Lifestyle and Nutrient Modulators of Neuroplasticity, Brain Health and Energy

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Age Related Cognitive Decline

The projected demographic shift towards a global elderly population reaching 2.1 billion by the year 2050 implies a significant escalation in the incidence of age-related disorders, which carry profound personal, social, and economic implications. This is further exacerbated by evidence linking nonpathological aging to functional deterioration in critical neural substrates underpinning cognitive faculties. Empirical research has consistently demonstrated that aging, even absent of pathological conditions such as dementia, is associated with a spectrum of cognitive declines. These include but are not limited to, decrements in memory recall, attentional capacity, processing speed, and executive functioning, potentially culminating in mild disability[i].

Yet it is known that approximately 40% of all dementia cases could theoretically be prevented or at least delayed if some 12 risk factors were eliminated; including, among others, hypertension, obesity, diabetes mellitus, depression, physical inactivity and smoking[ii],[iii].

Burnout-Related Cognitive Decline

Stress-related burnout is a clinical condition characterised by psychological and physical symptoms of exhaustion developed in response to long-term psychosocial stress[iv]. Burnout is also associated with impaired cognitive performance, most consistently demonstrated in the domains of executive function, working memory, attention and processing speed[v].

From a clinical research perspective, the imperative to address these personal and public health challenges is clear. There is a burgeoning interest in the potential of modifiable lifestyle factors to act as therapeutic modalities in mitigating the deleterious effects of aging and burnout on cognitive health. Thankfully there is a growing body of evidence that safe, cheap (relative to the costs of brain dysfunction), modifiable lifestyle factors beneficially support neuroprotective outcomes[vi].

Physical Activity

Regular physical activity is known for its role in enhancing cerebral blood flow, promoting neurogenesis, and upregulating neurotrophic factors, which collectively contribute to improved neural plasticity and cognitive reserve. Exercise intensity has also been studied and has demonstrated a positive correlation with extraneous physical activity and increased blood flow to the brain, improving executive function, increasing brain size, and decreasing the risk of neurocognitive decline[vii]. Spending time exercising in natural settings also lowers cortisol levels, the hormone associated with stress, and activates the parasympathetic nervous system, which promotes relaxation. The sights, sounds, and smells of nature have a soothing effect on the brain and can help individuals disconnect from work-related stressors[viii].

Cognitive Stimulation

Cognitive stimulation, whether through structured interventions or leisure activities, is recognised to fortify neural networks and facilitate the development of compensatory mechanisms. It is impossible to overestimate the significance of neuroplasticity in brain recovery[ix]. By rerouting neuronal pathways, creating new connections, and enlisting alternate regions to carry out disrupted duties, neuroplasticity enables the brain to make up for damaged areas. Individuals with neurological diseases or stress-related loss of function may experience  improvements if neuroplasticity is harnessed and enhanced through focused therapies and cognitive stimulation.


Nutritional optimisation, particularly dietary patterns rich in neuroprotective nutrients, has been implicated in the attenuation of oxidative stress and inflammation, processes intimately involved in neurodegeneration. The most common diets associated with cognitive protection include the Mediterranean diet, the Dietary Approach to Systolic Hypertension (DASH), and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND)[x]. All of these support the gut-brain axis by modulating gut microbiota composition, maintaining gut immunity and controlling inflammation. Macro food selection is the foundation of gut and brain health.


Burnout is a relatively common health problem especially in medicine and should be recognised in itself as a risk factor for accelerating age related cognitive decline[xi], but its prevalence varies according to a number of factors, both professional issues and various demographic factors[xii], e.g., worldwide, the prevalence of burnout varies from country to country; it ranges from 0% to 80.5% .

The differences in results are also caused by differences in burnout definitions, assessment methods, and research quality. However, brain structures such as the amygdala, hippocampus, caudate, and putamen are different in burnout individuals due to the nature of the neurophysiological functions of these structures[xiii]. The amygdala and hippocampus are core parts of the limbic system, which plays an important role in memory, emotion, emotional learning and behaviour, motivation, and reward.

A central theory about burnout syndrome in relation to the limbic system and its structures has substance: it has a direct impact on all three main dimensions of burnout syndrome: emotional exhaustion, depersonalisation, and lack of personal achievement.

Neural networks of the limbic system function as a group of brain structures that work together in harmony with other brain structures to control a variety of physiological and psychological functions including, as described, emotion, behaviour, motivation, memory formation, olfaction, sleep (dreaming), appetite, sexual drive, and so on. Yet stress responses vary significantly between individuals, both in terms of speed, severity and duration and adaptation and restoration to normal HPA-axis function. Based on the results of studies on the HPA-axis and neuroimaging of the limbic brain structures, it is possible to observe the great impact of chronic stress on the limbic structures in terms of HPA dysregulation, a decrease of brain derived neurotrophic factor, impaired neurogenesis and limbic structures atrophy[xiv]. The limbic system acts as a control centre for conscious and unconscious functions, regulating much of what the body does and its response to stressors ultimately shapes the outcomes.

Stress Management

There are at least six biological areas for the basis of individual differences in stress resistance (i.e., the ability to adapt successfully to stressful work events) that have been identified:

  1. The influence of the immune system on stress sensitivity and its impact on the HPA axis[xv];
  2. The role of norepinephrine and serotonin and related reduced prefrontal cortex self-regulation[xvi];
  3. The role of selected neuropeptides in the inhibitory mechanism of the impact of stress[xvii];
  4. The role of the hypothalamic–pituitary–adrenal axis in influencing stress susceptibility (variations in sex responses) and resistance to stress[xviii];
  5. The role of epigenetic modulation of gene expression in influencing stress susceptibility[xix];
  6. Neurobiological mechanisms by which lifestyle factors such as diet, exercise, and social engagement and support influence stress resistance[xx].

Lifestyle Medicine Offers Resolution

In addition to exercise, nutrition and cognitive engagement, stress management is essential. Evidence indicates that resilience to stress declines with each successive event. Social determinants of stress can be difficult for individual health care support, but there are numerous nutrient related supplements and lifestyle changes that can directly and indirectly mitigate the erosive effects, or restore functionality in primary tissues.

One lifestyle approach is to increase the frequency of restorative sleep as this enables the repair and clearance needed to correct and prevent neuronal damage and helps with learning and synaptic homeostasis. There are numerous strategies for improving sleep patterns, as well as supplements and lifestyle interventions. It may take experimenting with various combinations to mitigate long term insomnia, as well as aiding in the immediate need for sleep.

Effective Practices for a Healthy Sleep (not Exhaustive or necessarily individually effective)

  • Avoid caffeine, alcohol, or large dinner before bedtime
  • Avoid staying in bed if not asleep after 15-20 minutes
  • Be consistent—wake up at the same time during the weekdays, weekends, and vacations
  • Cut back screen time 2 hours before bedtime
  • Decrease fluid intake before bedtime
  • Exercise regularly during the day
  • Limit bright and blue light exposure in the evenings
  • Make the bedroom a comfortable and quiet place with a cool temperature
  • Sleep 7-8 hours every night
  • Stop using electronic devices 30-60 minutes before bedtime
  • Use the bed only for sleep and sex

Social Connections

Loneliness and the absence of meaningful conversation and interactions are seen as a profoundly problematic component of declining brain health. In one research study, there seems to be a connection between increasing social relationships and preserving brain matter. In a randomised control trial in 250 elderly adults, just one-hour sessions of scheduled group discussion three times a week were shown to have a statistically significant increase in brain volume on magnetic resonance imaging. It also showed increased performance in neuropsychology testing compared with peers without scheduled interaction[xxi].

Nutrients for Brain Health

Outside of macro food intake and avoiding detrimental food selections, there is a growing body of evidence that supplementation with key nutrients can support brain health and function, and improve limbic system capacity for stress recovery[xxii]. Advances in molecular biology have revealed the ability of food-derived signals to influence energy metabolism and synaptic plasticity and, thus, mediate the effects of food on cognitive function, which is likely to have been crucial for the evolution of the modern brain.

Dietary consumption of omega-3 fatty acids is one of the best-studied interactions between food and brain evolution. Docosahexaenoic acid (DHA) is the most abundant omega-3 fatty acid in cell membranes in the brain. But curcumin, flavonoids, B vitamins, Vitamins D and E, Choline, Antioxidants (Esp Vit C) calcium, zinc, selenium, copper and iron all have important roles in brain health and stress resilience.

Nootropics are a diverse group of substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired[xxiii]. Many are not available as a food supplement, but some such as Phosphatidylcholine are. Botanicals such as L-Theanine, Ginseng, Gingko, Ashwagandha and Rhodiola, as well as Saffron, which has substantive data sets supporting their role in brain and stress support[xxiv], are also available in single or compound formulas.



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[ii] Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimäki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbæk G, Teri L, Mukadam N. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020 Aug 8;396(10248):413-446.

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[vi] Dhana K, Agarwal P, James BD, et al. Healthy Lifestyle and Cognition in Older Adults With Common Neuropathologies of Dementia. JAMA Neurol. 2024;81(3):233–239.

[vii] Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Baker LD, Frank LL, Foster-Schubert K, et al. Arch Neurol. 2010;67:71–79.

[viii] Wicks C, Barton J, Orbell S, Andrews L. Psychological benefits of outdoor physical activity in natural versus urban environments: A systematic review and meta-analysis of experimental studies. Appl Psychol Health Well Being. 2022 Aug;14(3):1037-1061.

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[x] van den Brink AC, Brouwer-Brolsma EM, Berendsen AAM, van de Rest O. The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less Cognitive Decline and a Lower Risk of Alzheimer’s Disease-A Review. Adv Nutr. 2019 Nov 1;10(6):1040-1065.

[xi] Christensen, D.S., Garde, E., Siebner, H.R. et al. Midlife perceived stress is associated with cognitive decline across three decades. BMC Geriatr 23, 121 (2023).

[xii] Wallensten, J., Ljunggren, G., Nager, A. et al. Stress, depression, and risk of dementia – a cohort study in the total population between 18 and 65 years old in Region Stockholm. Alz Res Therapy 15, 161 (2023).

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[xiv] Chow Y, Masiak J, Mikołajewska E, Mikołajewski D, Wójcik GM, Wallace B, Eugene A, Olajossy M. Limbic brain structures and burnout-A systematic review. Adv Med Sci. 2018 Mar;63(1):192-198.

[xv] Verhaeghe, J.; Van Den Eede, F.; Van Den Ameele, H.; Sabbe, B.G. Neuro-endocrine correlates of burnout. Tijdschr. Psychiatry 2012, 54, 517–526

[xvi] Arnsten, A.F.T.; Shanafelt, T. Physician distress and burnout: The neurobiological perspective. Mayo Clin. Proc. 2021, 96, 763–769.

[xvii] Lehmann, M.J.; Lormes, W.; Opitz-Gress, A.; Steinacker, J.M.; Netzer, N.; Foster, C.; Gastmann, U. Training and overtraining: An overview and experimental results in endurance sports. J. Sports Med. Phys. Fit. 1997, 37, 7–17.

[xviii] Leistner, C.; Menke, A. Hypothalamic-pituitary-adrenal axis and stress. Handb. Clin. Neurol. 2020, 175, 55–6

[xix] Weisel, F.; Shlomchik, M. Memory B cells of mice and humans. Annu. Rev. Immunol. 2017, 35, 255–284

[xx] Romito, B.T.; Okoro, E.N.; Ringqvist, J.R.B.; Goff, K.L. Burnout and wellness: The anesthesiologist’s perspective. Am. J. Lifestyle Med. 2020, 15, 118–125.

[xxi] Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders. Mortimer JA, Ding D, Borenstein AR, et al. J Alzheimers Dis. 2012;30:757–766

[xxii] Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008 Jul;9(7):568-78.

[xxiii] Malík M, Tlustoš P. Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs. Nutrients. 2022 Aug 17;14(16):3367.

[xxiv] El Midaoui A, Ghzaiel I, Vervandier-Fasseur D, Ksila M, Zarrouk A, Nury T, Khallouki F, El Hessni A, Ibrahimi SO, Latruffe N, Couture R, Kharoubi O, Brahmi F, Hammami S, Masmoudi-Kouki O, Hammami M, Ghrairi T, Vejux A, Lizard G. Saffron (Crocus sativus L.): A Source of Nutrients for Health and for the Treatment of Neuropsychiatric and Age-Related Diseases. Nutrients. 2022 Jan 29;14(3):597.

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