We routinely have people come into the clinic wanting to address one or more disorders related to neurotransmitter imbalance including trichotillomania. When we explain our approach of using amino acid therapy, occasionally we will hear something like “I’ve tried 5-HTP before, but it didn’t work” or “5-HTP makes me sleepy, hungry, tired, (insert symptom here)”. I explain to these people that what they have done by taking only 5-HTP is cause further imbalance in the system, which will not address their underlying neurotransmitter dysfunction and could make it worse.
There are several reasons that taking only 5-HTP can make an underlying neurotransmitter imbalance worse. This post will discuss problems with the synthesis of neurotransmitters. Part 2 will discuss problems with the degradation (metabolism) of neurotransmitters. Part 3 will discuss what this means to you.
Synthesis of Neurotransmitters
The synthesis of serotonin and the catecholamines (i.e., dopamine, norepinephrine, and epinephrine) is illustrated here. The thing to note is that the same enzyme – Aromatic Amino Acid Decarboxylase (AAAD) – catalyzes (i.e., assists) the conversion of 5-HTP-to-serotonin and L-dopa-to-dopamine everywhere in the body. There is only so much of this enzyme to go around; this is very important.
If a person takes only 5-HTP, the production of dopamine (and the rest of the catecholamines, including norepinephrine and epinephrine) will be inhibited, as the enzyme AAAD will be used primarily for the conversion of 5-HTP into serotonin. This means that if you take only 5-HTP without the proper balance of L-dopa (or L-tyrosine) you will decrease the production of all the catecholamines, including dopamine, norepinephrine and epinephrine. This will make any underlying imbalance between serotonin and the catecholamines worse may lead to an exacerbation of your existing symptoms or create new symptoms.
However, this isn’t the only detrimental effect to taking 5-HTP without the proper balance of other amino acids. There are also issues with the degradation of neurotransmitter that can create further imbalances; this is the topic of Part 2 in this series.
I have read your post on “You can’t take just 5-HTP” with interest. However, I do have a question.
If the metabolism of 5-HTP into serotonin limits the availability of AAAD for the metabolism of L-dopa into dopamine as you state, how is increasing the L-dopa supply (either directly administered or, more safely, metabolysed from L-tyrosine) going to help? In other words, if AAAD is the rate-limiting step in the production of the above metabolic products, how is this remedied by increasing the availability of the metabolic precursors?
Can you explain this?
Hi Frank –
Thanks for the incredibly well thought out comment/question! I’ll give a brief answer here as well as provide you some resources for further information.
The simple answer is that we are trying to induce a balanced, competitive inhibition state at the organic cation transporter, which necessitates the proper amounts of both serotonin and catecholamine precursors. The longer answer is as follows:
Synthesis of serotonin from 5-HTP and dopamine from l-dopa is catalyzed by the same enzyme, L-aromatic amino acid decarboxylase (AAAD). Dopamine and serotonin amino acid precursor administration must be in proper balance. If only 5-HTP or 5-HTP that dominates dopamine at the enzyme is administered, it will block dopamine synthesis at the AAAD enzyme through competitive inhibition, leading to depletion of dopamine and the rest of the catecholamines.
Metabolism of serotonin and dopamine is catalyzed by monoamine oxidase (MAO). The activity level of MAO is not static. With increasing doses of 5-HTP, which lead to increased serotonin levels, MAO activity increases. Without a properly balanced increase in dopamine there will be increased metabolism of dopamine leading to depletion.
The synthesis, metabolism, and transport of serotonin and dopamine, along with their amino acid precursors, are primarily controlled by the functional status of transport, which is carried out by organic cation transporters (OCT). Serotonin, dopamine, and their amino acid precursors must be transported by OCT across cell walls. Transport dominates, controls and regulates synthesis and metabolism.
Administration of 5-HTP alone leads to increased unbalanced transport of serotonin. Competitive inhibition at the transporters will inhibit movement of dopamine and its precursors into areas that affect synthesis and metabolism, compromising and depleting dopamine (catecholamine) levels. Long-term administration of 5-HTP alone, or in an unbalanced manner, facilitates depletion of catecholamines, negatively affecting neurotransmitter-related disease processes.
For more information, please refer to the following:
https://neurosupport.com/wp-content/uploads/2015/11/03-dual-gate-lumen-model-of-renal-monoamine-transport_0702101.pdf
https://neurosupport.com/wp-content/uploads/2015/11/12-apress.pdf
https://neurosupport.com/wp-content/uploads/2015/11/16-5-htp-efficacy-and-contraindications.pdf
Thanks again for your question; if after reading the papers above you still have questions, please let us know –
Sincerely,
Dr Chad
what is the proper ration of L dopa to 5htp that someone should take.
i know for tyrosine to 5htp it is 10-1. 10 tyrosine to every 1 5htp.
is it different for Ldopa to 5htp?
Hi Josh,
Thanks for the comment/question. Unfortunately, their isn’t a ‘best range’ for L-dopa:5-HTP and individual needs can vary dramatically – we have seen ranges from near 1:1 to more than 100:1. Urine testing is often necessary to find the right balance (and it typically takes between 2-4 of these tests to optimize amino acid dosing): http://amino-acid-therapy.com/oct-assay-interpretation/.
Hope this helps –
Dr Chad
Ok, so is there an alternative, natural method you might be able to recommend? I have thought about getting on Paxil but who knows could mean I’m on that for the rest of my life as I know the withdrawal can leave someone in a much worse condition prior to the being on the medication. Much prefer a safe, natural remedy.
Hi Tatum,
Thanks for the comment/question; we typically use a blend of amino acids that we tailor to each person’s exact needs to help restore proper neurotransmitter function. The approach falls under the category of amino acid therapy; you can learn more about it here: http://www.amino-acid-therapy.com. Please contact us if we can assist you: http://naturalpathhealthcenter.com/contact-us/.
Sincerely,
Dr Chad