Top 13 Nutrients to Supplement for Long Term Brain Health and Memory

The populations of the longest-lived people with the healthiest brains have a nutrient-dense diet as a common denominator.  Well-designed research into the dietary patterns of these communities spread across the globe, has given clues about the importance of the nutrients and lifestyles that protect our bodies and brains with age.  These nutrients are abundant in the Mediterannean (MeDi) and MIND diets, patterns of eating with strong evidence pointing to their powerful brain-protective properties. Though it might seem like a given that we lose brain power with age, evidence suggests that the age-related risk of neurological decline can be cut by 50% or more with dietary changes in the context of your lifestyle.^1-4   A healthful diet is a foundation for a healthy brain, but sometimes we miss the mark on eating all of these brain food nutrients consistently.  Filling in the gaps with nutritional supplements can help to ensure your brain has all the fuel it needs to function properly long-term.  But which nutrients are best for brain health? 

This list explores the nutrients that stand out in the research for their brain-protective functions.  We focus on the nutrients that help with memory and focus, but more importantly give your brain long-term staying power.  The MeDi and MIND diets have shown the following components are powerful when consumed regularly: 

Omega-3 fatty acids

Your body can make many of the fat types that it needs to function, but this isn’t true for omega-3 fats. These essential fats must be obtained through dietary intake.  Although they can be found in plant foods, the most bioavailable sources come from cold-water fatty fish. The classic example is salmon, but they’re also found in mackerel, cod, herring, sardines, anchovies, krill, and oysters. The omega-3 content of these fish is the reason fish are considered an important brain-supportive component of the Mediterranean and MIND diets.  The type of omega-3 fatty acids is especially important when considering a supplement for brain health.  Consider a phospholipid form from herring roe and krill oils, which enables them to cross the blood brain barrier up to 10 times more efficiently than other forms.^5-6

Omega-3 fats, especially in the forms docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), play a key role in lowering inflammation in the brain.  With about 60% of the brain being composed of fat, these fatty acids are critical to the structure and function of neuronal cell membranes and their insulating myelin sheath. DHA has been shown to support membrane fluidity, important in neuron function to support learning and memory.  

Clinical and observational studies have shown a protective effect of omega-3 fat intake against developing cognitive decline and AD.  The OmegAD clinical trial observed supplementation with omega-3 fatty acids correlated with an increase in transthyretin (a marker that correlates with reduced accumulation of Aβ) as well as improved cognition on cognitive function tests. Overall, evidence suggests omega-3 supplements are most effective as preventive measures versus treatment for neurodegenerative disease.⁷

Vitamin D

The hormone-like vitamin D is found naturally in just a few foods, such as fatty fish (e.g., salmon, sardines), beef liver, and egg yolks. Beyond that, the sunshine vitamin is synthesized when your skin is exposed to the sun. In the modern world, Vitamin D deficiency is quite common due to reduced time outside and lower consumption of these vitamin D food sources. This is especially common as people age, as activity levels, sun exposure, ability to make vitamin D in the skin, and dietary intake decrease.⁸  If you’re looking for the best supplement form of vitamin D to support your brain health and beyond, you’ll want to choose one with cholecalciferol, also known as vitamin D3.  This is the same form that your body makes with sun exposure, and is more effective at raising vitamin D levels.⁹   

The role of vitamin D in bone health and calcium metabolism are well known and accepted, but vitamin D has a role throughout other systems of the body and is important in development and function of the nervous system. Vitamin D plays a part in immune system functioning, and sufficient levels of vitamin D are associated with a neuroprotective effect. Deficiency is associated with higher risk and worse outcomes in neurodegenerative diseases, including Multiple Sclerosis (MS).  

The clinical research around vitamin D supplementation is limited, but there is strong evidence pointing to its important protective role in the nervous system. The brain is rich in vitamin D receptors (VDR), indicating it’s need for vitamin D to function.  Low levels of vitamin D, and mutations in the VDR, are associated with higher risk of neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD), as well as worsened symptoms in PD.^8,10 In vitro studies have demonstrated the promising effect of Vitamin D on the immune system’s ability to break down amyloid beta plaques, which are a hallmark of AD.¹¹ Observational studies have shown the elevated risk of cognitive decline and neurodegenerative diseases associated with vitamin D deficiency.^10,12

Magnesium

Magnesium plays an important role in many functions throughout the body, including the brain. This relaxing mineral can be found in abundance in plant foods like nuts, seeds, leafy greens, and whole grains. These foods are abundant in the Mediterranean and MIND dietary patterns, but tend to be low in the American diet. As many as 50% of Americans eat less magnesium than recommended, with that figure jumping as high as 80% in the elderly.¹³ The magnesium supplements most effective for brain health come in the form of magnesium bisglycinate. Magnesium bisglycinate is easily absorbed, and because of the glycine component, is able to cross the blood brain barrier. 

In the brain, magnesium is important for regulating neurotransmitter release, preventing excessive excitation of neurons which can lead to cell damage and death.¹⁴ Low magnesium in the part of the brain important for memory is a risk factor for Alzheimer’s, and is also correlated with the tau tangles that are one of the hallmarks of the disease.¹⁵ Low levels of magnesium intake are also correlated with risk of other neurodegenerative diseases like Parkinson’s.¹⁴ 

Vitamin E

Vitamin E is not a single vitamin. It’s actually a family of eight antioxidant molecules, with the most active in humans being alpha- and gamma-tocopherols. Vitamin E is found in nuts and seeds, olive oil, fruits, and vegetables. It’s best absorbed when consumed with a healthy fat, since it’s a fat-soluble vitamin. 

Vitamin E has long been known to be essential for function of the nervous system, with low levels associated with ataxia, dementia, and Alzheimer’s disease (AD). The brain’s high metabolic rate puts it at higher risk of oxidative damage and therefore neuron degeneration.  This makes antioxidant intake vital to brain health.^16,17 One clinical trial demonstrated improvement in cognitive decline in an aging study population with higher intakes of vitamin E from food and/or supplements compared to those with low intake.¹⁶ Another study importantly found that both alpha- and gamma-tocopherols are importantly required in balance with each other to provide protection against the plaques and tangles that occur with AD.¹⁸

Vitamin B 

The B complex of vitamins is composed of eight B vitamins: B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), and B12 (cobalamin). Overall, this group of vitamins are found across the spectrum of foods in the Mediterranean diet. Vitamin B12 is most abundant in animal foods, like meat, fish, and organ meats. While others are found in plant foods, like vegetables, fruits, nuts and seeds, and whole grains.   

Importantly, vitamins B6, B9, and B12 work in concert to support brain health. They work together to break down homocysteine, a neurotoxic compound that is associated with atrophy in the brain and an increased Alzheimer’s risk. A randomized controlled trial showed that supplementation of these three vitamins in subjects with mild cognitive impairment for two years significantly reduced homocysteine levels, with a 29.6% lower rate of brain atrophy compared to the placebo group.¹⁹

Polyphenols

Separate from vitamins and minerals, phytonutrients are a nutrient component of plant foods that are the focus of exciting and groundbreaking research over the past few years. With high antioxidant and anti-inflammatory capacity, they play many roles in human health.  Polyphenols are especially powerful at reducing the risk of neurodegenerative disease. Highlighted among them are some forms called anthocyanins, flavonols, catechins, lutein and zeaxanthin which we’ll cover in more depth below.^20,21

• Anthocyanins 

Anthocyanins are the richly-colored pigments in foods like grapes, berries, cherries, currants, and wine. The deep red to purple/blue hues in also in plant foods signal anthocyanin content. These potent plant-based nutrients have antioxidant and anti-inflammatory properties. 

A diet high in anthocyanins from fruits and vegetables is linked to lower oxidative damage. Being a highly metabolic organ, the brain uses one fifth of the body’s total supply of oxygen, naturally producing more reactive oxygen species (ROS). ROS will cause oxidative damage to neurons which can progress to neurodegeneration without the protection of antioxidants.²² Research into anthocyanins has shown that grape seed extract, rich in anthocyanins, reduced amyloid beta plaques in an Alzheimer’s mouse model by almost 50%. Further trials are investigating this promising outcome.²³

Flavonols, including kaempferol, myricetin, and quercetin, are found in leafy greens, fruits, berries, nuts, olive oil, and tea. They have antioxidant properties that protect against neurotoxicity and enhance energy in the brain. 

New and groundbreaking research in the past few years is showing how powerful flavonols are at reducing risk of neurodegenerative disease and strengthening our brain power!  Consumption of leafy greens and green tea have been well-studied regarding their reduced risk of AD and cognitive decline.  Both are rich in kaempferol, myricetin, and quercetin. Mouse studies have shown kaempferol and myricetin treatment improved learning and memory with antioxidant activity.²⁴

• Catechins

Catechins are flavonoids that are found primarily in green tea. They also exist in black tea, but due to the fermentation process catechins are at a lower concentration than in green tea. They are potent neuroprotective antioxidants.  

They appear to exert their effects by directly inhibiting inflammatory pathways to protect neurons from injury .²⁵ Drinking tea, especially green tea, regularly may reduce the risk of dementia onset. This effect is increased with increased consumption of tea .^26,27

The compounds lutein and zeaxanthin are carotenoids – pigments that give plant foods a yellowish to reddish hue. They can be found in colorful foods like carrots, tomatoes, red peppers, squash, and leafy greens. 

Well known for their benefits to eye health, lutein and zeaxanthin are also important in cognitive health. In fact, they accumulate in the retina and brain, giving a clue to their critical function in brain health.²⁸ They likely work through anti-inflammatory and antioxidant processes, that ultimately support neuron function.  Lutein has been shown to directly change expression of inflammation-associated genes.²⁹  Their antioxidant activity protects the fatty acids (DHA) in neuronal cell membranes from oxidation. Oxidation of DHA has been shown to occur at higher rates in those with dementia and cognitive decline.³⁰

Curcumin

Another brain-protective phytonutrient, curcumin, is found in turmeric root.  It’s one of the most widely-studied phytonutrients, with strong antioxidant properties.  With turmeric consumed frequently in India, it’s considered a potential explanation for their relatively low rates of Alzheimer’s in the aging population.³¹  As a supplement, it’s needed in large amounts.  Nevertheless, it can be a helpful addition to your brain nourishment routine.  

Another potent antioxidant and anti-inflammatory compound, curcumin helps to protect critical fats in the brain from oxidation.³¹  It’s also thought to bind and destabilize amyloid plaques.³² Curcumin consumption is connected to improved cognitive function as well as mood.³³

Fiber and Probiotics

Fiber is unique among the nutrients detailed here.  It’s a type of carbohydrate in plant foods that is neither digested nor absorbed by our bodies.  Yet, it’s considered an important component of a diet that promotes optimal brain function by reducing inflammation, improving insulin regulation, and modulating the immune system.³⁴ It’s estimated that the typical fiber intake in the United States is around 15 grams per day, compared to the recommended 25-35 grams per day.³⁵  

There is two-way communication between our gut and our brain, called the Gut-Brian Axis. Fiber, specifically prebiotic fiber, is digested by the microbiome - the thousands of non-pathogenic bacteria that live in our digestive tracts. A healthy, diverse microbiome metabolizes fiber into compounds called short-chain fatty acids (SCFAs).  SCFA’s are neuroactive, reducing neurological inflammation and regulating the immune system.  They appear to impair the ability of amyloid beta to form into plaques in AD, and reduce severity of symptoms in PD and MS.³⁶

Nutrient Synergy

While clinical trials for single nutrients often show inconsistent results, it’s important to note that nutrients exert their protective effects when consumed in combination with others (as in a Mediterranean dietary pattern).  Each of these nutrient superstars works best in synergistic relationships with others, and not on their own.  Some important examples include: 

• Fatty Acids (EPA and DHA) and Fat-Soluble Vitamins (Vitamins D and E): Fats are required for these vitamins to be absorbed. In return these vitamins participate in antioxidant pathways that protect fats in the brain from damaging oxidation. 

• Magnesium and Vitamin D: Magnesium is required for proper function of Vitamin D.  It plays a role in converting vitamin D from its inactive, storage form, into its active form.  Without sufficient magnesium, vitamin D won’t be able to function as efficiently.³⁷

• Catechins and Quercetin: As a whole, polyphenols work synergistically to perform their neuroprotective function. An example of this is catechins and quercetin work in synergy to protect against amyloid beta aggregation, as well as reduce neuronal injury.  Given separately they don’t exert the same effects.³⁸

As you can see, each nutrient works as part of the brain-health team. This is why a Mediterranean-type diet, coupled with a multi-nutrient supplement is the best approach to long-term brain health.  

If you decide to add a supplement to your brain health routine, remember to look for synergistic nutrient partners that work best together.  Keep in mind that more isn’t always better!  Diet-achievable dosages are ideal compared to megadoses that can sometimes be dangerous.  And, remember that you can’t outsupplement a nutrient-poor diet.  These nutrients work in partnership within the complex matrix of the foods that contain them.  Lastly, choose the forms of each nutrient that are most bioavailable to your body and brain

If you are looking for a comprehensive brain health supplement or vitamin that includes most of the nutrients in the above list, then consider RELEVATE. RELEVATE is a science-based nutritional supplement that supports brain health, memory, cognition and focus – now and for years to come.  RELEVATE fills the gaps between what most people eat and evidence-backed diets that are healthiest for your brain.  With 17 critical nutrients from 8 brain beneficial food groups (most of which are the top nutrients included in this list), RELEVATE is the only nutritional supplement specifically designed upon the scientific data of long-term brain health associated with Mediterranean and MIND diets.    

---

References

1. Agarwal, P. et al. MIND Diet Associated with Reduced Incidence and Delayed Progression of Parkinsonism in Old Age. J. Nutr. Heal. Aging 22, 1211–1215 (2018).
2. Devore, E. E., Kang, J. H., Breteler, M. M. B. & Grodstein, F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann. Neurol. 72, 135–143 (2012).
3. Morris, M. C. et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimer’s Dement. 11, 1007–1014 (2015).
4. Morris, M. C. et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimer’s Dement. 11, 1007–1014 (2015).
5. Sugasini, D., Yalagala, P. C. R., Goggin, A., Tai, L. M. & Subbaiah, P. V. Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol. J. Nutr. Biochem. 74, (2019).
6. Hachem, M. et al. Brain targeting with docosahexaenoic acid as a prospective therapy for neurodegenerative diseases and its passage across blood brain barrier. Biochimie 170, 203–211 (2020).
7. Wood, A. H. R., Chappell, H. F. & Zulyniak, M. A. Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer’s disease. Eur. J. Nutr. 1–16 (2021) doi:10.1007/S00394-021-02655-4/TABLES/2.
8. Gold, J., Shoaib, A., Gorthy, G. & Grossberg, G. T. The role of vitamin D in cognitive disorders in older adults. Eur. Neurol. Rev. 14, 41–46 (2018).
9. Tripkovic, L. et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am. J. Clin. Nutr. 95, 1357–1364 (2012).
10. Banerjee, A. et al. Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics. Int. J. Alzheimers. Dis. 2015, (2015).
11. Fiala, M. & Mizwicki, M. T. Neuroprotective and immune effects of active forms of vitamin D3 and docosahexaenoic acid in Alzheimer disease patients. Funct. Foods Heal. Dis. 1, 545–554 (2011).
12. Koduah, P., Paul, F. & Dörr, J. M. Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases. EPMA J. 8, 313 (2017).
13. Rosanoff, A., Weaver, C. M. & Rude, R. K. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr. Rev. 70, 153–164 (2012).
14. Kirkland, A. E., Sarlo, G. L. & Holton, K. F. The Role of Magnesium in Neurological Disorders. Nutrients 10, (2018).
15. Xu, Z. P. et al. Magnesium Protects Cognitive Functions and Synaptic Plasticity in Streptozotocin-Induced Sporadic Alzheimer’s Model. PLoS One 9, e108645 (2014).
16. Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C. & Wilson, R. S. Vitamin E and Cognitive Decline in Older Persons. Arch. Neurol. 59, 1125–1132 (2002).
17. La Fata, G., Weber, P. & Mohajeri, M. H. Effects of Vitamin E on Cognitive Performance during Ageing and in Alzheimer’s Disease. Nutrients 6, 5453 (2014).
18. Morris, M. C. et al. Brain Tocopherols Related to Alzheimer Disease Neuropathology in Humans. Alzheimers. Dement. 11, 32 (2015).
19. Smith, A. D. et al. Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS One 5, e12244 (2010).
20. Han, X., Shen, T. & Lou, H. Dietary Polyphenols and Their Biological Significance. Int. J. Mol. Sci 8, 950–988 (2007).
21. Pohl, F. & Lin, P. K. T. The Potential Use of Plant Natural Products and Plant Extracts with Antioxidant Properties for the Prevention/Treatment of Neurodegenerative Diseases: In Vitro, In Vivo and Clinical Trials. Molecules 23, (2018).
22. Speer, H., D’Cunha, N. M., Alexopoulos, N. I., McKune, A. J. & Naumovski, N. Anthocyanins and Human Health—A Focus on Oxidative Stress, Inflammation and Disease. Antioxidants 2020, Vol. 9, Page 366 9, 366 (2020).
23. Wang, Y. J. et al. Consumption of grape seed extract prevents amyloid-β deposition and attenuates inflammation in brain of an alzheimer’s disease mouse. Neurotox. Res. 15, 3–14 (2009).
24. Holland, T. M. et al. Dietary flavonols and risk of Alzheimer dementia. Neurology 94, e1749 (2020).
25. Spencer, J. P. E. Flavonoids and brain health: Multiple effects underpinned by common mechanisms. Genes Nutr. 4, 243–250 (2009).
26. Tomata, Y. et al. Green Tea Consumption and the Risk of Incident Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. Am. J. Geriatr. Psychiatry 24, 881–889 (2016).
27. Liu, X. et al. Association between tea consumption and risk of cognitive disorders: A dose-response meta-analysis of observational studies. Oncotarget 8, 43306–43321 (2017).
28. Vishwanathan, R., Neuringer, M., Max Snodderly, D., Schalch, W. & Johnson, E. J. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr. Neurosci. 16, 21–29 (2013).
29. Johnson, E. J. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr. Rev. 72, 605–612 (2014).
30. Mohn, E. S. & Johnson, E. J. Lutein and Cognition Across the Lifespan. Nutr. Today 52, 183–189 (2017).
31. Gómez-Pinilla, F. Brain foods: the effects of nutrients on brain function. Nat. Rev. Neurosci. 9, 568 (2008).
32. Reddy, P. H. et al. Protective Effects of Indian Spice Curcumin Against Amyloid Beta in Alzheimer’s Disease. J. Alzheimers. Dis. 61, 843 (2018).
33. Gomez-Pinilla, F. & Nguyen, T. T. J. Natural mood foods: The actions of polyphenols against psychiatric and cognitive disorders. Nutr. Neurosci. 15, 127 (2012).
34. Westfall, S. et al. Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis. Cell. Mol. Life Sci. 74, 3769–3787 (2017).
35. Shi, H. et al. A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites. doi:10.1186/s40168-021-01172-0.
36. Silva, Y. P., Bernardi, A. & Frozza, R. L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. (Lausanne). 11, 25 (2020).
37. Uwitonze, A. M. & Razzaque, M. S. Role of magnesium in vitamin d activation and function. J. Am. Osteopath. Assoc. 118, 181–189 (2018).
38. Renaud, J. & Martinoli, M. G. Considerations for the Use of Polyphenols as Therapies in Neurodegenerative Diseases. Int. J. Mol. Sci. 20, (2019).