Serotonin

What is Serotonin?

Serotonin also known as 5-hydroxytryptamine (5-HT) is an inhibitory neurotransmitter involved in sleep regulation or sleep cycle and digestive system regulation. It also acts as a hormone which helps regulate mood.

Serotonin is considered to be one of the main mood neurotransmitter as it can increase feelings of happiness and a sense of wellbeing.

Serotonin is found in the brain and the digestive system (gut and intestines). Majority of serotonin is made in the gut. About 80% to 90% of the body's serotonin is produced in the digestive tract and stored within intestinal cells where it regulates digestion and maintains stomach function. The remainder 10 to 20% of serotonin is found in the blood and the pineal gland located in the centre of the brain. The serotonergic modulatory neurotransmitter pathway arises in the raphe nuclei found in the brainstem which extends throughout the brain and the spinal cord. Serotonin plays a role in many cognitive functions which includes memory, learning and behaviour. It also plays a role in appetite, emotions, sleep, regulating mood (well-being, happiness), regulating insulin and modulating pain perception.

Low serotonin levels or inefficient synthesis is linked to various health conditions which includes irritable bowel syndrome (IBS), cardiovascular disease, and osteoporosis.

Tryptophan is an essential amino acid as the body cannot synthesise it and needs to be obtained from the diet. This amino acid is a precursor for serotonin which then converts to the hormone melatonin that helps aid restful sleep. 5-Hydroxytryptophan (5-HTP), also known as oxitriptan is another amino acid created in the biosynthesis of tryptophan and is the precursor for serotonin.

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Health Benefits of Serotonin

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Regulates appetite

Many neurotransmitters regulate appetite and are associated with eating behaviour.

Serotonin plays a major role in appetite control and if available in sufficient amount it can reduce craving for carbohydrates. Serotonin and SSRIs have an inhibitory effect on feeding behaviour suppressing appetite. [R]

Some people who may be low in serotonin can often find themselves with an increased appetite but with an extreme craving for carbohydrates.

Other neurotransmitters involved in appetite control includes dopamine and endocannabinoids. These neurotransmitters are involved in the release of ghrelin which increases hunger or leptin which increases satiation. These neurotransmitters act as a messenger and send signals to the hypothalamus a part of the brain involved in the mesolimbic pathway or pleasure pathway.

Helps boost mood

Tryptophan is an essential precursor to the neurotransmitter serotonin which when sufficient helps boost mood and is known as the happy hormone. Serotonin is involved in regulating mood, sleep cycle, circadian rhythm, digestive system, happiness and wellbeing. A deficiency of tryptophan can lead to low mood.

The brain uses serotonin to regulate mood and cognition.

Low levels of tryptophan has shown to cause an increase in anxiety levels and low mood which can lead to depression. [R] [R] [R]

Many of the health benefits of tryptophan are dependent on the conversion to the neurotransmitter serotonin and its subsequent conversion to 5-HTP and melatonin.

Serotonin plays a role in emotional stability. When serotonin levels peak, the main female reproductive hormone estrogen also peaks. Estrogen is also linked to various behaviour. Very low levels of estrogen increases emotionality. When serotonin levels are optimal a person will feel naturally calm with a balanced mood. The person is likely to feel optimistic and hopeful with a general positive outlook.

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With optimal levels of functioning serotonin the person can be patient and appear good natured. Serotonin can also make a person feel reflective or thoughtful.

Estrogen is a hormone associated with feeling of nurturing, loving and caring and especially needed by both mother and developing child.

Serotonin is also involved in behaviour and could reduce aggression. Too little serotonin is linked to fearfulness or anxiety.

Serotonin is involved in processing emotions and can affect mood.

Low serotonin and 5-HTP can cause depression and anxiety. Most prescribed antidepressants act by increasing serotonin activity in the brain. Many studies are showing that supplementation with tryptophan or 5-HTP can help increase serotonin levels reducing depression and anxiety.

Supplementing with tryptophan or 5-HTP helps with serotonin production in the brain and intestines.

Serotonin counteracts the effects of catecholamine neurotransmitters norepinephrine and epinephrine which can induce anxiety and fear.

Regulates Circadian Rhythm

The circadian rhythm is the body’s natural clock and works according to sunrise and sunset. Naturally our mind and body should be awake or awakening during sunrise and feeling sleepy after the sun sets. It is also important to get natural sunlight as you awaken after sunrise as natural daylight helps to regulate the hormone serotonin (“feel good hormone”) which is essential for the production of melatonin. Low serotonin levels are common in those who suffer from depression, a condition which is linked to insomnia.

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Since the invention of the light bulb and all artificial light the body’s circadian rhythm is following an unnatural pattern. It is important to avoid artificial light as much as possible however certain lights can be beneficial for health. As an example people who live in northern climates and experience little sunlight may find benefit using SAD lamps in the day time which help mimic the sun’s natural light and may increase vitamin D production.

Helps aid in sleep

Serotonin is involved in the regulation of the circadian rhythm (the wake sleep cycle) and is influenced by light exposure.

Serotonin can improve sleep cycle when it converts to melatonin.

Tryptophan is usually used as a sleep aid as it is needed to convert to serotonin. This essential amino acid has many health benefits in the body. It is able to convert to vitamin B3 which also helps with sleep.

Insomnia due to disruptions to the circadian rhythm can be helped by melatonin, an essential hormone that helps regulate sleep. Although supplements can be taken it is better to allow the body to produce this naturally as not much is known in terms of health risks associated with supplemental intake of melatonin.

Melatonin is a natural hormone that regulates sleep and is produced in the pineal gland from serotonin during sleep in the absence of light.

Melatonin is produced from tryptophan after conversion of serotonin to 5-htp and you can enhance this by changing your sleep environment such as blocking out as much light as possible. It is recommended that your bedroom uses blackout curtains or blinds so the room is darker. Your bedroom should also be pitch black. You can keep your door closed to block out light from the hallway if this is left on.

Melatonin has been shown to improve sleep. [R]

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Cereal fortified with tryptophan have shown to help with falling asleep and aid in restful sleep. [R]

Your sleep environment can directly impact the quality of your sleep. Very minor tweaks can be made to improve your sleep.

Melatonin drops during full moon at which time people may have sleep difficulty.

Avoid technology as much as possible. Artificial lights from phones, tablets etc will interfere with the body's ability to naturally produce melatonin. Even waking up and being exposed to artificial light for a minute can interfere with melatonin production. It may be helpful to wear sunglasses to avoid hallway lighting when needing to go to the toilet to empty bladder at night. Another option is to wear blindfolds for a better night sleep. Sometimes blindfolds can feel uncomfortable and instead using a piece of cloth or comfortable fabric over the eyes may help.

5HTP can help with sleep and has shown to increase vivid dreams. 5HTP is usually produced in the body from the amino acid tryptophan, so if you are already taking tryptophan for sleep or dream clarity avoid taking 5HTP. 5HTP pauses the initial REM periods of sleep giving deep sleep in usually the first few cycles. In the last few cycles a REM rebound occurs which makes up for the REM periods – this creates highly vivid REM sleep in the latter part of sleep which can enhance recall.

L-tryptophan has also been used for sleep apnea however more research and studies are needed to understand the role it plays in this condition and whether it is effective for this condition. [R]

If tryptophan does not help aid in sleep it may be due to lack of cofactors. Inositol may help instead, which is a B vitamin and may help aid in sleep. See agonists for more information.

Melatonin which is converted from serotonin is antiviral and anti-inflammatory and acts as a powerful antioxidant. [R].

May help with menstrual disorder

Some menstrual disorders such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are linked to an imbalance of the neurotransmitter serotonin which requires tryptophan for its production. One study has shown that increasing serotonin through tryptophan supplementation during the luteal phase can help women suffering from PMDD. 6 grams per day of tryptophan reduced mood swings, tension and irritability symptoms of PMDD. [R]

Women need more serotonin than men.

Needed for healthy digestive system

Majority of serotonin production takes place in the digestive system where it plays an important role in gastrointestinal motility. The serotonin in the digestive system is stored in the chromaffin cells of the intestines. Serotonin regulates digestion and maintains proper functioning of the gut and stomach.

Various gut bacteria species are needed for the production of serotonin as well as the other neurotransmitters GABA, norepinephrine, dopamine, acetylcholine and the hormone melatonin. These beneficial bacteria also use the same neurotransmitters and chemicals to support their functions.

Serotonin also plays a role in leaky gut and inflammatory conditions showing a positive role in preventing these conditions.

Supports functions of neurotransmitters and hormones

Serotonin regulates the release of cortisol, prolactin and growth hormone. It is also a precursor for the inhibitory calming neurotransmitter GABA.

Serotonin increases prolactin which is a hormone made by the pituitary gland and causes breast growth as well as milk production. Low dopamine levels are associated with low levels of prolactin. Prolactin has significant influence in the reproductive system, when prolactin levels increase estrogen and testosterone levels decrease. Stress can cause a rapid and high increase of prolactin.

Prolactin regulates behaviour with high amounts showing to increase aggression (maternal type aggression) in animal based studies as well as studies on women. [R]

Prolactin is also involved in the immune system function and acts as a cytokine.

Prolactin when balanced amounts are available also supports metabolism including fat metabolism.

Cortisol is also the other hormone that increases in times of stress but like prolactin has various essential functions in the body and needed in small or sufficient amounts. The effect of serotonin on prolactin release is evident that women need more serotonin than men due to its effect on the growth of breast tissue and lactation.

GABA is an important inhibitory neurotransmitter which has a calming effect on the nervous system and depends on serotonin as well as melatonin levels.

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Serotonin can increase creativity and enhance focus levels.

Serotonin has shown to increase when hormones such as estrogen and testosterone also increase.

Estrogen functions throughout the body and especially in the brain areas that control emotions. Estrogen increases serotonin and the number of serotonin receptors in the brain which when activated increase endorphins in the brain that can help with improved mood.

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Oregano oil increases estrogen levels which may help to increase serotonin.

Serotonin and dopamine both regulate mood and can help reduce feelings of anger, anxiety and relieve stress. Serotonin also helps regulate sleep and appetite. A deficiency of serotonin can lead to conditions such as PMS in women.

Involved in cognition (Memory and Learning)

Serotonin plays a role in cognitive processes and affects learning and memory. Serotonin interacts with estrogen which also plays a role in cognitive functions.

Supports important bodily functions

Serotonin plays a role in various bodily functions which includes control of temperature and respiration. [R] [R]

Serotonin has shown to regulate blood pressure. [R]

Serotonin plays a role in bone density and may regulate bone growth. In women serotonin rises along with estrogen which regulates bone metabolism. Serotonin synthesis also relies on some bone supporting nutrients such as calcium and vitamin D3. [R]

Involved in pain response

Serotonin is involved in the perception of pain and when levels become low it causes sensitivity to pain which may cause chronic pain.

Serotonin Receptors

Serotonin has seven families which run from 5-HT1 to 5-HT7 and 15 receptor subtypes of serotonin.

Each serotonin receptor have a specific role within the body.

5HT1A, 5HT2A, 5HT2C, 5HT4, 5HT6, 5HT7 all play a role in regulating depression and anxiety.

5-HT1A

5-HT1A is involved in neuronal inhibition, regulation of sleep, feeding, thermoregulation, hyperactivity (associated with anxiety) and hypoactivity (associated with depression).

5HT1A Serotonin receptor agonists have shown to increase memory, learning, pain tolerance (analgesia). However agonists decrease anxiety, depression, aggression and can also decrease learning.

5HT1A agonists increases dopamine release in the prefrontal cortex. If serotonin is low this may mean dopamine will also be low.

Partial agonists for 5HT1A can decrease positive, negative, and cognitive symptoms of schizophrenia.

5HT1A agonists reduce serotonin release and synthesis.

5-HT1A partial agonists include the drugs Buspar (Antianxiety), Vitazodone/Vibryd(Antidepressant). The antipsychotic drugs Clozapine/Clozaril, Ziprasidone/Geodon, Aripiprazole/Abilify are also partial agonists for the 5-HT1A receptors.

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5-HT1B

5-HT1B receptors play a role in autoregulation of serotonergic neurotransmission. Disorders of serotonergic function are linked to 5-HT1B receptors and can affect emotional regulation, mostly because this receptor subtype can inhibit the release of various neurotransmitters including serotonin, GABA, acetylcholine, and glutamate. [R]

5-HT1B antagonists increases a person’s preference for alcohol intake. It may be because there is a connection between this receptor and GABA which is an inhibitory neurotransmitter that shuts down neuronal signalling in the same way as alcohol.

5-HT1B agonists can increase OCD symptoms and vasoconstriction but decrease aggression.

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5-HT1B receptors inhibit the release of serotonin, dopamine, GABA, acetylcholine, and glutamate [R]

5-HT1B receptors decreases glutamtergic transmission.

Some medications used for migraines and vasoconstrictors are 5-HT1B agonists and include Ergotamine, Oxymetazoline, Sumatriptan and Zolmitriptan.

5-HT1B Partial agonists include Dextromethorphan (cough medicine) and Ziprasidone (Geodon – antipsychotic drug).

Antagonists and inverse agonists Methiothepin (antipsychotic), Yohimbine (aphrodisiac), Metergoline (dopamine agonist), Aripiprazole (Abilify). These antagonists can increase cravings for alcohol.

5-HT1D are involved in locomotion, muscle tone and implicated in the manifestation of anxiety.

5-HT2A plays a role in neuronal excitation, learning and peripheral vasoconstriction platelet aggregation.

The effects of the various psychedelics which includes LSD, psilocin and mescaline depend on the activation of the 5-HT2A receptor. [R]

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Research is showing that 5-HT2A antagonists may be useful in treatments for psychosis, alcohol and cocaine dependence which is likely because 5-HT2A antagonists interfere with the heightened state of dopamine activity associated with these conditions [R]

Serotonin plays an important role in immune system function and shown to activate monocytes (immune system cells) and modulates cytokine and chemokine production in lipopolysaccharides. Cytokine and chemokines are created in the gut and some cytokines are inflammatory. Lipopolysaccharides are toxic byproduct of the breakdown of substances that are used to synthesise neurotransmitters.

When they leak out into the bloodstream from a leaky gut it causes inflammation. Inflammation is implicated in the symptoms of depression. Low serotonin can lead to a leaky gut as most of the intestinal production of serotonin is dependent on a healthy digestive system and a healthy gut colony of beneficial gut bacteria. Processed sugar intake can release cytokines which leads to inflammation.

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Mexamine is a full agonist for many of the serotonin receptors and includes 5-HT2A receptors.

5-HT2A partial agonist drugs inlcude Efavirenz (antiretroviral), Mefloquine (antimalarial) and Lisuride which is an antiparkinson drug and is also a dopamine agonist and antagonist.

5-HT2A antagonist include Trazadone, Mirtazapine (Remeron), typical and atypical antipsychotics. Remeron has shown to increase appetite.

5-HT2B

5-HT2B receptor is involved in stomach contraction and regulates cardiac structure and functions.

5-HT2B antagonists have been used as a treatment for migraine headaches. [R]

Some research is showing the potential for 5-HT2B antagonists as treatments for chronic heart disease.

MDMA (Ecstasy), LSD-25 and most SSRIs are 5-HT2B agonists. [R]

Chlorphentermine which acts as an appetite suppressant is a 5-HT2B agonist. Activation of 5-HT2B receptor has shown to increase risk of valvulopathy. [R]

5-HT2B antagonists include Aripiprazole (Abilify) and Amisulpride (Solian (antipsychotic)).

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5-HT2C

Studies are showing that 5-HT2C receptor activation regulates appetite and food consumption. The 5-HT2C receptor when activated in the hypothalamus has shown to control appetite and can be seen with the weight loss drug known as Lorcaserin.

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Aripiprazole/Abilify a 5-HT2C agonist may be expected to reduce positive symptoms of schizophrenia by reducing dopamine release [R]

Agonists of the 5-HT2C receptor reduces dopamine release. 5-HT2C receptor agonists increases acetylcholine release in the prefrontal cortex. Both agonists and antagonists of this receptor have antidepressant effects. [R]

5-HT3

5-HT3 receptor is involved in nausea and vomiting and implicated in anxiety symptoms.

5-HT4

5-HT4 receptors are involved in gastrointestinal motility and can be found in alimentary tract, urinary bladder, heart and adrenal gland.

The 5-HT4 receptor helps with the movement of food across the GI tract with agonists showing to promote intestinal peristalsis, increase gastric emptying and decrease esophageal reflux. [R]

These receptors are also found in the central nervous system and peripheral nervous system.

The 5-HT4 receptors helps with cognitive processes such as memory and learning. [R]

The 5-HT4 receptors agonists have antidepressant effects.

5-HT5A

5-HT5 receptors are involved in memory and learning with 5-HT5A playing a role in memory consolidation. [R]

5-HT5A has vasoconstrictive and vasodilatory effects. 5-HT5A is involved in a range of psychiatric conditions.

Agonist includes Valernic Acid a phytochemical found in the valerian plant. Antagonist include Risperdone which is an antipsychotic drug.

5-HT6

5-HT6 receptor plays a role in various functions which includes motor control, emotionality, cognition, memory and learning.

Antipsychotic drugs act as antagonists of 5HT6 receptors. Antagonism of 5-HT6 receptor has shown to increase glutamatergic and cholinergic neurotransmission. [R]

It has also shown to facilitate catecholamines dopamine and norepinephrine release in the frontal cortex.

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5-HT6 facilitates GABAergic signalling [R]

5-HT6 activation prevents release of the excitatory neurotransmitters dopamine and norepinephrine in the frontal cortex.

5-HT6 receptor agonists have shown to improve learning and memory in animal studies.

5-HT6 antagonists have been used in treatment of symptoms in patients with Alzheimer’s disease [R]

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5-HT7

5-HT7 receptors play a role in in thermoregulation, circadian rhythm, learning, memory, mood regulation and sleep.

There is mounting evidence supporting a role for the 5-HT7 receptor in depression. [R]

Agonist / Synergist

Vitamins B3, B9, B6, B3, B1, B12, D3, C

Amino acid Tryptophan, 5-HTP

Fats Fish oil (DHA & EPA Omega 3 Fats)

Minerals Magnesium, iron, calcium

Herbs and Spices St. John’s Wort, passionflower, hops, ginseng, nutmeg

Hormone Pregnenalone, testosterone, melatonin, insulin

Brainwaves Alpha, Beta, Delta

Medications SSRIs, SNRIs, Atypical Antipsychotics, Prozac

Other Exercise, sunlight exposure, physical touch (massage, cuddling etc), pain reduction, stress reduction, meditation practices, relaxation, nutritional balancing, eating organic (reduce pesticide), improving gut health, carbohydrates, positive and happy thoughts, cold showers

Magnesium and vitamin B6 is needed to convert tryptophan to serotonin

Magnesium glycinate or citrate forms may be better than other forms that may be inorganic

Tryptophan is needed for the synthesis of serotonin and melatonin

Melatonin is synthesised from serotonin

Melatonin is a sleep inducing chemical. Copper is responsible for producing melatonin, taking copper may increase intense dreams

Tryptophan also supports production of GABA an important inhibitory neurotransmitter which requires serotonin and melatonin for its synthesis

Tryptophan converts to 5-HTP and serotonin

Cholesterol is needed for expression of serotonin receptors

Vitamin B6 deficiency can cause a host of health issues related to mood disorders such as depression and mood swings as it is involved in converting tryptophan into the mood regulating hormone serotonin.

Vitamin B6 plays an important role in aiding sleep by helping to convert tryptophan into serotonin and then into melatonin.

The conversion of 5-htp to serotonin requires zinc, vitamin B6 and vitamin C.

Vitamin B6 is an important co-factor and helps with amino acid metabolism

Serotonin conversion to melatonin is assisted by B5 and maintaining natural circadian rhythm by avoiding artificial lighting after dark and especially once in bed.

Serotonin increases prolactin release and selective serotonin reuptake inhibitors (SSRIs) can cause hyperprolactinemia with sexual side effects linked to the use of these drugs with symptoms including milk production that can occur in men.

Monoamine oxidase A (MAO-A) is involved in the breakdown of the neurotransmitters serotonin, epinephrine, norepinephrine and dopamine.

A healthy gut is important for serotonin production with an estimated 90 percent of serotonin being produced in the digestive tract by healthy gut bacteria

Serotonin converts to melatonin in ideal conditions or settings (darkened room and no artificial light for the sleep duration)

SAM-e may increase serotonin levels

Vitamin B2 is needed by the body to convert vitamin B6 and folate into forms it can use.

Vitamin B2 can help in the absorption of vitamins such as B1, B3, and B6 as well as minerals such as iron, zinc and folic acid. Most of the B vitamins also work well together and are needed by the body.

Vitamin B6 plays an important role in aiding sleep by helping to convert tryptophan into serotonin and then into melatonin.

Melatonin is an important hormone which helps to regulate sleep and wake cycle. Vitamin B6 deficiency has been linked to low production of serotonin which helps produce melatonin. A lack of melatonin causes insomnia.

Studies have shown B6 intake is involved in improvement of mood, anxiety, food cravings and back pain. This may be due to the role that vitamin B6 plays in the synthesis of neurotransmitters such as serotonin which helps to regulate mood. Vitamin B6 with magnesium supplementation has also shown to significantly improve PMS symptoms.

Tryptophan to 5-HTP Synthesis

Tryptophan converts to 5-HTP (5-Hydroxytryptophan) and requires vitamin B3 (niacin), B9 (folate), iron and calcium via enzyme tryptophan hydroxylase (TPH).

5-HTP then converts to serotonin (5-HT, 5-hydroxytryptamine) and requires zinc, vitamin B6 (pyridoxal-5-phosphate), vitamin C(ascorbic acid), magnesium and the enzyme DOPA decarboxylase (DDC).

DOPA decarboxylase (DDC) is needed for the synthesis of dopamine from L-DOPA and serotonin from L-5-hydroxytryptophan.

DDC catalyzes the conversion of aromatic amino acids tryptophan, phenylalanine and tyrosine into their corresponding amines dopamine, norepinephrine, epinephrine and serotonin.

In the final step the pineal gland converts serotonin to melatonin which needs darkness and occurs during deep sleep.

Pantothenic acid (Vitamin B5) is essential for melatonin production.

Vitamin B6 and B12 are needed for the myelin sheath around nerve cells for efficiency and speed of neurotransmission through the brain.

Other B vitamins such as B1 and B12 are also needed for synthesis of serotonin as all B vitamins work synergistically for amino acid metabolism.

B vitamins are needed for the synthesis of many of the neurotransmitters and regulate energy release in brain cells.

Vitamin B9 (Folate) is needed for the production of the serotonin, melatonin, dopamine, and norepinephrine. Methylfolate is the natural form of vitamin B9 found in foods which is able to cross the blood-brain barrier and is the form needed by the central nervous system.

Prozac (an SSRI medication) has shown to upregulate neurogenesis, helping the brain to create new neurons which can increase brain plasticity and potentially reverse aging of the brain. [R]

Folate (natural active form of vitamin B9) regulates tetrahydrobiopterin (BH4 or THB) levels.

BH4 is needed to convert tryptophan into serotonin.

BH4 plays a vital role in cognitive functions and is needed by enzymes in the body that help with dopamine and serotonin synthesis. BH4 is also used by enzymes nitric oxide synthases (NOS) that help to form nitric oxide (NO). It is also an essential cofactor for aromatic amino acid hydroxylases.

Folate helps the body with producing healthy new cells and needed for the synthesis of serotonin, acetylcholine, dopamine and norepinephrine. Folate deficiency can impair memory and cause irritability.

Folate deficiency can decrease BH4 levels which will reduce synthesis of dopamine and serotonin.

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Nutrients that support BH4 levels include folate or the supplement Methylfolate (MTHF), Curcumin and vitamin C.

Methyl folate prevents oxidation of BH4 into BH2. Ensuring adequate supply of NOS enzymes will also help prevent breakdown of BH4.

Copper is needed by MAO enzyme to break down serotonin

Inositol works with choline which when combined form lecithin, an essential component for cell membranes which protect cells from oxidation and protect the myelin sheath. This is important for regulating nerve transmissions

Many studies are showing potential benefits of inositol on mental health conditions such as anxiety, schizophrenia, Alzheimer’s disease, obsessive compulsive disorder (OCD) and attention deficit-hyperactivity disorder ADHD. Reports of inositol use reveal an increased levels of energy and improved memory, mental alertness and concentration. It has also shown to be helpful with treating anxiety.

Inositol can help regulate mood through its involvement in the manufacturing of serotonin, melatonin, dopamine, norepinephrine, acetylcholine and GABA. These neurotransmitters require inositol for transmitting messages between the brain cells. A deficiency of inositol has been linked to various mental health problems which includes depression, anxiety and panic attacks where many of the neurotransmitters are out of balance.

Vitamin D has role in regulating various hormones and neurotransmitters essential for brain health and preventing depression. These include adrenaline, epinephrine, norepinepherine (noradrenaline), dopamine and serotonin. The adrenal gland regulates tyrosine hydroxylase which is the rate limiting enzyme involved in the production of neurotransmitters which is achieved by the gland with activated vitamin D.

A deficiency of this vitamin can lead to depression and seasonal affective disorder (SAD).

Sunlight exposure helps raise vitamin D3 levels which is needed for optimal levels of serotonin release

Calcium can help induce sleep as it aids the brain in utilizing tryptophan, an essential amino acid that helps the body’s ability to naturally manufacture melatonin. Dairy products such as cheddar cheese are abundant in both tryptophan and calcium which help aid in sleep.

Iodine along with selenium plays a very important role in the thyroid by supporting and maintaining its functions in the body. Iodine is needed for T4 and T3 production. In the brain these hormones are needed to activate neurotransmitter serotonin and others such as dopamine, norepinephrine, acetylcholine and GABA. Deficiency in iodine is linked to poor cognitive functions and intellectual disability.

A deficiency in thyroid hormones T4 and T3 can lead to problems with cognition, memory, focus, concentration, sleep, mood and recall.

T4 and T3 hormones regulate gene expression by switching the genes on or off. The genes are needed to regulate neurotransmitters that regulate mood.

Studies have shown that low levels of serotonin are linked to low T3 levels which can affect mood, happiness with symptoms related to depression, social behaviour and anxiety. [R]

GABA which also requires serotonin is also involved in anxiety and needs iodine for its mood balancing functions.

Chromium plays an important role in mood which is regulated by serotonin. This may be due to its effect on insulin and its effects on glucose metabolism.

Studies on animals and humans has shown that chromium reduces activity of 5-HT 2A serotonin receptor.

Aldehyde dehydrogenase enzyme is involved in the breakdown of serotonin, melatonin, dopamine, norepinephrine and epinephrine.

Aldehyde dehydrogenase is needed to process acetaldehyde (a byproduct of alcohol) into acetic acid.

Aldehyde dehydrogenase enzyme requires molybdenum.

Vitamin B12 is a cofactor needed for the production of serotonin and other neurotransmitters which includes, norepinephrine, GABA and dopamine.

B12 deficiency also has an impact on mood, emotions and sleep which can contribute to psychiatric disorders.

B12 deficiency is linked to neurological conditions such as epilepsy, cognitive decline, Parkinson’s, Alzheimer’s and dementia.

Some parts of the brain needed for cognitive functions such as memory and learning are affected by folate deficiency. Additionally high homocysteine levels have been associated with neurological disorders which can also be an indicator for low levels of B12 and other deficiencies such as B6 and B9.

Deficiency of B12 can cause oxidative damage to brain cells leading to cognitive decline. In addition to B12 vitamin B9 is also needed to help the nerves function properly. [R] [R]

Many of the B-complex vitamins also play an important role in keeping the nervous system healthy and the brain functioning properly.

Vitamin B12 deficiency can cause high homocysteine which is also linked to neurodegenerative disorders and can cause damage to the myelin sheath of the neurotransmitters.

L. plantarum increases serotonin and dopamine

Probiotics can improve gut health facilitate the production of serotonin in the digestive system. Approximately 90% of serotonin is made in the digestive tract

Escherichia, streptococcus and enterococcus produce serotonin [R]

Estrogen increases serotonin production, serotonin receptor levels and serotonin receptor sensitivity

In the first two weeks of a women's cycle which is known as the follicular phase, estrogen levels are higher after increasing gradually following menstruation. The increase of estrogen has shown to correlate with elevated levels of serotonin.

Serotonin needs estrogen for its synthesis, prevents degradation, and inhibits reuptake of serotonin. Low estrogen levels may cause serotonin levels to get low which can affect mood

When serotonin levels are sufficient or optimal, estrogen has antidepressant effects and stabilizes mood.

Serotonin and estrogen function synergistically and depend on each other for their role in mood and behaviour.

Estrogen is a serotonin and dopamine modulator.

Omega‐3 fatty acids are important for brain development especially in the early years and is involved in regulating serotonin.

Higher intake of EPA and DHA (Omega 3 fatty acids) during neurodevelopment can support serotonin synthesis, storage, release, and receptor function.

Alpha waves which are associated with meditation and relaxed states of mind promote the release of serotonin which can boost mood and increase creativity.

Positive thinking and practicing gratitude.

Inhibitory neurotransmitters serotonin, GABA and hormone melatonin are linked to slower brainwaves which include alpha, theta and delta.

Norepinephrine is needed for the synthesis and release of melatonin in the pineal gland during sleep. [R]

Excitatory neurotransmitters acetylcholine, dopamine, norepinephrine and epinephrine are linked to faster brainwaves such as beta and gamma frequency waves.

There may be a link between testosterone levels and serotonin function. Women tend to need more serotonin than men.

Bergamot and patchouli essential oils can stimulate release of serotonin and dopamine.

All amino acids can prevent tryptophan uptake which can interfere with serotonin synthesis – usually this can be corrected by taking carbohydrates with tryptophan to help cross the blood brain barrier. The insulin response from carbohydrate intake allows absorption of tryptophan.

Tryptophan intake requires cofactors B6, B12, C, calcium, magnesium, and zinc which are needed to metabolize tryptophan into 5HTP and then convert to serotonin. Having these nutrients in sufficient amounts may reduce need to take drugs that are associated with side effects such as serotonin reuptake inhibitors (SSRI’s).

Tryptophan should not be taken with an SSRI as it may cause excess serotonin.

Tryptophan should be taken in the later part of the morning as part of formulas to increase serotonin synthesis later in the afternoon.

Amino acid balance in the body is important for the synthesis of neurotransmitters and maintaining homeostasis.

It is important to get sufficient levels of sunlight preferably in the 3 hours after sunrise and 3 hours before sunset to avoid harmful intense UV rays. Daily sunlight can help stabilize the circadian rhythm.

L-Tryptophan supplementation can significantly increase serotonin synthesis more efficiently than from dietary intake especially if there is a deficiency as most food source of tryptophan compete with other amino acids.

MAOIs reduce serotonin breakdown, medications such as Isocarboxazid (Marplan) and phenelzine (Nardil) act as MAOIs.

Some medication increase serotonin release which includes Amphetamines (ADHD medication, MDMA), Anorectics (appetite suppressants (dexadrine)), Anti-migraine medications such as triptans (Axert, Amerge, Imitrex) carbamazepine, (Tegretol) and valproic acid. [R] [R]

Bupirone and Lithium stimulate post synaptic receptors. [R]

Pain medications (opioid pain medications) including codeine (Tylenol with codeine), fentanyl (Duragesic), hydrocodone meperidine (Demerol), oxycodone (Oxycontin, Percocet, Percodan) and tramadol (Ultram) can increase serotonergic activity.

Serotonin Reuptake Inhibitor (SSRI) are a class of drugs often prescribed for depression and include the SSRI Antidepressants Paxil, Prozax and Zoloft.

Ultram is an SSRI and activated mu-receptor. Trazadone is a Serotonin Agonist and Reuptake Inhibitor (SARI).

Tricyclic Antidepressants includes Elavil (amitriptyline), Tofranil (imipramine), and Pamelor (nortriptyline).

Serotonin and norepinephrine reuptake inhibitors (SNRIs) include the antidepressants duloxetine (Cymbalta) and venlafaxine (Effexor).

Norepinephrine-dopamine reuptake inhibitor (NDRI) includes Bupropion (Wellbutrin, Zyban) which are used as antidepressants and as tobacco addiction medications.

Illicit drugs such as LSD, Ecstasy, cocaine and amphetamines increase serotonin levels. [R]

Over-the-counter cough and cold medications containing dextromethorphan (Examples include Delsyn, Mucinex DM) can raise serotonin levels.

Anti-nausea medications such as granisetron, metoclopramide (Reglan), droperidol (Inapsine) and ondansetron (Zofran) increase serotonin.

The antibiotic Linezolid (Zyvox) interact with some antidepressants which can cause serotonin syndrome. [R]

Ritonavir (Norvir) is an anti-retroviral medication used to treat HIV/AIDs can cause serotonin syndrome when taken with SSRIs and SNRIs. [R]

Beta, alpha and delta brainwave frequencies are linked to the production of serotonin.

Alpha brainwave frequency 10 Hz may increase serotonin release. This frequency is linked to improved mood, mental clarity, arousal, reduced headache and stimulates the body.

Beta brainwave frequency range from 18 Hz to 24 Hz may induce feelings of euphoria and ecstasy (runners high). Serotonin release occurs around 22Hz.

Delta brainwaves at a frequency between 1 Hz to 3.5 Hz is the slowest of all brainwaves and is related to the unconscious mind (sleep, dreamless deep sleep) state of mind. It is experienced in deep dreamless and restful sleep, unconscious of the material world. These waves are dominant in babies until they reach the age of 1. Needed for healing and regeneration of the brain and body. An example of this brainwave is found in the deepest stage of sleep where dreaming does not occur. In this deep stage it is likely serotonin is converted into melatonin.

When serotonin increases the levels of neurotransmitters GABA, endorphins, dopamine, oxytocin and endocannabinoids also increases.

In prefrontal cortex (PFC) low dopamine and high 5HT can lead to aggression.

Emotion processing areas of the brain includes amygdala and the prefrontal cortex.

Endocannabinoids work with 5HT to modulate the HPA-Axis.

When serotonin increases the hormones DHEA, progesterone, estrogen and thyroid hormone levels also increase.

Cold showers may increase serotonin.

Exercise and diet are some of the natural ways to help with serotonin production without the use of drugs. [R]

Antagonists

Neurotransmitters

Amino Acids BCAAs

Medications Serotonin re-uptake inhibitors (SRIs), 5-HT2A antagonist

Other High fructose corn syrup, Carbidopa-levadopa, Caffeine, Chronic stress, high protein low carbohydrates intake, Ma huang, diet pills

BCAAs (Branched chain amino acids which includes luecine, isoleucine and valine) compete with tryptophan which can impact levels of neurotransmitter serotonin and its synthesis. [R]

When serotonin increases the neurotransmitters epinephrine (adrenaline), norepinephrine (noradrenaline), acetylcholine and glutamate decreases.

When serotonin increases the hormones cortisol, testosterone and estrogen levels decrease.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme for central serotonin biosynthesis and certain substances can inhibit quantity of TPH enzyme.

High fructose corn syrup may reduce tryptophan absorption in the gut which can reduce the amount of TPH enzyme and reduce serotonin production. [R] [R]

Carbidopa-levadopa is a medication used for Parkinson’s which raises levels of dopamine however can affect tryptophan levels which will interfere with serotonin production. [R] [R]

Caffeine may reduce brain serotonin synthesis by inhibiting tryptophan hydroxylase. [R]

Caffeine can reduce brain serotonin/dopamine ratio by blocking adenosine α1 and α2 receptors within the central nervous system. [R]

Chronic stress which causes increased stress hormone cortisol reduces serotonin and other neurotransmitters such as dopamine.

Excessive or high protein intake with low carbohydrate consumption can lower serotonin production.

Opioid pain medications can use up serotonin but can also raise levels too high which can lead to serotonin syndrome.

Ma huang, ephedra can use up dopamine and serotonin and raise norepinephrine to levels which can cause adverse effects.

Diet pills as well as prescription diet pills such as phen-fen, Fasting, phentermine deplete dopamine and serotonin levels.

Serotonin re-uptake inhibitors (SRIs) medications which are prescribed for mood conditions (dysphoria) prevent serotonin from being reabsorbed into storage vesicles. This makes more serotonin available to stimulate the neurons. Examples of SRIs include Prozac, Paxil, and Zoloft.

Lowered levels of estrogen can lower serotonin levels.

Increasing GABA can lower excess serotonin levels.

5-HT2A antagonist can or may lower high serotonin levels.

MAO breaks down serotonin after functions have ended, high levels of this could significantly reduce serotonin levels.

Food Sources of Serotonin

The body needs tryptophan to make serotonin. This amino acid is essential and can be obtained from the diet.

Animal food sources of tryptophan include beef, chicken, turkey, goose, duck, fish (such as salmon), cheese, eggs and milk.

Plant based food sources of tryptophan include nuts (peanuts), pumpkin seeds, sesame seeds, soy bean, soy products, alfalfa, baked beans, beet, broccoli, brussel sprouts, carrots, cauliflower, celery, spinach, sweet potato, turnip, watercress, endive, fennel chive and spinach.

Foods such as whole wheat, potatoes, brown rice, lentils and oats are ideal carbohydrates to take with foods rich in tryptophan.

The spice nutmeg which is an MAOi can increase tryptophan uptake especially when added to milk. The antioxidant spice turmeric is also sometimes added to the milk.

Eggs may be more healthful and provide more nutrients if yolk is not overcooked as fats tend to oxidize when fried or heated.

Cheese contains the amino acid tryptophan and can increase dreams.

Turkey also helps aid sleep and increase dreams. It is the amino acid tryptophan found in turkey that can help with sleep. Eating turkey in the afternoon or for supper can help set the mood for better sleep in the evening. Tryptophan does not easily cross the blood brain barrier and is best utilized when taking at least a teaspoon to 1 tablespoon honey with the turkey.

Eating protein rich food such as chicken or turkey which are also high in tryptophan along with some simple carbohydrates will help tryptophan to cross the blood brain barrier.

Oats and bananas contain tryptophan that will help aid sleep.

Tart cherry juice or extract can help aid in sleep. Montmorency sour cherries (Prunus Cerasus) naturally contain melatonin which is known to aid with sleep. Tart cherry is available as a drink and also in supplemental extract form.

Milk is another source of relaxing nutrients that may help with sleep. You can add some barley malt extract syrup to boost its sleep inducing properties. Milk helps as it contains high amounts of calcium that can help with a good night’s sleep inducing a natural state of relaxation.

Rotate your diet to get the optimal benefits out of the food you eat, rotating helps ensure adequate needs of the body are met sufficiently.

Carbohydrates that have starch such as pasta, potatoes, rice, polenta, breads, cereals and pancakes may also help synthesise serotonin as these carbs may help tryptophan to cross the blood brain barrier. It should be ingested without fats or proteins to speed up digestion and convert tryptophan to serotonin.

Prebiotic foods are also helpful as they feed healthy bacteria and are mostly included in starchy carbohydrate foods. It may help to eat foods such as pasta and potatoes cold as it becomes resistant starch which allows a gradual release of sugar in the blood stream which may help to avoid a rapid spike in blood sugar levels.

Recommended Daily Allowance

There are no set amounts of recommended neurotransmitters. Neurotransmitter synthesis depend on the nutrients obtained from the diet or supplementation. Brainwave frequencies and other practices such as meditation can also effect levels of neurotransmitters.

Neurotransmitters are made from protein and amino acids. They also need other cofactors such as vitamins and minerals for synthesis.

Dietary protein is therefore essential and getting adequate, sufficient supply of all nutrients in the correct balance is essential.

A healthy adult needs between 40 and 70 grams of daily protein intake. This can go up to as much as 90 grams for active and athletic people.

Diet and nutritional supplementation can be tweaked to meet the requirement of necessary nutrients and ensuring adequate levels of neurotransmitters.

Neurotransmitters operate at different times of the day and are largely dictated by light exposure. Serotonin and dopamine are produced mostly during daylight hours. During dark hours the serotonin converts to melatonin and more GABA is present.

Brainwaves also correspond with the different neurotransmitters. In the morning the brain has alpha waves which increase to beta waves throughout the day. Gamma waves may also facilitate the daylight hours and ideal for higher learning. The alpha and beta waves facilitate acetylcholine and dopamine.

Other factors such as the seasons and a woman’s monthly menstrual cycle can also determine the amount of specific neurotransmitters needed and at which point of the cycle. For example in the luteal phase GABA is the primary inhibitory neurotransmitter as this part of the phase we see a spike in the hormone progesterone which works synergistically with this calming neurotransmitter. Serotonin will also be present at this time as well as more conversion into melatonin to facilitate sleep.

Serotonin will be more available during the follicular phase which seems to increase with the rise of the female reproductive hormone estrogen.

In northern climates during winter with the lack of sunlight there is likely to be a lower production of serotonin or higher amounts of this may convert to melatonin possibly through daylight hours shortening. This may pick up slightly as spring emerges. Many people also find that spring makes them feel motivated.

Everyone is unique and a person’s life experience may dictate more of what neurotransmitter may be required on any given day. An example is a highly stressed person is very likely to be needing more serotonin and dopamine and possibly other neurotransmitters as the chronic stress quickly depletes all neurotransmitters and can lead to a state of depression.

Checking deficiency levels of neurotransmitters can help determine what may be needed along with using brainwave measuring device which uses electroencephalography (EEG) may help identify the neurotransmitters needed and balancing levels.

Serotonin Supplementation

Amino acid tryptophan is available as a single supplement in powder form or capsules.

Tryptophan is the main amino acid precursor for serotonin and is often the most common to supplement with in order to increase production of serotonin. Niacin supplements can also help increase serotonin. It is also important to have adequate levels of the necessary cofactor nutrients to help with serotonin synthesis.

High protein meals should be avoided when supplementing with tryptophan as all amino acids prevent tryptophan from crossing the blood brain barrier. Tryptophan can effectively cross blood brain barrier when taken on an empty stomach and with some carbohydrates such as fruit or fruit juice, or a teaspoon of honey. It is important to avoid hot beverages when taking tryptophan or any other amino acids.

If supplementing with Tryptophan with any adrenal issues it is important to take high dosed vitamin B5 and vitamin C to help support adrenal health.

5-HTP can be taken instead of tryptophan. The effects of 5-HTP are different from Tryptophan where 5-HTP may induce more sleepiness. It may be ideal to take tryptophan in the morning and 5thp before bedtime.

In some countries tryptophan requires a prescription. 5-HTP which is a metabolite of tryptophan may be more readily available in countries where tryptophan is restricted.

Tryptophan is a precursor to niacin as well as serotonin which relies on niacin.

High tryptophan intake can reduce uptake of tyrosine.

Hyperthyroidism has been demonstrated by some studies observing low dietary intake of tryptophan.

Tryptophan or 5-HTP can also help increase serotonin. Omega 3 fatty acids and folate supplements may also help when trying to raise serotonin levels with supplements. Other supplements to consider are multivitamins, antioxidants, vitamin B complex, selenium, chromium, vitamin E and ginko biloba.

Supplements that support acetylcholine may also be helpful in raising serotonin levels as small amounts are needed to activate release of dopamine and serotonin.

Phosphatidylserine can stimulate acetylcholine which is necessary for cognitive functions such as memory and is needed to stimulate the release of dopamine and serotonin.

Deficiency Symptoms of Serotonin

Signs and symptoms of serotonin deficiency include:

Depression
Anxiety
Pain sensitivity
Unhappy (dissatisfaction)
Apathy
Irritability
Anger or frustration
Impulsivity
Depression
Loss of pleasure towards things you once enjoyed
Difficulty staying positive or feeling joy
Low mood on cloudy days
Less socializing
Lack of enjoyment in relationships
Prone to isolation
Sleep problems (insomnia, sleep difficulty or disturbed sleep)
Poor dream recall
High fear levels (phobias, anxiety, panic)
Pain sensitivity
Difficulty concentrating
Impatience
Carbohydrates cravings*
Constipation
Short attention span
Scattered thought patterns
Craving sweets
Craving high carbohydrate foods (mostly simple carbs such as pasta, white bread etc).

High sugar and high carbohydrate foods also increase dopamine as well as serotonin and both neurotransmitters are linked to feelings of pleasure and increase positive mood.

Increasing serotonin production may lower fear levels.

Although there is limited evidence that low serotonin is a cause of depression it is associated with depression, however many other neurotransmitters, hormones and other factors may also play a more significant role in depression.

Chronic stress is quite common in most people and if improperly managed can cause health implications which affects neurotransmitter balance and will consequently affect mood leading to mood related conditions. Stress increases cortisol which is found to be high in people with depression along with low levels of serotonin.

Selective serotonin reuptake inhibitors (SSRI) are drugs that act by keeping serotonin across a gap (cleft) to receptors on the nerve cells (neuron) and keeping it in this gap. Under normal physiological conditions serotonin is reabsorbed by the nerve cells and recycled (reuptake). SSRI simply inhibit this reuptake process. SSRIs do not help synthesise serotonin but instead create the illusion of sufficient levels of serotonin when actually a deficiency of serotonin still exists.

Serotonin is linked to emotion and mood with a deficiency linked to depression and anxiety related disorders. Serotonin is known as the happy hormone and when levels are low it can greatly impact mood and lead to mood related disorders.

Vitamin B5 (Pantothenic acid) which is also known as the anti-stress vitamin is involved in the production of hormones in the adrenal glands. Cortisol is a hormone produced by the adrenal gland which is needed to balance the effects of stress. Various nutrients which includes pantothenic acid are needed by the adrenal glands in the manufacturing of important hormones such as cortisol, progesterone and epinephrine. High levels of stress can rapidly deplete pantothenic acid and produce symptoms of adrenal fatigue. Supplementing with additional amounts of this nutrient can help replenish these essential hormones. [R] [R]

High protein diets along with very low carbohydrate diets or omitting carbohydrates can reduce serotonin production causing a host of symptoms that affect the mental state and feelings of happiness and wellbeing.

Low serotonin with high dopamine levels has been linked to kleptomania.

Serotonin is needed for mood regulation which is why low levels affect mood and reduced serotonin activity is linked to depression.

Carbohydrate cravings may increase during winter and is linked to seasonal affective disorder SAD. This may be because during winter period serotonin levels may be lower than in any other seasons. The lack of sunlight needed to produce vitamin D in the body also plays a role. If serotonin levels are low carbohydrate cravings may be a response or sign that tryptophan is needed to cross blood brain barrier to help with serotonin synthesis.

People with low serotonin may find that they are craving more carbs in the winter months.

Although low serotonin is associated with depression some studies are showing that some people with low serotonin may not feel depressed. [R]

Carbohydrate cravings can be caused by low blood sugar, sleep deprivation as well as serotonin levels. Carbohydrates also help tryptophan to cross the blood brain barrier. Carbohydrate cravings can be a good indicator of low serotonin. Carbohydrate intake such as honey quickly increase serotonin levels by allowing tryptophan to cross the blood brain barrier, the main precursor needed for serotonin synthesis.

Women need more serotonin than men which may explain the excess carb craving seen in women. Serotonin also acts with the dominant female sex hormone estrogen.

Women have more problems with carb cravings which can be seen commonly during luteal phase of the menstrual cycle which results from low serotonin. Women also have a problem with staying on task at hand again due to serotonin lowering effects and also decrease in estrogen.

As women go through their monthly cycle the presence of more estrogen increases the requirement for sufficient serotonin levels as estrogen decreases serotonin receptor density. Both estrogen and serotonin work synergistically for cognitive functions and balanced mood. Around the follicular phase when estrogen rises higher women need more serotonin to avoid cravings which are usually carb based and for balanced mood, wellbeing and to stay focused (improving concentration).

Men with higher body fat have more aromatase enzymes which increases estrogen and this can create a craving for carbohydrates. Higher body fat may mean that more carbohydrates are needed for an increase in serotonin which will in effect reduce cravings for carbs.

Tryptophan is difficult to cross the blood brain barrier and all other amino acids compete for absorption, this can cause reduced levels of serotonin.

Having little or no carbohydrates in the diet can make it more difficult to allow tryptophan to cross the blood brain barrier. Tryptophan or 5HTP supplementation along with some carbohydrates and excluding other amino acids during ingestion may help the amino acid to cross the blood brain barrier.

Serotonin may have a role in patience. Study on mice show that they are more likely to be patient and await a reward if serotonin levels are sufficient. [R]

Balanced neurotransmitters are needed for quality sleep. Having adequate levels of serotonin will maintain quality sleep patterns as it regulates circadian rhythm and is needed to form melatonin.

Certain neurotransmitters are produced in sleep which includes GABA along with the conversion of serotonin to melatonin. Acetylcholine is produced during REM sleep which occurs around 2-3am depending on the time a person has fallen asleep. [R]

Dieting or reducing food intake significantly reduces the building blocks for neurotransmitter production such as proteins and amino acids which are the main precursors. Various cofactor nutrients such as vitamins and minerals are also needed for the production of neurotransmitters and insufficient amounts can impair production.

Studies have shown that dieting can impair neurotransmitter function and lead to depression. [R]

Dieting overall may not be an effective strategy for reducing weight as the continued depletion of tryptophan will increase cravings for carbohydrates which can consequently cause weight gain. Low serotonin can lead to weight gain, depression, excessive craving for carbohydrates, eating disorders (binge eating, bulimia), severe PMS and seasonal affective disorder (SAD).

Low serotonin also lowers melatonin the sleep hormone which requires serotonin as a precursor. This can lead to poor sleep patterns causing insomnia. Sleep disturbances lead to mood issues and feeling tired throughout the day.

Low serotonin along with low dopamine reduces focus, impairs cognitive function and affects mood as well as pain threshold.

Impaired conversion of tryptophan to serotonin can affect mood and cognition.

Depression is linked to lowered levels of various neurotransmitters including serotonin, dopamine and norepinephrine. Other factors also play a role in depression such as hormonal imbalance, oxidative stress as well as general stress.

High fear levels characterised by phobias, anxiety and panic disorders are linked to serotonin deficiency.

Lowered levels of serotonin are linked to aging. Estrogen is needed to increase serotonin, in menopausal women this hormone declines significantly. Low serotonin is also linked to low levels of testosterone. When serotonin is reduced this hinders the production of melatonin which requires serotonin.

Tryptophan or 5-HTP supplementation can help increase serotonin which can improve many of the symptoms associated with low serotonin. Tryptophan levels influences lowered or increased levels of serotonin and many of the symptoms of low or high tryptophan can be attributed to serotonin synthesis.

Causes of low serotonin include:

Impaired gut health (healthy gut bacteria strains help produce serotonin from tryptophan in intestines)
Low tryptophan intake
Tryptophan deficiency - low in those with autism
High intake of competing amino acids
Lack of carbohydrates (helps to cross the blood brain barrier)
High or excessive BCAA intake
Inadequate cofactor nutrients
Malnutrition or poor diet
Dieting
High stress levels (causes high cortisol)
Inflammatory conditions
High pesticide levels (impairs gut health)
Deficiency of precursor and cofactor nutrients
Vitamin D deficiency
Low estrogen
Low testosterone
Aging
Menopause
Parasite infestation (pinworms and other parasites use up serotonin and deplete nutrients)
Pain

Tryptophan converts to another amino acid 5-HTP and is a precursor for the neurotransmitter and hormone serotonin and melatonin. A deficiency can also lead to a deficiency of serotonin and melatonin which greatly impacts sleep.

Tryptophan is important for cognition as it is needed to produce neurotransmitter serotonin which has a very important role in cognitive function, memory and learning as well as balancing mood.

[R]

Elevated blood levels of BCAA deplete tryptophan in the brain, which causes low serotonin.

Tryptophan and serotonin type of depression

Low mood can be linked to either low tryptophan or low tyrosine and in many cases even both. Each type has various clues that can help pinpoint to which is causing the low mood. In low moods linked to tryptophan there is also a low production of serotonin, a key neurotransmitter that helps balance mood. When tryptophan is very low there is a craving for sweets and foods high in carbohydrates. People with this type of craving will find they are wanting to eat simple carbs more of the time such as white bread, pasta, rice and other simple carbs. Sleep is also a major clue to low mood associated with low tryptophan as it is linked to insomnia which may be corrected with supplementation. Tryptophan needs carbohydrates to be able to cross the blood brain barrier which explains the cravings for carbohydrates. Gut health is also important as most of the serotonin is produced in the gut. Foods high in pesticide aggravate gut health, impair digestion and reduce tryptophan levels. Women suffering from PMS or PMDD with mood swings and irritability during late luteal phase are likely to be low in serotonin and may notice a reduction of symptoms on taking oral supplementation of tryptophan.

Depression can be a balancing act between the two neurotransmitters serotonin which needs tryptophan and norepinephrine which needs tyrosine or phenylalanine. There needs to be a healthy balanced ratio of both neurotransmitters. In some cases taking high doses of tryptophan to increase serotonin can cause psychiatric and depressive symptoms to become worse when other neurotransmitters such as dopamine or norepinephrine may be deficient. If serotonin levels are low then tryptophan use may be very helpful and reduce associated symptoms of deficiency but if norepinephrine or dopamine is low these can be made worse, in this case tyrosine or phenylalanine should help address symptoms associated with depression.

People with high fear levels (phobias, anxiety, etc.) are usually deficient in serotonin. The amino acid tryptophan is converted into niacin which is converted into serotonin.

Supplementation of tryptophan or niacin will increase serotonin production and lower fear levels. Prozac and other similar drugs increase serotonin by decreasing its degradation, enabling the users to live life with less fear. It's easy to do the same thing by increasing tryptophan in the diet or supplementing with more niacin which may be a safer option.

People who crave excess carbohydrate food may end up reaching for more simple sugars such as processed sugar are likely to be deficient in tryptophan. However although the sugar helps cross the blood brain barrier and stimulates the pleasure inducing feelings associated with dopamine release which will only work for a shorter duration needing to increase more sugar next time in order to get the same response. This excessive sugar intake may be counterproductive in the long term creating all kinds of health imbalance. Excess simple sugars are also converted to saturated fats which if out of balance with essential fatty acids adds to more health related problems.

The healthiest approach of replenishing tryptophan levels and serotonin synthesis is a healthy diet that also supports the gut health as healthy bacteria can help synthesise serotonin in the intestines.

A PET scan of the human brain showed that it can take 5 hours for tryptophan to convert to serotonin after ingestion of amino acid consumption. [R]

Most psychiatric and medical professionals rely on symptoms and the diagnosis of certain conditions associated with neurotransmitter imbalance instead of directly observing neurotransmitter levels. Medications are prescribed to see if symptoms are corrected and treatment is continued if there are signs of improvement.

Holistic practitioners use certain other test to determine neurotransmitter levels.

Neurotransmitter Tests are available that can give a full profile of the levels of each neurotransmitters.

Urine Amino Acids Test (UAA) can help determine the level of precursor amino acid for the corresponding neurotransmitter. For serotonin the precursor amino acid level to check for will be tryptophan and for dopamine the levels of phenylalanine and tyrosine will need to be evaluated.

Neurotransmitter Test can show the overall levels of neurotransmitters which can be compared against the UAA.

Comparisons can be made between amino acid availability and actual amount of neurotransmitters it is being converted to.

The Metabolic Analysis Profile Test (MAP test) can give some indication of breakdown of neurotransmitters.

Other tests are also available to help determine if neurotransmitters have high or low levels of enzymes involved in breaking down the neurotransmitter such as tests for MAOs or DAOs.

Hair mineral analysis can show a profile of nutritional status to help determine levels of vitamins and minerals.

Evaluating BH4 levels can also be helpful in determining the levels of dopamine and serotonin as these two neurotransmitters need this for synthesis.

Using a combination of these tests may help identify clearer details of the overall neurotransmitter levels.

Evaluating symptoms related to the fluctuations of neurotransmitters against these test may also help with determining neurotransmitter levels.

DHEA which increases when serotonin increases is found to be low in those with schizophrenia*. Having low serotonin may also mean reduced DHEA.

Toxicity Symptoms of Serotonin

R High serotonin is uncommon however is possible through improper supplementation or chronic intake of drugs that increase serotonin. It is unlikely to be a result of dietary food intake.

Signs and symptoms of excess serotonin including symptoms of serotonin syndrome include:

Serotonin Syndrome
Hyperthermia
Poor cognitive functions
Reflexes
Myoclonus (sudden twitching or jerking of muscle(s))
Rapid heart rate
Irregular heartbeat
High blood pressure
Unconsciousness
Loss of Gastrointestinal (GI) control
Dilated pupils
Muscle rigidity
Agitation
Anxiety [R]
Diarrhea
Loss of coordination
Muscle twitching
Muscle spasms
Vomiting
Diarrhea
Fever
Shivering
Seizures
Agitation
Depression
Apathy (Emotional flatness or dullness)
Passivity (acceptance of whatveer happens without resistance / response)
Insomnia or other sleep problems
Difficulty concentrating and learning
Poor memory (amnesia)
Impaired decision making (Indecisive, unable to make decisions and to act on them)
Sexual dysfunction

5HT1A, 5HT2A 5HT2C 5HT4, 5HT6, 5HT7 all play a role in regulating depression and anxiety.

Some studies show that patients with anxiety produced more serotonin in the amygdala.

[R ]

Monoamine oxidase A (MAO) is involved in the breakdown of the neurotransmitters serotonin, dopamine, epinephrine and norepinephrine, after their function has ended.

Study on a Dutch family with a genetic defect causing a deficiency of MAO-A (needed to degrade serotonin and norepinephrine) showed an increase of anger (related to Norepinephrine) and suppression of fear (linked to high serotonin).

The men in this family had double the normal levels of norepinephrine and nine times the normal levels of serotonin. The high norepinephrine made them get angry easily and the high serotonin almost completely eliminated any feelings of fear. This combination resulted in high aggression and violent behavior. They get angry and have no fear of the consequences of attacking those who make them angry.

[R ] [R] [R] [R] [R] [R]

High serotonin increases violent tendencies common in men, however other factors such as exposure to violence such as in a war zone also plays a role.

If too much tryptophan is converted in serotonin and with MAO deficiency this can lead to high levels of serotonin which can reduce fear to such a level so as to create aggressive behaviour.

Excessive tryptophan symptoms will be similar to excessive serotonin and a condition known as serotonin syndrome which can be life threatening and requires urgent medical intervention.

Anxiety related disorders are usually a result of high serotonin. Anxiety symptoms are the hallmarks of excess serotonin.

The following medications can increase serotonin levels:

Selective serotonin reuptake inhibitors (SSRIs)
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
Antidepressants such as trazodone, duloxetine (Cymbalta) and venlafaxine (Effexor)
Bupropion (Wellbutrin, Zyban) antidepressant and tobacco-addiction medication
Tricyclic antidepressants
Opioid pain medications
Lithium
Monoamine oxidase inhibitors (MAOIs)
Over the counter cough and cold medications containing dextromethorphan
Anti-nausea medications such as metociopramide (Reglan) and ondansetron (Zofran)
Anti-migraine medications such as triptans (Axert, amerge, Imitrex)
Carbamazepine (Tegretol) used to treat epilepsy and nerve pain
Valproic acid (Depakote) used to treat bipolar disorder
Linezolid (Zyvox) antibiotic
Ritonavir (Norvir) a protease inhibitor and an antiretroviral medication used to treat HIV/AIDs

Illegal drugs including LSD, Ecstasy, cocaine and amphetamines can increase serotonin levels and excessive use can lead to serotonin syndrome.

Serotonin syndrome is a life threatening condition where serotonin levels are elevated to dangerous amounts and can be a result of overconsumption or overdose of supplements or medications that increase serotonin.

Medications such as Dextromethorphan have shown to induce serotonin syndrome [R]

Serotonin plays a role in the perception of reality with psychedelic drugs involved in the serotonin pathways altering a person’s view of reality.

Herbal supplements such as St John’s wort, ginseng and nutmeg also increase serotonin.

Nutritional supplements such as 5-HTP and SAM-e also increase serotonin.

High serotonin levels may be reduced by increasing factors that lower levels, such as taking supplements or medications that act antagonistically. 5-HT2A antagonist lower serotonin.

Lowering estrogen if in excess or if estrogen dominant conditions are present and increasing GABA may also help.

Increasing nutrient intake that support MAO function can also help breakdown serotonin.

Certain drugs such as Prozac increase serotonin by decreasing its degradation and long term use can increase serotonin to high toxic levels.

Excess serotonin may trigger the body to flush out more of it to the point enough of the neurotransmitter is reduced causing much of the symptoms of serotonin deficiency (instead of toxicity) such as low mood and issues with sleep.

A deficiency of serotonin as well as toxic build-up of serotonin can both cause insomnia. People with sleep difficulties will not feel well rested and difficulty with sleep will make a person feel tired and fatigued. A toxic build-up of serotonin may also mean that it is not adequately converting to melatonin which needs darkness as well as some nutritional cofactors.