Trait: Serotonin Synthesis

Dr Haran Sivapalan


January 20, 2020

Your latest Serotonin Synthesis trait analyzes how effectively you produce (or 'synthesize') serotonin. This has an effect on the function and activity of your brain and digestive system.

What is serotonin?

Serotonin (also known as 5-HT) is often dubbed our “happiness hormone.”

It is a neurotransmitter (i.e. a nerve communication molecule) involved in the regulation of our mood and emotions, including feelings of anxiety, surprise and happiness.

Brain circuits that use serotonin also control our sleep pattern, food intake, processing of pain, and so-called ‘cognitive’ functions, such as attention, memory, decision-making and problem solving.

Serotonin’s actions are not just restricted to the brain, it plays an important role in our enteric nervous systemthe network of nerves that controls the function of our gut.

In addition to acting as neurotransmitter, serotonin also acts as a hormone – a chemical signal that is transported in the bloodstream. Cells lining our digestive system produce serotonin, which then enters the bloodstream, where it has an effect on blood clotting, wound healing and blood flow.

Within the gut itself, serotonin plays a role in the movement of our intestines, secretion of enzymes and immune function.

Alongside dopamine, adrenaline, noradrenaline and histamine, serotonin belongs to a class of chemically-related neurotransmitters known as monoamines.


  • Serotonin (5-HT) is an important neurotransmitter involved in mood, emotion, cognition, sleep, food intake and control of our digestive system.
  • Serotonin affects our digestive health, including the movement of our intestines, secretion of enzymes, and immune function of the gut lining.

What are the roles of serotonin?

Serotonin is a key neurotransmitter in the brain and spinal cord (collectively termed our central nervous system), as well as in our enteric nervous system (the network of nerves that control our gut).

Neurotransmitters are chemicals that transmit a signal from one nerve (or neuron) to another, across a gap called a synapse.

When a serotonergic nerve is stimulated, serotonin is released from special storage chambers called synaptic vesicles. Serotonin then travels across the synapse (or synaptic cleft) and binds to receptors on a receiving or post-synaptic nerve. The act of serotonin binding to receptors activates the post-synaptic neuron, and the nerve impulse is conducted onwards. In this way a signal is passed from one neuron to another.

Serotonin transmits signals between neurons in large brain networks that control emotion, cognition, sleep, and food intake.

Mood and emotion

In the popular press, serotonin is often inextricably linked with feelings of happiness.

In reality, serotonin plays an important role in regulating several different emotions, including fear, disgust, anger, surprise and sadness.

One key area involved in processing emotions is our limbic system – a network of interconnected structures deep within the brain that register and respond to emotional stimuli, e.g. a snake, or a smiling face.

The limbic system is particularly rich in serotonergic neurons (nerves that use serotonin), which become activated when we’re exposed to emotional stimuli and experience various emotions.

Furthermore, changes in serotonin levels and, thereby, the activity of serotonergic neurons in the brain, affect the way we process and experience emotion.

For example, studies show that increased activity of serotonergic neurons is associated with enhanced recognition of both happy and fearful facial expressions.

Serotonin is also heavily involved in our mood. Mood, which is different from emotion, refers to our predominant emotional state over a longer time period.

Mental illnesses that affect mood, such as depression and anxiety disorders, are associated with changes in the function and activity of serotonergic brain circuits.

Similarly, drugs such as antidepressants, which increase activity in serotonergic brain circuits, can help elevate our mood.


  • Serotonin is important for the activity of brain circuits that allow us to process and experience different emotions.
  • Serotonin influences our mood - longer lasting emotional states.


Serotonin is also important for complex cognitive functions, such as learning, memory, attention, decision-making and problem solving.

These cognitive functions are carried out, in part, by networks of serotonergic nerves (neurons) that are distributed widely across the brain.

For example, networks of serotonergic nerves that project from a brain structure called the hippocampus to our cortex (the outer layer of brain) are thought to subserve our ability to learn and remember.


  • Serotonin influences our ability to think, remember, plan and make decisions.


Serotonin both directly and indirectly affects our sleep/wake cycle.

It is a complicated relationship, but it’s generally thought that serotonin acting directly within the brain promotes wakefulness.

By contrast, serotonin also gets converted to melatonin – our body’s natural sleep hormone - and this makes us feel sleepy. To read more about melatonin, check out the Night-time Glucose Regulation (Melatonin) blog.

To simplify things, we can say that we require a healthy balance of serotonin and melatonin to ensure we get a good night’s sleep.


  • Serotonin helps to regulate our sleep cycle.
  • Serotonin is required to produce melatonin - our body's sleep hormone.

Food intake

Whether or not we feel full is influenced by more than just how much food is physically churning away in our stomach.

Our brains have complex networks of neurons that control our appetite, desire for food, satiety (feelings of fullness) and food intake. Serotonin interacts with these brain networks to regulate how much food we eat.

As explained in the Leptin Resistance blog, many of these appetite-controlling circuits involve a brain structure called the hypothalamus.

Our hypothalamus has a specialized group of neurons (called POMC neurons) that, when stimulated, suppress our appetite. Serotonin can directly activate these neurons, thereby curbing our appetite and reducing our food intake.

In addition to POMC neurons, our hypothalamus contains another set of neurons (called AgRP neurons) that do the exact opposite – they increase our appetite when activated. Serotonin inhibits these neurons, which also reduces food intake.


  • Serotonin acts on brain circuits that control food intake, appetite and satiety (feelings of fullness).
  • Under normal conditions, serotonin may act to reduce appetite and food intake.

Digestive system function

Did you know our gut has its own nervous system, sometimes referred to as our ‘second brain?’

The enteric nervous system is the large network of nerves that controls movement of our gastrointestinal tract (a process called peristalsis), secretion of digestive enzymes, local blood flow to the gut, and the immune function of our digestive system, including the composition of bacteria living in our gut (our gut microbiome).

Just as it facilitates communication between neurons in the brain, serotonin is also a key neurotransmitter for nerves of our enteric nervous system.

Serotonin therefore plays an important role in the digestion and absorption of food and our overall gut health.

As well as nerves in the enteric nervous system, our intestinal lining also produces serotonin. Our gut has specialized cells called enterochromaffin cells, which secrete serotonin directly into the intestines. This stimulates the movement of our bowels and also the production of mucus. Mucus acts both as lubricant for passing food and as a protective barrier for our gut.

Serotonin released by our enterochromaffin cells does not directly facilitate communication between nerves and therefore is not classified as a neurotransmitter. Instead, it is classed as a paracrine hormone – a chemical signal (hormone) that acts on nearby cells (paracrine).


  • Serotonin is a neurotransmitter in our enteric nervous system - the network of nerves in the digestive system that controls movement, enzyme secretion, immune function of our gut.
  • Serotonin hormone is produced by enterochromaffin cells in our gut lining.
  • Serotonin hormone is important for our digestive health.

Platelet function

Serotonin produced by enterochromaffin cells in the gut eventually finds its way into our bloodstream, where it is taken up by blood cells called platelets.

Platelets are tiny cells (so-called because they look like small dinner plates) that help to form blood clots. If you’ve ever cut yourself shaving, you’ll notice that the bleeding soon stops. This is because platelets move to the cut and plug the hole in the blood vessel wall – a process facilitated by serotonin.

When platelets release serotonin, it causes other platelets to accumulate and form a clot (a process known as platelet aggregation).

The release of serotonin by platelets also causes narrowing of local blood vessels (vasoconstriction), which helps to reduce bleeding.


  • Serotonin released by blood cells called platelets helps to form blood clots, reduce bleeding and promote wound healing.

Where is serotonin made?

Within the brain and central nervous system, where serotonin acts as a neurotransmitter, serotonin is made by nerve endings.

In the gut, 90% of serotonin is produced by enterochromaffin cells that line the intestines. This is the hormone form of serotonin.

The remaining 10% of serotonin in the gut is produced by nerve endings within the enteric nervous system, where serotonin acts as a neurotransmitter.


  • Serotonin neurotransmitter is produced by nerve endings in the brain and enteric nervous system.
  • Serotonin hormone is produced by enterochromaffin cells in the gut lining.

How is serotonin made?

Serotonin is derived from the amino acid tryptophan.

Amino acids are the building blocks of proteins, 9 of which are classified as essential amino acids – meaning our bodies cannot produce them ourselves, so we must obtain them from our diet. Tryptophan is one such essential amino acid. It is found in foods such as eggs, poultry, beans, and legumes.

Studies have shown that supplementing your diet with tryptophan can increase the production of serotonin.

Producing serotonin

Tryptophan is converted into serotonin (5-HT) in two stages.

1) Tryptophan --> 5-HTP

In the first stage, tryptophan is converted into another amino acid called 5-HTP (5-hydroxytryptophan). This reaction is catalyzed (sped up) by the enzyme tryptophan hydroxylase (TPH).

We actually have two forms of TPH enzyme:

  • TPH1 is mainly produced by enterochromaffin cells in your gut lining. It is therefore responsible for making the hormone form of serotonin that helps with bowel movement and secretion.

  • TPH2 is the form of TPH produced by nerve endings, both in the brain and in the enteric nervous system. TPH2 therefore produces the neurotransmitter form of serotonin, which allows nerves to communicate with one another.

Your latest trait looks at the levels of both TPH1 and TPH2 enzymes, which influences how effectively you produce serotonin in the brain and central nervous system (TPH2), enteric nervous system (TPH2), and gut (TPH1).

For your TPH (both TPH1 and TPH2) enzyme to function properly, it requires another molecule called BH4 (tetrahydrobiopterin). BH4 is an example of what we call a “cofactor” – a substance that is needed by certain enzymes to carry out chemical reactions. You can learn more about BH4 in your BH4 Synthesis and Recycling traits.

2) 5-HTP --> Serotonin (5-HT)

In the second stage of serotonin synthesis, 5-HTP (5-hydroxytryptophan) is converted into serotonin. This reaction is catalysed by the enzyme AADC (aromatic L-amino acid decarboxylase).

AADC requires the active form of Vitamin B6, known as pyridoxal phosphate, as cofactor to function efficiently and produce serotonin.

Supplementing your diet with 5-HTP has been shown to increase serotonin levels in the body.


  • Serotonin is made from the amino acid tryptophan.
  • Tryptophan is converted in two stages into serotonin.
  • Your TPH enzyme is responsible for the first stage of serotonin production.

Why does TPH activity matter?

As explained above, TPH is responsible for the first stage of serotonin production (tryptophan --> 5-HTP).

When a substance is produced over multiple stages / chemical reactions, it is the slowest stage / reaction that determines how quickly that substance is produced overall. We call this slowest stage the “rate-limiting step.” It’s analogous to a running relay, in which the person running the slowest leg has the biggest impact on the overall finish time.

The reaction carried out by TPH is the rate-limiting step in the production of serotonin.

The activity of TPH therefore essentially determines how effectively you make serotonin.

On that note, assuming other factors (e.g. the breakdown of serotonin) are unchanged, high activity of TPH enzymes leads to greater production of serotonin.

Conversely, low TPH activity of TPH enzymes leads to lower production of serotonin.

Furthermore, lifestyle factors that alter TPH activity will influence how much serotonin you produce. For example, long term psychological stress can reduce TPH activity, therefore leading to lower serotonin production.


  • TPH activity strongly affects how effectively you produce serotonin.
  • Lifestyle factors that affect TPH activity will influence how much serotonin you produce.

Why is serotonin synthesis important?

Brain and central nervous system

As serotonin is a key neurotransmitter in the brain, our levels of serotonin affect nerve activity within circuits that regulate mood, sleep, appetite and cognition.

Changes in serotonin production therefore influence the way we feel, think and behave.

For example, excessively high serotonin production is associated with anxiety, sleep disturbances, and changes in appetite.

By contrast, low serotonin levels increase the risk of low mood, binge eating, and sleep disturbances.


Changes in the production of serotonin hormone by the gut lining also has a significant impact on our digestive health.

Altered serotonin levels have been linked to digestive discomfort, changes in bowel frequency (e.g. diarrhoea / constipation) and inflammation.


  • Serotonin synthesis / production influences the activity of our brain, which affects the way we think and behave.
  • Serotonin production affects our digestive health.


Your latest trait examines variants of your TPH1 and TPH2 genes, which encode the TPH enzymes in your gut (TPH1) and neurons (TPH2) respectively.

Variants of these genes can affect the activity and quantity of the TPH enzymes, which, in turn, influence how well you produce serotonin in the brain, enteric nervous system and gut.


  • FitnessGenes analyze your TPH1 and TPH2 gene variants to see how well you produce serotonin in the brain and gut.

Dr Haran Sivapalan

A qualified doctor having attained full GMC registration in 2013, Haran also holds a first-class degree in Experimental Psychology (MA (Cantab)) from the University of Cambridge and an MSc in the philosophy of cognitive science from the University of Edinburgh. Haran is a keen runner and has successfully completed a sub-3-hour marathon during his time at FitnessGenes.

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