Our brain is a remarkable and flexible organ, responsive to numerous stimuli throughout our lifespan. Food is one of those inputs over which a high level of personal control exists, yet for many the concept that our brain can be enhanced, sustained, and evolved by the selection of what is eaten remains a mystery.
From early development to periods of age-related decline the long-term timeline represents a series of milestone opportunities to intervene, engage and support optimal brain health and sustainability. Brain health and wellbeing is closely associated with other metabolic events. Research has demonstrated that people with conditions such as heart disease, high blood pressure, obesity and diabetes are more likely than those without such conditions to experience age-related cognitive decline. The risks of developing those metabolic conditions is increased by poor diet and insufficient exercise as well as other lifestyle choices, suggesting there are things you can do to lower the chances of developing dementia and other conditions that result in a loss of brain function.
Its no surprise that two nutritional approaches in particular, the Mediterranean diet and the MIND diet both of which encourage fresh produce, legumes and nuts, fish, whole grains and olive oil have been repeatedly shown in scientific studies to offer strong and variable protection against cognitive decline[1],[2],[3].
Caution comment
It should be noted that nutrition studies, including those designed to explore neuroprotective diets, are often prone to high levels of variability in terms of data collection from food intake to various scoring systems, time frames and cohorts of insufficient scale, to qualify outcomes. However, careful management of food choices to favour those recommended in these two diets carry no risk and mechanistically contribute to multiple points of intervention of value for health and wellbeing[4].
Colourful fruits and vegetables
The more colourful the produce on your plate, the better the food usually is for your brain.
In one 2021 observational study published in the journal Neurology, researchers followed more than 77,000 people for about 20 years. They found that those with diets high in flavonoids, natural substances found in colourful fruits, berries and vegetables, dark chocolate and some wines were less likely than those who consumed fewer flavonoids to report signs of cognitive aging[5].
The MIND diet specifically points to berries, a good source of fibre and antioxidants, as having cognitive benefits. The Annals of Neurology published a paper way back in 2012 that looked at more than 16,000 people aged 70 and older for more than a dozen years. It concluded that older women who ate more blueberries and strawberries had delayed rates of cognitive decline: perhaps by up to 2.5 years[6]. More recently a paper released in Nutrients in April 2022 found that middle aged men with insulin resistance when taking a daily dose of blueberries had improved executive ability[7].
Gut and brain -intersecting paths
The connection between your gut and brain is embedded in our genes, and it begins in the womb. The gut and brain originate from the same cells in the embryo. One of the primary mechanisms the brain and gut use to remain connected is through the vagus nerve, a two-way chemical messaging path that explains amongst many communication links why stress can trigger feelings of anxiety in your mind and butterflies in your stomach. The primary interface being the microbiome in the gut, a collection of organisms and genes that far exceed those of human origin, all of which are susceptible to changes in diet and related genetic expressions[8]. It has been conservatively estimated that the gut contains more than 500 types of bacteria, over 10 trillion cells, i.e., 1.3 times more microbes than the human body, and constitute > 99% of the genes in our body[9].
A growing body of research shows that improving the quality of a person’s diet can have a significant effect on mental health in part through the enhancement of microbiome function and metabolic by products. Above the protective mucus layer that tops the epithelial surface sits the body’s largest collection of friendly (and occasionally unfriendly) microbes. The gut microbiota (as it is called) partners with us for important physiological functions including facilitating our metabolism, helping to reinforce the stability of the gut’s epithelial barrier, providing nourishment for the intestinal cells, and even producing neurotransmitters[10],[11],[12],[13],[14].
An analysis of 16 studies found that dietary interventions significantly reduced depression symptoms. Multiple other studies have supported the connection between the foods selected, the microbiome and related healthful outcomes and brain functionality[15].
Other food groups of note
Fish as a source of omega three fatty acids support healthy brain function and aging[16],[17]. Nuts, seeds, whole grains (when not adversely reactive) legumes and olive oil all have numerous strands of compelling evidence of enhancing function and longevity of cognitive function[18],[19],[20].
Butyrate
Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders [21].
In brief, SCFAs might directly or indirectly communicate along the microbial gut brain axis by activating G protein-coupled receptors of which GPR43 and GPR41, which were renamed as free fatty acid receptor 2 (FFAR2) and FFAR3, respectively, are the most investigated mechanisms. Or inhibiting histone deacetylase (HDAC), with butyrate being the most potent inhibitor of class I and IIa HDACs. They can enter the bloodstream, activate the vagus pathway, facilitate the secretion of other hormones or neurotransmitters, interfere with the immune response, and finally participate in neuropathology’s.
‘Hidden Hunger’ of the brain and body
Here in the UK, nutrient needs are claimed to be met by the somewhat mercurial ‘balanced diet’ which in many cases is as difficult to define as it is to consume. The primary assumption being that all foods are equal, that all one needs to consider is a caloric volume, and nutrient content is of little value.
Nothing could be further from the truth. Nutrient density is as vital or more so than caloric volume, our body and especially our brain requires access to essential nutrients to thrive and develop. Without exploring the vast array of studies reflecting the consequences of missed nutrient intake from the first 1000 days to old age, a recent review in the International Journal of Food Science added weight to prior work demonstrating the insidious decline of minerals in the fruit and vegetables produced and consumed in the UK[22].
Analysis of long-term trends of the mineral content of fruits and vegetables from three editions of the UK’s Composition of Foods Tables (1940, 1991 and 2019) was undertaken. All elements except phosphorus declined in concentrations between 1940 and 2019 – the greatest overall reductions during this 80-year period were Na (52%), Fe (50%), Cu (49%) and Mg (10%); water content increased (1%). Which means that even if consuming a MIND based diet, it’s likely that essential mineral content is insufficient, suggesting a role for supplementation, as well as indicating a strong long term need for improved crop production techniques[23].
The regular supplementation of essential nutrients, such as long-chain-polyunsaturated fatty acids, vitamin E and mineral elements, have been shown to minimise inflammation, enhance antioxidative defenses, and lower the risk and incidence of age-related diseases, such as cardiovascular diseases and neurodegenerative diseases[24].
Summary
The brain is susceptible to organic and non-organic interactions. Psychological, biological and environmental influences change and shape the health and function of this most complex of tissues. Yet our very lineage has evolved because our brains have grown and developed over millennia to accommodate, adapt, and change our world.
But this comes at a cost. The longer we live the greater the need to feed, nourish and support brain function, for personal and societal burdens are growing at a rate that exceeds most country’s capacity to manage.
The Global Burden of Disease study, published in the Lancet in Jan 2022 which provides forecasting estimates for 204 countries, estimates that the number of adults (aged 40+) living with dementia is expected to increase from approximately 57 million in 2019 to 153 million in 2050[25]. The new analysis examines the impact of major dementia risk factors on projections, and urges significant intervention through lifestyle changes, expanded health and social care resources and investment in research to find much-needed treatments.
Small but meaningful changes to lifestyles and food intake, the earlier the better, should become a clear route of hope for those that can access simple, natural and health providing foods. For those that are denied access, or struggle to consume enough, supplementation of vital nutrients, fats and bacteria provide a safe, accessory approach to short and long term brain food selection.
References
[1] Michelle Luciano, Janie Corley, Simon R. Cox, Maria C. Valdés Hernández, Leone C.A. Craig, David Alexander Dickie, Sherif Karama, Geraldine M. McNeill, Mark E. Bastin, Joanna M. Wardlaw, Ian J. Deary. Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort Neurology Jan 2017, 88 (5) 449-455
[2] Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1007-1014
[3] https://www.nia.nih.gov/health/what-do-we-know-about-diet-and-prevention-alzheimers-disease
[4] Duplantier SC, Gardner CD. A Critical Review of the Study of Neuroprotective Diets to Reduce Cognitive Decline. Nutrients. 2021 Jun 30;13(7):2264..
[5] Tian-Shin Yeh, Changzheng Yuan, Alberto Ascherio, Bernard A. Rosner, Walter C. Willett, Deborah Blacker Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women
Neurology Sep 2021, 97 (10) e1041-e1056
[6] Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol. 2012 Jul;72(1):135-43.
[7] Krikorian R, Skelton MR, Summer SS, Shidler MD, Sullivan PG. Blueberry Supplementation in Midlife for Dementia Risk Reduction. Nutrients. 2022 Apr 13;14(8):1619.
[8] Horn J, Mayer DE, Chen S, Mayer EA. Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders. Transl Psychiatry. 2022 Apr 20;12(1):164.
[9] Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE, Jaggar M, Long-Smith CM, Lyte JM, Martin JA, Molinero-Perez A, Moloney G, Morelli E, Morillas E, O’Connor R, Cruz-Pereira JS, Peterson VL, Rea K, Ritz NL, Sherwin E, Spichak S, Teichman EM, van de Wouw M, Ventura-Silva AP, Wallace-Fitzsimons SE, Hyland N, Clarke G, Dinan TG. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99:1877–2013
[10] Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31.
[11] Firth J, Marx W, Dash S, Carney R, Teasdale SB, Solmi M, Stubbs B, Schuch FB, Carvalho AF, Jacka F, Sarris J. The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials. Psychosom Med. 2019 Apr;81(3):265-280
[12] Caricilli AM, Castoldi A, Câmara NO. Intestinal barrier: A gentlemen’s agreement between microbiota and immunity. World J Gastrointest Pathophysiol. 2014;5(1):18-32.
[13] Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.
[14] Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK. Specialized metabolites from the microbiome in health and disease. Cell Metab. 2014 Nov 4;20(5):719-730.
[15] Ghosh TS, Rampelli S, Jeffery IB, Santoro A, Neto M, Capri M. et al. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut. 2020;69:1218–28
[16] Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005 Dec;62(12):1849-53.
[17] Cole GM, Ma QL, Frautschy SA. Omega-3 fatty acids and dementia. Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):213-21.
[18] Theodore LE, Kellow NJ, McNeil EA, Close EO, Coad EG, Cardoso BR. Nut Consumption for Cognitive Performance: A Systematic Review. Adv Nutr. 2021 Jun 1;12(3):777-792.
[19] Mazza E, Fava A, Ferro Y, Moraca M, Rotundo S, Colica C, Provenzano F, Terracciano R, Greco M, Foti D, Gulletta E, Russo D, Bosco D, Pujia A, Montalcini T. Impact of legumes and plant proteins consumption on cognitive performances in the elderly. J Transl Med. 2017 May 22;15(1):109.
[20] Guasch-Ferré M, Li Y, Willett WC, Sun Q, Sampson L, Salas-Salvadó J, Martínez-González MA, Stampfer MJ, Hu FB. Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults. J Am Coll Cardiol. 2022 Jan 18;79(2):101-112.
[21] Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016 Oct;99:110-132.
[22] Mayer AB, Trenchard L, Rayns F. Historical changes in the mineral content of fruit and vegetables in the UK from 1940 to 2019: a concern for human nutrition and agriculture. Int J Food Sci Nutr. 2022 May;73(3):315-326.
[23] Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006 Sep-Oct;10(5):377-85..
[24] Businaro R, Vauzour D, Sarris J, Münch G, Gyengesi E, Brogelli L, Zuzarte P. Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease and Depression. Front Nutr. 2021 May 14;8:669846.
[25] GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022 Feb;7(2):e105-e125.