to their limited absorption in the upper gastrointestinal tract, polyphenols largely reach the colon intact, where they modulate the microbiota. Polyphenols can directly influence the growth of certain bacterial species, either by stimulating or inhibiting them. Bacterial growth is typically stimulated when the microbes can metabolize polyphenols, whereas inhibition results from the natural antimicrobial properties of these compounds.  (Lippolis et al., 2023).  

Examples of bacterial species that are stimulated by polyphenol intake include Akkermansia muciniphila, Bacteroides thetaiotaomicrom, Faecalibacterium prausnitzii, Bifidobacterium spp., and Lactobacillus spp., while taxa inhibited include Escherichia coli, Clostridium perfringens, and members of the phyla Firmicutes, and Proteobacteria (Lippolis et al., 2023; Rodriguez-Daza et al., 2021). 

Benefit Areas 

To date, several studies have described associations between specific groups of polyphenols and mortality. Polyphenols are thought to promote β-oxidation, inhibit adipocyte differentiation, and counteract oxidative stress (Yoo et al., 2024). Specifically, prebiotic effects of polyphenols are believed to be associated with the promotion of microbial activity and the reduction of pathogenic bacteria within the gut (Yoo et al., 2024). Research has demonstrated that polyphenols have various health benefits, including: 

    • Xanthohumol, a polyphenol found in hop plants, re-shaped individual gut microbial taxa in an enterotype-dependent manner (Jamieson et al., 2024). 
    • Enzyme-catalyzed treated grape marc, a source of bioactive polyphenols, produced cello-oligosaccharides that were highly fermentable by fecal microbiota, producing acetate and propionate in in vitro human fecal bacteria samples (Liu et al., 2024). 
    • Elderberry juice rich in anthocyanins significantly increased Firmicutes and Actinobacteria and decreased Bacteroidetes in overweight and obese adults (Teets et al., 2024). 
    • Wild blueberry polyphenols improved vascular and cognitive function and decreased 24-hour ambulatory systolic blood pressure in healthy older adults (Wood et al., 2023). 
    • Phenolic acids supplementation aided in glycemic control in adults with type 2 diabetes (T2D) (Amadi et al., 2025).  
    • Anthocyanin consumption significantly improved cognitive function in adults with an elevated risk of dementia according to their inflammation status (Borda et al., 2024).  
    • Tannin supplementation significantly improved irritable bowel syndrome (IBS) severity scores in adults with IBS (Molino et al., 2025).  
    • Anthocyanin-rich supplement enhanced intermittent high-intensity running performance in active males considered to be responders to the supplement (Perkins et al., 2024). 
    • Olive oil polyphenol intake significantly reduced malondialdehyde-modified low-density lipoprotein levels in males 35-50 years of age (Tsujino et al., 2024). 
    • Curcumin supplementation prevented deterioration of glycemic control and improved physical and psychological quality of life and depression in patients with coronary slow flow phenomenon (Soltani et al., 2024).  
    • Supplementation with powdered rose petal extract standardized to contain 2-3% isoquercetin and 63.82% of total polyphenol content, significantly reduced body fat without affecting lean mass in overweight adults (Sudeep et al., 2024).  
    • Polyphenol rich extract from sea asparagus significantly lowered blood pressure at baseline and following an aerobic performance test in patients with transient ischemic attack and minor strokes (Najar et al., 2024). 
    • Resveratrol supplementation led to significantly higher rates of oocyte maturity and higher-quality embryos in women with polycystic ovary syndrome undergoing assisted reproduction (Ardehjani et al., 2024).  

 

Sources 

Polyphenols are natural compounds found in a wide variety of plants, fruits, vegetables, and nuts (Lackner et al., 2024; Loke et al., 2024). Over eight thousand polyphenolic compounds have been identified in plant species, and the effects of these compounds on the gut microbiota vary (Suther et al., 2024). Depending on the amount of phenol rings the polyphenols contain, in addition to the structural elements that connect the rings together, polyphenols are classified into different groups such as flavonoids, phenolic acids, tannins, stilbenes, and lignans (Jawhara, 2024). For example, fruits and vegetables such as blueberries, pomegranate, celery, and grapes are rich in the polyphenol’s anthocyanins, flavonols, flavones, and resveratrol respectively (Jawhara, 2024). Several factors influence polyphenol-rich food absorption in the small intestine, including structural complexity and polymerization, and in general 90-95% of polyphenols enter the large intestine undigested. The gut microbiota can then metabolize polyphenols into absorbable simple phenolic compounds, and these dietary phenolic compounds and aromatic metabolites reinforce the gut microbiota through their prebiotic properties (Yoo et al., 2024).  

Dose Range 

It is widely accepted that including a variety of polyphenol-rich foods, such as fruits and vegetables, as part of a balanced diet is vital for maintaining overall health and well-being. In the United States, dietary guidelines recommend a daily intake of 2 ½ cups of vegetables and 2 cups of fruits daily (Dietary Guidelines for Americans, 2020). However, evidence regarding the ideal intake of polyphenols for health benefits remains inconclusive, and no standardized daily intake recommendations have been established to date. A Canadian community health survey reported that adults aged 19 years and older consumed an average of 1119.3 mg of polyphenols per 1000 kcal/day, while children aged 2-18 consumed approximately 473.0 mg per 1000 kcal/day (Biancaniello et al., 2024). Research on four of the most common dietary polyphenols (epigallocatechin gallate, catechins, quercetin, and trans-resveratrol) suggests that effective doses may range from 5 to 1260 mg per day. Additionally, Jamieson et al., (2024) observed an enterotype-dependent modulation of gut microbial taxa following eight weeks of supplementation with 24 mg/day of the polyphenol xanthohumol. Similarly, Teets et al., (2024) observed changes in gut microbiota after five weeks of consuming 720 mg/day of anthocyanin polyphenols, naturally found in elderberry juice, in adults with overweight or obesity. Health benefits associated with polyphenol supplementation have been reported at doses between 320 mg/day for 12 weeks to 800 mg/day for 8.5 weeks. These benefits include improvements in vascular and cognitive function, as well as enhanced quality of embryos in women with polycystic ovary syndrome respectively (Wood et al., 2023; Ardehjani et al., 2024.) Additionally, a daily dose of 480 mg/day for 8 weeks of polyphenol intake was shown to reduce IBS severity (Molino et al., 2025). Nonetheless, further studies are needed to assess the long-term safety and efficacy of polyphenol supplementation strategies (Loke et al., 2024).  

Recent Research 

Polyphenols are widely studied not only for their prebiotic properties but also for their protective effects against various chronic diseases. Currently, fifty-five studies listed on ClinicalTrials.gov are recruiting participants to investigate the impact of polyphenol supplementation on diverse health outcomes, such as cognition and mental health, cardiometabolic risk, and joint health, amongst others (ClinicalTrials.gov, 2025). Moreover, searching of “polyphenols” on PubMed retrieved twenty-two clinical trials published in 2025 so far, ranging from the effects of polyphenols on microRNA modifications linked to insulin sensitivity, potentiating effects of L-citrulline in athletic performance and vasodilation, and effects on cognitive function and neuroprotective biomarkers. 

An acute, randomized, controlled, crossover trial by Villalva et al., (2025) evaluated the effects of a cocoa-carob blend (CCB), rich in polyphenols, in participants with T2D and overweight/obesity. Twenty participants consumed three interventions, each separated by a two-week washout period: 1) hypercaloric breakfast (high in sugar and saturated fat, control), 2) the same hypercaloric breakfast + 10 g of CCB, containing 1.6 g of total polyphenols, and 3) the same breakfast + 10 g CCB consumed the night before. Assessments included clinical markers of T2D, satiety evaluation, analysis of exosomal miRNA expression, and ex vivo determination of inflammation modulation. No effects on glucose homeostasis (glucose, insulin, and GLP-1) were found in the study population, however, eight exosomal miRNAs were significantly modified when supplementing with CCB, with three of the miRNAs (miR-20A-5p, miR-23A-3p, and miR-17-5p) associated with improvements in insulin sensitivity. CCB supplementation additionally caused a decrease in feelings of hunger. These results are likely attributed to a combination of the mechanisms of action reported for both polyphenols and dietary fibre, bioactive constituents of CCB.  

A randomized, double-blind, placebo-controlled pilot trial by Mollace et al., (2025) investigated the effects of supplementing with bergamot polyphenolic fraction and L-citrulline on athletes performance and blood flow. A total of ninety male cyclists were randomized to consume either 1) 500 mg/day Bergamot Polyphenolic Fraction Gold® (BPFG), 2) 1000 mg/day BPFG, 3) 1000 mg/day L-citrulline, 4) 2000 mg/day L-citrulline, 5) 500 mg/day BPFG + 1000 mg/day L-citrulline, 6) 1000 mg/day BPFG + 1000 mg/day L-citrulline, 7) 500 mg/day BPFG + 2000 mg/day L-citrulline, 8) 1000 mg/day BPFG + 2000 mg/day L-citrulline, or 9) Placebo, for three months. Baseline and at three-month pre- and post-exercise biochemical, reactive vasodilation (RHI), and maximal oxygen consumption were measured for all participants. The combination of BPFG and L-citrulline produced a significant synergistic effect, increasing nitric oxide release and RHI for all dose combinations. Cardiorespiratory fitness improved significantly with BPFG and L-citrulline combination, resulting in substantially higher maximum oxygen uptake, ventilatory thresholds, and peak power, along with a significantly lower heart rate for all BPFG + L-citrulline dose combinations. These results suggest that co-supplementation with bergamot polyphenolic fraction and L-citrulline may offer antioxidant and endothelial-protective benefits, representing a supplementation strategy for improving athletic performance. 

A randomized, double-blind, placebo-controlled crossover clinical trial by Carrillo et al., (2025) evaluated the relationship between brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB) activity, and cognitive performance in adults undergoing a polyphenol-rich dietary intervention. Ninety-two healthy adults were randomized to consume 1) 600 mg/day of an encapsulated concentrate of fruit, vegetable, and berry juice powders (containing 119 different polyphenolic compounds), or 2) placebo for 16-weeks, with a 4-week washout between treatments. Cognitive function was assessed using the Stroop Test, Trail Making Test, and Reynolds Intellectual Screening Test (RIST), while plasma levels of CREB and BDNF were measured using ELISA. The polyphenol-rich product group significantly improved cognitive performance, compared to placebo. Additionally, plasma levels of CREB and BDNF were notably elevated following consumption of the polyphenol-rich product, indicating enhanced neuroprotective activity. These findings suggest that polyphenol-rich nutraceuticals can modulate neurobiological mechanisms underlying cognitive improvements, primarily through the reduction of oxidative stress and the regulation of signaling pathways associated with synaptic plasticity. 

How are polyphenols used in the marketplace? 

According to The Business Research Company (2025), global polyphenols market size reached an estimated $2.44 billion USD in 2024, and is expected to reach $2.79 billion USD this year. Longer term projections expect the polyphenol market to reach $4.99 billion USD by 2029, with a compound annual growth rate (CAGR) of 15.7%. Key market drivers include the growing demand for personalized and targeted supplements, the expansion in plant-based and vegetarian diets, increasing use in pharmaceutical and healthcare products, rising consumer awareness of the benefits of herbal products over synthetic drugs, and the integration of polyphenols into anti-aging and beauty products. Product launches have emerged as a key trend gaining popularity in the polyphenols market, and many companies are developing new products to meet industry demand. With over 8000 different forms of polyphenols, the applications are large and diverse, including functional beverages, functional foods, dietary supplements, cosmetics and toiletries, animal feed, and natural dyes.  

References:

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Ardehjani, N., Agha-Hosseini, M., Nashtaei, M., Khodarahmian, M., Shabani, M., Jabarpour, M., Fereidouni, F., Rastegar, T., & Amidi, F. (2024). Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial. Journal of Ovarian Research, 17(1):143. doi: 10.1186/s13048-024-01470-9. 

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