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Saturday, December 27, 2014

How to INCREASE Serotonin ~Production~ Naturally - Focus on Raising "Tryptophan Hydroxylase" Enzymes

There's been a great deal of conjecture spread across the internet, usually in the form of user-basis articles, regarding this topic; and methods / supplements used to increase serotonin production often are not only cited improperly, but also completely off of the map and lacking relevance!

Stay specific, if you write an article saying that something increases serotonin PRODUCTION; you should be referring to the only way that serotonin is produced by the body, and that is by the enzyme tryptophan hydroxylase !

It's not valid to say that amino acid supplements increase production of any single neurotransmitter, they are merely "raw materials", they are incapable of increasing serotonin PRODUCTION, yes, you can RAISE the serotonin LEVEL by providing more raw materials, but only if there is enough tryptophan hydroxylase to catalyze the reaction and create serotonin FROM THEM.

This is proven science, so if you want to understand this , then you need to know how it works. 

Moving forward.

So there are two major supplements that can increase TRYPTOPHAN HYDROXYLASE; which is guaranteed to increase serotonin production. 

Interestingly, they are two supplements very profoundly involved and mentioned repeatedly in a multitude of brain articles related to depression and cognitive function.....

The second one also can raise thyroid hormones, specifically T4, and can also increase neurogenesis ; new brain cell growth. 

1.) VITAMIN D ; something more people should be taking, especially during winter months, it's dirt cheap and also increases dopamine production factors as well as tryptophan hydroxylase which will increase serotonin production. Vitamin D should be a core supplement you take and the first one you decide to take no matter if you are skinny, obese, diabetic, hypothyroid, hypogonadal, have dementia or whether you are on the healthy side of the field and work out often and are building mass - as Vitamin D supports sex hormone production and also modulates aromatase addition, it is crucial for thyroid hormone production.

 2014 Jun;28(6):2398-413. doi: 10.1096/fj.13-246546. Epub 2014 Feb 20.

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.


Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.


autoimmunity; behavior; brain function; oxytocin; prenatal; vasopressin
[PubMed - indexed for MEDLINE]
I recommend an organic, and olive oil based Vitamin D pill such as the one below. It is one of the most highly recommended Vitamin D supplements, is backed by AMAZON; who rarely sponsors supplements, and has over 615 positive reviews.
2.) The second supplement to raise tryptophan hydroxylase, and thus serotonin production is known as ; BACOPA MONNIERI extract(!).

 2011 Mar 8;134(1):55-61. doi: 10.1016/j.jep.2010.11.045. Epub 2010 Dec 1.

Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation.



To examine the effect of Bacopa monniera leaf ethanolic extract (BMEE) on the serotonergic system of postnatal rats with reference to learning and memory.


From postnatal day (PND)-15-29, rats were treated with BMEE (40 mg/kg BW+0.5% gum acacia) by oral gavage. Behavioural tests (Y-maze, hole-board and passive avoidance) were used to evaluate their learning (PND-32-37) and retention of memory (PND-47-53). Effect of BMEE on neurotransmitter system was analyzed by ELISA and semi-quantitative polymerase chain reaction (PCR).


Oral administration of BMEE improved learning and retention of memory significantly in all behavioural tasks. Following BMEE treatment, the level of serotonin (5-HT) increased while dopamine (DA) decreased significantly. We also found variation in the level of acetylcholine (ACh). However, no significant changes were observed in the level of ACh and glutamate (Glu). The level of 5-HT was significantly elevated up to PND-37 and was then restored to normal level on PND-53. Interestingly, concomitant up-regulation was recorded in the mRNA expression of serotonin synthesizing enzyme tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) on PND-29 and PND-37, which was restored on PND-53.


The results suggest that BMEE treatment significantly enhances the learning and retention of memory in postnatal rats possibly through regulating the expression of TPH2, 5-HT metabolism and transport.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
[PubMed - indexed for MEDLINE]

My recommended BACOPA supplement is the below, I've used it many times and if you need proof I can show you mine and others blood work where 5-HT metabolites and serotonin levels were increased! ;) 


  1. Great article! I suffer from very low serotonin and also low dopamin, but high adrenaline.
    Tryptophan and 5-htp didn't help me at all. Now I will try this!

    Which bacopa extract did you use?
    Any more advices would be appreciated :) Thank you!

    1. I used the Bacopa Gold mentioned above, I have used another extract at one point but I don't remember the brand.
      Low serotonin and low dopamine together coupled with high adrenaline?
      It's a little more unusual but I s'pose biochemically it makes sense, dopamine reduces norepinephrine and adrenaline when it activates the D2-like receptors.
      Have you tried Vitamin D?
      You may also have luck with using Zinc, and folic acid, both of which tend to reduce adrenalines by reducing excess copper, if that's an issue for you.
      Might want to get hair copper levels checked just to be sure, also there are sex-dependent differences, if you are a male, estrogen excess or deficiency can play a role in these types of disturbances. Progesterone , Pregnenolone and DHT are also involved in the regulation of both dopamine and adrenaline, as well as serotonin.

      If your pregnenolone levels are low, or your levels of 3-alpha-diol are low, and you are a male, this can cause high norepinephrine...unfortunately, there isn't yet a way to raise 3-a-diol specifically if DHT (Dihydrotestosterone) isn't converting to it properly.....

  2. I'm a male and my Vitamin D is fine.
    I'm not sure about the copper levels, but I've used zma & a B-complex time over time.
    The weird thing is that besides low serotonin, noerpinephrine and high adrenaline, my test & estrogen levels are both low but still in the normal range, prolactin is slightly up.
    Just doesn't make sense for me!

    1. No that does kinda make sense, testosterone is responsible for stimulating the production of dopamine, and if testosterone is low, then estrogen is also normally low, because they go hand in hand.....
      At the same time, dopamine is crucial to stimulating testosterone production, you could try something that regenerates dopamine, or something like L-Dopa/Mucuna Pruriens extract?
      Raising serotonin might help a little, but I would focus on the hormonal spectrum. The adrenaline issue is most likely sending your cortisol through the roof, which is lowering your testosterone levels ---- so you may want try an anti-cortisol agent coupled with a dopaminergic supplement of some sort..or see if you can get prami or requip from your doc.
      With all of this being said, it's important to note that there are other factors determining test production, and low serotonin usually correlates with higher end testosterone, but not in the presence of lower dopamine as well - in other words, it's usually more comfortable, and less side-effect producing , when you have high dopamine and low serotonin, but this is when peak health is achieved....
      Preferably though, you want normal serotonin levels, and dopamine that is higher than the serotonin.....

    2. The thing is, often it is where primary or secondary hypogonadism is present, you would have both low T & Low E2 - but not in the normal range, hence hypo, but since yours are in the normal range, and yet BOTH are low, that seems to indicate either something bombarding your hypothalamus, or some other factor we haven't identified.
      How old are you for example ?
      What's your social status, and what is your body fat percentage..these are all factors in test production..
      E-mail me at


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