The cell’s energy-producing organelles, the mitochondria, can be hampered by oxidative stress. By protecting mitochondria, phytonutrients can help brain cells produce energy at their best, maintaining proper neuronal function, enhancing synaptic activity, and supporting cognitive processes such as memory, learning, and mood regulation. (Zhang et al., 2019).

One feature of neurodegenerative diseases is persistent inflammation. Rahman et al. (2020) claim that phytonutrients like curcumin from turmeric and resveratrol from grapes help reduce inflammation in the nervous system while also maintaining cognitive function.

According to Poles et al. (2021b), certain micronutrients have been demonstrated to promote the synthesis of brain-derived neurotrophic factor (BDNF), a protein that aids in the development and survival of neurons and promotes brain regeneration and repair. By enhancing BDNF levels, these micronutrients may improve synaptic plasticity, support cognitive performance, and potentially slow the progression of neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease (Puri et al., 2022).

Brain plasticity, sometimes referred to as neuroplasticity, is the brain’s ability to reorganize and form new neural connections in response to circumstances, education, and environmental changes. Maintaining cognitive ability over time, healing from brain damage, and adjusting to new circumstances all depend on neuroplasticity (Fujimura et al., 2002; Kolb and Whishaw, 1998). Brain plasticity is improved by phytonutrients through:

Some refer to BDNF, a protein that supports neuronal development, survival, and differentiation, as “fertilizer for the brain.” It has been demonstrated that certain phytonutrients, such as curcumin (found in turmeric), resveratrol (found in grapes and berries), and flavonoids (found in berries and gloomy chocolate), raise BDNF levels, which in turn promote neuroplasticity by promoting the development of new neural pathways and the fortification of preexisting ones (Hannan et al., 2020; Kolb and Whishaw, 1998).

For example, flavonoids from food items like blueberries have been associated to enhanced plasticity of synaptic connections, which helps the nervous system adapt and learn novel information more efficiently (Fujimura et al., 2002). Additionally, plants can enhance plasticity of synaptic cells, which is the strengthening and shrinking of synapses and is essential for memory and learning.

Neuroplasticity may be impeded by inflammation and oxidative stress. By lowering oxidative stress, phytonutrients shield neurons from harm and help the brain adjust and reorganize. It has been demonstrated that polyphenols, such as those in green tea, lessen oxidative neuronal damage, promoting long-term neuroplasticity (Nath et al., 2023).

Numerous studies have shown that phytonutrients can encourage neural stem cells—the cells that develop into new neurons—to proliferate. In animal models, flavonoids such as curcumin and those in apples and blueberries have been demonstrated to promote the growth of brain stem cells. According to Hussain et al. (2023), these substances stimulate signaling pathways that encourage the development of new brain cells (Sharma et al., 2024).

The hippocampus is one part of the brain whose function is crucial for mood control, memory, and learning. Hippocampal neurogenesis is essential for cognitive function. According to research, phytonutrients like epicatechins, which are present in dark-colored chocolate and tea, and resveratrol, which is found in grapes and red wine, can increase neurogenesis in this area, improving memory as well as learning (Hussain, 2023).

In order to promote flexibility and adaptive brain function, neurogenesis facilitates the synthesis of new neurons, which then integrate into the brain’s networks. Flavonoids and anthocyanins, which are present in berries like cherries and blueberries, promote neuroplasticity and neurogenesis, which improves the brain’s capacity for memory formation and learning (Basu et al., 2021; Koponen et al., 2007).

Polyphenols, a diverse group of naturally occurring compounds found abundantly in fruits, vegetables, tea, wine, and other plant-based foods, are renowned for their potent antioxidant properties (Wang et al., 2021a). As antioxidants, they play a critical role in neutralizing free radicals—unstable molecules that can cause cellular damage when their levels become excessive (Chen et al., 2022). In the human brain, where high oxygen consumption and lipid content make neurons particularly vulnerable, this antioxidant action is especially important (Khan M. S. et al., 2023). Free radicals can trigger a cascade of oxidative stress, a harmful process that damages cellular structures such as proteins, lipids, and DNA (Patel et al., 2024a; Pande and Akoh, 2010). Over time, such oxidative damage contributes to the onset and progression of various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and other forms of cognitive decline (Lee and Park, 2022). By scavenging these reactive oxygen species and reducing oxidative stress, polyphenols help preserve the integrity of neuronal cells and promote healthy brain aging (Zhao et al., 2025). Consequently, regular consumption of polyphenol-rich foods is believed to support cognitive function, protect against memory loss, and maintain overall neurologicalhealth (Khan M. S. et al., 2023; Pande and Akoh, 2010).

Neurodegenerative disorders and cognitive impairment are associated with chronic inflammation. By regulating the expression of inflammatory substances including cytokines and processors (like COX-2), polyphenols lessen inflammation. This lessens the risk of inflammation-induced damage to brain tissue (Hasan et al., 2024).

Certain polyphenols, particularly resveratrol (found in the wines and grapes), have been shown to promote neurogenesis, the process by which new neurons are formed in the brain. This is essential for memory, learning, and the recovery from brain trauma. Furthermore, neurogenesis plays a critical role in halting age-related cognitive decline.

Polyphenols can alter different brain pathways of signaling, including those linked to transmitters such as dopamine, serotonin, and acetylcholine. These neurotransmitters are important in mood regulation, memory, and cognitive process (Wang et al., 2021b; Kim and Lee, 2023). According to Islam et al. (2022), polyphenols have the potential to improve dopamine signaling, which is crucial for motivation, focus, and learning, by modulating oxidative stress, enhancing synaptic plasticity, and supporting the survival of dopaminergic neurons—factors that collectively contribute to better cognitive and emotional functioning.

Polyphenols have the ability to cross the blood-brain barrier, a selective permeability barrier that protects the brain from harmful substances. Because of this, polyphenols can directly interact with the brain to produce their beneficial effects, including enhancing cognitive function, reducing neuroinflammation, and protecting against neurodegenerative diseases (Islam et al., 2022).

I. Research indicates that polyphenols can enhance cognitive processes including memory retention, learning, and attention. For example, polyphenols found in berries, such as blueberries, have been demonstrated to enhance memory function and postpone age-related cognitive decline (Travica et al., 2020).

A wide range of foods, including tea, chocolate, fruit such as apples, and kiwi fruit, contain catechins, which belong to the flavan-3-ol polyphenol family (Zanwar et al., 2014). While polyphenols are prevalent in green tea and its extracts, catechins comprise one-third of the polyphenols in brewed green tea. According to Liu et al. (2018), only a tiny percentage of the catechins that are taken physically are really accessible; the majority passes through the portal vein and into the liver, where phase II enzymes transform them into derivatives of methyl, glucuronide, and sulfate. The gut bacteria play a major role in the biotransformation of catechins producing their metabolites. The colon becomes a bioreactor with a vast capacity to metabolize catechins due to the vast gene pool of gut bacteria (Van Duynhoven et al., 2011). The gut microbiota may use glycosidic bonds, C-ring fission, and other processes to break down the heterocyclic configurations of catechins into smaller compounds such as phenylvalerolactones and phenylvaleric acids (Li and Van de Wiele, 2023). These newly produced microbial compounds may enter the circulation after navigating the colon epithelium (Luca et al., 2020). Microbial biotransformation may produce catechin metabolites with more biological activities than the underlying components (Chen et al., 2020). Catechins may encourage the growth of beneficial gut bacteria, which might result in prebiotic effects, according to in vitro research (Hursel and Westerterp-Plantenga, 2013). According to in vitro fermentation research, green tea’s catechins boost the numbers of beneficial bacteria like Lactobacillus and Bifidobacterium species while lowering those of harmful bacteria like Clostridium species. Several animal studies have shown that catechins reduce the ratio of Firmicutes to Bacteroidetes while increasing the diversity of the gut microbiota (Wang et al., 2018a). Recent research suggests that catechins may regulate gut flora to produce therapeutic benefits and effects similar to those of prebiotics. Specifically, after using catechins, the populations of Bacteroides and Firmicutes decreased while those of Proteobacteria and Actinobacteria increased in the intestinal mucosa of people with inflammatory bowel disease (IBD) (Barnett et al., 2013).

The primary curcuminoids found in the rhizomes of plants belonging to the Araceae and Zingiberaceae families are curcumin. Turmeric, a popular Asian spice, uses it as an active component and is used as a culinary colorant, nutritional spice, and herbal medicine (Shen and Ji, 2019). While curcumin metabolism mostly occurs in the liver, the intestines and gut flora additionally contribute significantly to this process. Dihydrocurcumin, tetrahydrocurcumin, hexahydrocurcumin, and octahydrocurcumin (Dei Cas and Ghidoni, 2019; Pandey et al., 2020) are the products of curcumin’s double bond breakdown in hepatocytes and enterocytes. According to earlier studies, bacterial species rose 69% in those receiving curcumin treatment while they fell 15% in the control group. Many Blautia species saw a decline in relative abundance as a result of the treatment, however the following species showed steady increases: Bacteroides, Clostridium, Citrobacter, Enterobacter, Enterococcus, Klebsiella, and Pseudomonas. Curcumin dramatically changed the ratio of beneficial to pathogenic microbiota by decreasing the number of Prevotellaceae, Coriobacterales, Enterobacteria, and Enterococci and increasing the number of butyrate-producing bacteria, Bifidobacteria, and Lactobacilli. Changes to the intestinal microbiota may also help clarify the way curcumin decreases hyperlipidemia and controls immunological responses, in addition to its anti-inflammatory properties and anti-colonotropic carcinogenicity characteristics (Peterson et al., 2018).

Red wine, apples, kale, onions, and cherries are all rich sources of quercetin, a polyphenolic flavonoid. When quercetin is attached to sugar moieties like rhamnose or rutose, it produces quercetin glycosides and rutin by replacing one of the OH groups with a sugar group (Guo and Bruno, 2015). The liver is where quercetin is mostly processed. Quercetin is transported to the liver for metabolism after absorption. Here, it passes through phases I and II, producing metabolites that are then transported by the circulation to various bodily locations (Dabeek and Marra, 2019). Quercetin’s environmental effects on the gut are significant enough to affect the regulation of the microbiota.

Food-pathogenic bacteria including Vibrio parahaemolyticus, E. coli, S. aureus, and Listeria monocytogenes may be present in the human gut microbiota. Infections linked to hospitals or the community may also be clinically significant. Quercetin’s antibacterial and prebiotic properties may help reduce the number of harmful microbes in the stomach (Lan et al., 2021; Liu et al., 2019; Xie et al., 2017). The study by Lan et al. found that quercetin administration increased gut microbiota diversity and resulted in noticeable alterations in the three main groupings of gut microbiota (Bacteroidia, Clostridium, and Bacilli). Ruminococcus decreased and Lactobacillus increased after quercetin administration (Lan et al., 2021).

Chlogenic acid (CGA), one of the most prevalent polyphenols in the human diet, is found in a variety of foods and plants, including tea, coffee, wormwood, apples, and coffee seeds (Naveed et al., 2018; Nwafor et al., 2022). It provides several health benefits. Because of its anti-oxidative, anti-inflammatory, anti-cancer, and anti-neurodegenerative properties, chlorogenic acid has shown a number of positive benefits (Naveed et al., 2018). Because of its hydrophilic nature, chlorogenic acid has poor oral bioavailability and absorption due to its inability to cross lipophilic membrane barriers (Cowan et al., 2014). While the small intestine absorbs a little amount of chlorogenic acid, the gut bacteria break it down into smaller pieces in the large intestine (Chen et al., 2018; 2019). Rapid hydrolysis of chlorogenic acid by resident microflora in the colon and subsequent further metabolism by host enzymes might lead to the release of other metabolites into the circulatory systems. Researchers discovered that the coffee’s chlorogenic acids were rapidly broken down by the colonic microbiota, resulting in the production of eleven catabolites after just 6 h of incubation. By regulating the populations of some advantageous microorganisms (such as Burkholderiales, Desulfovibrio, Klebsiella, Desulfovibrionales, and Bifidobacterium), chlorogenic acid may benefit the host (Song et al., 2019).

One of the most prevalent plant non-flavonoid phenolic substances is phenolic acid, also known as phenolcarboxylic acid, which is a member of the polyphenol family (Dinkova-Kostova and Kostov, 2012). They include one phenolic hydroxyl and at least one carboxylic activity (Liu, 2004). Cinnamic acid and its derivatives (ferulic, paracoumaric, caffeic, and sinapic acids) and hydroxybenzoic acid and its derivatives (gallic acid, vanillic acid, parahydroxybenzoic acid, syringic acid, and protocatechic acid) are included in this group (Liu, 2013). Citrus fruits, berries, apples, coffee, kiwis, cereals, wheat flours, onions, and artichokes are just a few of the foods that contain phenolic acids (King and Young, 1999; Kumar and Goel, 2019). Phenolic acids can be produced by the gut bacteria by secondary metabolism of other polyphenols, in addition to dietary sources (Chandrasekara, 2019).

Isoflavonoids, flavonols, flavones, flavanols, and flavanones are all members of the polyphenol family (Liu et al., 2019; Bruneton, 2016). Although they belong to the flavonoid family as well, anthocyanins are covered in a different paragraph because of their unique characteristics and potential health benefits. Two aromatic rings connected by the three carbons, or C6-C3-C6, make up the majority of flavonoids. Banjarnahor and Artanti (2015), Häkkinen and Törrönen (2000) state that this chain is frequently closed in a C-ring, an oxygenated heterocycle. They are categorized as flavonols, flavones, flavanols, flavanones, anthocyanidins, or isoflavonoids based on variations in the general structure of the heterocyclic C-ring (Banjarnahor and Artanti, 2015; Häkkinen and Törrönen, 2000). Many plants have “colorful hues” due to flavonoids, which are universal pigments that come in yellow, red, and purple colors. Through their function as co-pigments, flavonoids aid in pigmentation even when compounds are not readily apparent. Here, anthocyanosides are protected and co-pigmented by colorless flavones and flavonols. The two main constituents of the flavonoid class known as flavonols, which are some of the most prevalent flavonoids in diet, are quercetin and kaempferol (King and Young, 1999). Numerous plants may contain flavonoids, although only in trace amounts (King and Young, 1999; Bruneton, 2016; Bobinaite et al., 2012). While flavonoids may be found in many different colored plants, they are often found in tea, onions, and apples (Gupta and Prakash, 2014). Citrus fruits, herbs, and tomatoes all contain flavanones. Lettuce, cabbage, onions, and olives all contain flavanols. Olives and celery both contain flavones. Flavanols are found in tea, red wine, and pears. Lastly, soy products are the primary source of isoflavones (Gupta and Prakash, 2014; Amiot et al., 2012; Parker et al., 2007).

The general metabolism of flavonoids results in the production of anthocyanins, a subfamily of flavonoids (Liu, 2004; Bruneton, 2016). Red, pink, blue, or purple fruits and vegetables are the most prevalent sources of anthocyanins, including cyanidin, pelargonidin, delphinidin, and malvidin (Lin et al., 2017). Anthocyanins range in hue from vivid orange to purple. The absorbance wavelength changes from orange-colored pelargonidin to purple-colored delphinidin as the degree of hydroxylation increases. Plums, cherries, and berries (including elderberries, blackcurrants, and blueberries) are especially rich in anthocyanins. They may also be found in beverages like red wines and fruit juices, as well as in root vegetables like radish plants, beets, and red onion bulbs (Amiot et al., 2012; Derbel and Ghedira, 2005; Scalbert and Williamson, 2000; Vlachojannis et al., 2015). Anthocyanins are also found in red cabbage and eggplant.

Flavonoids and tannins are members of the same phenolic chemical family. Condensed tannins and hydrolyzable tannins are the two categories into which they are separated based on their architecture and biogenetic origin (Ghosh, 2015; Bruneton, 2016; Scalbert and Williamson, 2000). Condensed tannins are chemical substances that are oligomers or polymers made up of units of flavan-3-ols connected by type C4→C8 and/or C4→C6 bonds. They are also referred to as catechins or proanthocyanidins. Although tannins cannot be hydrolyzed, they can break down into colorful pigments called anthocyanidins when heated and handled with an acid (Bruneton, 2016; Scalbert and Williamson, 2000; Chung et al., 1998). After hydrolysis, hydrolyzable tannins, as opposed to condensed tannins, can pass through the intestinal barrier (Amiot., 2012). Pomegranate bark, sorghum, barley seeds, tea, wine, cocoa beans, carob beans, and plums can all contain high levels of tannins (Amiot et al., 2012; Derbel and Ghedira, 2005; Scalbert and Williamson, 2000; Chung et al., 1998).

Numerous molecular kinds with a similar fundamental chemical structure are included in the class of organosulfur substances (Liu, 2013). Depending on the subclass, an aglycone is made up of an amino acid, the molecular framework of glucose via a sulfur link, and a sulfate band via the nitrogen atom of the methoxy group located around a carbon atom (Sugiyama and Hirai, 2019). Sulforaphanes, isothiocyanates, native compounds, and compounds made from allyl sulfides are all members of the organosulfur biological family (Bruneton, 2016; Amiot et al., 2012). When glucosesinolates hydrolyze, physiologically reactive isothiocyanates are produced (Sugiyama and Hirai, 2019). Glucosinolates and garlic sulfur derivatives are the two organosulfur compounds most frequently present in plant-based diets (Amiot et al., 2012). Particularly in Brassicaceae or cruciferous vegetables such as (cabbage, cauliflower, turnip, broccoli, black radish, and mustard), the content of glucosinolates varies according to the species, plant part, culture, and environment (Derbel and Ghedira, 2005). These substances give forth powerful flavors and aromas. Mustard seeds contain isothiocyanate, although cruciferous vegetables like cauliflower and cabbage are the primary source of sulforaphane (Jeffery et al., 2003). Another excellent source of sulfur compounds is garlic.

Only around 20 of the 800+ distinct molecules that make up the vast family of carotenoids—which range in hue from yellow-orange to red—are found in the diet, according to Amiot et al. (2012) and Bruneton (2016). The general structure of a carotenoid is a polyene hydrocarbon molecule with nine to eleven double-bonded bonds which may end in rings (Fiedor and Burda, 2014). The two types of fat-soluble substances known as carotenoids are carotenes and xanthophylls. Taxaxanthin, zeaxanthin, lutein, and cryptoxanthin are among the compounds of the first class. Lycopene, carotene, and carotene are the symbols for carotenes. Lutein, zeaxanthin, lycopene, and carotene are the antioxidants known as carotenoids that have been the subject of the greatest research. Carotene is the most well-known precursor of vitamin A (Gupta and Prakash, 2014; Fiedor and Burda, 2014). The natural environment is full with carotenoids, which are very vulnerable to oxidation. They are accumulated by the chloroplasts of all photosynthetic tissues (Van der Sluis et al., 2001). Carotene, lutein, violaxanthin, and neoxanthin are found in the leaves of nearly all plants. Fruits can also include carotenoids, such as chloroplastic carotenoids found in flower petals (including those of the common marigold, pansy, and French marigold) and other derivatives (such lycopene and capsanthin). Sweet potatoes, Brussels sprouts, broccoli, kale, carrots, spinach, tomatoes, peppers, citrus fruits, seeds, certain kinds of mushrooms, and leafy greens like lettuce and arugula are among the many plants that contain carotenoids (Derbel and Ghedira, 2005; Bohn, 2019; Niroula et al., 2019; Tan and Norhaizan, 2019) (Figures 4, 5).

1,3,7-trimethylxanthine is another name for caffeine, a member of the alkaloid family (Bruneton, 2016; Ashihara et al., 2008). However, due to its substantial contribution to daily phytochemical intake, demonstrated health benefits, and frequent mention in nutritional guidelines like those published by the French Agency for Food, Environmental and Professional Health and Safety (ANSES), caffeine was added as a family in its own right (Heckman et al., 2010). Coffee, kola nuts, tea, mate leaves, and guarana seeds are all sources of caffeine, the most widely used psychoactive ingredient in the world (Heckman et al., 2010; WHO, 2013).

Participants in the World Health Survey (WHS) came from 52 geographically diverse nations, primarily low- and middle-income countries, and were administered the extended version of the questionnaire, which included specific questions regarding their fruit and vegetable consumption (FAO, 2013; Patel et al., 2022; Beking and Vieira., 2011). They were asked two primary questions: 1 How many servings of fruit do you usually consume in a day? and 2 How many servings of vegetables do you typically consume each day? To simplify reporting and avoid the need to average intake over multiple days, participants were instructed to consider a “typical day” as any day when they consumed fruits or vegetables (FAO, 2013; Khan and Lee, 2023). Trained interviewers showed participants visual aids—cards illustrating standard serving sizes of fruits and vegetables commonly consumed in their region (Zhao et al., 2024). Based on the survey guidelines, a standard serving of vegetables was generally considered to be one cup of raw leafy greens (like spinach or salad), half a cup of cooked or raw chopped vegetables (such as carrots, tomatoes, pumpkin, Chinese cabbage, maize, or beans), or half a cup of vegetable juice (Wang et al., 2025). For fruits, a single serving was defined as one medium-sized fruit (such as a banana, apple, or orange), half a cup of chopped, cooked, or canned fruit, or half a cup of fruit juice (Chen et al., 2021). Because the questionnaire did not collect data on the regular consumption of other food groups, this study focused exclusively on phytonutrient intake derived from fruits and vegetables (Patel et al., 2022).

The WHO Global Environment Monitoring System/Food Contamination Monitoring and Assessment Programme (GEMS/Food) developed a methodology for grouping countries with similar dietary consumption into clusters and establishing a representative diet for each of these clusters starting in the early 1990s. The WHO and FAO provided quantitative data that demonstrated the availability of specific fruit and vegetable kinds by nation, but the WHS did not record the exact types of fruits and vegetables that each respondent consumed. The per capita food availability information that serves as the foundation for the diets is derived from the FAO’s annual statistics on farming, production of food, imports, and exports, which are released as FAO supply utilization accounts (Sy et al., 2013). The amounts of food that are produced plus imported, adjusted for exports, and used for seed or animal feed are all included in the statistics on food availability, which displays the total amount of food available per person. These figures serve as a proxy for real consumption rather than reflecting it. Based on FAO data from 1997 to 2001 and the geographic proximity of the countries within the statistical clusters, the WHO designated geographic diet groupings, known as GEMS/Food clusters, using a letter-coding scheme (A to M) in 2006 and used cluster analysis to divide the world’s countries into thirteen statistical clusters of seven to twenty-two counties each (FAO, 2013). Geographic proximity was not taken into consideration when the WHO created new cluster groups and diets in 2012 based on FAO data from 2002 to 2007. We produced updated food consumption estimations for the thirteen regions identified by the 2006 regional diet clusters using this data on food availability. This involved weighting the data for each country according to its population size and calculating weighted average consumption quantities for each regional diet cluster. The FAO numbers were changed from kg/year to g/d for the purposes of this study. The FAO data from 2002 to 2007 were organized in a hierarchical framework of 18 major food categories, and estimates of food accessibility were supplied for 415 different food categories or combinations of related foods. Sixty-seven fruit types and forty-two vegetable categories were chosen for this study. Olives and their liquids were categorized as fruit, but nuts and seeds were not. Pulses, herbal cures, roots, and tubers like potatoes and cassava were not included in the vegetable categories, but juices were. “Not elsewhere specified,” or “nes,” was a description used in some of the FAO-approved food categories. The FAO utilized the “nes” categories to record the availability of foods that did not fit into a certain category. Some countries probably utilized the “nes” categories to report on foods that were already under a specific category, especially if such foods were not very important in their local communities (Sy et al., 2013; ARS, 2012). Through each geographic diet cluster, food intakes compared to fruits and vegetables labeled as “nes,” except for the “Juice of Vegetables nes” and “Fruit Prpnes” categories, were distributed to the appropriate fruits and vegetables groupings in proportions that reflected the corresponding abundance of nourishment in each category.

For instance, the consumption of “Pome Fruit Nes” was divided across the distinct categories of “Apples,” “Pears,” and “Quinces” based on the total consumption of the fruit as well as the relative availability of each of these three categories across each regional diet cluster. This methodology is in line with earlier evaluations of food consumption based on FAO data (A Vieira, personal communication) (FAO, 2012). The previously assigned “nes” categories were reallocated to create 48 vegetable categories and 58 fruit categories.

Data on phytonutrient concentrations for certain antioxidants, flavonoids, and a phenolic acid (ellagic acid) were available for specific fruits and vegetables in each of the FAO vegetable and fruit categories. This study includes nine phytonutrients, which are primarily present in vegetables and fruits and belong to the major classes of phytochemicals. We determined how much was consumed of a hormone called quercetin for the flavanone and flavonol subclasses of flavonoids, respectively. These two flavonoids comprise the majority of the flavonoid subclasses ingested in the diet, according to previous studies conducted with a Spanish population (Sy et al., 2013). The National Nutrient Database for Standard Reference, which contains Release 25 of the United States Department of Agriculture (USDA), was used to determine the amounts of carotenoid pigments (a-, b-, b-cryptoxanthin, lutein/zeaxanthin, and lycopene) (Bhagwat et al., 2013; Cuartero et al., 2011). Both public and unpublished sources provided information for this database. Carotenoid levels for two relevant food categories—cassava leaves and cashew apples—were absent from the USDA database. The b-Carotene values for these items were obtained from another data source (Crozier et al., 1997; Daniel et al., 1989). The values for hesperetin, quercetin (measured as mg aglycone/100 g edible part), and anthocyanidins (the total of cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin) were obtained using the most recent edition of the USDA’s flavonoid database (Ali et al., 2011). Methodically gathered from several foreign sources, the USDA database includes analytically comprehensive flavonoid data. The single or most important source of flavonoid concentration-related information utilized in several international studies on phytonutrient intakes has been this database of flavonoid values. With moisture content adjustments, the flavonoid levels for concentrated juices and food that had dried that were lacking were filled in using the information from single-strength juices or food in its natural form. Flavonoid levels for missing cooked meals were computed using raw food data, assuming a 25% retention rate (Amakura et al., 2000). There is no information on ellagic acid concentrations in the USDA databases. The ellagic acid equivalent amount of foods classified as FAO fruits and vegetables was derived using a database of values collected from published studies (Anttonen and Karjalainen, 2005; Williner et al., 2003). The database of ellagic acid values contained ellagic acid from a range of sources (such as free ellagic acid, ellagitannins, and others), with the findings provided as ellagic acid equivalents. The tests were carried out after acid hydrolysis. For seventeen different fruit varieties that were part of the study, ellagic acid amounts that were not zero were discovered. A number of the FAO’s fruit and vegetable classes corresponded to particular goods, such spinach or bananas. Some categories, such as “Carrots and turnips” and “Cabbages and other brassicas,” however, had many meals. The available phytonutrient data pertaining to the typical raw and/or cooked forms of the food(s) that would be typically ingested were matched with each FAO category. Based on averages of the data on phytonutrient content for turnip greens, mustard greens, radish, kohlrabi, collards, cabbages, Brussels sprouts, and cress, the category “Cabbages and other brassicas” was developed for this study (Bowman et al., 2013; Cuartero et al., 2011). Because there was a lack of more specific information on the consumption of specific foods within these broad categories, the available phytonutrient concentration measurements were averaged to create a representative phytonutrient concentration in order of the profile (phytonutrient amount per 100 g of food as consumed) for each FAO category. Among the fruits or vegetables that belonged to certain groups, the observed anthocyanidin quantities differed significantly. Red grapes, for instance, which are categorized as “Grapes,” contain a relatively high concentration of anthocyanidins (Ali et al., 2011; Daniel et al., 1989). However, the USDA flavonoid database does not include information on the anthocyanidin concentrations of green grapes, which are also categorized as “Grapes,” despite the fact that they are likely not a substantial source of these flavonoids (Cantos et al., 2002). For items (such green grapes) with lacking anthocyanidin data, we assumed a zero value to give a more realistic average anthocyanidin concentration. What is considered inadequate consumption of fruits and vegetables? The WHO panel on food, nutrition, and the prevention of chronic illness recommended 400 g or more of fruits and vegetables per day, excluding potatoes, cassava, and other tubers (WHO/FAO, 2003). 400 g of fruits and vegetables, or at least five servings daily with an average serving size of 80 g, is considered poor intake according to WHO standards (Hall et al., 2009; Table 4).

A person’s metabolism may often be changed by environmental variables like nutrition and exercise, and diet-induced metabolism also significantly affects brain function via changing epigenetic processes (Banerjee et al., 2024; Adhikary et al., 2024b). For instance, by regulating the DNA methylation processes on an intracisternal A particle (IAP), which is situated close to the site where transcription of the polymorphous yellow Agouti gene starts, micronutrients from the mother’s diet affect phenotypic variation (Gao and Zhang, 2017; Adhikary et al., 2024b). The metabolic effects of the epigenetic process are thought to be experienced by different age groups, and the prevailing nutritional circumstances in the area have a discernible impact on the DNA methylation process in the growing brain.

Iron consumption affects the accessibility of S-adenosyl methionine (SAM), a chemical contributor for DNA methylation (Bermudez and Freeman, 2019). Information obtained from several research suggests that dietary supplements may be able to change the intricate relationships between metabolism, epigenetics, and immune system function following brain trauma (Bourre et al., 2000; Banerjee et al., 2023). These studies suggest that supplements may control the complex chemical processes that lead to brain injury recovery and adaptation. According to Smith et al. (2020), some dietary interventions may help mitigate the consequences of brain injury and may lead to new therapeutic alternatives.

Neuronal DNA methylation is influenced by this DNA methylation process, and neuronal DNA methylation influences behavioral outcomes like memory and attention. The amount of the metabolite folate in the rat offspring’s brain may also be increased by supplementing the mother’s food with folic acid during the whole pregnancy (Blatt et al., 2016; Adhikary et al., 2024c; Banerjee et al., 2022). This is linked to a reduction in the overall methylation of the DNA. Furthermore, the microbial population residing in the small intestine influences the host’s metabolic functions and might be a significant contributor to the complex interplay between neuroepigenetics and metabolic processes. In addition to their neuroactive and HDAC-inhibiting qualities, dietary fibers ferment to produce short-chain fatty acids, which are sourced from microorganisms (David et al., 2014). HDAC inhibitors have been demonstrated to improve memory retention in an Alzheimer’s disease model utilizing APP/PS1 mice (Saha and Pahan, 2006). A condition known as the D aging model, which is subsequently linked to the development and progression of AD, also showed the effects of a probiotic diet on memory as well as brain function (Saha and Pahan, 2006). These results imply that compounds produced by microbes could have an impact on epigenetics. Finally, the physical characteristics of the human brain make it easier to treat neurological conditions. The metabolic mechanisms that modify the epigenome depend on all of the metabolites that are derived from food. Intervention may change how metabolism and epigenetics interact, changing how the brain works and eventually healing brain illnesses.

In recent years, there has been increasing consensus on the significance of the interplay between immune function and metabolism in elucidating how cells respond to various stressors. This convergence has led to the emergence of a new field known as immunometabolism, which focuses on investigating the potential widespread effects of alterations in internal metabolic processes on immune responses (Bercik et al., 2011; Adhikary et al., 2024d). Microglia immunometabolism is a key regulator of cerebral immune responses in both healthy and diseased conditions within the neurological system. The notion that metabolic changes play a major role in controlling microglial responses is supported by the findings of recent studies (Sadeghdoust et al., 2024). It has been suggested that there is a connection between glucose-mediated glycolytic activity, microglial activation, and inflammatory mediators. According to a research by Devanney et al., 2020, the glucose analog 2-deoxyglucose (2-DG) efficiently decreased glycolysis, which in turn stopped the production of cytokines that promote inflammation like IL-6 and IL-1 that are activated by lipopolysaccharide in immature microglia. However, metabolic alterations favor oxidative phosphorylation, microglia activation results in a pro-inflammatory response.

The relationship between activating microglia, OXPHOS activation, and ATP production is thoroughly examined by the researchers of the Holland et al. study (Devanney et al., 2020; Adhikary, 2021). Furthermore, stimulated microglia (astrocytes) can either produce inflammatory chemicals or exhibit anti-inflammatory qualities, depending on their metabolic state (Kim et al., 2010). According to recent research, a mismatch between the body’s immune and metabolic systems is one of the primary causes of neurological disorders. The activation of anti-inflammatory immune system responses in microglia in APP/PS1 animal models with Alzheimer’s illness was found to positively correlate with higher levels of cytoplasmic phosphofructokinase fructose 2,6-bisphosphatase B3, an important enzyme involved in glycolytic metabolism. The relationship between immune responses and metabolic processes, which in turn controls microglial cell activity and preserves brain homeostasis, is greatly impacted by changes in the food supply. It has been shown that eating too many calories from an obese and high-fat diet affects the immunometabolism of microglial cells by altering circadian activity (Milanova et al., 2019).

The interplay between the body’s defensive systems and the epigenetic imprint often result in a closed loop. On the other hand, IL-6 regulates other genes and biological processes via altering histones and DNA methylation (Hu et al., 2017). The control of the production of cytokinin, an inflammatory mediator that contains tumor cellular destruction factor, has been linked to these postulated mechanisms. Nuclear factors, such as the transcription factor NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells), are known to have a major impact on the proinflammatory immune response. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) have been found to regulate the acetylation and deacetylation of its p65 subunit, respectively. In a Parkinson’s disease animal model, Jmjd3 induced microglial overactivation, which has been linked to worse dopaminergic neuron loss and an intensification of the autoimmune response. It has been shown that one way HDAC3 elicits an immunological response is by activating transcription factor 2 (ATF2)-bound sites. Neurological conditions including Parkinson’s disease have been linked to both the immune response and the regulation of epigenetic modifications (Zhang and Wang, 2019). The Jumonji domain containing 3 (Jmjd3) chromatin H3K27me3 demethylase is essential for the distinct epigenetic regulation of microglia polarization in the immunological pathogenesis of Parkinson’s disease. In addition to learning and memory impairments, mice with selective deletion of polycomb restricting complex 2 (PRC2), a protein complex involved in epigenetic regulation, also exhibit seizures. Phenolic components in dietary supplements have been demonstrated to impact immune system function through epigenetic modifications. The proliferation of genes required for clearing activity is also inhibited by this loss.