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 number 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 appeal 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 placed in the proper context, the following basic chemical properties 2 — 15 explain the failure of 5-HTP to achieve consistent results.
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 AAAD , which freely catalyzes the conversion of 5-HTP to serotonin.
Generally, efficacy studies related to 5-HTP fall into one of two categories: 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 results 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 previous therapy including all available antidepressant drugs as well as electro convulsive therapy.
Complete recovery was seen in 43 of the There 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 significantly 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 results 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 significant 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 by 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 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. A literature review revealed that more studies have been reported using 5-HTP in combination 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 previous 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 APRESS , published 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. In one study , women who took 5-HTP for just 2 weeks lost an average of 4. Their counterparts in the placebo group only lost 0. Not only does 5-HTP help to suppress appetite, but studies have also shown that people who take 5-HTP tend to reach for less carbohydrates and fats. However, there is evidence that low serotonin could be a trigger.
Related Posts. October 26th, August 13th, At the end of the study, the women who took 5-HTP reported greater feelings of satiety, or fullness, when eating, which led to a decreased food intake. While these studies were very small, they showed some promise that 5-HTP could help weight loss efforts. Selective serotonin reuptake inhibitors are a common treatment for depression. These medications work by preventing the body from breaking down serotonin, thereby increasing the amount that is available in the body.
Unfortunately, there is not a lot of research to support this. An older meta-analysis examined the results of studies on 5-HTP and tryptophan in relieving depression symptoms. While the authors reviewed more than studies related to the topic, they found that few studies used high-quality methods.
The researchers concluded that there was not enough evidence to say that 5-HTP had a greater effect than a placebo on depression. However, they did note that some of the studies found that 5-HTP could be better than placebo in some people.
These studies were too old, however, to represent the latest clinical research methods. Another challenge in using 5-HTP to treat depression is that the supplement does not usually last long in the body, which rapidly absorbs and eliminates it. If researchers could find a way to make 5-HTP last longer in the body, it may show more promise as a depression treatment, according to one study. Some natural medicine proponents believe that taking 5-HTP supplements can help reduce anxiety and panic.
However, most of the research about 5-HTP and anxiety is 15—20 years old. One research study from found that taking 5-HTP reduced anxiety and panic in people with panic disorder. However, the researchers did not find any difference in anxiety in other participants who did not have a panic disorder. Doctors know that a lack of serotonin is likely to play a role in anxiety and panic. However, studies have not yet proven that using 5-HTP to increase serotonin is an effective strategy for reducing anxiety.
Much of the focus on using 5-HTP for pain relief surrounds the treatment of fibromyalgia , a condition that causes chronic nerve pain.
Studies on 5-HTP and fibromyalgia are limited and too old to provide significant results. A study from , for example, found that taking the supplement may help reduce symptoms in participants with primary fibromyalgia syndrome, but larger and newer studies are necessary to confirm these results.
However, a small study in an animal model found that 5-HTP might reduce the perception of pain. Supplement manufacturers sell 5-HTP in a variety of dosages. These include , , and milligram mg capsules. Some supplement manufacturers may also add 5-HTP to multivitamins. There is no specific recommended daily allowance for 5-HTP. Most people will take 50— mg per day after starting at a lower dose of 25 mg and increasing the dose weekly. It is vital to remember the FDA do not regulate supplements.
A person should purchase supplements from a reputable manufacturer and store them as the label advises. According to some research , taking 5-HTP may increase serotonin but deplete or reduce the amounts of other neurotransmitters. These include dopamine and norepinephrine.
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