Serotonin plays important roles in the resolution of mood, sleep, and appetite.
Serotonin is an inhibitory neurotransmitter synthesized by enzymes that act on tryptophan and/or 5-HTP.
Neurotransmitters are divided into two basic categories:
– Excitatory neurotransmitters stimulate the brain and body.
– Inhibitory neurotransmitters calm the brain and body.
Just as levels of individual neurotransmitters are important in maintaining optimum health, so is the proper balance between your excitatory and inhibitory systems.
Serotonin, generally regarded as the “happiness molecule,” contributes to the feelings of calm and well-being that eases depression and anxiety, supports sleep, and decreases appetite.
Serotonin is stored in presynaptic vesicles and released to transmit electrochemical signals across the synapse. Extensive research has been conducted surrounding serotonin and acts as a target for symptoms like low mood, compulsions, anxiousness, and headaches.
Serotonin acts, in most cases, as an inhibitory neurotransmitter and, like GABA, modulates neuron voltage potentials to inhibit glutamate activity and neurotransmitter firing. Serotonin neurons have large numbers of axons and are important in integrating neural circuits. This also provides an explanation for serotonin’s role in so many health concerns.
References:
– How to increase serotonin in the human brain without drugs [L]
– Carcinoid Syndrome [L]
Kamoun P, Douay O. Sérotonine et autisme [Serotonin and autism]. Ann Biol Clin (Paris). 1980;38(4):201-5. French. PMID: 6160783.
Leibowitz SF. The role of serotonin in eating disorders. Drugs. 1990;39 Suppl 3:33-48. doi: 10.2165/00003495-199000393-00005. PMID: 2197074.
Stasi C, Sadalla S, Milani S. The Relationship Between the Serotonin Metabolism, Gut-Microbiota and the Gut-Brain Axis. Curr Drug Metab. 2019;20(8):646-655. doi: 10.2174/1389200220666190725115503. PMID: 31345143.
Moroianu LA, Cecilia C, Ardeleanu V, Pantea Stoian A, Cristescu V, Barbu RE, Moroianu M. Clinical Study of Serum Serotonin as a Screening Marker for Anxiety and Depression in Patients with Type 2 Diabetes. Medicina (Kaunas). 2022 May 11;58(5):652. doi: 10.3390/medicina58050652. PMID: 35630069; PMCID: PMC9146121.
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Elevated serotonin may be associated with symptoms of:
- increased anxiety,
- agitation
- and diarrhea (IBS- like symptoms).
Serotonin levels may be increased by low protein or high-carbohydrate meals, insulin, and tryptophan or 5-HTP supplementation. Many mood altering medications, including SSRIs and SNRIs, may influence serotonin levels. L-theanine may affect serotonin function.
Note: Significantly elevated serotonin levels may be associated with additional pathology (i.e. carcinoid tumor). Suggest further work up depending on the clinical picture.
Serotonin signaling in the central nervous system (CNS) may influence mood, appetite, sleep, memory and learning, homeostasis, and sexual behaviors. Altered levels of urinary or plasma serotonin are thought to play a role in many disorders including anxiety, depression, obsessive compulsive disorder and phobias.
Elevated plasma serotonin and platelet serotonin levels are a common finding in autistic patients, and may contribute to psychiatric disorders such as schizophrenia.
There are a great many serotonin receptors with different affinities, expression and function.
The main diseases that may be associated with elevated levels of serotonin are neuroectodermal tumors, in particular carcinoid tumors arising from gastrointestinal (GI) enterochromaffin cells.
Only about 10% of midgut carcinoids produce enough serotonin to cause symptoms.
Symptoms of serotonin excess (Serotonin Syndrome), are wide-ranging. A triad of symptoms including altered mental status (usually anxiety), neuromuscular hyperactivity or hyperreflexia, and autonomic instability, is suspicious for serotonin excess.
Exogenous estrogens have been shown to raise both serotonin and 5-HIAA levels in postmenopausal women.
Medications that may increase serotonin include:
- serotonin reuptake inhibitors (SSRIs)
- monoamine oxidase inhibitors (MAOIs)
- antidepressants: bupropion, trazodone
- migraine medications
- pain medications
- lithium
- dextromethorphan (cough suppressant)
- antiemetics
The gastrointestinal tract produces about 80% of the body’s serotonin. During the “first pass” through hepatic circulation, monoamine oxidase A (MAO-A) metabolizes 30-80% of GI serotonin to 5-hydroxyindoleacetic acid (5-HIAA).
Serotonin metabolism requires selenium, magnesium and vitamin B3 as cofactors.
Mutations, or single nucleotide polymorphisms (SNPs), in MAO-A may affect serotonin degradation. SNPS or mutations in serotonin receptors may affect responses to serotonin.
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Low serotonin may contribute to mood concerns including anxiety, OCD, depression, anger and a sense of discontentment. Low serotonin may also be associated with poor sleep quality and appetite changes, as well as chronic fatigue, rheumatoid arthritis, and over-all lassitude. Failure to regenerate tetrahydrobiopterin [BH4], an essential cofactor for serotonin synthesis, may decrease serotonin levels, and could be reflected in urine. BH4 regeneration may be supported by folates, vitamin B3, C, molybdenum and zinc.
Additionally, production of serotonin requires vitamin D, iron and vitamin B6. Tryptophan is the essential precursor of serotonin. 5-HTP may increase serotonin, and L-theanine may affect serotonin function.
Serotonin signaling in the central nervous system (CNS) may influence mood, appetite, sleep, memory and learning, homeostasis, and sexual behaviors. There are a great many serotonin receptors with different affinities, expression and function. Decreased serotonin levels have been associated with obsessive-compulsive disorder (OCD), anger, insomnia, and depression. Some eating disorders and migraine headaches may also be related to low serotonin levels.
Low urinary serotonin levels during pregnancy have been associated with increased risk of premature birth. In the peripheral nervous system, low levels of serotonin may affect gastrointestinal motility (constipation), and possibly bone mass.
Low serotonin levels have been associated with irritable bowel syndrome. Cyproheptadine is an antihistamine that decreases serotonin levels.
Studies indicate that serotonin depletion is more likely to affect mood in those with a family history of mood disorders. Mutations or single nucleotide polymorphisms (SNPs) in specific enzymes may affect serotonin synthesis or degradation. Several SNPs have been identified and linked to depression; research continues in this area.
Serotonin is unable to cross the blood-brain barrier and must be synthesized in the peripheral and central nervous system. Tetrahydrobiopterin, iron and Vitamin B6 are required cofactors for serotonin synthesis.
The gastrointestinal (GI) tract produces about 80% of the body’s serotonin. During the “first pass” through hepatic circulation monoamine oxidase (MAO) metabolizes 30-80% of GI-derived serotonin to 5-hydroxyindoleacetic acid (5-HIAA).
Serotonin may also be converted to 5-HIAA in the lungs. Urine and plasma levels of serotonin may vary with the intake of certain foods rich in serotonin, and medications that alter serotonin levels.
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Serotonin levels may be increased by exercise, increased daylight (or daylight equivalent) exposure, low-protein or high-carbohydrate meals, insulin, or by Tryptophan or 5-hydroxytryptophan (5-HTP) supplements.
Some studies indicate that therapeutic massage may also elevate serotonin levels.
The herbs St. John’s wort and ginseng may elevate serotonin levels.
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