Neurohacking, also sometimes called brain hacking, is the attempt by healthy individuals to optimize brain function and enhance cognitive performance. Neurohacking may be undertaken with different goals in mind, but is often employed in pursuit of enhanced analytical ability, improved career or academic performance and achievement, or elevated creative expression.¹

Neurohacking may have some preventive value and many individuals are drawn to neurohacking as a means of building brain wellness and staving off age-related diminishment of brain function.² However, it is not a treatment strategy for cognitive decline, cognitive impairment, or dementia.

Neurohackers may attempt to improve several aspects of brain or cognitive function, such as:

• Enhancing brain metabolic function, mental processing speed, memory recall, decision-making, critical thinking, and mood;
• Increasing focus, stamina, and energy; and/or
• Reducing mental stress and brain fog.

Two important concepts frequently discussed in the context of brain hacking are neuroplasticity and cognitive reserve (or resilience).

• Neuroplasticity is the ability to fine-tune neural connections by strengthening or forming new connections and pruning or eliminating connections that are not used. This process facilitates efficient learning and adaptation to varying circumstances.³



Neurohacking

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• Cognitive reserve is a term used to describe the brain’s ability to transmit messages via alternative pathways across neuronal networks. A robust system of redundant or interchangeable neuronal networks acts as a resource that can be tapped to increase the speed of brain function or provide alternative pathways to maintain or recover cognitive function when pathways fail. A lifetime of varied experiences within complex environments is believed to expand cognitive reserve, increasing the number of options available for responding and functioning in the face of challenges such as stress or neuronal damage.^3,4

Individuals’ neurohacking goals may depend partly on age; for instance, older individuals are often concerned about neuroprotection and preserving healthy brain function, while younger individuals typically focus more on improving mental performance and stamina with nootropics (brain-boosting substances) and other brain hacking techniques.

A comprehensive approach to neurohacking relies on a variety of complementary strategies, including dietary and lifestyle changes and the use of nootropic drugs and supplements, brain-training activities and games, and neurotechnologies (eg, electrical stimulation devices) designed to increase brain fitness.²

This Protocol focuses on “Nutritional Neurohacking,” which refers to the use of nutritional supplements and dietary approaches that may help optimize brain health and function.

To better understand the research presented in this section, it helps to first understand common methods investigators use to assess the nootropic potential of any given intervention. Researchers use a variety of cognitive assessment tools in nootropic research. These may include tests of overall cognition, like the mini-mental state examination (MMSE), especially when screening for cognitive impairment or dementia. More specific tests, often administered together as a “battery,” provide detailed information about cognitive function and are generally more helpful for assessing cognitive performance in healthy subjects. Cognitive test batteries are generally designed to evaluate several specific cognitive domains, including⁵:

• Memory
  • Working memory, in particular, is frequently included in assessments of healthy cognitive function and involves temporarily retaining and manipulating a small body of information to successfully execute a complex cognitive task.⁶ Speed and accuracy are also important factors in evaluating cognitive performance.
• Attention
• Abstract reasoning
• Language
• Visuospatial skills—ability to visualize and manipulate three-dimensional objects
• Executive function—ability to complete complex tasks using organizing, planning, flexibility, and working memory skills

The nutrients in this section have been shown to improve one or more aspects of brain or cognitive function in healthy individuals. The nutrients are presented in alphabetical order. Note that because we have focused on research on cognitive function in healthy subjects, some nutrients often associated with brain health (eg, low-dose lithium) may not appear in this list. This is because the research supporting these nutrients generally involved people with underlying neuropsychiatric or neurological disorders rather than healthy people.

Importantly, “Nutritional Neurohacking” should be regarded as a holistic approach that emphasizes healthy eating and overall nutrition in conjunction with targeted nutrient supplementation. For instance, a randomized placebo-controlled trial published in November 2022 found that 12 weeks of supplementation with members of the vitamin B family, Bacopa monnieri, and Ginkgo biloba improved attentional performance and some aspects of mood in participants who habitually consumed a healthy diet but not in those who did not consume a healthy diet.⁷

Acetyl-L-Carnitine

The amino acid L-carnitine is needed for cellular fat metabolism and mitochondrial energy production. It is made in the body and stored in tissues with high metabolic demand such as skeletal muscles, heart muscle, and the brain. Acetyl-L-carnitine is a form of carnitine that crosses the blood-brain barrier and therefore may modulate nerve activity by enhancing production of nerve growth factors, neurotransmitters, and neurohormones.⁸ In addition, acetyl-L-carnitine may help restore nerve cell membrane integrity and function, enhance mitochondrial function, and protect against neurotoxins.⁹ One randomized placebo-controlled trial that included 96 subjects greater than 70 years old and suffering from fatigue, most of whom also reported poor concentration or impaired memory, found treatment with 2 grams acetyl-L-carnitine twice daily for 180 days not only improved scores on a screening test of overall cognitive status (the MMSE), but also reduced mental and physical fatigue, fatigue after exercise, sleep problems, and muscle pain.¹⁰ A randomized placebo-controlled trial in 90 healthy participants between 22 and 66 years old examined the effects of a combination supplement providing 1,500 mg acetyl-L-carnitine plus 15 mg vinpocetine (a synthetic compound derived from a chemical in periwinkle [Vinca minor]) and 150 mg of huperzine A (a substance extracted from toothed clubmoss [Huperzia serrata]). After 28 days, global memory scores had improved in the supplemented group more than in the placebo group.¹¹

Ashwagandha Extract

Ashwagandha (Withania somnifera) is a plant from India used in traditional Ayurvedic medicine to rejuvenate the body and promote health in all tissues. Ashwagandha is considered an adaptogen, meaning it mitigates the stress response and increases resilience.¹² In a controlled trial in 60 healthy adults with moderate-to-high perceived stress levels, those receiving 225 mg or 400 mg of ashwagandha daily for 30 days performed better on various cognitive tests at the end than at the beginning of the trial, although the improvements were not significantly different from those seen with placebo.¹³ A placebo-controlled trial with 125 healthy participants reporting moderate-to-high perceived stress levels found 300 mg of a sustained-release ashwagandha formulation for 90 days improved memory and focus, reduced cortisol levels, and improved sleep quality and psychological well-being.¹⁴

Bacopa monnieri

Bacopa monnieri is a plant native to India and used in traditional Ayurvedic medicine to enhance memory, reduce anxiety, and regulate blood glucose levels.¹⁵ Clinical trials in healthy adult participants have shown 300 mg of bacopa extract daily for 90 days to 12 weeks improved scores on memory and mood tests, visual processing speed, learning rate, and general cognitive function relative to placebo.^16-18 In a randomized placebo-controlled trial that included 60 medical students, taking 150 mg of a standardized extract of bacopa twice daily for six weeks resulted in improved performance on tests of attention and working memory.¹⁹ A trial that included 60 older participants found those who received bacopa, at doses of 300 or 600 mg per day for 12 weeks, performed better on tests of memory, attention, and cognitive processing compared with those who received placebo, indicating an improvement in working memory.²⁰ Bacopa also inhibited acetylcholinesterase activity, an effect that would modulate availability of the neurotransmitter acetylcholine and has been associated with neuroprotection.²¹ Furthermore, the benefits of bacopa on cognition persisted at a follow-up testing session four weeks after stopping the supplement.²⁰ A randomized placebo-controlled trial in 28 healthy adults over age 55 found those given 320 mg of bacopa extract per day for 12 weeks, accompanied by three hours per week of cognitive training, had slower reaction speed but increased accuracy on cognitive tests compared with those given placebo plus cognitive training.²²

Some evidence suggests bacopa may have immediate, short-term nootropic activity, making it appealing to those interested in brain hacking. In a small crossover trial with 17 healthy participants, improved performance was noted on multitasking cognitive tests given one and two hours after a single dose of 320 mg or 640 mg of a standardized and highly concentrated extract of bacopa compared with placebo. Bacopa also reduced levels of salivary cortisol (the primary stress hormone in the body) and had positive effects on mood in this trial, suggesting bacopa may work in part as an adaptogen—an agent that increases stress resilience.²³ In a similar trial, 24 healthy volunteers had better sustained performance on repetitive cognitive tests shortly after taking one dose of 320 mg bacopa extract compared with 640 mg of bacopa or placebo.²⁴

Blueberry Extract

Blueberries are well known for their high content of polyphenols called anthocyanins. Numerous studies and clinical trials indicate blueberry extract and anthocyanins may enhance cognitive function in healthy individuals. In a systematic review that included 10 controlled trials using blueberry extract in healthy adults and children and five controlled trials in older adults with mild cognitive impairment, the main cognitive effect was found to be memory improvement.²⁵ Another review of 11 trials in older adults with no or mild cognitive impairment found blueberry interventions can improve memory, working memory, executive function, processing speed, and attention, as well as brain blood flow.²⁶ A meta-analysis of six randomized controlled trials found blueberry supplementation significantly improved performance on one working memory test.²⁷

Some clinical evidence shows blueberry supplements have acute benefits on cognitive function. A placebo-controlled crossover trial in 35 healthy middle-aged adults found taking a single 25-gram dose of freeze-dried wild blueberry powder improved performance on tests of cognitive function, particularly those involving more demanding mental tasks.²⁸ In a placebo-controlled trial that included 30 healthy college students, those who received 600 mg of polyphenols from blueberries and grapes performed better on prolonged, demanding mental testing that began 90 minutes after supplementation.²⁹

Carotenoids

Lutein and zeaxanthin are fat-soluble nutrients in the carotenoid family. They are highly concentrated in the macula, a region of the eye’s retina responsible for central vision, where they protect against damage from oxidative stress and short-wavelength blue light.³⁰ They also accumulate more than other carotenoids in brain tissue such that, together, lutein and zeaxanthin represent 66–77% of the brain’s carotenoid content and have an important role in reducing free radicals and mitigating neuroinflammation.³¹ Multiple studies have correlated higher intake and concentrations of these carotenoids with lower risk of Alzheimer disease and better cognitive function in healthy younger and older adults.^30,32 Brain imaging studies in healthy older adults have revealed taking 10 mg lutein plus 2 mg zeaxanthin daily for one year can increase brain activity during learning and resting-state (a measure of neuroplasticity), and brain structure with less decline in the volume of brain gray matter (made up largely of nerve cell bodies) in individuals who responded better to supplementation.^33-37

A meta-analysis of nine randomized controlled trials found, in healthy adults, carotenoid supplementation using lutein, lutein plus zeaxanthin, astaxanthin, or beta-carotene can improve various measures of cognition.³⁸ For example, a randomized placebo-controlled trial in 59 young, healthy adults 18–25 years old compared the effects of 13 mg or 27 mg of combined lutein, zeaxanthin, and a related carotenoid called meso-zeaxanthin to placebo. Researchers found that, after six months, carotenoid supplementation led to decreased levels of an inflammatory cytokine (interleukin-1β), increased brain-derived neurotrophic factor (BDNF) levels and antioxidant capacity, and better performance on tests of memory, attention, and processing speed.³⁹ Similarly, lutein plus zeaxanthin, at doses of 10 mg and 2 mg, respectively, improved tests of memory, reasoning, and complex attention after one year in a placebo-controlled trial with 51 healthy subjects aged 18–30 years.⁴⁰ In a randomized placebo-controlled trial that included 90 participants aged 40–75 years who were healthy but reported problems with memory, attention, or concentration, 10 mg lutein plus 2 mg zeaxanthin once daily for six months improved performance on certain cognitive tests related to learning and memory.³¹ A trial in 91 healthy individuals between 18 and 60 years old with low macular carotenoid concentrations found one year of supplementing with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin enhanced performance on memory tests more than placebo.⁴¹

Creatine

Creatine is an amino acid derivative found in cells throughout the body with potential positive effects on muscle, bone, and brain health.⁴² Creatine has well established benefits on muscle strength and function and is recognized for its ability to enhance exercise performance.⁴³ Although it is synthesized mainly in the liver and kidneys, the brain is also able to make creatine, suggesting its importance to brain cells. Creatine plays an important role in cellular energy (adenosine triphosphate, or ATP) production, particularly when energy demands are high such as during exercise, complex mental exertion, sleep deprivation, and some neurological disorders.^43,44

Dietary creatine comes from seafood and meat, and observational evidence suggests higher dietary creatine intake is associated with better cognitive function in older adults.^45,46 A number of clinical trials have examined the effects of creatine supplementation on cognitive function in healthy adults of various ages and results have been mixed. In general, it appears creatine supplementation may improve some aspects of cognitive function, particularly short-term memory and reasoning, and its effects appear to be more pronounced in stressful conditions such as low oxygen levels, sleep deprivation, or complex and demanding cognitive tasks.^43,47,48 Trials lasting up to seven days typically used doses of 20 grams per day and longer trials (2–24 weeks) used 5 grams per day, but optimal doses for raising brain creatine concentrations and enhancing brain function are not yet known.^43,47

Curcumin

Curcumin is a well-known biologically active flavonoid extracted from turmeric that has anti-inflammatory and oxidative stress-reducing properties. Curcumin has broad positive effects throughout the body, and crosses the blood-brain barrier giving it neuroprotective potential.⁴⁹ A 2021 meta-analysis used data from eight randomized controlled trials with a combined total of 389 participants, including four trials in healthy older participants, two in Alzheimer disease patients, and two in schizophrenia patients. The included trials used various doses of different types of curcumin preparations. The analysis found, in general, that curcumin therapy for at least eight weeks can improve working memory.⁵⁰ Another meta-analysis suggested curcumin may be more useful for improving cognitive function in healthy older individuals than decreasing symptoms in those with Alzheimer disease or schizophrenia.⁵¹

A randomized placebo-controlled trial in 60 healthy older volunteers who received 400 mg of a lipid formulation providing 80 mg curcumin found the formulation improved attention and memory one hour later. In addition, taking the curcumin supplement daily for four weeks improved performance on tests of working memory and mood.⁵² The same dose and form of curcumin, taken daily for 12 weeks, improved working memory and decreased fatigue in a placebo-controlled trial with 80 participants between 50 and 80 years old.⁵³ However, another placebo-controlled trial in 39 healthy men and women between 45 and 74 years of age found no cognitive benefit from a much higher (2,000 mg per day) dose of the same curcumin preparation (providing 400 mg curcumin) after 12 weeks.⁵⁴

In 40 subjects, aged 51–84 years, 90 mg of a different bioavailable form of curcumin twice daily for 18 months improved performance on tests of memory and attention relative to placebo, and was also found to reduce accumulation of abnormal amyloid and tau (proteins implicated in Alzheimer disease) in the brain.⁵⁵ However, a trial that included 96 healthy older participants found 500 mg of another curcumin preparation three times daily was not better than placebo for preserving cognitive function over 12 months.⁵⁶

French Maritime Pine Bark Extract

French maritime pine bark is high in polyphenols with widely studied free radical-scavenging and anti-inflammatory effects. A patented standardized extract of concentrated polyphenols from French maritime pine bark, called Pycnogenol, has been shown to have broad anti-aging effects, and clinical trials indicate it may enhance cognitive function in healthy adults.^57,58 In an eight-week trial, taking 100 mg Pycnogenol per day led to improved performance on tests of attention, memory, executive function, and mood in 53 healthy college students. In addition, cognitive test results were better in the Pycnogenol-treated students than in a group of matched students who took no supplements and served as controls.⁵⁹ In a controlled trial in 59 healthy professionals aged 35–55 years with high oxidative stress levels, those treated with 150 mg Pycnogenol daily for 12 weeks had reduced levels of circulating free radicals and greater improvements in mood, attention, and memory compared with untreated controls.⁶⁰ Another trial examined the effects of 100 mg Pycnogenol daily for 12 months in 44 healthy participants aged 55–70 years with high oxidative stress levels and compared them with similar individuals who received no Pycnogenol; the Pycnogenol-treated participants experienced reductions in oxidative stress levels and improvements in multiple cognitive measures, but the untreated participants did not.⁶¹ Measures of oxidative stress and memory also improved in a trial in 101 healthy older subjects, aged 60–85 years, who took 150 mg Pycnogenol daily for three months compared with a matched control group who received placebo.⁶² Pycnogenol has also demonstrated beneficial effects in patients with mild cognitive impairment.⁶³

Ginkgo biloba

Ginkgo biloba is a widely used medicinal plant known to improve blood flow and lower high blood pressure. Many clinical trials have examined its potential role in supporting healthy brain function, slowing cognitive decline, and improving dementia, but results have been mixed.⁶⁴ A meta-analysis of randomized controlled trials in different types of participants and using various doses of different ginkgo extracts was unable to show treatment with ginkgo had a significant effect on memory, executive function, or attention.⁶⁵ Nevertheless, a review of the clinical research found a specific ginkgo extract was more likely to enhance cognition when used in doses of 240 mg or more per day, for 24 weeks or longer, and in older individuals with mild dementia.⁶⁴

Cognitive benefits have been reported following single doses of ginkgo ranging from 120–360 mg in healthy young subjects in the 2.5–6 hours following treatment.^66,67 While a number of trials have found no benefit from long-term ginkgo use in healthy individuals,^68-72 it is interesting to note that several clinical trials have found supplementing with ginkgo for 2–6 weeks improved cognitive performance in healthy middle-aged women specifically during complex or demanding memory tasks.^73-75 In one trial with 30 healthy participants between 41 and 83 years of age, 120 mg ginkgo twice daily for 28 days increased brain electrical signaling associated with complex processing of visual information in healthy older participants but not younger participants.⁷⁶

Several clinical trials assessed the acute effects of single doses of a combination of ginkgo and ginseng extracts in healthy young adults and reported improved cognitive performance in the six hours following supplementation.^77-79 In one placebo-controlled trial, 256 healthy middle-aged participants who received 320 mg of a ginkgo-plus-ginseng combination daily for 12 weeks experienced improvements in memory that were sustained for two weeks after supplementation ended.⁸⁰

Ginseng

Ginseng plants, including Panax ginseng (Korean or red ginseng) and Panax quinquefolius (American ginseng), are commonly used around the world for their adaptogenic (stress-regulating) effects. Ginsenosides, the main active compounds in various types of ginseng, have demonstrated anti-inflammatory, oxidative stress-reducing, and neuroprotective effects, and a growing body of evidence indicates they may help reduce the risks of cognitive decline and central nervous system diseases.⁸¹

A standardized extract of American ginseng, in single doses of 100, 200, and 400 mg, has been found to improve cognitive performance after 1,3, and 6 hours in placebo-controlled crossover trials in healthy young and middle-aged volunteers.^82,83 For example, in a placebo-controlled trial that included 61 healthy young and middle-aged participants, a single 200 mg dose of a standardized American ginseng extract led to enhanced performance on a test of working memory and attention four and six hours after supplementation; in addition, taking the same 200 mg supplement daily for two weeks reduced mental fatigue, enhanced mood, and further improved cognitive test scores. Furthermore, ginseng appears to modulate the gut microbiome composition, which may contribute to its cognitive effects.⁸⁴

Korean ginseng has also been the subject of clinical trials in healthy individuals. Single 200–400 mg doses of Korean ginseng have been reported to improve cognitive function and mitigate mental fatigue during demanding mental tasks in healthy young individuals.^85-87 A trial in 51 healthy participants found taking 1,000 mg Korean ginseng daily for eight weeks not only improved scores of overall cognitive function, but also increased volume of gray matter (brain tissue composed mainly of nerve cell bodies and other cells) compared with placebo.⁸⁸ Daily treatment with 418 mg of a ginsenoside-enriched preparation of Korean ginseng was found to be more effective than 768 mg per day of a non-enriched Korean ginseng powder or placebo for mitigating the negative effects of stress on cognition after one, five, and 12 days in a crossover trial that included 50 healthy individuals with a high degree of occupational stress.⁸⁹

Gotu Kola

Gotu kola (Centella asiatica) is an Asian medicinal plant that has demonstrated neuroprotective effects through its abilities to reduce inflammation, oxidative stress, and mitochondrial dysfunction, while increasing neuronal connections.^90,91 A standardized extract of gotu kola was found to raise levels of blood choline in a trial in adults in their twenties.⁹² In one placebo-controlled trial that included 28 healthy older participants, 750 mg gotu kola extract daily for two months improved working memory and increased brain electrical activity during cognitive tasks, but neither 250 nor 500 mg daily had these effects.⁹³ A meta-analysis that included five randomized controlled trials found gotu kola increased alertness and reduced anger, which could improve mental function; however, the available research was not sufficient to draw conclusions about its ability to enhance cognition.⁹⁴

Green Oat Extract

Green oat (Avena sativa) has been used historically to treat anxiety and insomnia, and preclinical evidence suggests it can positively impact brain function.⁹⁵ In laboratory research, green oat extract was found to inhibit two enzymes that have a role in mental and cognitive health: monoamine oxidase-B (MAO-B) and phosphodiesterase (PDE).⁹⁶ MAO-B inhibition can result in higher levels of neurotransmitters like dopamine, while PDE inhibition can lead to changes in neurotransmitter signal transmission.^97,98 In a controlled trial in 20 healthy participants, a single 800 mg dose of green oat extract improved performance on tests of working memory, processing speed, and attention relative to placebo, and altered brain electrical signaling.⁹⁹ A trial in healthy middle-aged adults who self-reported feeling their memory had diminished also demonstrated acute cognitive improvement on tests of speed, memory, and executive function within six hours after taking 800 mg, but not 1,600 mg, of green oat extract.¹⁰⁰ Another trial included 132 healthy individuals who received either 430 mg, 860 mg, or 1,290 mg of green oat extract or placebo daily for 29 days. Cognitive testing on the first day of supplementation revealed 1,290 mg of green oat had an acute benefit on working memory and multitasking, and more substantial improvement was measured on day 29 in those taking either 430 or 1,290 mg.⁹⁵ However, in 37 healthy older adults participating in a placebo-controlled crossover trial, 1,500 mg green oat extract per day for 12 weeks was not found to affect scores on tests of cognitive function.¹⁰¹

Lion’s Mane

Lion’s mane (Hericium erinaceus) is a mushroom used as food and in herbal medicine. It is reported to have a broad array of health benefits, including enhancing brain function and alleviating anxiety, depression, and fatigue.¹⁰² In a randomized placebo-controlled trial in 34 healthy individuals over 50 years old, taking four 800 mg capsules of powdered lion’s mane daily for 12 weeks improved scores on the MMSE, a measure of cognitive status, more than placebo.¹⁰³ Other clinical research indicates lion’s mane may be beneficial for improving cognitive function in patients with mild cognitive impairment,¹⁰⁴ and preserving cognitive abilities in those with early-stage Alzheimer disease.¹⁰⁵

L-Theanine & Caffeine

L-theanine is a nonessential amino acid found primarily in green and black tea and possessing mood- and cognitive-enhancing effects and potential utility as a brain hacking nutrient. Meta-analyses of randomized controlled trials suggest supplementing with 200–400 mg L-theanine daily may reduce symptoms of stress and anxiety.¹⁰⁶ These effects may be due in part to its ability to modulate nerve activity by affecting neurotransmitter signaling.¹⁰⁷ Some evidence shows taking L-theanine can modulate brain electrical activity during mental tasks 50 minutes later and in proportion to the dose up to 400 mg.¹⁰⁸

A randomized controlled trial in 30 healthy volunteers found 200 mg L-theanine daily for four weeks led to improved scores on tests of verbal fluency (the ability to come up with words in specified categories) and executive function, and the improvement was more pronounced in those whose baseline scores were lower. In addition, scores on scales measuring symptoms of depression, anxiety, stress, and sleep all improved in those receiving L-theanine.¹⁰⁹ A controlled trial in 50 middle-aged and older adults found 100.6 mg L-theanine for 12 weeks improved attention, resulting in enhanced working memory and executive function.¹¹⁰

Caffeine, which is also found in tea leaves, has been found to improve cognitive performance, especially on long-duration tasks. People interested in brain hacking often employ caffeine as part of their regimen. It is thought L-theanine plus caffeine could synergistically enhance brain function through their complementary actions: caffeine has mainly been shown to increase cognitive stamina and self-reported alertness, arousal, and vigor, while L-theanine has been shown to improve self-reported relaxation, tension, and calmness.¹¹¹ A meta-analysis of data from six controlled trials found single doses of various amounts of L-theanine plus caffeine increased alertness and improved performance on some tests of attention.¹¹² For example, a placebo-controlled trial in 44 healthy subjects, aged 18–34 years, found 97 mg L-theanine plus 40 mg caffeine increased focused attention during a demanding cognitive task, while increasing self-reported alertness and decreasing tiredness.¹¹³ Another trial found 50 mg caffeine plus 100 mg L-theanine improved memory, focus, speed, and accuracy within 90 minutes in 27 healthy young participants.¹¹⁴ However, a placebo-controlled crossover trial that included 24 healthy young adults found the addition of 50 mg L-theanine appeared to reverse the short-term positive effects of 75 mg caffeine on brain blood flow and cognitive performance at 30 minutes post-dose.¹¹⁵

Magnesium

Magnesium participates in numerous cellular activities including energy production and synthesis of proteins and DNA. By participating in and facilitating the transport of other ions across the cell membrane, magnesium also helps regulate muscle cell contraction and nerve cell excitability, protecting nerve cells from over-excitation that can lead to nerve cell death.^116-118 Aging is associated with decreased total body magnesium, although blood magnesium levels tend to remain normal.¹¹⁶ It has been suggested that lower magnesium concentrations contribute to chronic inflammation and oxidative stress, and are a factor in many age-related health problems.^116,119

Clinical evidence indicates magnesium may be helpful in preventing or treating neurological disorders such as anxiety, depression, migraine, chronic pain, and stroke.^117,118 An observational study with 2,508 participants aged 60 years and older found higher dietary magnesium intake was correlated with higher composite scores on tests of cognitive function.¹²⁰ Findings from other observational studies that monitored healthy older adults have found higher magnesium intake was linked to lower odds of developing mild cognitive impairment and dementia.^121,122

Magnesium L-threonate in particular has been shown to cross the blood-brain barrier more readily than other forms of magnesium, and preclinical research suggests it is neuroprotective, reduces neuroinflammation, inhibits beta-amyloid deposition in brain tissue, enhances brain function, and slows cognitive decline.^116,123-125 One randomized placebo-controlled trial that included 44 subjects, aged 50 to 70 years, with memory and concentration complaints, anxiety, and sleep problems found 12 weeks of magnesium L-threonate supplementation, at a dose of 1.5–2 grams per day depending on body weight, significantly improved overall cognitive performance relative to both baseline and placebo.¹²⁶

Mango Leaf Extract

Mango leaf and its active constituent mangiferin have been studied for their effects on brain function and memory. Mangiferin has been shown to enhance electrical signaling in the brain and exert neuroprotective effects by reducing inflammation and oxidative stress, supporting mitochondrial function, modulating neurotransmitter activity, and preserving BDNF.^127,128 Findings from animal research suggest mangiferin may protect the brain against the negative impacts of sleep deprivation, aging, and toxins.¹²⁸ In a randomized, placebo-controlled, crossover trial that included 70 healthy participants between 18 and 45 years old, overall cognitive function improved at 30 minutes, three hours, and five hours after taking a single 300 mg dose of a standardized mango leaf extract. Participants demonstrated better memory, attention, and ability to perform complex tasks when supplemented with the mango leaf extract versus placebo.¹²⁹

Medium Chain Triglycerides

While most commonly eaten fats are composed of long-chain fatty acids, medium chain triglycerides (MCTs) are composed of medium-chain fatty acids like caprylic and capric acids extracted from coconut or palm oils. MCTs can be metabolized directly into energy or converted into ketone bodies that provide energy for brain cells. Eating foods fortified with MCTs has been found to improve cognitive function in frail and cognitively impaired elderly individuals.^130,131 A four-week controlled trial that included 30 healthy young adults found those given a drink providing 12 or 18 grams per day of MCTs performed better on tests assessing executive function and attention after 2–3 weeks compared with those given a placebo drink.¹³² In a controlled trial, 32 healthy elderly subjects added MCTs to their diet, beginning with 6 grams per day and increasing over a three-week period to a daily amount of 18 grams per day, while 31 similar participants took no MCTs. After three months, the MCT-supplemented participants had improved walking balance, possibly indicating enhanced brain-muscle communication.¹³³

MCTs may also have an immediate positive impact on brain function. A controlled crossover trial found 20 healthy elderly volunteers performed better on a cognitive test of attention after eating a single MCT-enriched meal providing 19.9 grams of MCTs than after a meal rich in long-chain triglycerides.¹³⁴ A similar trial in 19 cognitively healthy individuals over 60 years old found attention, executive function, and global cognitive function scores were higher after a meal containing 20 grams of MCTs compared with a meal without MCTs.¹³⁵

Multivitamin/mineral Supplements

Multivitamin/mineral supplements have been reported to improve mental health, perceived stress level, physical stamina, and energy level, as well as some aspects of cognitive function, in adults with inadequate nutritional status or subclinical neurological or psychological symptoms.¹³⁶ Clinical research has shown a high-dose B-vitamin supplement can lower oxidative stress and inflammation, support myelination, and may improve mood by reducing levels of homocysteine, an amino acid linked to cognitive impairment.^137-140

In a large randomized controlled trial, 2,262 older individuals with an average age of 73 years were given a commercial multivitamin/mineral supplement, 500 mg cocoa flavanols, or placebo to take daily for three years. They also underwent annual cognitive assessments through telephone interviews. At the end of the trial, the multivitamin/mineral group showed improvements in memory, executive function, and global cognition relative to placebo, and the effect was more pronounced in those with cardiovascular disease.¹⁴¹

In a randomized trial that compared changes in cognitive function in 60 healthy subjects under 60 years old given either a multivitamin/mineral supplement, vitamin D, or vitamin C for eight weeks, those receiving the multivitamin/mineral had greater improvements on tests of working memory, learning, motor planning, and visual strategizing.¹⁴² In a randomized placebo-controlled trial in 108 healthy adults, aged 30–70 years, taking a multivitamin providing high doses of B vitamins for six months increased functional connectivity between key regions of the brain thought to be involved in cognitive functions related to reward and emotional processing; although no cognitive tests were administered.¹⁴³

Despite some potential positive effects of multivitamins on brain health, several trials have not noted any cognitive benefits from multivitamin/mineral supplementation in healthy women.^144,145 A trial in 97 healthy women under 50 years of age compared the effects of two doses of multivitamins to placebo. After eight weeks, those receiving multivitamins had increased energy use during cognitive testing; however, there were no differences in cognitive performance between the supplemented and placebo groups.¹⁴⁶

Omega-3 Fatty Acids

The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are concentrated in the brain where they help maintain nerve cell membrane fluidity and function and reduce neuroinflammation and brain oxidative stress.¹⁴⁷ DHA is the most abundant fatty acid in the brain, and is involved in nerve growth, function, and plasticity, making it particularly interesting in the context of nutritional brain hacking.¹⁴⁸ Among other things, DHA appears to facilitate the vital actions of B vitamins (B12 and folic acid or folate) on overall cognition and promote synthesis of the brain phospholipid phosphatidylserine.^149,150 Observational research suggests high fish, EPA, and especially DHA intake can slow brain aging and support healthy cognitive function.^151,152 Recent evidence suggests DHA bound to phosphatidylcholine is more efficiently incorporated into the brain and has stronger anti-inflammatory and antioxidant effects than other forms of DHA.^147,153

The association between levels of omega-3 fatty acid and cognitive function was assessed in a clinical trial including 2,183 dementia-free patients from the Framingham Heart Study. A higher omega-3 index, defined as the concentration of DHA and EPA in red blood cells, was associated with increased hippocampal volumes and better abstract reasoning. These observations were maintained for EPA and DHA individually. In a subset analysis examining non-carriers of the APOE-e4 genotype, a genetic marker indicating increased susceptibility to Alzheimer disease, higher DHA concentrations or omega-3 index scores were associated with larger hippocampal volumes. Conversely, in APOE-e4 carriers, higher EPA concentrations were associated with better abstract reasoning and a higher omega-3 index was related to lower white matter hyperintensity burden, which possibly corresponds with a lower risk of some cerebrovascular problems.¹⁵⁴

Although findings from clinical trials have reported mixed results, a meta-analysis of data from 15 randomized controlled trials found DHA supplementation, with or without EPA, improved cognitive performance, especially in individuals with mild memory complaints. EPA/DHA combination doses greater than 1 gram and DHA doses greater than 580 mg per day were needed for these benefits to be significant.¹⁵⁵ For example, in a placebo-controlled trial in 176 healthy adults between 18 and 45 years old whose dietary intake of DHA was low, supplementing with 1.16 grams of DHA per day for six months was found to improve performance on tests of reaction time and memory¹⁵⁶; however, in a trial in healthy participants aged 18–35 years, lower doses of 450 mg DHA plus 90 mg EPA or 200 mg DHA plus 300 mg EPA, taken for 12 weeks, did not improve cognitive performance or mood parameters.¹⁵⁷ Furthermore, two randomized placebo-controlled trials performed after the meta-analysis found no effect of DHA plus EPA supplementation on cognitive function in healthy adults or older adults with self-reported memory problems despite adequate dosing and trial duration.^158,159

One controlled trial that included 285 subjects at high risk of cognitive impairment due to coronary artery disease examined the possible benefits of very high doses of EPA and DHA; after 12 months of supplementing with 1,860 mg EPA plus 1,500 mg DHA, improvements in verbal fluency, language, memory, and visual-motor coordination were found, and these improvements persisted until the end of the trial at 30 months.¹⁶⁰

Interestingly, not all clinical trials have shown superiority of DHA over EPA as a nootropic. In a randomized placebo-controlled trial in 310 healthy adults under 50 years of age, those given a supplement providing 900 mg EPA plus 360 mg DHA per day for 26 weeks had greater improvements on all but one test of speed and accuracy of memory than those given 900 DHA plus 270 mg EPA or placebo.¹⁶¹

Phospholipids

Phospholipids, including phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine, are nutrients made up of two fatty acids (which are repelled by water) linked by a phosphate group (which is water-soluble). They are important components of all cell membranes and are produced in the body or obtained in the diet. Phospholipids are especially abundant in the brain, where they help stabilize nerve cell membranes and myelin sheaths, regulate neuronal responsiveness to signaling factors including neurotransmitters, and support neuroplasticity.^162,163 Phospholipid supplements have been found to improve cognitive performance in healthy infants fed standard formula (but not breast milk), reduce stress-induced cognitive deficits in healthy adults, and improve mental functioning in older adults with cognitive impairments.¹⁶³ In one trial, 54 healthy male subjects experiencing highly stressful conditions were given either 2.7 grams of milk-derived phospholipids per day or placebo for six weeks; those given phospholipids had shorter reaction times on an attention-switching test administered after an experimental stressor.¹⁶⁴ In another placebo-controlled trial that included 75 chronically stressed men, taking a 1% phospholipid-rich milk beverage daily for 42 days blunted the negative impact of stress on cognitive function.¹⁶⁵

Choline is an essential nutrient with many functions, including acting as a methyl donor for many biochemical reactions and serving as a precursor for phosphatidylcholine and acetylcholine synthesis. Evidence suggests most individuals do not meet adequate daily intake levels.¹⁶⁶ Several forms of choline have been studied in the context of brain structure or function:

• Phosphatidylcholine is the main source of dietary choline and is found in foods such as egg yolks, milk products, soy foods, and peanuts.¹⁶⁷ An observational study that followed 2,492 men for nearly 22 years found those with the highest phosphatidylcholine intake had a 28% lower risk of dementia compared to those with the lowest intake. In addition, a subset of participants who underwent cognitive testing found higher phosphatidylcholine intake was correlated with better cognitive performance.¹⁶⁸
• Citicoline (cytidine diphosphocholine, or CDP-choline) is used in supplements as a source of choline. Clinical evidence suggests citicoline may be a more effective supplement for delivering choline than phosphatidylcholine. Moreover, choline in citicoline may be less prone to conversion to trimethylamine N-oxide (TMAO), a compound produced by gut bacteria that is linked to atherosclerosis.¹⁶⁹ A placebo-controlled trial that included 100 healthy men and women, 50–85 years old, with age-related memory decline found 500 mg citicoline daily for 12 weeks improved performance on memory tests.¹⁷⁰ Another trial included 40 healthy volunteers and found 500 mg citicoline per day for two weeks reduced levels of a marker of oxidative stress and improved scores on tests of reaction time and memory better than placebo.¹⁷¹ In a placebo-controlled trial in 75 healthy male adolescents, 28 days of supplementing with 250 mg or 500 mg of citicoline daily led to increased attention and reaction speed and decreased impulsivity.¹⁷²
• Alpha-glycerylphosphorylcholine (α-GCP) is another source of choline and therefore a possible precursor of phosphatidylcholine and acetylcholine. Research suggests α-GCP has anti-aging effects in the brain that reduce brain oxidative stress and loss of neurons and brain immune cells.¹⁷³ In older subjects with mild cognitive impairment, 400 mg α-GCP twice daily for 2–3 months was found to modulate patterns of brain electrical signaling in ways associated with improved cognitive function.^174,175 Clinical trials have also indicated α-GCP may be beneficial in patients with dementia disorders as well as after cerebrovascular events like transient ischemic attack (TIA) and stroke.¹⁷⁶
• Dimethylaminoethanol (DMAE), a choline precursor reported to optimize brain production of acetylcholine, has demonstrated free radical-scavenging effects.¹⁷⁷ A placebo-controlled trial in 80 subjects with emotional disturbance found a multi-nutrient supplement containing DMAE improved mood and altered brain electrical activity in a way that indicated increased attention.¹⁷⁸

Phosphatidylserine can be synthesized from phosphatidylcholine or phosphatidylethanolamine, but is more readily produced from phosphatidylcholine and phosphatidylethanolamine that are high in the omega-3 fatty acid DHA.^149,179 Phosphatidylserine supports cognitive functions such as short- and long-term memory, learning, attention, problem-solving, language, and communication, as well as neuromuscular activities such as rapid motor responses and reflexes. The brain’s phosphatidylserine content appears to diminish with aging,¹⁷⁹ and several clinical trials in older adults with self-reported memory concerns have found phosphatidylserine supplementation, at 300 mg per day, can improve memory and other aspects of cognitive function.^180-183 In addition, a placebo-controlled crossover trial in 18 healthy male college students found 400 mg phosphatidylserine per day for 14 days improved speed and accuracy on a cognitive test known as serial sevens, in which the test subject is asked to count backwards by sevens starting at 100.¹⁸⁴

Pyrroloquinoline quinone (PQQ)

Pyrroloquinoline quinone (PQQ) is an essential nutrient and potent antioxidant that contributes to a variety of cellular functions, such as mitochondrial biogenesis and gene expression.³⁴² Preclinical studies suggest PQQ exhibits neuroprotective properties and has been found to support neuronal growth, decrease reactive oxygen species (ROS) production, and inhibit glutamate-induced apoptosis.^343-345 Clinical evidence suggests PQQ can help improve cognitive function in healthy individuals. In a study of 41 healthy subjects given 20 mg PQQ or placebo once daily for 12 weeks, those given PQQ had significantly improved scores on cognitive tests of attention and memory, as well as improved blood flow to the prefrontal cortex, compared with placebo.³⁴⁶ A controlled trial randomized 64 healthy subjects aged 40-80 years to receive 21.5 mg PQQ or placebo daily and found that those given PQQ displayed significantly improved memory, reaction time, attention, and executive function compared with placebo.³⁴⁷ A separate study found that adults aged 20-40 years given 20 mg PQQ daily for 12 weeks had a significant improvement in processing speed and executive speed after eight weeks compared with placebo.³⁴⁸

Rhodiola rosea

Rhodiola rosea is a plant that grows mainly in the arctic and has well documented adaptogenic effects. Rhodiola has been used historically to increase physical endurance, work productivity, longevity, resistance to high-altitude sickness, and to treat fatigue, depression, anemia, impotence, gastrointestinal ailments, infections, and nervous system disorders.¹⁸⁵ Multiple preclinical studies indicate rhodiola may improve learning and memory through effects such as increasing brain metabolism, inhibiting apoptosis and breakdown of acetylcholine, and reducing inflammation and oxidative stress.¹⁸⁶ In a placebo-controlled trial in 112 healthy young adult volunteers, those who received 500 mg rhodiola per day for 10 days had small-to-moderate gains in performance on cognitive tests involving memory; those who received 60 mg ginkgo per day had similar improvements; and those who received 500 mg rhodiola plus 60 mg ginkgo per day had more substantial improvement in cognitive performance than those who received herbal treatment alone or placebo.¹⁸⁷ In an open-label controlled trial in 80 cognitively healthy, mildly anxious subjects, those who received 200 mg rhodiola twice daily reported less anxiety, anger, stress, confusion, and depression than participants who did not receive treatment. However, they did not report any improvement in cognitive performance compared with those who received no treatment.¹⁸⁸

Rosemary, Spearmint, & Peppermint

Rosemary (Rosmarinus officinalis), spearmint (Mentha spicata) and peppermint (Mentha piperita) have been studied for their effects on brain function. It is thought that rosmarinic acid, an aromatic phenolic compound found in these and other mint-family plants, may contribute to neuroprotection through its ability to cross the blood-brain barrier and exert anti-inflammatory and free radical-scavenging effects.¹⁸⁹ In addition, preclinical research indicates rosmarinic acid and essential oils from rosemary, spearmint, and peppermint interact with neurotransmitter receptors and may inhibit the activity of acetylcholinesterase, an enzyme that breaks down acetylcholine.^190,191

Rosemary. In a controlled trial in 80 healthy adults, ingesting 250 mL of rosemary-infused water led to improvements in cognition and increased oxygen uptake by the brain compared with ingesting the same amount of plain water.¹⁹² A placebo-controlled crossover trial in 28 older adults found a test assessing speed of memory improved during six hours after a single 750 mg dose of powdered rosemary leaf, an amount thought to reflect feasible culinary intake, but worsened in the hours following a 6,000 mg dose.¹⁹³

Ongoing use of rosemary has also been studied for its effects on cognition. In a randomized placebo-controlled trial with 44 healthy adults, taking an alcoholic extract containing rosemary, sage, and lemon balm for two weeks was found to improve a measure of short-term memory in a subgroup of participants under 63 years old, but not in the older participants.¹⁹⁴ In a randomized placebo-controlled trial in 78 healthy university students, 500 mg of rosemary twice daily for one month was found to improve measures of memory, mood, and sleep.¹⁹⁵ However, in a trial where 40 healthy young subjects with low energy were given either 1,700 mg rosemary combined with 2,000 mg black pepper or placebo one hour prior to undergoing cognitive testing, the herbal combination was not found to impact alertness or cognitive performance. Interestingly, the participants wore nose clips to eliminate possible aromatic effects from the rosemary.¹⁹⁶

Aromatherapy is another possible way to achieve the brain benefits of rosemary and other aromatic herbs. A controlled trial in 144 healthy volunteers reported rosemary essential oil, diffused into the atmosphere, improved memory and alertness.^197,198 In one trial that included 20 healthy volunteers, performing cognitive tests in an environment with diffused rosemary aroma led to greater speed and accuracy.¹⁹⁹

Spearmint. A spearmint extract high in rosmarinic acid has been the subject of several clinical trials investigating its potential nootropic effects. In a placebo-controlled trial in 142 young healthy participants, those who received 900 mg of a spearmint extract standardized to contain 14.5% rosmarinic acid and 24% total phenolic compounds daily for 90 days had greater improvement in scores on cognitive tests measuring aspects of attention than those who received placebo.²⁰⁰ Reactive agility, the ability to react to a stimulus quickly and efficiently, was also enhanced after supplementing with the same dose of the same high-rosmarinic acid spearmint extract, but not after placebo.²⁰¹ In a placebo-controlled trial with 60 older participants with age-related memory impairment, the same treatment was also found to improve some tests of working memory as well as self-reported ability to fall asleep.²⁰²

Peppermint. In a placebo-controlled trial with 24 healthy young participants, within three hours after a single 100 microliter dose of encapsulated peppermint essential oil, performance on a demanding cognitive task was improved and mental fatigue after prolonged cognitive exertion was decreased.¹⁹⁰ Aromatherapy using peppermint essential oil was found to improve memory and alertness in a controlled trial with 144 healthy participants.¹⁹⁷

Sage Extract

Sage (Salvia officinalis and other species) is a polyphenol-rich plant that has been used historically to improve memory, quicken the senses, enhance brain function, and delay cognitive decline.²⁰³ Active components from sage have demonstrated actions such as decreasing inflammatory signaling, lowering oxidative stress, modulating neurotransmitter levels, reducing amyloid-induced neurotoxicity, and increasing BDNF release.^203-205 Several clinical trials in healthy young adults have shown a single dose of sage extract (S. officinalis or S. lavandulaefolia), in varying doses, can have a short-term positive impact on memory and attention as well as mood.²⁰³ In a placebo-controlled crossover trial in 26 healthy athletes, a single 600 mg dose of a sage extract with compounds from both S. officinalis and S. lavandulaefolia, taken two hours prior to fatiguing exercise, was also found to reduce perceived exertion level and improve post-exercise scores on tests of memory.²⁰⁶ A placebo-controlled crossover trial in adults over 65 years old compared the immediate short-term effects of single doses (167 mg, 333 mg, 666 mg, or 1,332 mg) of a standardized sage extract on cognitive performance at 1, 2.5, 4, and 6 hours post-dose. The trial found 333 mg resulted in the greatest improvement on memory performance, and improved scores on tests of attention, in this older demographic.²⁰⁷ Longer-term use of sage may also have cognitive benefits. In a randomized placebo-controlled trial with 94 healthy participants, those given 600 mg of an extract containing components from the same two sage species had better scores on some memory tests administered two and four hours after treatment compared with those given placebo; after 29 days of daily treatment, the improvement in memory was even more pronounced.²⁰⁸

How Does a Healthy Diet Improve Brain Function?

What you eat and your overall nutrition status has a profound effect on brain structure and function, affecting markers of neuroplasticity and influencing cognition and mood.²⁰⁹ A healthy diet is a central pillar of any brain hacking regimen. Brain-boosting nutrition includes “brain foods” such as fruits and vegetables, legumes, nuts, olive oil, fatty fish, lean meat, and low-fat dairy, all of which have been associated with improved cognition.²¹⁰ Importantly, a brain-healthy diet avoids the reduction in neuroplasticity caused by a high-calorie or high-saturated fat/high-sugar diet, which promote neuroinflammation and oxidative stress, adversely affect the size and function of a critical brain region known as the hippocampus, and are associated with cognitive and mood disorders.^209,211,212

One important way diet affects brain function is by modulating the gut microbiome. Increasing evidence indicates intestinal bacteria are linked to the central nervous system via the gut-brain axis, such that changes in microbiome composition can influence nerve growth and activity.^213,214 Gastrointestinal tract function is orchestrated by neurons of the enteric nervous system—a nervous system that is independent but interconnected with the central nervous system. Through connecting nerves, such as the vagus nerve, bioactive molecules like neurotransmitters and hormones transmit signals between the gut and brain, as well as the immune system.²¹⁵ The gut microbiome plays a critical role in regulating gut-brain communication by producing chemicals that modify hormone and neurotransmitter release, and possibly induce epigenetic changes (changes in DNA structure that impact gene expression) in the central nervous system.^216,217 Dietary compounds like prebiotic fibers, probiotic microorganisms, polyphenols, fatty acids, and other antioxidants and phytochemicals may have nootropic effects in part through their ability to support microbial balance in the gut.²¹³ For example, flavonoids, which are found in plant-based foods and have been linked to decreased neuroinflammation and enhanced cognitive performance, help shape the gut microbiome through prebiotic actions. Furthermore, most flavonoids are transformed into biologically active compounds by intestinal bacteria, highlighting the interrelatedness of gut microbes, nutrition, and brain health.²¹⁸

The section below titled “Foods and Food Components that May Enhance Brain Function” lists several “brain foods” and/or food components that have been shown in studies to improve some aspect of brain or cognitive function. The foods or food components are listed categorically in descending order of confidence that they may positively affect brain or cognitive function. The determination of the degree of confidence in the potential brain health benefits is based on the quantity and quality of the research in which potential benefits have been reported. Specifically, confidence is considered high if supportive evidence derives from multiple randomized controlled trials (RCTs) and observational studies, medium if the evidence derives from conflicting RCTs or compelling observational studies, and low if the evidence derives from observational studies only.

Foods and Food Components that May Enhance Brain Function

Berry and Grape Polyphenols

Food source(s):

• Blueberries
• Grapes
• Strawberries
• Raspberries
• Blackberries

Potential Mechanism(s)^219,220:

• Reducing inflammation and oxidative stress
• Decreasing abnormal protein accumulation
• Increasing levels of neurotrophic factors that promote brain cell growth and connectivity
• Modulating signaling pathways that decrease nerve cell death

Suggested Intake (Brain Benefits):

• 1–2 cups fresh blueberries or mixed berries
• 795 mg berry polyphenols daily

Scientific Evidence:

Study 1

• Study Design: RCT
• Subjects: 38 healthy older adults
• Dose: 24 grams of freeze-dried blueberries (equivalent to one cup of fresh blueberries) versus no blueberries for 90 days
• Results: Increased blood levels of anthocyanins and phenolic by-products correlated with improved cognitive performance²²¹

Study 2

• Study Design: Crossover trial
• Subjects: 40 healthy subjects between 50 and 70 years old
• Dose: Mixed berry juice providing 795 mg per day of polyphenols from blueberries, blackcurrant, elderberry, lingonberries, and strawberries, as well as tomatoes versus placebo drink for five weeks
• Results: Improved performance on a test of working memory (the ability to retain and manipulate a small body of information to execute a complex cognitive task)²²²

Study 3

• Study Design: RCT
• Subjects: 40 healthy adults aged 20–30 years
• Dose: Smoothie containing 75 grams (about 2.6 ounces, or one-half cup) each of blueberries, strawberries, blackberries, and raspberries versus placebo smoothie with the same amounts of glucose, fructose, vitamin C, and water
• Results: Cognitive stamina was maintained over six hours of testing in those given the berry smoothie, but declined as expected due to mental fatigue in those given placebo²²³

Study 4

• Study Design: Systematic reviews of multiple RCTs
• Results: Berry interventions can improve brain blood flow and cognitive function domains including executive function, attention and memory, and processing speed^224,225

Study 5

• Study Design: Long-term observational/correlational study
• Subjects: 16,010 participants aged 70 years and older
• Results: Higher intake of flavonoids, especially from berries, was associated with a delay in cognitive aging of as much as 2.5 years²²⁶

Confidence of Efficacy: High*

 

Citrus Polyphenols

Food source(s):

• Oranges and 100% orange juice

Potential Mechanism(s)^220,227:

• Enhancing brain blood flow
• Reducing neuroinflammation and oxidative stress
• Improving function of the blood-brain barrier—the selectively permeable layer of cells that line the brain’s blood vessels and limits entry of pathogens, toxins, and various other molecules

Suggested Intake (Brain Benefits):

• 500 mL (about 16 ounces) of 100% orange juice
• 70–300 mg citrus flavanones daily

Scientific Evidence:

Study 1

• Study Design: Systematic reviews of multiple RCT
• Results: Flavone-rich 100% orange juice can improve cognitive function in healthy middle-aged and older adults^220,227

Study 2

• Study Design: Observational/Correlational
• Subjects: 2,031 elderly individuals
• Results: Higher citrus intake was correlated with better cognitive performance²²⁸

Study 3

• Study Design: Observational/Correlational
• Subjects: 13,373 elderly participants
• Results: Higher citrus intake was associated with lower risk of dementia²²⁹

Confidence of Efficacy: High*

 

Water

Potential Mechanism(s):

• Preventing deleterious effects of dehydration on brain function^230,231

Suggested Intake (Brain Benefits):

• 1.6–2.5 liters (about 7–8 cups) of water spread over two-hour intervals through the day

Scientific Evidence:

Study 1

• Study Design: Intervention crossover trial
• Subjects: 40 healthy pilots
• Dose: High-fluid diet (80 fluid ounces per day from water, other beverages, and food) versus low-fluid diet (40 fluid ounces per day) for two weeks
• Results: Better flight performance and spatial cognition test scores²³²

Study 2

• Study Design: RCT
• Subjects: 101 healthy individuals
• Dose: 300 mL (about 10 ounces) of water versus no water during four hours of exposure to a temperature of 30°C (86°F)
• Results: No water intake resulted in mild dehydration, poorer memory and attention, decreased energy, and increased feelings of anxiety and depression, whereas drinking water mitigated these negative cognitive effects²³³

Study 3

• Study Design: Intervention crossover trial
• Subjects: 12 healthy college-aged men
• Dose: 500 mL of water before bedtime and on waking versus no water overnight for 12 hours
• Results: Increased alertness and improved performance on a test of visual perception and reaction time; drinking 100 mL of water after 12 hours of water avoidance also led to improved performance on the same cognitive test²³⁴

Study 4

• Study Design: RCT
• Subjects: 92 college students
• Dose: 200 mL (about 7 ounces) of water every two hours (totaling 1.6 liters or almost 7 cups per day) vs 100 mL every two hours or 110 mL every hour
• Results: 200 mL every two hours had the best effects on mood and cognitive performance²³⁵

Study 5

• Study Design: Intervention crossover trial
• Subjects: 75 children 9–11 years old
• Dose: 2.5 liters of water per day for four days versus ordinary (presumably insufficient) water intake or restricted water intake
• Results: Improved performance on certain cognitive tests with greater water intake than with ordinary intake²³⁶

Study 6

• Study Design: Observational/Correlational
• Subjects: 230 adolescents
• Results: Higher hydration status was correlated with better cognitive performance; sugary beverage intake was associated with poorer cognitive function²³¹

Confidence of Efficacy: High*

 

Cocoa Polyphenols

Food source(s):

• Dark chocolate

Potential Mechanism(s)^237-240:

• Increasing brain blood flow and oxygenation, as well as influencing brain electrical signaling after short-term consumption
• Increasing nerve growth factor levels with daily consumption

Suggested Intake (Brain Benefits):

• 35 grams (about 1 ounce) of dark chocolate in a sitting
• 10 grams of chocolate with 99% cocoa content daily

Scientific Evidence:

Study 1

• Study Design: RCT
• Subjects: 98 individuals aged 18–24 years
• Dose: 35 grams (about 1 ounce) of dark chocolate versus 35 grams of low-flavanol white chocolate
• Results: Improved performance on a test of verbal memory (remembering information presented via written or spoken words) and some tests of verbal learning (learning through reading or listening) two hours later²⁴¹

Study 2

• Study Design: RCT
• Subjects: 140 postmenopausal women
• Dose: 10 grams of chocolate with 99% cocoa content daily versus no chocolate for six months
• Results: Slightly improved performance on tests of cognitive flexibility and processing speed²⁴²

Study 3

• Study Design: RCT (Negative)
• Subjects: 100 participants over age 65
• Dose: 50 grams of high-flavanol dark chocolate (providing 410 mg of cocoa flavanols) versus 50 grams of low-flavanol dark chocolate (providing 86 mg of cocoa flavanols) daily for eight weeks
• Results: No differences in cognitive performance²⁴³

Study 4

• Study Design: Systematic reviews of RCTs
• Subjects: Young adults
• Results: Cocoa flavanols can improve neuroplasticity and cognitive function in early adulthood²³⁷

Confidence of Efficacy: Medium*

 

Carotenoids

Food source(s):

• Leafy greens (spinach, kale, et al)
• Carrots
• Avocadoes

Potential Mechanism(s):

• Lutein, in particular, accumulates in the retina of the eye and in the brain where it protects against oxidative damage and supports nerve function^244,245

Suggested Intake (Brain Benefits):

• Estimates of lutein content suggest ¼ cup of cooked kale or ½ cup of cooked spinach may provide a meaningful amount of lutein²⁴⁶

Scientific Evidence:

Study 1

• Study Design: RCT
• Subjects: 84 adults, aged 25–45 years, with overweight or obesity
• Dose: One Hass avocado per day versus no avocado for 12 weeks
• Results: Raised blood lutein levels and improved scores on a cognitive test measuring the ability to control attention; cognitive improvement appeared to be independent of lutein levels and may have been related to other compounds in avocadoes²⁴⁷

Study 2

• Study Design: Two literature reviews and a meta-analysis of multiple RCTs
• Results: Lutein or lutein plus zeaxanthin (a closely related carotenoid) supplementation may help preserve cognitive function and brain health^245,248,249

Study 3

• Study Design: Observational/Correlational
• Subjects: 2,796 participants aged 60 years and older
• Results: Higher dietary intake of lutein plus zeaxanthin was correlated with higher scores on cognitive tests²⁵⁰

Study 4

• Study Design: Observational/Correlational
• Subjects: 6,390 participants aged 50 years and older
• Results: Higher lutein plus zeaxanthin intake was linked to better performance on memory tests²⁴⁴

Study 5

• Study Design: Observational/Correlational
• Subjects: 2,886 community-dwelling adults aged 60 years and older
• Results: Higher intake of avocadoes, despite being lower in lutein than green vegetables, was associated with better cognitive performance²⁵¹

Confidence of Efficacy: Medium for lutein-rich foods*

 

Caffeine

Food source(s):

• Coffee beans
• Tea leaves
• Cocoa beans

Potential Mechanism(s) :

• Stimulating the central nervous system and possibly affecting mood and brain activity by acting synergistically with other compounds from caffeine-containing plants, such as L-theanine, theobromine, and polyphenols^252,253

Suggested Intake (Brain Benefits):

• 1–3 cups of coffee per day

Scientific Evidence:

Study 1

• Study Design: Research review of multiple RCTs
• Results: Despite mixed findings, the evidence overall suggests caffeine enhances short- and long-term memory in adults and elderly individuals and may increase cognitive processing speed²⁵²

Study 2

• Study Design: Two meta-analyses of observational data
• Results: Modest coffee consumption was associated with lower risk of cognitive disorders^254,255
  • Note on Toxicity:
    Increasing the dose suddenly or taking a high dose (>400 mg) of caffeine has been reported to cause hyperstimulation of the nervous system triggering cardiac and other toxic effects, including death, particularly in children and youth using caffeinated energy drinks^256-258

Confidence of Efficacy: Medium*

 

Fish

Food source(s):

• Salmon
• Mackerel
• Herring
• Trout

Potential Mechanism(s):

• Reducing neuroinflammation and brain oxidative stress and supporting neural tissue structure and function¹⁵²

Suggested Intake (Brain Benefits):

• At least 2 fish servings per week
• 2.2 mg of omega-3 fatty acids per day

Scientific Evidence:

Study 1

• Study Design: RCT
• Subjects: 57 elderly participants living in a retirement home and having no or mild dementia
• Dose: MIND diet fortified with fish spread providing 2.2 grams of omega-3 fatty acids daily versus MIND diet alone
• Results: Higher scores on cognitive ability screening test in those given supplemental fish²⁵⁹

Study 2

• Study Design: Observational/Correlational
• Subjects: 84 healthy participants 31–59 years old
• Results: Eating fish at least two times per week was associated with brain structure differences related to lower risk of mild cognitive impairment²⁶⁰

Study 3

• Study Design: Observational/Correlational
• Subjects: 1,127 participants 45–64 years of age
• Results: Higher intake of fish and omega-3 fatty acids, especially DHA, were linked to lower risk of dementia later in life²⁶¹

Study 4

• Study Design: Multiple observational/correlational studies
• Subjects: Individuals of all ages
• Results: Fish consumption has been associated with better brain function in children, adolescents, adults, and older individuals^262-266

Confidence of Efficacy: Medium*

 

Nuts

Food source(s):

• Walnuts
• Other tree nuts
• Peanuts

Potential Mechanism(s):

• Reducing oxidative stress and inflammation, and improving vascular function²⁶⁷

Suggested Intake (Brain Benefits):

• 30–60 grams (about 1–2 ounces) per day

Scientific Evidence:

Study 1

• Study Design: Systematic review of five RCTs
• Results: Adding walnuts to the diet improved aspects of cognitive performance in three out of the five trials²⁶⁸

Study 2

• Study Design: Systematic review of observational data
• Results: Walnut consumption in particular was associated with better cognitive performance in adults of various ages²⁶⁹

Study 3

• Study Design: Two reviews of observational evidence
• Results: Nut consumption was correlated with better cognition, enhanced brain function, and slower cognitive decline with aging^267,270

Confidence of Efficacy: Medium for walnuts*

 

RTC = Randomized controlled trial

*High = supportive evidence from multiple randomized controlled trials (RCTs) and observational studies; Medium = little or conflicting evidence from RCTs, or compelling observational evidence only; Low = little supportive evidence and only from observational studies

The section below titled “Foods and/or Food Components that May Harm Brain Function” lists several foods and/or food components that have been shown in studies to potentially harm some aspect of brain or cognitive function. The foods or food components are listed categorically in descending order of confidence that they may negatively affect brain or cognitive function. The determination of the degree of confidence in the potential brain health detriments is based on the quantity and quality of the research in which potential harms have been reported. Specifically, confidence is considered high if supportive evidence derives from multiple RCTs and observational studies, medium if the evidence derives from conflicting RCTs or compelling observational studies, and low if the evidence derives from observational studies only. Note that in some cases the confidence determination varies based upon quantity consumed or underlying health conditions of the population in question.

Foods and/or Food Components that May Harm Brain Function

Alcohol

Description:

• Wine
• Beer
• Spirits

Potential Mechanism(s):

• Neurotoxic effects²⁷¹

Scientific Evidence:

Study 1

• Study Design: Meta-analysis of multiple controlled trials
• Results: Alcohol has a short-term negative impact on working memory function in healthy adults²⁷²

Study 2

• Study Design: Observational/Correlational
• Subjects: 2,416 adults
• Results: Light-to-moderate alcohol consumption in mid-life was not associated with cognitive function later in life²⁷³

Study 3

• Study Design: Observational/Correlational
• Subjects: 36,678 healthy middle-aged and older adults
• Results: Moderate alcohol consumption was correlated with negative changes in brain structure, with diminished total brain and brain cell (gray matter) volumes, and damage to interconnecting nerve fibers (white matter)²⁷⁴

Study 4

• Study Design: Observational/Correlational
• Subjects: 20,729 participants
• Results: Moderate alcohol use associated with increased iron accumulation in brain tissue; higher concentrations of iron in key brain region (basal ganglia) was associated with poorer cognitive performance²⁷⁵

Study 5

• Study Design: Review of observational data
• Results: Chronic heavy alcohol use (>2 drinks per day, a drink being 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of spirits) was associated with long-term brain damage and increased risk of cognitive impairment and dementia²⁷¹

Study 6

• Study Design: Review of observational data
• Results: Mixed findings on the effects of light (≤1 drink per day) to moderate (>1–2 drinks per day) alcohol consumption, but it is unlikely to be beneficial²⁷⁶

*Confidence of Harmfulness:

• High for heavy consumption
• Low for light-to-moderate consumption

 

Gluten

Description:

• A protein found primarily in wheat and present in smaller amounts in grains such as rye, barley, spelt, and kamut

Potential Mechanism(s)^277,278:

• Gluten-induced nutrient malabsorption in patients with celiac disease, an autoimmune hypersensitivity to gluten
• Neuroinflammation due to leaky gut-related toxemia in celiac disease patients

Scientific Evidence:

Study 1

• Study Design: Uncontrolled intervention trial
• Subjects: 11 patients newly diagnosed with celiac disease
• Results: Adherence to a gluten-free diet improved cognitive performance²⁷⁹

Study 2

• Study Design: Observational/Correlational
• Subjects: 147 patients
• Results: Having a neurological disorder without a known cause was associated with a 57% chance of testing positive for anti-gluten antibodies related to celiac disease, whereas the risk of such antibodies was 5% in those with neurological disorders of known cause and 12% in those without neurological disorders²⁸⁰

Study 3

• Study Design: Observational/Correlational
• Subjects: 1,396 participants with celiac disease or non-celiac gluten sensitivity
• Results: Both celiac disease and non-celiac gluten sensitivity were associated with high rates of self-reported neurological symptoms²⁸¹

Study 4

• Study Design: Research review
• Results: Gluten-free diet improves cognitive symptoms in patients with celiac disease^279,282

Study 5

• Study Design: Observational/Correlational
• Subjects: 13,494 women without celiac disease
• Results: Gluten intake was not related to cognitive capacity²⁸³

*Confidence of Harmfulness:

• High for celiac disease patients
• Low for those without celiac disease or known non-celiac gluten sensitivity

 

Western-style Diet

Description:

• High in fat and sugar

Potential Mechanism(s)^284-287:

• Altering the gut microbiome, triggering neuroinflammation, compromising the integrity of the protective blood-brain barrier, and rapidly impairing brain function
• Contributing to obesity, cardiovascular disease, and type 2 diabetes, all of which are related to loss of cognitive ability

Scientific Evidence:

Study 1

• Study Design: Research review, including RCTs
• Results: Dietary interventions that include lowering sugar and saturated fat intake, particularly Mediterranean diet interventions, have been found to improve cognitive function in some RCTs²⁸⁸

Study 2

• Study Design: Meta-analysis of multiple observational studies
• Results: A Western-style dietary pattern was correlated with altered size and function of the hippocampus, a brain region with an essential role in memory and learning; no individual component of this dietary pattern was linked to differences in brain structure^211,212

Confidence of Harmfulness: Medium*

 

Advanced Glycation End Products (AGEs)

Description:

• AGEs are proteins or fatty acids that have been damaged through spontaneous, non-enzymatic, chemical reactions with glucose. They both exist in food and form in the body.

Potential Mechanism(s)^289-291:

• Disrupting normal cellular function, triggering inflammation, and accelerating aging
• Raising brain oxidative stress levels, impairing mitochondrial function, increasing toxic protein accumulation, and suppressing production of BDNF, a protein that stimulates neuronal growth and connectivity, inhibiting neuroplasticity

Scientific Evidence:

Study 1

• Study Design: RCT (Negative)
• Subjects: 75 elderly participants with type 2 diabetes
• Results: Lowering dietary AGE intake did not enhance the pro-cognitive effects of a blood glucose-lowering diet after six months²⁹²

Study 2

• Study Design: Observational/Correlational
• Subjects: 684 older adults without dementia
• Results: Dietary AGE intake (estimated using diet records) was associated with faster cognitive decline during an average of three years of monitoring²⁹³

Study 3

• Study Design: Observational/Correlational
• Subjects: 4,041 Japanese subjects aged 60 years and older
• Results: Higher AGE levels in skin were associated with lower scores on tests of cognitive performance²⁹⁴

Study 4

• Study Design: Observational/Correlational
• Subjects: 3,389 adults in the Netherlands
• Results: Among 2,890 participants without dementia at the beginning of the study, those with higher skin AGE levels were more likely to develop dementia during a maximum of 18.7 years of monitoring; higher levels of AGE receptors were noted in the 1,021 participants with dementia at the beginning of the study²⁹⁵

Study 5

• Study Design: Observational/Correlational
• Subjects: 764 adults
• Results: Skin AGE levels were correlated with poorer cognitive performance and the relationship was similar in those with and without diabetes²⁹⁶

Confidence of Harmfulness: Low*

 

Glutamate

Description:

• An amino acid and excitatory neurotransmitter

Potential Mechanism(s):

• Excitotoxicity triggering neuroinflammation, oxidative stress, protein aggregation, mitochondrial dysfunction, and nerve cell death^297,298

Scientific Evidence:

Study 1

• Study Design: Two placebo-controlled intervention trials
• Subjects: Veterans with Gulf War Illness
• Dose: A challenge dose of glutamate, in the form of monosodium glutamate (MSG), versus placebo after eating a low-glutamate diet for one month
• Results: Glutamate inconsistently caused return of symptoms, although symptoms, including cognitive impairment, were reduced after the low-glutamate diet^299,300

Study 2

• Study Design: RCT
• Subjects: 159 dementia patients
• Dose: 900 mg glutamate in the form of MSG three times daily versus placebo
• Results: Dementia scores improved in those receiving glutamate³⁰¹

Study 3

• Study Design: Two research reviews
• Results: No compelling evidence for glutamate sensitivity as a cause of cognitive or other symptoms in otherwise healthy individuals^302,303

Confidence of Harmfulness: Low*

 

RCT = Randomized controlled trial

*High = supportive evidence from multiple randomized controlled trials (RCTs) and observational studies; Medium = little or conflicting evidence from RCTs, or compelling observational evidence only; Low = little supportive evidence and only from observational studies

Best Food Preparation Methods to Avoid AGEs

Advanced glycation end products (AGEs) are proteins or fatty acids that have been damaged through spontaneous, non-enzymatic, chemical reactions with glucose. AGEs can form in the body, especially in individuals with high blood glucose levels and those consuming large amounts of fructose, mainly as high fructose corn syrup. High concentrations are also present in processed foods, foods high in animal fat, foods browned using dry heating methods like grilling or baking, and foods cooked in fat such as deep-fried and pan-fried foods.^289,290

AGEs in the body can disrupt normal cellular function, triggering inflammation and oxidative stress, and contributing to an array of chronic conditions including cardiovascular disease, type 2 diabetes, and cancer, as well as psychiatric and neurological disorders.^289,290 It is thought AGEs are a major mediating factor in the relationship between a Western dietary pattern and poor cognitive and general health.²⁸⁹

AGEs form in foods due to interactions between oxidized lipids and protein or through browning—a chemical process, known as the Maillard reaction, induced by heat.³⁰⁴ Heat-related industrial procedures such as food processing, sterilization, packaging, and long-term storage can trigger the Maillard reaction.³⁰⁵ In home cooking, strategies for reducing dietary AGEs include:

• Eating a plant-based diet. Plant foods like grains, legumes, fruits, and vegetables contain lower amounts of AGEs and are less prone to AGE formation through cooking than animal foods that are high in protein and fat.^305,306 In addition, phytochemicals such as polyphenols and dietary fiber have the potential to inhibit AGE formation.³⁰⁴
• Cooking for shorter times at lower temperatures. Higher cooking temperatures and longer exposure to heat are known to increase AGE formation.³⁰⁶
• Using microwave cooking and moist cooking methods. Microwaving, steaming, stewing, poaching, and boiling result in less AGE formation than dry or oil-based cooking methods such as roasting, broiling, or frying, especially when preparing meats.³⁰⁶
• Incorporating acidic ingredients, such as lemon juice or vinegar. Because an acid pH inhibits AGE-related reactions, meat treatments such a marinades that use vinegar or lemon juice can limit AGE formation.^304,306

Gluten & Brain Function

Celiac disease is an autoimmune condition in which antibodies to gluten (a protein found in wheat and several other grains) cause inflammation and tissue damage in the digestive mucosa. About 1% of the US population have celiac disease. The symptoms of celiac disease include not only digestive and malabsorptive problems, but a wide range of harmful effects in other organ systems, including the brain.^277,282 A 1996 study found that, among 147 participants with a range of neurological disorders, 57% of those whose disorders had no known cause tested positive for anti-gliadin antibodies (antibodies to a fraction of gluten), while these antibodies were only detected in 5% of those whose disorders had known causes. In addition, only 12% of study participants without neurological problems had positive anti-gliadin antibody tests.²⁸⁰ Mild cognitive symptoms of celiac disease, referred to as “brain fog,” have been reported to improve during the first year of treatment with a gluten-free diet in newly diagnosed celiac disease patients.^279,282 In addition, individuals with non-celiac gluten (or wheat) sensitivity can experience cognitive problems involving memory, attention, mental processing speed, and executive function (ie, the cognitive skills needed to control and coordinate cognitive activities and behaviors) that may improve on a gluten-free diet.^277,307 However, an observational study in 13,494 women without celiac disease found gluten intake was not related to cognitive capacity, suggesting those without celiac disease or non-celiac gluten sensitivity are unlikely to benefit from gluten avoidance.²⁸³

Does Monosodium Glutamate (MSG) Impair Brain Function?

Glutamate is an amino acid that acts as an excitatory neurotransmitter. In healthy conditions, glutamate transport across the blood-brain barrier is tightly controlled, but conditions such as stress, infection, trauma, and neurological disease can impair blood-brain barrier function and allow excess glutamate into the cerebrospinal fluid.^308-310 Changes in the gut microbiome may also affect blood-brain barrier function and brain glutamate concentrations.^298,311 Over-activation of glutamate-sensitive receptors in the brain can further degrade blood-brain barrier function and trigger excitotoxicity, neuroinflammation, increased oxidative stress, protein aggregation, mitochondrial dysfunction, and nerve cell death, and is considered a possible contributor to cognitive disorders, depression, reduced neuroplasticity, and neurodegenerative diseases like Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Huntington disease.^297,298,311

Cognitive dysfunction can be a symptom of glutamate-mediated illness, but because glutamate can stimulate receptors throughout the body, symptoms such as fatigue, pain, migraine, and digestive problems may co-occur. It has been proposed that a low-glutamate diet may benefit people with these symptoms. Biologically active free glutamate is naturally found in foods such as soy sauce, aged cheeses, seaweed, mushrooms, and tomato sauce, and is also a common food additive (in the form of monosodium glutamate [MSG] or yeast extract) for flavor enhancement. In a clinical trial in 40 patients with Gulf War Illness, a condition characterized by cognitive impairment and a cluster of symptoms involving multiple body systems, one month of adherence to a low-glutamate diet resulted in symptom improvement.³⁰⁰ Another trial that included participants with Gulf War Illness also found reducing glutamate intake for one month improved cognitive function.²⁹⁹ While these findings are intriguing, it is important to note that there is little evidence to support dietary glutamate sensitivity as a cause of cognitive problems or other ailments.^302,303 In fact, one placebo-controlled clinical trial that included 159 institutionalized dementia patients found adding 900 mg of glutamate, in the form of MSG, to the diet three times per day for 12 weeks led to cognitive benefits.³⁰¹

While specific “brain foods” can be helpful or harmful to brain function, a broad set of healthy eating habits and good overall nutrition may have the advantage of cumulative and synergistic effects of the multiple components of the diet.³¹² Factors such as culture, ethnicity, and geographical location, as well as personal tastes and preferences, provide important context when considering the best diet for an individual.²⁸⁸ In general, eating habits emphasizing a variety of minimally processed plant foods, as well as fish, lean meats, and low-fat dairy foods, have the strongest evidence showing cognitive benefits.^210,288

Mediterranean Diet

A Mediterranean diet, which emphasizes plant foods such as vegetables and fruits, whole grains, legumes, nuts and seeds, and olive oil, as well as a modest amount of fish, limited amounts of dairy products, eggs, and poultry, and little to no red meat and sugar, has been extensively studied and is widely recognized as one of the healthiest eating patterns.^313,314 The diet is rich in anti-inflammatory and free radical-scavenging nutrients, and has been shown to improve gut microbiome balance and promote cardiovascular and metabolic health, which can contribute to brain health.^313,315,316

Adherence to a Mediterranean diet has been correlated with lower risks of depression, cognitive decline, and neurodegenerative disorders in multiple observational studies.^315-317 A clinical trial that included 487 cognitively healthy older adults with overweight or obesity and metabolic syndrome found increased adherence to a three-year lifestyle intervention that included a low-calorie Mediterranean diet and physical activity led to greater improvement in memory.³¹⁸ Another trial compared a Mediterranean diet, supplemented with lean pork two to three times weekly to increase adherence, to a low-fat diet in 35 individuals with normal cognitive health and elevated cardiovascular risk. The trial was designed as a crossover trial in which participants were assigned to eat each of the test diets for eight weeks with an eight-week break in between. The modified Mediterranean diet increased cognitive processing speed and improved emotional function relative to the low-fat diet phase.³¹⁹ In a similar trial with 41 participants at high risk of cardiovascular disease, a Mediterranean diet supplemented with 3–4 servings of dairy per day improved processing speed and measures of mood and mental clarity after eight weeks compared with a low-fat diet.³²⁰ A 6.5-year Mediterranean diet intervention that included either additional extra virgin olive oil or nuts also appeared to improve performance on cognitive function tests relative to a low-fat diet intervention. This study involved 522 individuals with high cardiovascular risk participating in a long-term trial designed to detect the effects of diet on heart health.³²¹ Not all results have been positive, however. In one randomized controlled trial that included 137 healthy adults over 65 years of age, changes in cognitive function were no different in those assigned to the Mediterranean diet intervention than those assigned to eat their habitual diet after six months, suggesting possible benefits from a Mediterranean diet in healthy individuals may require more time to be detectable.³²²

DASH

Dietary Approaches to Stop Hypertension (DASH) is a set of nutrition guidelines developed to prevent and treat high blood pressure. DASH is a low-fat diet that emphasizes fruits, vegetables, whole grains, nuts and seeds, legumes, and low-fat dairy products, and restricts saturated fat, cholesterol, red and processed meats, and sugar.²⁸⁸ In a study of 16,144 women 70 years of age and older participating in the Nurses’ Health Study, greater long-term adherence to DASH guidelines was correlated with better performance on cognitive tests. In fact, the cognitive difference between those with high versus low adherence to DASH was noted to be equivalent to one less year of cognitive aging.³²³ In a controlled trial that included 124 participants with prehypertension or mild hypertension and overweight or obesity, four months of a low-calorie DASH diet plus an exercise program involving 30 minutes of aerobic exercise three times weekly was found to improve measures of executive function, memory, and learning, as well as psychomotor speed, while DASH alone improved only psychomotor speed.³²⁴

MIND Diet

A recently developed set of dietary recommendations incorporates the brain-protective aspects of the Mediterranean diet and DASH guidelines and is called the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. The MIND diet focuses on consumption of 10 brain-healthy food groups (green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, seafood, poultry, olive oil, and wine) and avoidance of five unhealthy food groups (red meats, butter and stick margarine, cheese, pastries and sweets, and fried/fast foods).²⁸⁸

Some observational studies have correlated the MIND eating pattern with better cognitive function, fewer depressive symptoms, and increased brain volume, and its effects appear to be stronger than either the Mediterranean or DASH diet.^325-327 Findings from one observational study suggest adherence to the MIND diet may reduce the negative impact of exposure to fine particle air pollutants on brain volume.³²⁸

In a controlled trial in 40 women with obesity, following a low-calorie MIND diet for three months improved performance on tests of memory and attention more than a standard low-calorie diet. In addition, changes in brain structure in a region involved in critical thinking and executive function were seen on magnetic resonance imaging (MRI) in women who followed the MIND diet, suggesting the diet reversed some effects of obesity on the brain.³²⁹ In another controlled trial, 68 postmenopausal women with obesity participated in a program consisting of the MIND diet with or without a three-times-a-week aerobic exercise program for three months. All participants experienced improvements in measures of cognitive function, but the effects were stronger in those who exercised.³³⁰ A trial in 57 cognitively healthy elderly subjects found including canned fish and fish spread, in an amount equivalent to an average of 2.2 grams of omega-3 fatty acids per day, while following MIND recommendations led to greater improvement in cognitive performance than the MIND diet alone.²⁵⁹