5HTP, Serotonin and Melatonin

5HTP, Serotonin and Melatonin

5-HTP, or L-5-Hydroxytryptophan, is a direct precursor to serotonin, which in turn, produces melatonin in the pineal gland; 5-HTP is a dietary supplement to improve mood and to improve sleep.

5-HTP has become a popular supplement for many, so it is time for an objective review.

How do you ‘make’ Melatonin?

First, there is the amino acid Tryptophan, this is the precursor to Serotonin, which in turn is the precursor to Melatonin.

Are you consuming enough tryptophan?

Tryptophan is an essential amino acid, meaning you do not make it for yourself, you must consume it. You can obtain it from free-range eggs, turkey, chicken, fish, dairy, cheese, peanuts, soy, pumpkin, wheat and sesame seeds.

The problem is threefold:

  • People do not eat enough tryptophan-containing foods.
  • The tryptophan to serotonin conversion is not very efficient. Why is that? Because it involves several steps - tryptophan is involved in the body’s nitrogen balance, and is used to make niacin. And niacin is used to make serotonin. 
  • For the majority of serotonin production, your microbiome is also involved, so overall serotonin production depends on how good your microbiome is! 

According to UT Southwestern researchers it is known that 90 per cent of Serotonin is made in the gut (3). 

It seems sunshine plays a part in this via vitamin D. And B-12 and folate have a role. We know that Seasonal Affective Disorder, SAD, a form of depression, occurs due to a lack of sunshine and lowered serotonin levels.

High Serotonin has been shown to be linked to lowered levels of IBS, less infection and illness. But is it 'cause or effect'?

A second study, this time from Caltech, involved killing off all the gut bacteria in mice. As a result, they made no serotonin. From the various studies Professor Hsiao concluded that the Enterochromaffin cells in the gut lining made serotonin when stimulated by certain spore-forming bacteria, as did some gut bacteria on their own (1).

Until this research, it was thought that serotonin was produced only by nerve cells and immune platelets.

The many roles of serotonin

Serotonin, or  5-hydroxytryptamine or 5-HT is a neurotransmitter used in the Central Nervous System to carry signals between nerve cells in the brain and the rest of your body.

Serotonin is often called the ‘happy hormone’ because it is involved in memory and mood. And now the UT and Caltech research has clarified the involvement of your gut bacteria, we understand another one of the main steps in the gut-brain axis. It further explains why the use of drugs, (for example, cancer drugs, or testosterone inhibitors in men), can result in depression or poor sleep (2). The drugs damage your microbiome and that impacts serotonin production.

Serotonin impacts the body’s control centre, the Hypothalamus, to control hormone secretion by the anterior pituitary gland and is thus involved in a wide variety of physiological behaviours.  Serotonin appears to be involved in not just mood, circadian rhythm, sleeping, and neuro-endocrine function, but also in digestion, nausea, sexual function, wound healing and blood clotting (2). 

A word of warning: If you take anti-depression drugs, it is not advisable to take 5HTP as - depending upon the drug - excessive Serotonin can be produced and this can cause serious harm.

5HTP and melatonin

5 Hydroxytryptophan lies between tryptophan and serotonin in the production chain. It is actually the direct precursor to 5 Hydroxytryptamine (Serotonin). Taking 5 HTP as a supplement ensures there is no shortage of the most essential ingredient.

It is also immediately converted, with no intermediary steps, and one of the reasons why 5HTP has been shown to relieve depression (4). 

5HTP is produced commercially from the seeds of an African plant known as Griffonia simplicifolia, so no one need have problems with dairy or meat eating.

But what does this all have to do with Melatonin?

The problem with serotonin is two fold; its production can be very inconsistent as explained above; and it doesn’t appear to cross the Blood Brain Barrier (BBB) into the pineal gland. So, for melatonin production by the pineal gland at night, the serotonin production has to be made inside the pineal gland. Since there are no gut bacteria, the only production can come from having enough direct precurosrs.  5HTP does cross the BBB allowing serotonin to be made ‘on the other side’. It's a 2-step process - 5HTP immediately converts to N-acetyl serotonin, which is converted into melatonin.

Why not just take melatonin? As a research review on melatonin (5) puts it, “we cannot make enough to meet demand for supplements and commercial melatonin is mainly produced by chemical synthesis, which can be highly polluting”

But more than this; there may well need to be human self-regulation involved, just as there is with glutathione, the other powerful antioxidant in the human body. Melatonin may need to be something we produce ourselves, and where we regulate production.

When we are young, given the correct ingredients, we can make a lot of melatonin; ever wondered why teenagers sleep so much? If you gave them a pill of melatonin, quite simply it could cause overload.

However, when we are old, we make less melatonin. Do both groups need the same level of supplementation? And as we've explained, the levels of precursor ingredients could be wanting, or excessive.

Next, how much melatonin is enough. Even the experts cannot agree. With cancer, some ‘experts’ are suggesting 20 mg before bed; others are suggesting 3 x 60 mg per day. We know that taking glutathione pills can be dangerous, and you should allow the body to self-regulate. Why would the same not apply to the other big antioxidant, Melatonin? 

Chris Woollams, former Oxford University Biochemist added, “As we have previously told you, you don’t just make melatonin at night - you  also make it by day (6). It is a massive antioxidant and anti-inflammatory. It helps clean up the microenvironment of your cells and protects your whole body. You need both pineal gland production and gut production. You simply must have the right level of ingredients; day and night. 

For all our followers in Australia, New Zealand, South Africa and Europe there is the basic problem that Doctors cannot prescribe more than 3 mg anyway; and most don’t like doing even that. If I take Melatonin, for some reason I get depressed! So I stopped. But since one of my good friends was given 5HTP by his medical team when he was in Hospital, I’ve been using it, and consistently I am sleeping better.

However, subjective that might seem, it makes sense to me to make your own healthy 24-hour level of Melatonin, by night in your pineal gland and, by day, by your bacteria in a healthy microbiome. 5HTP seems to be the simple answer. 5HTP is natural and available easily online.”

Go to: melatonin - self-defence against cancer



  1. Caltech - Microbes Help Produce Serotonin in Gut; April 9 2015,  Cell,  Elaine Hsiao et al. https://www.caltech.edu/about/news/microbes-help-produce-serotonin-gut-46495 
  2. Serotonin Involvement in Physiological Function and Behavior; Alan Frazer and Julie G Hensler - https://www.ncbi.nlm.nih.gov/books/NBK27940/
  3. How happiness may also keep you healthy - https://chriswoollamshealthwatch.com/your-illness/general-health/how-happiness-may-also-keep-you-healthy/ 
  4. L-5-Hydroxytryptophan in depression: the first substitution therapy in psychiatry? The treatment of 99 out-patients with ‘therapy- resistant’ depressions. van Hiele LJ.  Neuropsychobiology. 1980, 6(4):230–240.
  5. Melatonin biosynthesis pathways in nature and its production in engineered microorganisms; Synth Syst Biotechnol; 2022 Mar; 7(1): 544–553. 
  6. Tan DX, Reiter RJ. Mitochondria: The birth place, battle ground and the site of melatonin metabolism in cells. Melatonin Res. 2019;2:44–66.


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