Eating for Your Neurotransmitters

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

These chemical messengers play a key role in managing many bodily processes, as well as central actions that take place in your brain such as learning, memory, mood, and cognition.

As with many chronic illnesses, the establishment of the problem—and restoring balance—starts with the foods you eat. 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. Neurons secrete neurotransmitters after being triggered by an action potential when there is an unbalanced charge in the ions. The neurotransmitter 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, it 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 norepinephrine. 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, and fibromyalgia.

Some of the best known neurotransmitters include:

– Acetylcholine

– Dopamine

– Epinephrine (adrenaline)

– GABA

– Glutamate or glutamic acid

– Norepinephrine (noradrenaline)

– Serotonin

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. A study of healthy middle-aged adults found that diet quality was associated with mood and cognitive processing speed. Participants who followed an optimal, nutrient-dense diet had a higher intake of nutrients such as magnesium and zinc with higher blood levels of vitamin B6 and folate.

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 have in sufficient amounts for a healthy brain and communication throughout the body, which are discussed below.

Building Blocks of Neurotransmitters

There are many nutrients that are 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 also certain foods that are known for their overall benefits for the brain. One example is tea, most likely due in part to the amino acid L-theanine, which influences dopamine and GABA levels in the brain.

The individual neurotransmitters have their own required substrates, including many of the nutrients listed above. Let’s review some of the key neurotransmitters and their connection with diet, including whether you can consume the neurotransmitter through food and ways to ensure you have 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 such as the pancreas, liver, and intestines. 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 rich in arginine include legumes, poultry, eggs, fish, and dairy. Foods containing histidine include chicken, fish, oats, and soybeans.

Because glutamate is a major exhibitory neurotransmitter, its extracellular levels remain tightly regulated. Excess levels of glutamate are linked to negative health effects, such as neurotoxicity and oxidative stress. Therefore, it is important to avoid glutamate agonists that might mimic the effects of glutamate, especially in conditions in which the blood-brain functions incorrectly.

One of the most studied glutamate agonists is monosodium glutamate (MSG). MSG has been shown to have potential negative health effects that might be connected to the consumption of glutamate. In a rat study, MSG led to renal damage and increased levels of serum creatinine, uric acid, and BUN as well as increased markers associated with apoptosis (cell death). Carnitine supplementation helped to ameliorate these effects through its antioxidant properties.

There have been many reports of negative associations of MSG in humans, but the literature has mixed results. MSG is thought to cause headaches in some individuals. A systematic review found that MSG administration with food led to decreased incidence of headache compared to administration without food. The authors concluded that more research is needed on this topic. A randomized controlled trial studied the effects of consistent MSG intake on flavor preferences and food choices. The treatment group received a broth containing 3.8 grams of MSG daily, while the control group received a sodium-matched broth without added MSG. After four weeks, researchers found that females in the treatment group had diminished perception of umami intensity and less of a desire to eat savory foods. The authors concluded that this change in flavor preferences could have an impact on food choices and metabolic health.

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 synthesized in the gut, generally thanks to your friendly bacteria species such as Lactobacillus.

There are studies demonstrating a potential benefit of consuming GABA, despite most scientific consensus saying GABA does not cross the blood-brain barrier. 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) compared to 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 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.

A systematic review of fourteen studies found limited to moderate evidence for the use of dietary or supplemental GABA for stress relief and low evidence for its effect on sleep. Doses for stress relief varied considerably in the studies considered in this review. Higher doses were required for sleep benefits and prolonged supplementation may be needed to see a change.

A separate systematic review studied the ability of certain herbs to affect sleep by acting on GABA receptors. Valerian root, Magnolia sp., chamomile, and passionflower all influence GABA receptors or increase GABA availability through other mechanisms.

So, where can you find GABA in your diet? Foods such as soybeans, adzuki beans, fermented foods, white tea, and tomatoes are sources of GABA. One study found fermented soybean to be a good source of a glutamic acid-producing bacteria, which is used to create GABA.

Serotonin

Consuming serotonin might not have a beneficial effect on your brain and mood because it cannot pass the blood-brain barrier. Exogenous serotonin is generally metabolized upon ingestion, which could lead to a temporary increase in plasma 5-HIAA levels, 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 rapidly cleared.

Like GABA, the gut microbiome can synthesize serotonin by metabolizing tryptophan. Almost all serotonin is found in the gut, where it plays an important role in digestion. Due to the gut-brain axis, serotonin also influences mood disorders such as depression.

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 rich in tryptophan, other foods that are high in tryptophan include whey, soy, and cashews. 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 blood brain barrier, it must compete with large neutral amino acids (LNAA). The ratio between tryptophan and LNAA determines how much tryptophan makes it into the brain, and therefore, how much is available for serotonin synthesis. Consuming tryptophan-rich foods with carbohydrates rather than protein helps to increase the uptake of tryptophan. Glucose and insulin increase the uptake of LNAA into the skeletal muscles, but tryptophan is left alone to cross the blood brain barrier.

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 experienced a reduction in the tryptophan to LNAA ratio. However, there was no impact on the anxiety of the participants. They responded 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.

A study compared the effects of consuming a low tryptophan diet (5 mg/kg body weight) or a tryptophan-rich diet (10 mg/kg body weight) on mood. Those who consumed 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 Positive Affect Negative Affect Schedule (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 the tryptophan to LNAA ratio could affect decision-making and risk propensity. Men of a normal weight received either a high carbohydrate and high protein breakfast, or a low carbohydrate and low protein breakfast. Plasma neurotransmitter concentrations were measured, and participants completed several different tasks while receiving a functional MRI scan. The high carbohydrate breakfast led to a significant increase in plasma tryptophan. Men with higher fat mass experienced greater plasma tryptophan changes and increased risk aversion.

A separate group of researchers 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 nineteen 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 maximize the benefits of tryptophan in your diet, you must have sufficient levels of vitamin B6 since B6 plays a role in the synthesis of tryptophan to serotonin.

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 that affect serotonin have not been definitely proven, and some side effects have been associated with taking them. Therefore, if you wish to supplement with tryptophan to enhance your serotonin levels, be sure to discuss this with your health care 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.

Protein-rich foods are a great place to start for tyrosine. Those richest in tyrosine include dairy, eggs, beans, fish, and meat such as beef and chicken. However, it takes 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 various brain regions. It led to increased dopamine in the hypothalamus, which caused 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 neurotransmitter 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.

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, which 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 gastrointestinal (GI) tract.

About half of synthesized dopamine is created in the gut, but it is 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 the body 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 fatty acid synthesis, protein homeostasis, and serving as the main substrate for acetylcholine. Choline must enter the brain and then convert to acetylcholine. It crosses the blood-brain barrier 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 during 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 in certain populations. Men, postmenopausal women, and pregnant and lactating women are at the highest risk of a choline 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 with a European population, most groups had intake levels of choline below the adequate intake set by the U.S. Institute of Medicine (IOM). Sources of choline include eggs, fish, and whole grains.

A randomized, double-blind study sought to study the effects of choline supplementation during pregnancy on the processing speed of infants. While many studies on the effects of choline have been performed on animals, this study involved women in their third trimester of pregnancy. Women used a combination of diet and supplementation to either consume 480 mg or 930 mg per day of choline. Infants performed various tests to evaluate processing speed and spatial memory at different points up until 13 months of age. Infants of the mothers who consumed 930 mg/d of choline experienced significantly quicker processing speeds, although a linear improvement effect was noted for infants in the other group as well.

Conclusion

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

Consumption of the neurotransmitters themselves may or may not have health benefits—and in some cases, may 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, you might experience adverse symptoms.

If you plan to make food or supplement changes, have food or supplement allergies, or have questions about which foods or supplements are best suited to your personal needs, talk to your doctor, nutritionist, dietician, or another member of your healthcare team for personal options based on your individual circumstances.

 

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