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Try out PMC Labs and tell us what you think. Learn More. This article has been retracted. Retraction in: Neuropsychiatr Dis Treat. Lhydroxytryptophan 5-HTP is the immediate precursor of serotonin. It is readily synthesized into serotonin without biochemical feedback. This nutrient has a large and strong following who advocate exaggerated and inaccurate claims relating to its effectiveness in the treatment of depression and a of other serotonin-related diseases.
These assertions are not supported by the science. Under close examination, 5-HTP may be contraindicated for depression in some of the very patients for whom promoters of 5-HTP advocate its use. In the United States, the nutritional supplement 5-hydroxytryptophan 5-HTP became available over the counter in April of Its intuitively seductive 5 htp reviews has encouraged its increasing use while disregarding the actual science which stands in sharp contrast to the general perceptions of the public and many physicians.
When 5 htp reviews in the proper context, the following basic chemical properties 2 — 15 explain the failure of 5-HTP to achieve consistent. The following scientific facts are generally accepted without dispute:. In central nervous system disease states associated with synaptic serotonin dysfunction, synaptic serotonin levels in the brain must be increased to induce optimal outcomes.
When infinitely high amounts of 5-HTP are administered, it is theoretically possible to achieve infinitely high levels of serotonin. One limiting factor is the availability of the enzyme L-aromatic amino acid decarboxylase AAADwhich freely catalyzes the conversion of 5-HTP to serotonin. Generally, efficacy studies related to 5-HTP fall into one of two : open nonblinded and double-blind, placebo-controlled studies. One naturopathic physician, who is considered by some to be a 5-HTP expert, 17 interprets the from an open study on his web site as follows: 18 He reported one of his more impressive studies that involved 99 patients who were described as suffering from therapy resistant depression.
These patients had not responded to any therapy including all available 5 htp reviews drugs as well as electro convulsive therapy. Complete recovery was seen in 43 of the 5 htp reviews are two points that require further discussion. First, the naturopath claims that only 5-HTP was administered to patients in the study. It affects the response to 5-HTP dosing values by ificantly increasing the availability of 5-HTP in the central nervous system. There are more published studies examining the use of 5-HTP in combination with another substance than the use of 5-HTP alone.
This statement reveals a lack of understanding of the complex and large impact the placebo effect has in treating patients with depression. The are conflicting and, in the main, do not provide convincing evidence for an antidepressant effect for 5-HTP. While there are some published pilot studies relating to small groups of subjects, the majority of these smaller studies conclude by noting that more studies are needed. The peer-reviewed literature supports the assertion that use of 5-HTP alone in the management of depression is associated with efficacy no greater than placebo and that its use is controversial.
When catecholamine neurotransmitter levels influence depression, administration of 5-HTP alone is contraindicated since it may deplete dopamine and norepinephrine, thereby worsening the disease and its underlying cause.
The most ificant side effects and adverse reactions may occur with long-term use many months or longer. Administration of 5-HTP alone depletes catecholamines dopamine, norepinephrine, and epinephrine. Based on monoamine transporter optimization MTO studies, managing depression and other centrally acting monoamine-related diseases requires a combination of properly balanced dopamine and serotonin amino acid precursors. 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 5 htp reviews monoamine oxidase MAO. The activity level of MAO is not static. 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 5 htp reviews, 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 le 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. A literature review revealed that more studies have been reported using 5-HTP in 5 htp reviews with another substance than using 5-HTP alone due to the lack of efficacy of 5-HTP alone.
One combination examined includes the use of 5-HTP with carbidopa. Carbidopa inhibits peripheral conversion of 5-HTP to serotonin and l -dopa to dopamine. Additionally, a study reported that in animals 5-HTP caused increased turnover of both dopamine and norepinephrine. They hypothesized that 5-HTP is taken up by catecholaminergic neurons, transformed into 5-HT that, in turn, could act as a false transmitter, possibly increasing the turnover of catecholamines. In other words, it is unknown whether 5-HTP augments or reduces catecholaminergic neuronal functions.
Serotonin and dopamine systems exist in two distinctly different and separate states. The endogenous state occurs when no supplemental amino acid precursors Figure 1 are administered. The competitive inhibition state occurs when at least one serotonin and one dopamine amino acid precursor Figure 1 are administered simultaneously. In the unbalanced state, amino acid precursors of serotonin or dopamine dominate the opposite system in synthesis, metabolism, and transport, leading to depletion of nondominant monoamine neurotransmitters Figure 2.
Sulfur amino acids may deplete dopamine. Sulfur amino acids may deplete serotonin. Amino acid precursors of serotonin and dopamine in the competitive inhibition state are intertwined during synthesis, metabolism, and transport to the point that they function as one system. This is a deep-seated interaction as discussed in the novel concept of apical regulatory super system APRESSpublished in The paper discusses how the serotonin and dopamine systems, when properly balanced in the competitive inhibition state, function as one system.
In this state, functions regulated only by serotonin in the endogenous state can be regulated by manipulating dopamine levels, and functions regulated only by dopamine in the endogenous state can be regulated by manipulating serotonin. Most importantly, if only one precursor of the serotonin and dopamine system is administered or it is administered in a manner that dominates the other system either serotonin or dopamine in synthesis, metabolism and transport, neurotransmitter depletion of the dominated system will occur.
When this depletion of the nondominant system is great enough, any effects observed with administration of the single or dominant amino acid will no longer be observed. A study involving properly balanced serotonin and dopamine amino acid precursor dosing values guided by MTO published in and documents that administration of properly balanced serotonin and dopamine precursors is not only highly effective for managing depression, but can also be used to differentiate bipolar depression cycling heavily on the depressive pole from unipolar depression major affective disorder.
To achieve optimal efficacy, minimal side effects, and prevent depletion of other amino acids and neurotransmitters, 5-HTP must be administered in proper balance with dopamine amino acid precursors along with proper levels of sulfur amino acids.
Synthesis and metabolism are controlled by transporter function. Transporters move serotonin, dopamine and their amino acid precursors into and out of cells to sites where synthesis and metabolism occur. MTO is an in situ method for determining the functional status of OCT responsible for establishing serotonin and dopamine levels throughout the body. Optimization requires establishing serotonin in the Phase 3 optimal range while dopamine is in 5 htp reviews Phase 3 optimal range. The Phase 3 optimal ranges of serotonin and dopamine are independent of one another.
When both serotonin and dopamine are in their respective phase 3 optimal ranges, optimization has occurred. Optimal group cannot be obtained without 5 htp reviews. The following are group effective therapeutic ranges defined by MTO during simultaneous administration of serotonin and dopamine precursors:. The effective therapeutic ranges listed above are independent of each other. For example, in one patient, a daily 5-HTP dosing value of 2, mg per day with an l -dopa dosing value of 30 mg per day may be required for proper balance of transport to place both serotonin and dopamine 5 htp reviews their respective Phase 3 optimal ranges.
Another patient may require 25 mg per day of 5-HTP with 2, mg of l -dopa for Phase 3 optimization. Dosing values 5 htp reviews for transporter optimization are highly individualized. To understand the extreme variability in the dosing levels of 5-HTP and the other amino acid precursors, it is important to understand why these transporters react so differently from one individual to the next.
Neurotransmitters facilitate the flow of electric als across the synapse between the pre- and post-synaptic 5 htp reviews. When a change in the overall flow of electricity across the synapse is needed, a al is sent throughout the body that encodes the identical transporters to regulate and control neurotransmitter flow in the specific manner required to optimize this flow. This process may damage areas regulating affect and mood, leading to depression. Since serotonin and dopamine do not cross the blood—brain barrier, the total of serotonin and dopamine molecules present in the brain is a function of the amount of nutrients amino acid precursors available to be synthesized into new neurotransmitter molecules.
If the amount of neurotransmitter molecules is low or inadequate, a relative nutritional deficiency exists. Optimal efficacy and minimized side effects are not a function of achieving sufficiently high amino acid dosing levels; they are a function of achieving a proper balance between serotonin and dopamine. Intuitively, the potential is extraordinary, but from a practical level efficacy is no better than placebo. In review of the science, effective integration of 5-HTP into a patient management plan is much more complicated than simply giving some 5-HTP in order to have more serotonin throughout the system.
Administration of 5-HTP alone is contraindicated for depression and any 5 htp reviews involving a catecholamine component due to its ability to facilitate depletion of these neurotransmitters. Administering serotonin or dopamine amino acid precursors should never involve administration of only one amino acid. Improperly balanced amino acid precursors are associated with decreased efficacy, increased side effects, and depletion of the nondominant system.
AS has no disclosures to reveal. National Center for Biotechnology InformationU. Journal List Neuropsychiatr Dis Treat v. Neuropsychiatr Dis Treat. Published online Jul Author information Copyright and information Disclaimer.
This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. An expression of concern has been published for this article. See Neuropsychiatr Dis Treat. This article has been cited by other articles in PMC. Abstract Lhydroxytryptophan 5-HTP is the immediate precursor of serotonin.
Introduction In the United States, the nutritional supplement 5-hydroxytryptophan 5-HTP became available over the counter in April of The argument for using 5-HTP When placed in the proper context, the following basic chemical properties 2 — 15 explain the failure of 5-HTP to achieve consistent. The following scientific facts are generally accepted without dispute: In central nervous system disease states associated with synaptic serotonin dysfunction, synaptic serotonin levels in the brain must be increased to induce optimal outcomes.
Serotonin does not cross the blood—brain barrier. Short-term efficacy of 5-HTP alone Generally, efficacy studies related to 5-HTP fall into one 5 htp reviews two : open nonblinded and double-blind, placebo-controlled studies. Monoamine depletion by amino acid precursors Serotonin and dopamine systems exist in two distinctly different and separate states. Open in a separate window. Figure 1. Synthesis pathway of serotonin and catecholamines. Abbreviation: 5-HTP, 5-hydroxytryptophan.5 htp reviews
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L-Tryptophan and 5-Hydroxytryptophan (5-HTP) Supplements Review