Ensuring sufficient intake of micronutrients is essential for healthy neuronal growth, neurotransmission, and safeguarding against neurodegenerative conditions (see Table 1). Lack of specific vitamins and minerals is strongly associated with cognitive decline, mood issues, and neurodegenerative diseases (Lahoda Brodska et al., 2023).

B vitamins are crucial for brain health. In particular, vitamin B12 and folate are key players in one-carbon metabolism, influencing DNA methylation, nerve myelination, and homocysteine levels. Elevated homocysteine, often due to B12, folate, or B6 deficiencies, is associated with higher risks of Alzheimer’s, vascular dementia, and stroke (Moore et al., 2012). During pregnancy, inadequate folate intake markedly increases the risk of neural tube defects, highlighting the importance of proper prenatal nutrition for healthy neurodevelopment (WHO, 2025). Choline is an essential nutrient required for acetylcholine synthesis and membrane phospholipid metabolism, and prenatal choline availability can influence neurodevelopment and later-life cognitive trajectories (Paules et al., 2025; Mujica-Coopman et al., 2024). Iodine is likewise critical in early life because thyroid hormones are indispensable for fetal brain development; even mild-to-moderate iodine deficiency during pregnancy has been associated with poorer neurodevelopmental outcomes (De Escobar et al., 2007; Grossklaus et al., 2023).

Vitamin D is now recognized as a neurosteroid that affects neurogenesis, synaptic plasticity, and immune response. Low levels of vitamin D in the blood are linked to higher risks of multiple sclerosis, Parkinson’s disease, and cognitive decline. Mechanistically, vitamin D helps regulate calcium levels, reduces oxidative stress, and influences inflammation pathways (Sintzel et al., 2018).

Vitamin E, a potent lipid-soluble antioxidant, helps protect neuronal membranes from oxidative damage. A deficiency speeds up neurodegeneration and is linked to Alzheimer’s disease progression. Likewise, vitamin C is involved in neurotransmitter synthesis and helps combat oxidative stress (Ulatowski and Manor, 2015).

Minerals like magnesium, zinc, iron, and selenium are essential for maintaining brain health. A magnesium deficiency can interfere with NMDA receptor regulation, leading to increased excitotoxicity, which is linked to depression and epilepsy (Chen et al., 2024). Zinc is essential for synaptic plasticity, but abnormal levels may encourage amyloid buildup in Alzheimer’s disease (Kozin, 2023). Iron is necessary for dopamine production; however, too much iron can cause oxidative damage and is associated with a higher risk of Parkinson’s disease. Selenium, as part of antioxidant selenoproteins, protects neurons from oxidative stress (Solovyev, 2015). Clinical note: supplementation is not risk-free–excess intake of fat-soluble vitamins (A, D, E, K) may accumulate and cause toxicity, while high-dose iron or selenium can be harmful; supplementation should therefore be individualized (ideally guided by dietary assessment and laboratory evaluation) rather than assumed to be universally beneficial (Tardy et al., 2020).

Together, these micronutrients demonstrate how even minor dietary deficiencies can have a profound impact on neurological health. Table 1 summarizes core roles, clinical signals, and representative sources.

Nutritional vulnerabilities also differ by life stage: during prenatal/early development, micronutrient adequacy (e.g., iodine and choline) supports neurogenesis and myelination; in adulthood, diet quality interacts with cardiometabolic and inflammatory risk; and in ageing, reduced intake/absorption and multimorbidity can increase susceptibility to deficiencies and to adverse effects from unnecessary high-dose supplements.

Besides specific nutrients, overall dietary habits influence brain health via complex metabolic and inflammatory pathways. Western-style diets high in fat and sugar (see Table 2) are commonly associated with diminished cognitive abilities, less neurogenesis in the hippocampus, and a greater dementia risk (Kanoski and Davidson, 2011). Consistently, consuming these foods can cause insulin resistance, neuroinflammation, and gut microbiota alterations, all of which promote neurodegeneration.

Evidence for dietary patterns comes from multiple streams: observational cohorts linking habitual patterns to long-term cognitive outcomes, randomized or quasi-experimental dietary interventions assessing intermediate endpoints, and experimental/preclinical studies probing mechanistic plausibility; interpreting claims requires attention to this hierarchy of evidence.

On the other hand, the Mediterranean diet (MD). A diet that includes fruits, vegetables, whole grains, olive oil, fish, and nuts has been associated with slower cognitive decline and a reduced risk of Alzheimer’s disease. The anti-inflammatory and antioxidant properties of MD, along with its beneficial fatty acid profile, are thought to provide neuroprotective benefits (Nucci et al., 2024; Vlachos and Scarmeas, 2019).

The ketogenic diet (KD), which is high in fat and protein and very low in carbohydrates, induces ketosis and has been used for decades to treat refractory epilepsy. Recent evidence indicates that KD might also benefit neurodegenerative diseases by improving mitochondrial function, decreasing excitotoxicity, and boosting neuronal energy metabolism (Gano et al., 2014).

Plant-based diets rich in polyphenol-containing foods are linked to decreased neuroinflammation and enhanced vascular health, potentially reducing the risk of stroke and dementia (Tayab et al., 2022). However, strict vegan diets should ensure adequate intake of nutrients such as vitamin B12, iron, and omega-3 fatty acids to prevent neurological deficiencies (Ursea et al., 1975).

Certain bioactive compounds exhibit significant neuromodulator effects regardless of their caloric or macronutrient content (see Table 2). Polyphenols, found abundantly in berries, tea, coffee, and cocoa, are known for their strong antioxidant and anti-inflammatory properties. For polyphenols and omega-3 fatty acids, human evidence is strongest for observational associations and select randomized supplementation trials on intermediate outcomes, while many neuroprotective mechanisms (antioxidant signaling, microglial modulation, synaptic effects) remain largely supported by experimental and preclinical research; this should temper causal interpretation.

Flavonoids such as quercetin, epicatechin, and resveratrol enhance synaptic plasticity, boost BDNF (brain-derived neurotrophic factor) levels, and provide protection against amyloid pathology (Khomenko et al., 2025; Ge et al., 2011).

Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), are crucial for maintaining neuronal membrane fluidity and supporting neurotransmission. Supplementing with DHA has shown positive effects on cognitive function and depression, while deficiencies are associated with increased risks of Alzheimer’s disease and mood disorders (Tanaka et al., 2012).

Curcumin, which is derived from turmeric, has attracted interest because it can pass through the blood–brain barrier and affect various pathways such as amyloid aggregation, oxidative stress, and neuroinflammation (Yang et al., 2005).

Caffeine and theobromine, mild central nervous system stimulants present in coffee and cocoa, boost alertness and might offer long-term neuroprotection by modulating adenosine receptors (EFSA Panel on Dietetic Products and Nutrition and Allergies NDA, 2014; MartÃ-nez-Pinilla et al., 2015).

The beneficial impact of nutrition on neurological disorders involves several shared mechanisms. Antioxidants such as vitamins E and C, polyphenols, and selenium help control oxidative stress by neutralizing free radicals and preventing lipid peroxidation. Addressing neuroinflammation involves using omega-3 fatty acids, vitamin D, and polyphenols. Mitochondrial health can be supported by ketogenic diets and specific micronutrients that enhance energy metabolism and reduce excitotoxicity.

Neurotransmitter synthesis relies on cofactors such as B vitamins, iron, and vitamin C, which are essential for pathways that generate serotonin, dopamine, and acetylcholine (Al Mughram et al., 2022).

Epigenetic regulation involves nutrients such as folate, B12, and polyphenols that influence DNA methylation and histone modifications, thereby affecting gene expression in neuronal cells (Crider et al., 2012). Regarding the modulation of the gut–brain axis: Dietary fibres and polyphenols impact microbiota composition, resulting in the production of specific metabolites (Filosa et al., 2018).

Microbiome-mediated effects are partly conveyed by neuroactive metabolites, including short-chain fatty acids (e.g., acetate, propionate, butyrate) that can influence microglial maturation and blood–brain barrier integrity, and tryptophan-derived metabolites (e.g., indoles and kynurenine-pathway products) that modulate immune signaling and neurotransmission (Fock and Parnova, 2023).

Nutritional interventions are increasingly acknowledged as supplementary options for neurological conditions. Clinical trials, also referenced in Table 3, indicate that B-vitamin supplements reduce homocysteine levels and slow brain atrophy in individuals with mild cognitive impairment (Smith et al., 2018). Vitamin D supplements have been shown to alleviate fatigue and decrease relapse rates in multiple sclerosis. The ketogenic diet remains the preferred treatment for drug-resistant epilepsy, and recent studies suggest it may also offer benefits for Parkinson’s and Alzheimer’s diseases (Paul et al., 2017).

The Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets are associated with a reduced risk of dementia and stroke. Eating diets rich in polyphenols can improve memory and executive functions in older adults. While dietary interventions do not replace pharmacological treatments, they provide a valuable, affordable, and accessible way to support prevention. Personalized nutrition, guided by genomics and metabolomics, can improve dietary strategies customized to everyone’s risk profile (Nucci et al., 2024).

Air pollution is now recognized not only as a threat to the heart and lungs but also as a significant neurotoxic danger. Delicate particulate matter (PM2.5), nitrogen dioxide (NO₂), ozone, and ultrafine particles can infiltrate the respiratory system, reach the bloodstream, and cross the blood–brain barrier (BBB) (see Table 4) (Oberdörster et al., 2004; Xu et al., 2023).

Epidemiological studies link chronic exposure to PM2.5 with a higher risk of Alzheimer’s disease, Parkinson’s disease, and faster cognitive decline in aging populations. Autopsy studies have found amyloid plaques and tau pathology in children and young adults living in highly polluted urban areas, indicating that air pollution may trigger neurodegenerative processes decades before clinical symptoms appear (Calderón-Garcidueñas et al., 2012).

Mechanistically, inhaled particulates induce systemic inflammation, oxidative stress, and vascular dysfunction, which later impact the CNS. Ultrafine particles may directly translocate to the brain through the olfactory pathway, bypassing the BBB. These exposures disrupt microglial homeostasis, promote amyloid aggregation, and impair synaptic integrity (Elder et al., 2006).

Heavy metals such as lead, mercury, cadmium, and arsenic are persistent pollutants in the environment that are well-known for their neurotoxic effects, as explained in Table 5 (Jaishankar et al., 2014).

Lead exposure, especially during childhood, is linked to lower IQ, attention issues, and a higher risk of behavioural disorders (Lanphear et al., 2005). It disrupts synaptic pruning, calcium signalling, and neurotransmitter release (Bressler and Goldstein, 1991). Mercury, particularly as methylmercury, accumulates in seafood and leads to motor impairments, cognitive difficulties, and visual disturbances. It disrupts mitochondrial activity and increases oxidative stress within neurons (Novo et al., 2021). Exposure to arsenic through contaminated drinking water has been linked to memory problems and a higher risk of neurodegenerative diseases. It causes DNA damage, epigenetic changes, and interference with neurogenesis (Tyler and Allan, 2014; Benskey et al., 2012).

Although less researched, cadmium is linked to olfactory dysfunction and dopaminergic neurotoxicity, which are both relevant to Parkinson’s disease (Raj et al., 2021). These metals tend to bioaccumulate and cause prolonged neurotoxic effects, even with low exposure levels (Balali-Mood et al., 2021).

Epidemiological evidence strongly connects chronic pesticide exposure to Parkinson’s disease (PD). Certain compounds, such as paraquat, rotenone, and organophosphates, have been shown to cause selective dopaminergic neurotoxicity (Tanner et al., 2011).

Mechanistic studies (see Table 6) have shown that these pesticides impair mitochondrial complex I, increase reactive oxygen species (ROS), and activate pro-inflammatory pathways, thereby mimicking key features of PD pathology (Sherer et al., 2003). Genetic susceptibility (for example, polymorphisms in detoxification enzymes like GSTs or PON1) may further increase vulnerability to pesticide-induced neurotoxicity (Paul et al., 2017; (Menegon et al., 1998).

More broadly, gene–environment interactions (including detoxification enzymes, oxidative stress responses, and inflammatory signaling) represent a cross-cutting theme that supports a precision-neurology approach to risk stratification and targeted prevention.

Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), phthalates, and polychlorinated biphenyls (PCBs) (see Table 7), disrupt hormonal signaling pathways crucial for brain development and function (Gore et al., 2015). Because endocrine signaling and epigenetic programming are central during development, environmental exposures in critical windows may have long-lasting, and potentially transgenerational effects through heritable epigenetic alterations observed in animal models and increasingly explored in human epigenomic studies (Klibaner-Schiff et al., 2024).

Prenatal and early-life exposure to endocrine-disrupting chemicals (EDCs) is associated with an increased risk of autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), and cognitive impairments (Özel and Rüegg, 2023). For instance, BPA mimics estrogen, impacting neuroendocrine signaling, synaptic connections, and gene expression in the developing brain. Similarly, PCBs disrupt thyroid hormone regulation, which is crucial for proper neurodevelopment (Chung et al., 2011; Gilbert et al., 2020).

These compounds often work through epigenetic reprogramming, altering DNA methylation and histone modifications in neural tissues, resulting in long-lasting effects even after exposure ceases (Alavian‐Ghavanini and Rüegg, 2018).

Environmental exposures' neurotoxic effects affect multiple mechanistic pathways (see Table 8). Oxidative stress and mitochondrial dysfunction: Air pollutants, heavy metals, and pesticides cause ROS production and damage to mitochondria, leading to neuronal apoptosis.

Neuroinflammation occurs when environmental toxins activate microglia and astrocytes, resulting in persistent neuroinflammation (Kwon and Koh, 2020).

Disruption of neurotransmission: Lead hampers calcium signaling; pesticides disrupt dopaminergic transmission; mercury disturbs the balance of glutamatergic and GABA systems. Disruption of the blood–brain barrier (BBB): PM2.5 and heavy metals compromise BBB integrity, enabling neurotoxins to infiltrate the CNS. Epigenetic modifications: Arsenic, BPA, and PCBs influence DNA methylation and histone acetylation in neural cells, impacting long-term gene expression (Qin et al., 2021; Laufer et al., 2022).

Tackling environmental risk factors for neurological disorders involves two main strategies: providing targeted interventions for individuals and enacting broad policy reforms (see Table 9) (Reis et al., 2023).

Individual-level interventions involve nutritional strategies such as antioxidant-rich diets, omega-3 fatty acids, and selenium, which could help lower oxidative damage caused by pollutants. Although chelation therapy has been explored for heavy metal poisoning, its use remains limited and continues to be debated (Romieu et al., 2008; Smith, 2013).

Public health interventions play a vital role in safeguarding long-term neurohealth by reducing air pollution through clean energy policies, regulating pesticide use, and phasing out harmful endocrine-disrupting chemicals (EDCs) (Khosrorad et al., 2022; Wang et al., 2022; Shekhar et al., 2024; Kassotis et al., 2020).

Clinical considerations: Physicians should integrate environmental history into neurological assessment, particularly in cases of unexplained neurodegeneration or developmental disorders (National Academies Press, 1995).

Ultimately, environmental exposures are preventable factors that contribute to neurological disease burden, and reducing these risks could lead to substantial improvements in population brain health.

Regular physical activity is well-known as a key protective factor against neurodegenerative and psychiatric conditions such as migraine (Zhang et al., 2023). Epidemiological research shows that individuals who engage in regular exercise have a reduced risk of developing Alzheimer’s disease, Parkinson’s disease, stroke, and depression (Northey et al., 2018). Importantly, prolonged sedentary behavior appears to confer risk independent of meeting exercise targets, with higher sitting time associated with worse cardiometabolic profiles and increased risk of cognitive decline in older adults (Cai et al., 2023).

Exercise stimulates brain-derived neurotrophic factor (BDNF) signaling, which promotes synaptic plasticity, neurogenesis, and neuronal survival. Specifically, aerobic exercise enhances neurogenesis in the hippocampus and improves memory. Additionally, physical activity increases cerebral blood flow, decreases neuroinflammation, and enhances mitochondrial function (Erickson et al., 2019).

Clinical trials show that structured aerobic and resistance exercises enhance cognitive function in seniors with mild cognitive impairment (MCI), reduce depressive symptoms, and slow the progression of Parkinson’s disease.

Sleep is becoming more widely understood as essential for maintaining brain balance. Issues like poor sleep quality, sleep deprivation, or disruptions in circadian rhythm are associated with cognitive decline, mood disorders, and a higher risk of Alzheimer’s disease (Xie et al., 2013).

Circadian misalignment from shift work, chronotype mismatch, and exposure to artificial light at night can disrupt sleep–wake regulation and downstream metabolic and immune rhythms, with growing epidemiological interest in links to cognitive impairment and dementia progression (Filippini et al., 2024).

During deep sleep, the glymphatic system removes metabolic waste products, such as amyloid-β and tau proteins, from the brain. Persistent sleep disruption impairs this cleaning process, resulting in protein accumulation and neurodegeneration (Xie et al., 2013). Moreover, lack of sleep elevates oxidative stress, interferes with synaptic pruning, and impacts emotional regulation (Xie et al., 2013).

Sleep disorders like sleep apnea accelerate neurological decline due to intermittent hypoxia and systemic inflammation. Importantly, treatments such as cognitive-behavioral therapy for insomnia (CBT-I), continuous positive airway pressure (CPAP) for apnea, and circadian rhythm regulation methods have shown benefits in improving cognitive and emotional health (Trauer et al., 2015; Van Der Zweerde et al., 2019).

Chronic psychosocial stress is a key contributor to neurodegenerative and psychiatric disorders. Persistent activation of the HPA axis leads to sustained glucocorticoid exposure, which can hinder hippocampal neurogenesis, decrease dendritic complexity, and trigger neuronal apoptosis (McEwen, 2017; Lupien et al., 2009).

Social isolation and loneliness, along with low cognitive stimulation, are increasingly recognized as modifiable contributors to dementia risk–possibly through effects on stress physiology, depression, health behaviors, and reduced cognitive reserve, whereas lifelong learning and mentally stimulating activities may help build reserve and delay clinical expression of pathology (Wang et al., 2023).

Stress-related neuroinflammation, driven by microglial activation and pro-inflammatory cytokines, worsens mood disorders and speeds up neurodegeneration. Epigenetic changes, such as DNA methylation of glucocorticoid receptor genes, could increase vulnerability throughout life (Miller and Raison, 2016).

Protective approaches like mindfulness-based stress reduction (MBSR), yoga, and cognitive-behavioural therapy have proven effective in reducing anxiety, depression, and stress-related cognitive issues (Trauer et al., 2015).

Lifestyle also includes patterns of substance use, many of which have direct neurotoxic effects. Dose–response relationships are clinically important: regular moderate caffeine intake is often associated with neutral-to-beneficial cognitive outcomes in observational studies, whereas heavy intake can worsen anxiety, sleep, and blood pressure; for alcohol, heavy use is consistently harmful, and purported benefits of light-to-moderate intake are increasingly questioned due to confounding and genetic (Mendelian randomization) evidence suggesting no truly protective level (Topiwala et al., 2025).

Chronic alcohol consumption can lead to cortical atrophy, thiamine deficiency (resulting in Wernicke–Korsakoff syndrome), increased dementia risk, as well as to ischemic stroke (Mechtcheriakov et al., 2007). Nonetheless, some studies suggest that light to moderate alcohol intake, particularly wine, may offer neuroprotective benefits, largely thanks to polyphenols like resveratrol (Sechi and Serra, 2007).

Nicotine may boost alertness and concentration temporarily; however, long-term tobacco use is strongly linked to higher risks of stroke, cognitive decline, and vascular dementia (Anstey et al., 2007; Zhong et al., 2015).

Chronic use of cannabis, methamphetamine, and opioids can impair memory, executive functions, and emotional regulation. Moreover, highly potent synthetic drugs carry additional neuropsychiatric risks (Meier et al., 2012).

Moderate caffeine intake seems to support brain health, linked to a lower risk of Parkinson’s disease and enhanced cognitive function in older adults. Nonetheless, consuming too much can interfere with sleep and raise anxiety levels (Costa et al., 2010; Ascherio et al., 2001).

Lifestyle behaviors impact neurological health through various interconnected mechanisms. Neuroplasticity: Exercise and stimulating environments boost BDNF levels, support synaptic remodeling, and encourage new neuron growth. Inflammation and oxidative stress: Chronic stress, poor sleep, and substance misuse raise pro-inflammatory cytokines and reactive oxygen species (ROS). Energy metabolism: Physical activity improves mitochondrial function, whereas substance abuse hampers neuronal energy processes. Circadian regulation, including sleep habits and light exposure, influences circadian genes critical for cognition and mood. Epigenetic modifications: Stress and lifestyle choices affect gene expression by changing DNA methylation and histone structures.

Lifestyle modifications are increasingly integrated into neurological prevention and treatment frameworks: Exercise prescriptions are becoming more common as supplementary treatments for depression, dementia, migraine and Parkinson’s disease (Northey et al., 2018).

Sleep hygiene programs, along with circadian interventions, are advised to reduce cognitive decline and stabilize mood (Trauer et al., 2015; Kushida et al., 2012). Stress management techniques such as mindfulness, CBT, and yoga enhance resilience and reduce the likelihood of relapse in psychiatric disorders (Miller and Raison, 2016).

Public health campaigns focused on preventing substance abuse successfully lower the incidence of stroke, dementia, and psychiatric conditions (Zhong et al., 2015). Importantly, lifestyle interventions often work alongside nutritional and pharmacological therapies, providing a comprehensive and cost-effective strategy for brain health that can be utilized across various populations.

Across domains, excess ROS damages lipids, proteins, and mtDNA, impairing ATP production and calcium handling. Environmental pollutants (PM2.5, metals, pesticides) elevate ROS; poor diets and sleep loss compound this. Protective levers include antioxidant-rich dietary patterns (MD/MIND), omega-3s, and mitochondrial support via KD and physical activity (Barnham et al., 2004).

Mitochondria are especially susceptible because of their key functions in energy generation and calcium regulation. Mitochondrial dysfunction is commonly seen in Parkinson’s disease, Alzheimer’s disease, and ALS. Strategies like ketogenic diets, regular exercise, and antioxidant-rich foods support mitochondrial health, underscoring the therapeutic promise of focusing on this shared pathway (McGrattan et al., 2019).

Blood–Brain Barrier (BBB) integrity is increasingly recognized as a shared vulnerability point. Diets high in saturated fat and metabolic inflammation can increase BBB permeability, whereas antioxidants and microbiome-derived SCFAs may support tight-junction function; pollutants such as PM2.5 and certain metals can promote endothelial dysfunction and neuroimmune signaling; and lifestyle stressors including sleep deprivation and chronic stress may further amplify BBB disruption and neuroinflammation (Fock and Parnova, 2023).

Circadian rhythm disruption (irregular sleep timing, shift work, and nighttime light exposure) can act as a cross-cutting mechanism by altering glucose and lipid metabolism, inflammatory tone, mitochondrial function, and epigenetic regulation of clock-controlled genes, thereby potentially accelerating neurodegenerative and cerebrovascular processes (Filippini et al., 2024).

Microglia integrate signals from diet (saturated fats vs. polyphenols/omega-3s), pollutants (particulates, pesticides), and stress hormones. Chronic priming promotes cytokines (IL-1β, TNF-α, IL-6) and synaptic dysfunction. Exercise, vitamin D, and polyphenols down-tune pro-inflammatory tone (Heneka et al., 2015).

This indicates that inflammation acts as a crucial connection between nutrition, environment, and lifestyle (Vasefi et al., 2019).

One-carbon nutrients (folate/B12) govern methyl-donor availability; polyphenols modulate histone acetylation; pollutants (arsenic, BPA, PCBs) and chronic stress reprogram methylation at neurodevelopmental and stress-response loci. These marks help explain long-latency and life-course effects (Feinberg, 2018; Feinberg, 2007).

The gut microbiome plays a crucial role in brain health. Factors like diet, environmental toxins, and lifestyle habits affect microbial diversity and metabolism, which in turn influence neurological wellbeing via the gut–brain axis (Fock and Parnova, 2023). Nutritional elements like dietary fiber, polyphenols, and probiotics promote the production of short-chain fatty acids (SCFAs), supporting BBB integrity and decreasing inflammation (Sharon et al., 2019).

In contrast, Western diets, heavy metals, and specific pesticides disturb the gut microbial balance, causing dysbiosis and heightened gut permeability. This situation enables bacterial endotoxins such as lipopolysaccharides to enter the bloodstream, potentially causing neuroinflammation. Stress and disruptions in sleep also modify microbiota composition, strengthening the link between lifestyle and neurological susceptibility.

Microbiome-targeted therapies like prebiotics, probiotics, and fecal microbiota transplantation (FMT) are now under investigation as supplementary treatments for depression, autism, and neurodegenerative diseases.

Cerebrovascular health serves as a crucial endpoint of integration. Major risk factors for stroke and dementia include conditions like hypertension, diabetes, and obesity, which are mainly influenced by diet and lifestyle as shown in Table 11. Furthermore, environmental pollutants, such as air pollution and tobacco smoke, exacerbate vascular issues by damaging the endothelium and encouraging atherosclerosis (Jiang et al., 2016).

Protective dietary patterns like the Mediterranean and DASH, combined with physical activity and stress management, work together to enhance vascular health and glucose metabolism, thereby reducing the risk of both vascular and neurodegenerative diseases.

Considering the intricate relationships between nutrition, environment, and lifestyle, adopting a systems biology approach is essential for fully understanding their impact on neurological health. The use of multi-omics technologies such as genomics, epigenomics, metabolomics, proteomics, and microbiomics, alongside artificial intelligence (AI)- is growing to detect molecular markers linked to environmental and lifestyle factors. These methods will enhance precision medicine by tailoring interventions to each person’s genetic makeup, exposome, and lifestyle profile (Maitre et al., 2022).

The convergence of mechanisms suggests that multi-target approaches, rather than single-drug strategies, might provide more effective treatment results. For example, combining a Mediterranean diet with regular exercise, stress reduction techniques, and minimizing pollutant exposure can collectively help lower the risk of Alzheimer’s disease by addressing inflammation, oxidative stress, and vascular problems simultaneously.

Integrative medicine models, involving nutritionists, neurologists, psychologists, and environmental health specialists, point toward a future of holistic brain healthcare.

Dietary modification is one of the most accessible treatment options for neurological disorders. Evidence supports the use of. B vitamins and homocysteine reduction: Taking B12, B6, and folate supplements decreases homocysteine levels and slows brain atrophy in individuals with mild cognitive impairment (Smith et al., 2018).

Clinical limitations should be considered: ketogenic diets may increase cardiometabolic risk in some patients and can lead to micronutrient inadequacies without careful planning; supplements and high-dose antioxidants/polyphenols may interact with medications (e.g., anticoagulants, chemotherapeutics) or blunt training adaptations; and chelation therapy should only be used for confirmed heavy-metal toxicity under strict medical supervision.

Clinical studies show that vitamin D supplementation can lead to improvements in fatigue, motor function, and relapse rates in multiple sclerosis patients (Sintzel et al., 2018). The ketogenic diet, which is a recognized treatment for refractory epilepsy, is currently under investigation for its neuroprotective effects on mitochondrial function in Parkinson’s and Alzheimer’s diseases (Oliveira et al., 2023). Mediterranean and MIND diets: These dietary patterns lower dementia risk and enhance cognitive resilience, likely due to the combined effects of polyphenols, omega-3 fatty acids, and antioxidants. Polyphenol-rich supplements such as curcumin, resveratrol, and flavonoids are currently undergoing clinical trials to evaluate their anti-inflammatory properties and potential to improve cognition (Small et al., 2018).

Personalized nutrition, driven by nutrigenomics and metabolomics, offers the potential to customize dietary guidance based on each person’s unique genetic and metabolic profiles.

Reducing environmental exposures is a crucial yet often overlooked aspect of treatment. Pollution control efforts that lower exposure to PM2.5 and other air pollutants can reduce the risk of stroke, dementia, and cognitive decline. Implementing policy-level measures, such as switching to clean energy sources and cutting traffic emissions, is crucial (Wang et al., 2022). Heavy metal detoxification involves obtaining safe water, minimizing intake of contaminated food, and, in some instances, employing chelation therapy. Nutritional antioxidants can assist in reducing oxidative stress induced by metals.

Pesticide regulation by limiting workplace exposure, promoting safer alternatives, and monitoring residues in food can help decrease Parkinson’s disease rates. Avoiding endocrine disruptors through public education about BPA-free products, decreasing plastic consumption, and enforcing tighter regulations can help reduce neurodevelopmental risks.

Clinicians can take on a preventive role by including environmental history in neurological assessments.

Lifestyle modification is increasingly recognized as a crucial component in neurological treatment (Trauer et al., 2015; Schenkman et al., 2018). Exercise prescriptions involving structured aerobic and resistance training programs boost cognition in individuals with mild cognitive impairment, reduce depressive symptoms, and improve motor function in Parkinson’s disease.

In addition to physical activity and sleep interventions, cognitive training, structured neurorehabilitation, and social engagement programs can be considered complementary components of multidomain brain-health strategies, particularly for maintaining function and building cognitive reserve.

Sleep interventions like CBT-I, CPAP therapy, and circadian rhythm regulation improve glymphatic clearance and aid in preventing neurodegeneration (Hablitz et al., 2020). Stress management techniques such as mindfulness, yoga, and psychotherapy help reduce neuroinflammation and boost resilience against psychiatric disorders (Alhawat et al., 2024).

Reducing substance use, such as quitting smoking and moderating alcohol consumption, lowers the risk of dementia, stroke, and psychiatric comorbidities. These lifestyle strategies often complement pharmacological treatments, enhancing their effectiveness and reducing side effects (Pan et al., 2019; Osimo et al., 2020).

Given the link between nutritional, environmental, and lifestyle factors, interventions that target multiple domains can provide greater benefits compared to single-strategy methods (Ngandu et al., 2015).

Sustained adherence is a major barrier: dietary changes, exercise, sleep regularity, and exposure reduction are constrained by socioeconomic status, food environments, occupational schedules, and environmental inequities. Behavioral counseling, community-based programs, and digital support tools (when accessible and culturally adapted) may improve uptake and maintenance (Sindi et al., 2025).

The FINGER trial (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) demonstrated that a multidomain program incorporating diet, exercise, cognitive training, and vascular risk monitoring enhances mental performance in at-risk older adults. Similar studies conducted across Europe and Asia also endorse the effectiveness of integrated strategies in postponing dementia onset (Kivipelto et al., 2020).

These findings suggest that upcoming treatments need to be comprehensive, personalized, and multimodal, addressing several pathways simultaneously, including oxidative stress, inflammation, vascular dysfunction, and neuroplasticity.

Emerging technologies offer tools for tailoring interventions to the individual level. Nutrigenomics involves pinpointing genetic variants, such as APOE4 in Alzheimer’s disease, that influence individual dietary responses (Yassine et al., 2016).

Metabolomics and microbiomics: Profiling metabolic and microbial markers that predict disease risk and response to diet (Lagoumintzis and Patrinos, 2023).

Digital health and wearables: Monitoring sleep, physical activity, stress, and diet in real time to enable adaptive, personalized interventions (Minen and Stieglitz, 2021). Artificial intelligence (AI): Integrating multi-omics and exposome data to predict personalized treatment options (Maitre et al., 2022). Such approaches align with the paradigm of precision neurology, advancing beyond “one-size-fits-all” treatments toward personalized prevention and therapy strategies.

Therapeutic implications go beyond the clinic to include population-level interventions. Nutrition policies that promote healthy eating habits, such as reducing trans fats and subsidizing fresh produce (Rushing et al., 2023).

Urban planning strategies to improve air quality and promote active lifestyles.

Workplace wellness initiatives that target stress management, sleep quality, and ergonomic practices (Wang et al., 2022).

Education campaigns highlighting the neurotoxic risks of environmental pollutants and substance abuse (Zhong et al., 2015). By targeting both personal and societal factors, these interventions can significantly reduce the global impact of neurological disorders.

Most current evidence comes from cross-sectional or short-term studies, which limit the ability to establish causality. To better understand the timing between exposures and neurological outcomes, large-scale, longitudinal, and multicentre research is essential. For example, prospective birth cohort studies examining early-life nutrition and environmental factors could offer insights into the developmental origins of neurological vulnerability. Additionally, long-term intervention trials are vital to confirm the effectiveness of dietary and lifestyle changes in delaying or preventing disease onset.

Implementation science is also needed to bridge the efficacy–effectiveness gap—testing how integrative interventions can be delivered in routine care, adapted to different health systems, and made cost-effective and scalable (Sindi et al., 2025).

Future research should utilize systems biology frameworks that combine genomics, epigenomics, metabolomics, proteomics, and microbiomics. This strategy will enable a thorough understanding of the complex interactions among these fields, helping to clarify how genetic predispositions, environmental factors, and lifestyle choices interact.

Epigenetic mapping could reveal how a lack of nutrients or exposure to toxins changes neural gene expression (Mani et al., 2025).

Microbiome sequencing enhances comprehension of gut–brain interactions in neurodegenerative and psychiatric conditions (Jiang et al., 2025).

Metabolomics can identify circulating biomarkers that can predict dietary responses and the progression of diseases.

When combined with advanced computational tools like artificial intelligence (AI) and machine learning, these methods can improve the predictive modelling of personalized risk and treatment outcomes.

Personalized strategies based on genetic and metabolic profiles are usually more effective than general guidelines. For example, people carrying the APOE4 allele may respond differently to dietary fats regarding Alzheimer’s disease risk. Likewise, genetic variations in detoxification pathways can affect susceptibility to environmental toxins (Bermingham et al., 2024).

AI-enabled precision approaches raise practical challenges, including data privacy, algorithmic bias, and unequal access to personalized nutrition, digital health tools, and clean environments; addressing these is essential for ethical and equitable translation (Abrahams and Raimundo, 2025).

Creating precision nutrition and lifestyle medicine frameworks involves combining genetic, clinical, and behavioural data to develop personalized strategies. Wearable devices and digital health platforms provide real-time monitoring of diet, physical activity, sleep, and stress, enabling adaptive interventions.

Mechanistic insights into shared pathways highlight new therapeutic strategies: Use mitochondrial regulators such as NAD⁺ enhancers and sirtuin activators to decrease oxidative stress. As NAD⁺ levels decline with age, neuronal redox balance, DNA repair (like PARP), mitophagy, and ATP production are harmed, leading to more oxidative damage (Gore et al., 2015). Nutritional NAD⁺ precursors (such as nicotinamide riboside and nicotinamide mononucleotide) can restore NAD⁺ levels and improve mitochondrial quality control in preclinical models of neurodegeneration; early clinical trials outside neurology show target engagement and safety, supporting further CNS research. Sirtuin activators, including nutraceuticals like resveratrol and advanced small molecules, aim to enhance SIRT1/3 pathways, promoting mitochondrial biogenesis, antioxidant defenses, and synaptic resilience. Together, NAD⁺ boosters and sirtuin activators offer complementary approaches within the mitochondrial–redox pathway (Bonkowski and Sinclair, 2016).

Microbiome-targeted therapies consist of probiotics, prebiotics, and fecal microbiota transplants. The microbiome–gut–brain axis affects neuroimmune function, barrier integrity, and the production of neurotransmitter precursors (Filosa et al., 2018). Meta-analyses of clinical studies indicate that probiotics (and sometimes synbiotics) can help reduce depressive symptoms, likely through mechanisms involving SCFAs, cytokine regulation, and tryptophan metabolism. Prebiotics, however, yield more variable outcomes (Marx et al., 2020). Fecal microbiota transplantation (FMT) is being explored for neurological disorders such as Parkinson’s disease and post-infectious syndromes, with a growing number of case series and early-stage trials (Bruggeman et al., 2024). Nonetheless, large randomized controlled trials and standardized protocols are still required (Chen et al., 2025). Questions about safety, donor screening, and the longevity of benefits are crucial in translating these therapies into widespread use.

Epigenetic therapies, such as dietary methyl donors and drugs that modify epigenetic marks, seek to undo harmful gene regulation changes. Since adverse epigenetic modifications like DNA methylation and histone acetylation build up during injury and inflammation, reversing these is a logical approach to disease treatment. Adequate intake of one-carbon nutrients such as folate, B₁₂, and choline that supports the availability of methyl donors and can restore normal neural gene expression in developmental and stress-related models. Pharmacological inhibition of histone deacetylase (HDAC) boosts synaptic plasticity and memory in preclinical neurodegeneration models, and newer brain-penetrant HDAC/DNMT modulators with better selectivity and safety profiles are advancing. Key goals in translation include improving target specificity (e.g., HDAC2 versus HDAC1), determining optimal treatment timing, and combining therapies with rehabilitation and cognitive interventions (Abel and Zukin, 2008).

Neuroimmune modulators target microglial activation caused by environmental and lifestyle stressors. Microglial priming and NLRP3-inflammasome activation link these stressors to synaptic damage and the spread of tau and amyloid. Small-molecule NLRP3 inhibitors, like MCC950 and newer agents that can cross the blood-brain barrier, reduce IL-1β signalling and improve cognition and pathology in AD models (Liang et al., 2022; Johnson et al., 2023). CSF1R inhibitors, which temporarily deplete and then allow microglial repopulation, can reset harmful microglial states and lower amyloid and tau pathology in mice. Precision therapies that modulate, rather than eliminate, microglial phenotypes, along with careful safety monitoring for infection risk and vascular effects, are vital for translating these approaches into clinical practice.

These strategies could improve current pharmacological treatments by emphasizing a multimodal approach to disease modification instead of solely providing symptomatic relief.

Future research should extend beyond laboratory and clinical environments to encompass public health and policy domains. Key focus areas include launching nationwide dietary campaigns to lower salt and sugar consumption, offering subsidies for healthier foods, enacting stricter regulations on air pollution, pesticides, and endocrine disruptors, designing urban areas that encourage physical activity, reduce stress, and enhance sleep quality, and increasing access to preventive care, especially in low- and middle-income countries facing a growing prevalence of neurological diseases’ is rising.

Research priorities increasingly emphasize critical windows (prenatal development, adolescence, and ageing) and sex- and gender-specific differences in nutrition, toxin susceptibility, and lifestyle effects, which may inform tailored prevention and precision approaches. These policy initiatives will be essential in addressing the social factors that influence neurological health on a broad scale.

Ultimately, advancing neurological care relies on adopting an integrative approach that connects nutrition, environment, lifestyle, and pharmacology. This strategy involves interdisciplinary collaboration among neurologists, nutritionists, toxicologists, psychologists, and policy experts. Patient-centered strategies focus on education, empowerment, and self-management of modifiable risk factors. Translational pipelines speed up applying fundamental science discoveries into clinical and community settings. This model aims to improve outcomes for individuals with neurological disorders and reduce the global disease burden through proactive prevention.ion.