The meta-analysis of randomized controlled trials, published in Foods, focused on a variety of antioxidant-rich products from both naturally derived sources and supplemental forms.
Alongside vitamins C, B2 and D and xanthohumol, fermented papaya, peanuts and berry extracts were also identified as having potential cognitive-enhancing, gut-friendly benefits.
“These antioxidants may support the gut–brain axis primarily by increasing the production of short-chain fatty acids and improving gut barrier integrity, which helps mitigate oxidative stress—a factor often associated with cognitive decline and neurodegenerative diseases,” the authors wrote.
The gut-brain axis
Recent advances in research have described the importance of gut microbiota in influencing the emotional and cognitive centers of the brain with peripheral intestinal functions.
One of the first examples of the gastrointestinal microbe-brain interaction arose from observed improvements in patients with hepatic encephalopathy following a course of oral antibiotics. Now, some researchers believe that microbiota could even play a role in mood disorders such as anxiety and depression.
Antioxidants are thought to influence the gut microbiome by altering the redox environment in the gut, modulating the activity of gut bacteria and reducing inflammation. Some scientists now believe these changes in the gut microbiome can indirectly affect brain function by improving neurotransmitter balance and blood-brain barrier integrity.
However, study findings remain inconsistent due to methodological differences and population variability.
Hyży et al. therefore set out to take a closer look at clinical studies assessing the effects of antioxidants on the gut microbiome and brain functions, considering both potential mechanisms of action and research limitations.
Can antioxidants improve cognitive function?
The researchers, from the University of Warsaw, Poland, conducted an extensive literature search and identified six relevant RCTs which analyzed antioxidant interventions on human participants.
The studies exploring the impact of antioxidants on cognitive functions indicated beneficial effects, particularly on working memory and overall mental performance.
Supplementation with flavonoid-rich blackcurrant drinks and wild blueberry powder both seemed to improve cognitive test scores, particularly in populations prone to cognitive decline. In addition, peanuts—which are high in polyphenols—appeared to improve memory.
Antioxidant vitamins also appeared to positively impact cognitive resilience through pathways such as oxidative stress reduction and neuroprotection. However, the researchers warned that the studies exhibited significant heterogeneity.
“While these findings collectively suggest that antioxidant supplementation can enhance cognitive functions, variations in study outcomes underscore the influence of individual differences, such as baseline health status, dietary patterns and genetic predispositions,” they explained.
The role of antioxidants in modulating the gut microbiome
The impact of antioxidants on the gut microbiome varied across the studies. Vitamin supplementation provided the most consistent results, the researchers reported, with increased levels of beneficial bacteria like Akkermansia and Faecalibacterium and enhanced short-chain fatty acid production.
Polyphenol-rich foods such as berries and peanuts also generally promoted beneficial bacterial populations. While fermented papaya showed minimal direct microbiome effects, it appeared to contribute to overall gut health through oxidative stress reduction.
Xanthohumol—a hop flavonoid—showed highly variable effects depending on individual baseline microbiome composition. The researchers say this variability underscores the role of personalized nutrition in microbiome-targeted interventions.
“These results suggest that while antioxidants may influence the gut microbiome, their effects are limited and may depend on specific metabolic conditions and the baseline composition of the microbiome,” they wrote.
The need for personalized interventions
Based on their review, the researchers concluded that antioxidant supplementation may be particularly beneficial for individuals experiencing heightened oxidative stress or inflammation.
However, more research is needed to eradicate variability in study methodologies, population characteristics, types of supplements and durations of interventions.
“While there are shared benefits across these components […], the magnitude and mechanisms of their effects vary significantly,“ the researchers concluded. “This variability underscores the complexity of cognitive enhancement and the need to consider individual factors […] when designing interventions.”
Source: Foods 14(2), 2025. doi: 10.3390/foods14020176. “Effect of Antioxidants on the Gut Microbiome Profile and Brain Functions: A Review of Randomized Controlled Trial Studies” Authors: A. Hyży, et al.
