In order for the synthesis of monoamine neurotransmitters to occur, the amino acid precursors must undergo uptake into the cells performing synthesis. This process occurs in numerous places throughout the body including the central nervous system, kidneys, liver, gastrointestinal tract, mesentery, lungs and peripheral nerves. The cation uptake ports found in the proximal convoluted renal tubule cells are a prototype for amino acid uptake (see diagram below at the top center.16)
Diagram at left: The neurotransmitters and amino acid are filtered at the glomerulous are taken up in the proximal renal tubules by the cation ports of the proximal convoluted renal tubule cells. The proximal convoluted renal tubule cells then further filter the neurotransmitters and amino acids into separate areas where the neurotransmitters are metabolized and the amino acids are synthesized into new neurotransmitters that are then either excreted into the urine or secreted into the system via the renal veins.
Neurotransmitters synthesized by the kidneys are the source of urinary serotonin and catecholamines.16, 17, 18, 19 Serotonin and the catecholamines are synthesized by the kidneys, then excreted into the urine or secreted into the system via the renal veins.20 Uptake is affected by administration of a single amino acid precursor or improperly balanced amino acid precursors and may overwhelm and compete with uptake of the other amino acids. Administration of only L-dopa inhibits uptake of 5-HTP.44 Administration of only 5-HTP has the same effect on L-dopa uptake.
So to summarize, neurotransmitter synthesis is a complicated process. If you take amino acids improperly, you can cause further imbalance in the system due to decreased synthesis, increased metabolism by MAO and COMT and/or uptake competition.
So the point of all this is this: you have to take amino acids in the right balance to achieve long term results – and that is what we will discuss next.
16. Blood and urine 5-hydroxytryptophan and 5-hydroxytryptamine levels after administration of two 5-hydroxytryptamine precursors in normal man. Br J Clin Pharmacol. 1995 Mar;39(3):327-9 Wa TC, Burns NJ, Williams BC, Freestone S, Lee MR.
17. Derivation of urinary dopamine from plasma dopa. Clin Sci (Lond). 1988 Nov;75(5):515-20 Zimlichman R, Levinson PD, Kelly G, Stull R, Keiser HR, Goldstein DS.
18. Handling of dopamine and dopamine sulfate by isolated perfused rat kidney. Am J Physiol. 1986 Jun;250(6 Pt 2):F975-9 Buu NT, Duhaime J, Kuchel O.
19. Sources of human urinary epinephrine. Kidney Int. 1997 Jan;51(1):324-7 Ziegler MG, Aung M, Kennedy B.
44. Antagonistic actions of renal dopamine and 5-hydroxytryptamine: effects of amine precursors on the cell inward transfer and decarboxylation. Br J Pharmacol. 1996 Mar;117(6):1187-92. Soares-da-Silva P, Pinto-do-O PC.
5-htp is the best supplement i’ve used for anxiety and depression.
Hi Edward,
Thanks for sharing your experience. 5-HTP can help in the short term with sleep, as it helps to slow down the flow of information in the brain and is the direct precursor of melatonin. You may be one of the very few in the general population that actually suffers from a relative nutritional deficiency of tryptophan in the diet, and therefore need more 5-HTP to compensate. However, for the vast majority of people, taking only 5-HTP will cause depletion of dopamine over time.
Providing only 5-HTP does increase the amount of serotonin in the brain. In response to this, the body increases the amount of enzymes to break down some serotonin to maintain balance. However, these enzymes also breakdown dopamine, which is the main excitatory neurotransmitter that needs to be kept in balance with serotonin to keep everything working well. Because no dopamine precursor was given (i.e., L-tyrosine), relatively more dopamine than serotonin is broken down, so the imbalance between them becomes greater. This often leads to additional issues over time.
It works something like this: let’s say I have two bank accounts, both with $100 in them. I put $1,000,000 in one of them (which is like taking just 5-HTP), but leave the other one where it is. Now let’s say I take $90 out of both accounts (which is equivalent to the enzymes breaking down serotonin and dopamine non-selectively). The account with $1,000,000 isn’t affect much, but the account with only $100 in it is affected a great deal. Moreover, the imbalance between the two accounts has also gotten a lot more lopsided. This is similar to what happens if one takes only 5-HTP with no l-tyrosine (or vice versa, taking only l-tyrosine and no 5-HTP) – it can create greater imbalances over time and really deplete the competing system.
The key then is to provide the body a balanced blend of amino acids and precursors so that it can increase neurotransmitter levels in a balanced fashion. This will help eliminate symptoms due to the original imbalance without creating any new problems.
Thanks again for sharing your experience – I am very glad you have found better sleep using 5-HTP. This can be fine if used only sporadically, but if long term relief is needed, the research suggests that using a more balanced approach will provide lasting benefits for most people. If you’d like more information or to get started using this approach, don’t hesitate to contact me.
Sincerely,
Dr. Chad