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Eating for Your Brain: Neuroactive Compounds in Food

How healthy is your brain? Problems with mood disorders and neurodegenerative diseases like Alzheimer’s Disease seem to be almost epidemic. An important component of your brain’s health, including your mood and cognitive ability, relies on the balance of neurotransmitters.

These key communication devices move around your body to ensure everything signals correctly. As such, they play a key role in managing many body processes, as well as central actions that take place in your brain, such as mood, learning, memory, and cognition.

As with many chronic illnesses, the establishment of the problem—and the cure—starts with the foods you eat. So, it is important to know what to eat to ensure a healthy release and balance of your neurotransmitters. Let’s start with a quick overview of neurotransmitters themselves.

Neurotransmitters 101

Neurotransmitters are the chemical messengers neurons release to convey information within the brain and from the nervous system to other parts of the body. They process sensory information and control behavior. Neurons secrete neurotransmitters after what is known as an action potential when there is an unbalanced charge in the ions. This chemical messenger has the ability to cross the synapse between neurons and bind to a receptor. From there, it either continues the message to other neurons down the line, or if it has reached its end stop, stimulates a different kind of cell to perform a certain action, depending on the type of neurotransmitter and the type of cell.

Some neurotransmitters provide their signaling at the receptor, while others have post-receptor interactions and communication. Neurotransmitters can either be excitatory or inhibitory, and some perform both roles depending on the situation. An excitatory neurotransmitter is one that creates changes in the responding cell, while inhibitory ones block any changes that might occur.

Many neurotransmitters are synthesized in the gut as well as the brain, including dopamine, GABA, serotonin, and endocannabinoids. In fact, roughly 95% of serotonin in the body comes from the gut, where it acts as both a paracrine messenger and a neurotransmitter. Neurotransmitters also play a role in the immune system, signaling certain actions to occur. New evidence points to the potential for some immune cells to release neurotransmitters as well.

Studies have pointed to possible connections between dysfunction in neurotransmitters to several neurological and psychiatric disorders, including Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, borderline personality disorder, and fibromyalgia.

Some of the best known of the neurotransmitters—and the ones we will concentrate on—include:

– Glutamate or Glutamic acid
– GABA
– Serotonin
– Norepinephrine
– Epinephrine
– Dopamine
– Acetylcholine

Food for Brain Health

What you eat has the potential to impact your mood and improve your cognitive function. Many studies have looked to see whether negative moods inspired eating patterns or vice versa. In one study looking at 44 college students, the foods consumed over a two-day period had a correlation with mood. Eating a diet high in sodium, saturated fat, and calories correlated to a negative mood two days later. The dietary pattern corresponding with a more positive mood included consuming fewer calories, less saturated fat, and reduced sodium.

This food-mood connection likely comes from the effects of certain nutrients and foods on neurotransmitters, including consuming the neurotransmitters themselves. There are also important precursors to neurotransmitters you must ensure you have in sufficient amounts for a healthy brain and communication throughout your body.

Building Blocks of Neurotransmitters

There are many nutrients essential to the synthesis and regulation of neurotransmitters, including amino acids (especially the precursors tryptophan and tyrosine), choline, vitamin C, B-vitamins (especially B6, B12, and folate), large amino acids (i.e., valine, leucine, isoleucine, phenylalanine), zinc, iron, omega-3 fatty acids, and vitamin D. There are certain foods known for their overall benefits for the brain. One example is tea, most likely due in part because theanine increases serotonin, dopamine, and GABA levels in the brain.

The individual neurotransmitters have their own required substrates, including many of the nutrients listed above, which you generally need to get through your diet. Let’s review some of the key neurotransmitters and their connection with diet, including whether you can consume the neurotransmitter through food, how that might impact your levels, and ways to ensure adequate levels of the substrates.

Glutamate

Among its many jobs in the body, glutamate acts as the major excitatory neurotransmitter. Although you can find many foods containing glutamate, it does not cross the blood-brain barrier (BBB). Instead, dietary glutamate is generally used by other areas of the body, including as fuel for the cells of the gut lining. Dietary glutamate is metabolized by the enterocytes in the intestine, and circulating levels are generally low in the plasma and are tightly regulated. However, the total level of glutamate in the body increases with the amount ingested, so excessive consumption might lead to more absorption in the portal vein rather than metabolized in the gut.

The brain produces its own glutamate from glucose. The body requires alpha-ketoglutarate or the glutamate amino acids, which include glutamine, arginine, histidine, and proline, for the endogenous synthesis of glutamate. Consuming protein-rich foods, especially meat sources, will generally provide these amino acids. Foods richest in arginine include turkey breast, pumpkin seeds, soybeans, eggs, and sesame seeds. Foods containing histidine include turkey breast, soybeans, and eggs. Foods rich in proline include turkey breast, soybeans, certain cheeses, and eggs.

Because glutamate is a major exhibitory neurotransmitter, its extracellular levels remain tightly regulated. Excess levels of glutamate are linked to neurotoxicity and damage, most likely due to an over-activation of the glutamate receptors that ultimately trigger signaling pathways that cause necrosis (cell death due to lack of blood supply) or apoptosis (cell death due to normal growth and development). Therefore, it is important to avoid glutamatergic agonists that might mimic the effects of glutamate, especially in conditions in which the BBB functioning incorrectly. One of the most commonly studied due to its popularity in the food industry is monosodium glutamate (MSG).

MSG has been shown to have potential negative health effects that might be connected to the consumption of glutamate. In one mouse study, consumption of 40 and 80 mg/kg of MSG led to a significant increase in the plasma level of both glutamine and glutamate compared to the control mice consuming either distilled water or 10 mg/kg of L-glutamate. Although the brain levels of glutamine and glutamate did not undergo a significant change, there was evidence of neural inflammation, oxidative stress, and damage.

There have been many reports of negative associations of MSG in humans, but the literature has mixed results. In a human double-blinded, placebo-controlled, crossover study, 14 healthy men consumed a soda that contained either a placebo of 24 mg/kg of sodium chloride or 75 or 150 mg/kg of MSG. The serum level of glutamate increased by 556% 30 minutes after drinking the high dose of MSG and 395% in the low dose compared to the baseline levels. Comparatively, the placebo had 97.5% of the baseline level of serum glutamate. Four of the subjects experienced a headache after taking the low-dose, and one experienced a headache after taking the high dose. Blood pressure levels were also higher after consuming the MSG compared to consuming the sodium chloride.

In another study, fibromyalgia patients with IBS who benefited from an excitotoxin elimination diet had a significant return of their symptoms upon consumption of MSG compared to those who took the placebo.

GABA

Glutamate is also the precursor to gamma-aminobutyric acid or GABA, the main inhibitory neurotransmitter. In the brain, glutamic acid decarboxylase (GAD) converts glutamate into GABA. GAD also acts as the rate-limiting enzyme in the brain. GABA is also synthesized in the gut, generally thanks to your friendly bacteria. According to one study, 43% of human-gut derived strains of Bifidobacterium and Lactobacillus were able to produce GABA. The bacteria-produced GABA in the gut most likely plays a role in the enteric nervous system (ENS) and/or stimulates the vagus nerve, providing some of its benefits.

There are studies demonstrating a potential benefit of consuming GABA, despite most scientific consensus saying GABA does not cross the BBB. In one study, consuming a GABA-containing beverage reduced signs of fatigue and stress. There were also significantly lower levels of cortisol during the task in those who consumed the GABA at two different doses (25 mg and 50 mg), than those who did not. Consuming 50 mg of GABA led to a significant reduction in the scores for nerve strain compared to a control.

In those with chronic fatigue, there was a decrease in scores on a self-reported questionnaire for psychological fatigue, but this was not the case for those without chronic fatigue. Consuming just 25 mg of GABA did not impact fatigue levels, but consuming the 50 mg dose of GABA also increased performance, with a higher number of correct answers on a test. The researchers found that consuming GABA appeared to not impact the brain itself but instead exerted its effect on the peripheral organs.

Another study found that consuming 10 grams of chocolate with 28 mg of GABA mitigated the stress response during a task and led to a faster recovery from a stressed state to a relaxed state. Although these studies are promising, there are potential conflicts of interest, according to a review article.

So, where can you find GABA in your diet? Chia seeds are rich in GABA, especially if they are germinated. One study measured a 9.51 mg/100 g GABA content in non-germinated chia flour. Germination of the chia seeds led to an 11.4-fold increase in GABA levels. Fermented foods are another source of GABA, thanks to GABA-producing microbes. Lactic acid bacteria are generally the GABA producers. There were also food-derived strains, including L. brevis and L. plantarum species. These could be found in foods like kimchi, paocai, sourdough bread, cheese, and yogurt. One study found fermented soybean to be a good source of a new glutamic acid-producing bacteria, which is used to create GABA.

One thing to note: environmental stress might affect the GABA content of foods. In one study, 14 days or more of cold stress (exposing the spinach to temperatures that fluctuated between 2 and 8 degrees Celsius compared to 10 to 15 degrees Celsius) increased GABA levels in greenhouse-grown spinach, a food known to be rich in GABA. However, after the exposure, there was a reduction in the total glutamic acid content in the spinach. Other studies have found that pH changes might also impact GABA levels.

Serotonin

Consuming serotonin might not have a similar impact on your brain and mood because it cannot pass the blood-brain barrier. The serotonin is generally metabolized upon ingestion, which could lead to a temporary increase in plasma 5-HIAA levels, which is a metabolite of serotonin. Foods high in serotonin include banana, walnuts, and pineapple. In one study, consuming these serotonin-rich foods led to a significant elevation in 5-HIAA, peaking at about 2 hours after ingestion, but this is rapidly cleared. According to one study, alcohol might alter this and lead to a higher level of 5HTOL, which is another metabolite of serotonin, leading to negative side effects including diarrhea and headaches.

Like GABA, your gut microbiome can synthesize serotonin by metabolizing tryptophan. As stated, almost all of your serotonin is found in your gut, where it plays an important role in the ENS and acts as a paracrine hormone. More and more evidence point to serotonin’s role in gut health with low levels resulting in an imbalance of gut serotonin, which contributes to digestive problems.

Although consuming serotonin might not impact your brain levels of the neurotransmitter, consuming tryptophan might. This essential amino acid is necessary for the synthesis of serotonin. The dietary tryptophan-serotonin connection is much stronger than any of the other amino acid substrates of the other neurotransmitters. Although turkey has a reputation for being high in tryptophan, other foods high in tryptophan include eggs, soybeans, pumpkin seeds, white beans, sesame seeds, mung beans, split peas, and kidney beans, as well as some nuts and grains. Studies have found that consuming higher levels of tryptophan can lead to a higher synthesis of serotonin. Conversely, acute tryptophan deficiency has also been shown to negatively impact production of serotonin in the brain.

For tryptophan to pass the BBB, you need the leucine-preferring L1 system to compete with the large neutral amino acids (LNAA). The ratio between tryptophan and LNAA determines how much tryptophan actually makes it into the brain, and therefore, how much is available for serotonin synthesis.

For example, in one study, healthy participants consumed either a placebo or an acute tryptophan-depleting drink after a 12-hour fast. The drink had several large neutral amino acids and did not include tryptophan. Then, participants were asked to undergo some tasks. The group that took the tryptophan-depleting drink had a reduction in the tryptophan to LNAA ratio. However, there was no impact on the anxiety of the participants. They did respond slower to stimuli, although this did not impact their performance or accuracy. The researchers also found that there was a shift from a goal-directed response to a habitual one after taking the drink, which could be due to a shift in neurotransmitters.

One study compared consuming a low tryptophan diet (5 mg/kg body weight) to a tryptophan-rich diet (10 mg/kg body weight) on mood. Those who consumed the high levels of tryptophan experienced significantly lower scores on an anxiety questionnaire. They also had a significantly higher positive affect or mood scores on the PANAS questionnaire. The subjects were not clinically depressed prior to the study, but those who consumed the lower levels of tryptophan reached the threshold on a depression scale.

Another study looked at whether food with a high tryptophan to LNAA ratio influenced mood through altering serotonin levels. In a double-blind, placebo-controlled crossover study, participants consumed 300 mL of a drink with a favorable tryptophan to LNAA ratio (0.66 g tryptophan and a 0.19 TRP/LNAA ratio compared to 0.12 g tryptophan and a 0.02 ratio). They found that drinking just one serving increased the blood plasma ratio of tryptophan to LNAA and improved mood. It also reduced the dorsal caudate nucleus responses during the anticipation of a reward, increased the dorsal cingulated cortex responses during processing of fear, and increased the connectivity of the ventromedial prefrontal-lateral prefrontal connectivity in a resting state.

Consuming tryptophan-rich foods with carbohydrates rather than protein helps to increase the uptake of tryptophan. According to one study, carbohydrates can increase the ratio of tryptophan to other large amino acids by 20 to 45%. Glucose and insulin increase the uptake of LNAA into the skeletal muscles, but tryptophan is left alone to cross the BBB. Increased insulin also causes any free fatty acids to leave the albumin and enter adipocytes. This allows the albumin to bind to tryptophan and take it to the brain.

Another study used a bioavailable form of supplemental tryptophan made from egg protein hydrolysate. As part of the randomized, placebo-controlled, parallel trial, healthy middle-aged women took either 0.5 grams of the protein powder, which correlated to 35 mg of bioavailable tryptophan, or a placebo twice a day for 19 days. The researchers found that those who took the tryptophan demonstrated a reduced reaction to negative stimuli and instead had a happiness bias. They also had more energy, a lowered reaction time, and a longer attention span. Many of the participants also experienced a better quality of sleep consuming the tryptophan within 60 to 90 minutes before bed. The researchers concluded that there was a likely correlation between consuming the tryptophan and a higher serotonergic activity, leading to the positive benefits seen in those who took the supplement.

To gain the benefits of tryptophan in your diet, you must have sufficient levels of B6 as well. That is because B6 plays a role in the synthesis of tryptophan to serotonin, as well as other neurotransmitters.

Although food sources of tryptophan demonstrate benefits to mood and brain health due to its ability to increase serotonin production, the safety and efficacy of supplements have not been definitely proven, and some side effects have been associated with taking it. Therefore, if you wish to supplement with tryptophan to enhance your serotonin levels, be sure to discuss this with your health practitioner.

Catecholamines: Dopamine, Epinephrine, and Norepinephrine

The catecholamines include the neurotransmitters dopamine, epinephrine, and norepinephrine. These generally rely on the amino acid tyrosine for synthesis, but they might also use phenylalanine. Studies have found some promising findings on the impact of increasing tyrosine and enhanced mood and cognitive function. Many of the benefits of taking tyrosine supplements are greater under periods of stress, most likely due to it providing the substrates necessary to keep up with the catecholamine synthesis during stress. However, the ability for tyrosine to help with psychiatric disorders has limited evidence for its efficacy.

Protein-rich foods are a great place to start for tyrosine. Those richest in tyrosine include turkey, eggs, and soybeans. However, it requires more than just ingestion of protein to get the most out of consuming the substrates for the catecholamines. Much like tryptophan and serotonin, what you eat with it might influence its ability to impact neurotransmitter synthesis.

In one small human study, ingestion of a standard meal consisting of 30% fat, 20% protein, and 50% carbohydrate led to a more than 50-fold increase in the plasma levels of dopamine sulfate, which also led to a smaller but proportional increase in dopamine levels and that of L-DOPA. The increase could also be due to ingestion of dopamine sulfate and/or L-DOPA in the same food source. Ingestion of tyrosine could also lead to higher levels of dopamine sulfate.

High-fat diets might lead to altered dopamine expression and function. In one mouse study, a chronic high-fat diet (60% fat, 20.5% carbohydrate, and 18.5% protein compared to 12% fat and 69.5% carbohydrate) led to changes in the expression of dopaminergic genes, with differences in different brain regions. It led to increased dopamine in the hypothalamus, which leads to increased food take, as well as changes in the reward center. These changes might persist even after the diet changes.

Consuming the substrates might increase the levels in the body. Fava beans, a rich source of another dopamine precursor dopa, have also been shown to increase dopamine levels and impact the other catecholamines. In one small study, participants consumed 100 grams of pureed fava beans and pods alongside a study-controlled breakfast and lunch. The researchers found a dose-dependent response to the dopa content in the beans and that of the participants’ plasma. There was also a higher level of urinary dopamine corresponding to higher levels of dopa in the beans. During the period in which there were higher plasma dopa levels, there was a 15-fold increase in the plasma dopamine levels. There was also an increase in plasma norepinephrine levels and an increase in dopamine sulfate but not in norepinephrine sulfate or adrenaline sulfate.

Soybeans might also help increase levels of the catecholamines. One study using an isolated soybean peptide found that the levels of adrenaline decreased and dopamine increased compared to the levels of the previous day after ingestion of 8 grams of soy protein in 200 mL of water. This was a small study performed on just ten healthy volunteers aged 20 to 25 years old.

Consuming foods rich in the catecholamines might have limited impact on the active levels of the neurotransmitters in the body or brain. In one study, after consuming two meals rich in catecholamine foods including nuts, tomatoes, beans, and fruits, the subjects had higher levels of urinary free and deconjugated dopamine compared to controls. After the second meal, there was a 1.5-fold increase in free dopamine in the urine and a 20-fold increase in deconjugated dopamine levels, but they returned to baseline overnight. There was also an increase in free norepinephrine after the second meal and continued to be elevated overnight. There was no influence on the urinary levels of epinephrine. This supports that most catecholamines are metabolized into sulfate conjugates in the GI tract.

About half of synthesized dopamine is created in the gut, but then almost immediately inactivated using the sulfotransferase SULT1A3. Free dopamine can become norepinephrine and epinephrine, and these also tend to circulate in a sulfated form. Certain foods have been shown to inhibit the sulfotransferases that sulfurize the catecholamines, which could impact health as these catecholamines would be free to act as signaling molecules, either in their neurotransmitter or hormone capacity. These foods include red wine, citrus fruits, orange juice, lingonberry juice, bananas, coffee, tea, chocolate, and vanilla.

Acetylcholine

Choline has many jobs in the body (including playing a role in one-carbon methylation and membrane phospholipids), among them is its role as the main substrate for acetylcholine. Choline must enter the brain and then convert into acetylcholine. It crosses the BBB at a rate that is proportional to the serum levels. Cholinergic neurons contain choline-phospholipids that provide a precursor pool for the synthesis of acetylcholine, especially upon times of greater demand when extracellular fluid choline supplies are not sufficient for the requirements of acetylcholine.

Although the body can synthesize choline, it is considered an essential amino acid because the body cannot synthesize sufficient levels, especially certain populations. Men, postmenopausal women, and pregnant and lactating women are at the highest risk of a deficiency. Estrogen helps the body synthesize choline by inducing the PEMT gene, making premenopausal women the least likely to develop symptoms of deficiency. However, there are common genetic polymorphisms that might make one more susceptible to choline deficiency, including in the PEMT gene and the common MTHFR gene.

In a study on a European population, the majority of groups had intake levels of choline below the AI set by the U.S. IOM. The major sources of choline in the diet were meat, milk, eggs, and grain-based products. Similar statistics of inadequate dietary intakes are found in the U.S. Good sources of choline include eggs, turkey, soybean, chickpeas, and lentils.

In one rat study, a diet deficient in choline led to a decrease in the release of acetylcholine in the hippocampus. In the study, two groups of Wistar rats were allowed to eat freely from their food sources, which were the same other than the choline content. The choline deficient group had a 33.1% lower average level of choline in the CSF compared to the control, which was significant. The deficient rats also had impaired memory retention for a passive avoidance task due to a reduced ability to release acetylcholine.

Choline intake also has an impact on acetylcholine levels in the brain. In one rat study, supplementing with choline for 15 to 18 days led to a slight increase in the release of acetylcholine in the hippocampus. Under stimulation, it increased it two to three times, especially with the addition of nicotinamide. Acute choline consumption led to a slight but not significant increase in acetylcholine levels.

Conclusion

Can you increase and/or balance your neurotransmitters through your diet? Consuming adequate levels of the basic nutrients for neurotransmitters, including protein for the amino acids, vitamin C, the B-vitamins, and iron, can go a long way to a healthy brain and more balanced neurotransmitter levels.

However, consumption of the amino acids themselves may or may not have health benefits—and in some cases, might be detrimental to health. For the most part, the body tightly regulates neurotransmitter levels to avoid this, but if you consume excess amounts, such as the case of MSG, then you might find yourself in trouble. You might also experience problems if you have an issue that reduces the BBB’s ability to keep certain molecules out of the brain.

If you do choose to consume those that have been shown to have benefits, such as GABA and tryptophan, be sure to discuss it with your doctor or other healthcare practitioner ahead of time to reduce the risk of adverse effects.

 

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1 Comment

  1. Tom Commeau

    Thanks for sharing your thoughts on these forefronts of medical science and human health & well being. I really like your efforts to keep it simple (as much as possible, that is…!!!) and practical. I am intrigued as to how you have arrived (your life path), or better evolved, at this point in time and space to conceptualize and communicate these pearls. Such a delight to see such creations. As you know when we are in this mode, i.e. the mode you are in, we are closest to our Creator and are fulfilling our divine purpose in life. Thanks for sharing…….

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