The brain is very metabolically active and malleable with a great ability to change and respond to different conditions and stimuli. Therefore it requires factors that support both energy availability and also growth.
This includes presence and delivery of oxygen and nutrients to the brain, highlighting the importance of nutrient intake and optimal function of the respiratory, cardiovascular and digestive systems. Availability of energy to cells is also reliant on the normal function of hormones, in particular insulin but is also affected by oestrogen and thyroid hormones. All of these are considered trophic (growth) hormones and therefore support anabolic (tissue building) processes.
This blog looks at tropic factors that contribute to cognitive function and therefore interventions that can support cognitive health.
Nutrient intake and cognitive impairment
The nutrition gap is the difference between the levels of nutrients we are consuming and what we need for optimum health. This gap is a fundamental driver of poor health and chronic disease, including cognitive decline, and therefore it is so important to ensure optimum levels of nutrients are obtained.
Nutrients that are particularly important for cognitive function (this list is non exhaustive) include:
- Omega 3 fatty acids – particularly DHA which support cell membrane function and neuronal signalling as well as EPA aiding a normal inflammatory response. DHA is the predominant omega 3 fatty acid in the brain1
- B vitamins especially methyl folate and B12, these are responsible for normal nervous system function and the production of neurotransmitters. They also aid the clearance of homocysteine, a waste product which can contribute to cognitive decline.2
- Vitamin D- modulates inflammation and a deficiency is associated with cognitive issues3
- Zinc- major cofactor for enzymatic processes and an antioxidant, again deficiency can be associated with cognitive issues 4
- COQ10- essential for energy production, levels are shown to decline in the brains of dementia patients2
Even if nutrient intake is optimal, these nutrients still need to be absorbed and then transported to the brain, therefore digestive and cardiovascular function are essential.
Nutrient absorption relies on adequate stomach acid, digestive enzymes and bile production, if these are compromised it can have an influence on nutrient status regardless of nutrient intake.
Although not a main focus of this blog, it is important to mention that if the integrity of the gut lining is compromised, then larger molecules can pass across the digestive lining and trigger inflammation, known as leaky gut. A similar process also occurs in the blood brain barrier, and leaky gut is associated with leaky brain. Leaky brain will increase neuroinflammation leading to damage to neuronal tissue and therefore is a contributing factor to brain fog.5
Furthermore, the microbiome is essential for the production of neurotransmitters and short chain fatty acids, communicating with the brain via the vagus nerve. Although these neurotransmitters cannot cross the blood brain barrier, they elicit a positive benefit to the brain via activation of the vagus nerve.
For example, one study showed that people with Alzheimer’s disease who took probiotics (a mixture of L. acidophilus, L. casei, B. bifidum, and L. fermentum) experienced positive effects on cognitive functions like learning power and memory.6
Considerations for digestive support include7:
Poor digestive capacity/absorption – you may see symptoms such as bloating, reflux, low appetite, food intolerance, undigested food in stool. In these cases, you can support stomach acid and digestive enzymes with a full spectrum digestive enzyme complex and betaine HCl.
Reduced integrity of gut lining – indicated for inflammatory, atopic and autoimmune conditions and food intolerances. Nutrients such as lactoferrin, vitamin A, D and zinc, those that support anti-inflammatory pathways including omega 3 fatty acids, curcumin and quercetin. Mucous membrane support with slippery elm and marshmallow are important for repairing the digestive lining. Additionally supporting a healthy balance of digestive flora with a probiotic in order to support the production of short chain fatty acids is also useful.
Dysbiotic microbiome – indicated with many digestive issues including IBS but also for low immunity, dysbiosis often see as candida overgrowth causing thrush, and cognitive dysfunction. Live bacteria supplements containing supportive bacteria as well as prebiotic fibres support a healthy balance of digestive flora as well as supporting immunity and digestive function.
Not only do we need to be able to consume and absorb nutrients, but they need to be delivered to the site of action. The cardiovascular system and brain function are intrinsically linked. Reduced blood flow to the brain is a driver of dementia and can be seen acutely in stroke patients.8 This is a sliding scale and therefore if cardiovascular function is impaired there is a reduction of transportation of nutrients to the brain and waste products away from the brain. Approximately 40% of dementia cases are estimated to be preventable by targeting modifiable, primarily cardiovascular risk factors.9
Factors that can play a part in the development of CVD include inflammation, obesity, lack of exercise, insulin resistance, oxidative stress, smoking and chronic stress. Therefore lifestyle factors must be considered. In addition, cardiovascular supportive nutrients play an important role these include:
- NAC – through its capacity to synthesize glutathione, NAC has displayed many health-promoting properties with regards to CV health10
- Flavonoids – high in antioxidants, including phenolic acids, anthocyanins, and flavonoids. Epidemiological research indicates that a diet abundant in fruit and vegetables offers protection against CVD, and this may be attributed, in part, to the flavonoid content11
- Vitamin C – a powerful antioxidant that has received considerable interest for its possible role in heart health7
- B vitamins – without sufficient B vitamins, homocysteine can build up and bring about damage to arteries7
- Physical exercise is linked to longevity and can significantly reduce the risk of CVD, diabetes, high blood pressure, and obesity
- Chronic stress can contribute to high blood sugar, high blood pressure, insulin resistance, decreased absorption of nutrients, all of which impact adversely on CV health
The role of hormones in cognitive function
Whilst both bioavailability of nutrients and healthy function of mitochondria are essential, the ability to produce or utilise energy is also governed by the presence, or absence, of hormones.
Neuroendocrine communication is essential for healthy cognition, and it is worth noting that endocrine dysregulation is the only independent risk factor for cognitive decline.
Firstly, insulin is a trophic hormone as is responsible for the delivery of glucose to the cell. Therefore, mitochondrial function is reliant (in most instances) on the action of insulin for delivery of glucose into the cell in order to produce Most, if not all, tissues of the body, including the brain, express insulin receptors and are insulin sensitive.12 Accumulating evidence suggests that brain insulin signalling not only plays a key role in regulation of metabolism, but also in regulation of mood, behaviour, and cognition. In addition, there is comorbidity between dementia and type 2 diabetes.12
Alzheimer’s disease has been referred to a type 3 diabetes and the brain may become insulin resistant as much as 20 years before someone is diagnosed with type 2 diabetes. Defects in insulin signalling is associated with an increase of amyloid plaques in the brain, particularly in temporal lobe, hippocampus, and cerebellum.13
Therefore, improving insulin sensitivity, as early as possible, is an essential intervention for individuals experiencing cognitive impairment.
Many women complain of changes in their cognitive function during the menopause transition, with the majority reporting worsening of memory and depression. Several large prospective cohort studies have shown a three-fold increased risk of a major depressive episode during perimenopause compared with pre-menopause. Even women with no history of depression are still three times more likely to experience depression during the menopause transition compared with the pre-menopause.14,15
Oestrogen is a growth promoting hormone and therefore can stimulate the growth and development of nerve cells, particularly within the brain. It is known that oestrogen affects cholinergic (acetylcholine), dopaminergic (dopamine) systems and mitochondrial function within the brain. Oestrogen also stimulates synaptic plasticity, via activation of BDNF (brain derived neurotropic factor) and elicits neuroprotective effects.
The drop in oestrogen, due to menopause, has been shown to reduce nerve function within the brain, and physiological changes can be observed as reduced dendritic spines, decreased synaptic density, decreased numbers of specific synapses, changes in connectivity, and increases or reductions in grey matter volume in specific areas. There is also reduce acetyl choline and dopamine signalling, these essential neurotransmitters play a role in cognition and mood.14
Testosterone is essential for cognitive health and function in both men and women. It is supportive for wellbeing and vigour and a reduction of testosterone which occurs as we age can contribute to low mood and anxiety, there can also be physiological changes leading to depression. A study has shown that low testosterone and obesity independently and cooperatively can contribute to neuroinflammation which is consistent with low mood and depression as well as a risk factor for cognitive issues such as dementia and Alzheimer’s.16,17 Low serum testosterone has also been associated with Alzheimer’s disease.18
Low testosterone is also associated with muscle loss known as sarcopenia. Muscle is considered by some to be the “Anti-Ageing God” because maintaining muscle mass as we age helps to prevent falls but helps to improve insulin sensitivity, which as mentioned is important for cognitive health.
Studies have found that among people aged 65 years or older, those with a history of hypothyroidism were associated with an 81% increased risk of having dementia and among those, there was a more than 3-fold increased dementia risk with thyroid conditions that required thyroid hormone replacement treatment.19,20
Abnormal concentrations of thyroid hormones can lead to deterioration of cognitive processes through changes in neurotransmission, intensification of oxidative stress, or impact β-amyloid transformation and glucose metabolism in the central nervous system.21
Thyroid hormones are crucial for brain development, and influence brain function throughout life. In adults, hypothyroidism causes lethargy, hyporeflexia, and poor motor coordination, is associated with bipolar affective disorders, depression, or loss of cognitive functions. Subclinical hypothyroidism is often associated with memory impairment.21
Stress has been shown to be a contributing factor to many aspects of cognition including brain fog, depression and dementia. This is due to multiple pathways such as activation of the HPA (hypothalamus-pituitary-adrenal) axis, interference to sleep, increased inflammation, oxidative stress. In addition, cortisol (our stress hormone) itself has been shown to be a catabolic hormone and can cause atrophy of brain tissue – particularly in the hippocampus which is responsible for short term memory.22,23 Studies looking at patients with depression showed brain atrophy was associated with increased cortisol.24
Systematic reviews have shown activated HPA axis is associated with an increased risk of Alzheimer’s disease. It is hypothesised that HPA activation can mediate glucocorticoid priming of the immune cells of the brain, microglia, to become pro-inflammatory and promote a neurotoxic environment resulting in neurodegeneration.23
Supporting hormone regulation for healthy cognitive function
It can be seen that supporting hormone balance is essential for cognitive function. Consider supporting hormone regulation by:
Balancing blood sugar – consuming high fibre foods such as vegetables and wholegrains with lean protein and healthy fats slows down the release of sugar into the blood. Also, nutrients such as magnesium, chromium, zinc as well as cinnamon can support glucose uptake.
Improve insulin sensitivity – exercise and fasting for at least 12 hours over night have both been shown to improve insulin sensitivity.25
Support the adrenal glands – essential during menopause as the adrenal glands take over oestrogen production form the ovaries. It also important for blunting the HPA axis to reduce cortisol. Practising relaxation techniques such as mindfulness, meditation and yoga is useful. Adaptogenic herbs such as ashwagandha26 and nutrients including B vitamins (B5 and B6), vitamin C and magnesium are also useful.
Support testosterone – consider Fenugreek shown to increase total testosterone through an aromatase and 5α reductase inhibition, thereby blocking testosterone conversion to oestrogen and dihydrotestosterone, respectively. 27
Consider thyroid – it is important to investigate thyroid function (seek medical advice) if suspect dysfunction especially if concurrent with cognitive problems. Thyroid hormones require tyrosine, iodine, zinc and selenium for production and these nutrients can be useful in some cases.7
The above list is a good start, but it may be important to consider further interventions depending on factors that are most influencing each individual.
- The brain is highly metabolically active and requires a high amount of trophic support from nutrient intake, absorption and delivery as well as the normal regulation of the endocrine system.
- Inadequate intake of nutrients can influence brain function due to suboptimal levels of supportive nutrients. Of particular importance are omega 3 fatty acids, B vitamins, Vitamin D, zinc and magnesium as well as antioxidants
- If the digestive and cardiovascular systems are impaired this can impact the availability of nutrients to the brain and therefore should be considered in cognitive impairment.
- Insulin resistance is a major driver of cognitive decline due to multiple factors mainly by reducing energy availability to brain cells.
- During menopause insulin resistance increases whilst levels of oestrogen decrease, both of these affect cognitive function due to reduced trophic support
- The thyroid is responsible for metabolic rate in every cells in the body including neurones and other brain cells and is essential for cognitive development. Hypothyroidism increases risk of dementia.
- Stress is associated with increased brain fog, depression and dementia. Cortisol has been shown to cause atrophy of neuronal tissue and therefore is associated with neurodegeneration.
- Freund Levi Y, Vedin I, Cederholm T, et al. Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer’s disease: the OmegAD study. J Intern Med. 2014;275(4):428-436. doi:10.1111/joim.12166
- Tardy AL, Pouteau E, Marquez D, Yilmaz C, Scholey A. Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients. 2020;12(1). doi:10.3390/NU12010228
- Geng C, Shaikh AS, Han W, Chen D, Guo Y, Jiang P. Vitamin D and depression: mechanisms, determination and application. Asia Pac J Clin Nutr. 2019;28(4):689-694. doi:10.6133/APJCN.201912_28(4).0003
- Wallwork JC. Zinc and the central nervous system. Prog Food Nutr Sci. 1987;11(2):203-247. doi:10.1385/0-89603-046-6:135
- Mou Y, Du Y, Zhou L, et al. Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging. Front Immunol. 2022;13. doi:10.3389/FIMMU.2022.796288
- Dauncey MJ, Messier C, Takechi R, et al. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Frontiers in Aging Neuroscience | www.frontiersin.org. 2016;1:256. doi:10.3389/fnagi.2016.00256
- Bland J et al. Textbook of Functional Medicine.; 2008.
- Rost NS, Brodtmann A, Pase MP, et al. Post-Stroke Cognitive Impairment and Dementia. Circ Res. 2022;130(8):1252-1271. doi:10.1161/CIRCRESAHA.122.319951
- Nordestgaard LT, Christoffersen M, Frikke-Schmidt R. Shared Risk Factors between Dementia and Atherosclerotic Cardiovascular Disease. Int J Mol Sci. 2022;23(17). doi:10.3390/IJMS23179777
- Bueche CZ, Garz C, Kropf S, et al. NAC changes the course of cerebral small vessel disease in SHRSP and reveals new insights for the meaning of stases – a randomized controlled study. Exp Transl Stroke Med. 2013;5(1):1-8. doi:10.1186/2040-7378-5-5/FIGURES/6
- Sano A, Uchida R, Saito M, et al. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol (Tokyo). 2007;53(2):174-182. doi:10.3177/JNSV.53.174
- Tyagi A, Pugazhenthi S. Targeting Insulin Resistance to Treat Cognitive Dysfunction. Mol Neurobiol. 2021;58(6):2672-2691. doi:10.1007/S12035-021-02283-3
- De La Monte SM. Contributions of Brain Insulin Resistance and Deficiency in Amyloid-Related Neurodegeneration in Alzheimer’s Disease. Drugs. 2012;72(1):49. doi:10.2165/11597760-000000000-00000
- Russell JK, Jones CK, Newhouse PA. The Role of Estrogen in Brain and Cognitive Aging. Neurotherapeutics. 2019;16(3):649. doi:10.1007/S13311-019-00766-9
- Maki PM, Jaff NG. Brain fog in menopause: a health-care professional’s guide for decision-making and counseling on cognition. Climacteric. 2022;25(6):570-578. doi:10.1080/13697137.2022.2122792
- Ostatníková D, Lakatošová S, Babková J, Hodosy J, Celec P. Testosterone and the Brain: From Cognition to Autism. Physiol Res. 2020;69(Suppl 3):S403. doi:10.33549/PHYSIOLRES.934592
- Jayaraman A, Lent-Schochet D, Pike CJ. Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function. J Neuroinflammation. 2014;11(1):1-14. doi:10.1186/S12974-014-0162-Y/FIGURES/8
- Cherrier MM. Testosterone effects on cognition in health and disease. Front Horm Res. 2009;37:150-162. doi:10.1159/000176051
- Wieland DR, Wieland JR, Wang H, et al. Thyroid Disorders and Dementia Risk: A Nationwide Population-Based Case-Control Study. Neurology. 2022;99(7):E679-E687. doi:10.1212/WNL.0000000000200740
- Lemprière S. Hypothyroidism is associated with dementia risk. Nat Rev Neurol. 2022;18(9):510. doi:10.1038/s41582-022-00708-8
- Bernal J. Thyroid Hormones in Brain Development and Function. Endotext. Published online January 14, 2022. Accessed May 31, 2023. https://www.ncbi.nlm.nih.gov/books/NBK285549/
- Holleman J, Adagunodo S, Kåreholt I, et al. Cortisol, cognition and Alzheimer’s disease biomarkers among memory clinic patients. BMJ Neurol Open. 2022;4:344. doi:10.1136/bmjno-2022-000344
- Milligan Armstrong A, Porter T, Quek H, et al. Chronic stress and Alzheimer’s disease: the interplay between the hypothalamic-pituitary-adrenal axis, genetics and microglia. Biol Rev Camb Philos Soc. 2021;96(5):2209-2228. doi:10.1111/BRV.12750
- Lebedeva A, Sundström A, Lindgren L, et al. Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus. Acta Psychiatr Scand. 2018;137(6):491-502. doi:10.1111/ACPS.12860
- Vasim I, Majeed CN, DeBoer MD. Intermittent Fasting and Metabolic Health. Nutrients. 2022;14(3). doi:10.3390/NU14030631
- Remenapp A, Coyle K, Orange T, et al. Efficacy of Withania somnifera supplementation on adult’s cognition and mood. J Ayurveda Integr Med. 2022;13(2):100510. doi:10.1016/J.JAIM.2021.08.003
- Wankhede S, Mohan V, Thakurdesai P. Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study. J Sport Health Sci. 2016;5(2):176. doi:10.1016/J.JSHS.2014.09.005
If you have questions regarding the topics that have been raised, or any other health matters, please do contact our team of Nutritional Therapists.