What are Neurotransmitters-
A chemical substance released at the end of a nerve fibre by the arrival of a nerve impulse and, by diffusing across the synapse or junction, affects the transfer of the impulse to another nerve fibre, a muscle fibre, or some other structure.
A neurotransmitter influences a neuron in one of three ways: excitatory, inhibitory, or modulatory.
- Excitatory: As their name implies, excitatory neurotransmitters are responsible for exciting the neuron and causing it to pass a message to the next cell.
- Inhibitory: Inhibitory neurotransmitters are responsible for blocking and preventing chemical messages from being passed on further.
- Modulatory: Modulatory neurotransmitters are responsible for influencing chemical messengers. For example, they can adjust how cells communicate and can affect several neurons at the same time.
Key neurotransmitters
The first neurotransmitter to be discovered was a small molecule called acetylcholine. It plays a major role in the peripheral nervous system, where it is released by motor neurons and neurons of the autonomic nervous system. It also plays an important role in the central nervous system in maintaining cognitive function. Damage to the cholinergic neurons of the CNS is associated with Alzheimer’s Disease.
Glutamate is the primary excitatory transmitter in the central nervous system. Conversely, a major inhibitory transmitter is its derivative γ-aminobutyric acid (GABA), while another inhibitory neurotransmitter is the amino acid called glycine, which is mainly found in the spinal cord.
Many neuromodulators, such as dopamine, are monoamines. There are several dopamine pathways in the brain, and this neurotransmitter is involved in many functions, including motor control, reward and reinforcement, and motivation.
Noradrenaline (or norepinephrine) is another monoamine and is the primary neurotransmitter in the sympathetic nervous system where it works on the activity of various organs in the body to control blood pressure, heart rate, liver function, and many other functions.
Neurons that use serotonin (another monoamine) project to various parts of the nervous system. As a result, serotonin is involved in functions such as sleep, memory, appetite, mood, and others. It is also produced in the gastrointestinal tract in response to food.
Histamine, the last of the major monoamines, plays a role in metabolism, temperature control, regulating various hormones, and controlling the sleep-wake cycle, amongst other functions.
How do medications affect the action of neurotransmitters?
Scientists recognized neurotransmitters' value and role in your nervous system and the importance of developing medications that could influence these chemical messengers to treat many health conditions. Many medications, especially those that treat diseases of your brain, work in many ways to affect neurotransmitters.
Medications can block the enzyme that breaks down a neurotransmitter so that more of it reaches nerve receptors.
- Example: Donepezil, galantamine and rivastigmine block the acetylcholinesterase enzyme, breaking down the neurotransmitter acetylcholine. These medications are used to stabilize and improve memory and cognitive function in people with Alzheimer’s disease, as well as other neurodegenerative disorders.
Medications can block the neurotransmitter from being received at its receptor site.
- Example: Selective serotonin reuptake inhibitors are a type of drug class that blocks serotonin from being received and absorbed by a nerve cell. These drugs may help treat depression, anxiety and other mental health conditions.
Medications can block the release of a neurotransmitter from a nerve cell.
- Example: Lithium works as a treatment for mania partially by blocking norepinephrine release and is used in the treatment of bipolar disorder.
Building Blocks of Neurotransmitters
Many nutrients are essential to the synthesis and regulation of neurotransmitters including amino acids (especially the precursor's 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, Vitamin D. Certain foods are known for their overall benefits for the brain. One example is tea, most likely due partly 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.
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 friendly bacteria species such as Lactobacillus.
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 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 bananas and walnuts. 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 the 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.
A study compared the effects of consuming a low tryptophan (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 significantly higher positive affect or mood scores on the Positive Affect Negative Affect Schedule (PANAS) questionnaire. The subjects were not clinically depressed before the study, but those who consumed the lower levels of tryptophan reached the threshold on a depression scale.
To maximize the benefits of tryptophan in your diet, you must have a sufficient level of 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 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 healthcare 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 of 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 the 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 dopamine 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.
About half of the 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 choline deficiency. Estrogen helps the body synthesize choline by inducing the 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 the PEMT gene and the common MTHFR gene.
Sources of choline include eggs, fish, and whole grains.
Conclusion- You can eat your way to better brain health.
if you are taking any medication that would alter the neurotransmitter level in the brain. Please consult your healthcare practitioner.