Depression and anxiety disorders (IV): tryptophan supplementation, the role of 5HTP

Previous articles have described the relationship between diet and depression and anxiety, and this one begins to describe what classes of nutrients can improve depression and anxiety. Let’s start with the most mainstream nutrients for improving depression symptoms and anxiety.

The causes of depression have been controversial for many years, but one of the most clinically accepted causes is an imbalance of neurotransmitters in the central nervous system, with the Serotonin Hypothesis being the most widely accepted. The current understanding of depression is that three neurotransmitters are believed to influence depressive symptoms, of which serotonin is the most important. The SSRI class of antidepressants currently being prescribed mainly affects the reabsorption of serotonin, while the SNRI class affects the reabsorption of serotonin and norepinephrine.

While the gut and other tissues of the body can produce serotonin, none can pass the healthy blood-brain barrier, so serotonin as a neurotransmitter must be synthesized in the central nervous system. When protein foods are digested and metabolized into amino acids, tryptophan can enter the central nervous system via a carrier (but needs to compete with other LNAAs), and serotonin is enzymatically metabolized to 5-HTP first, a process that requires multiple cofactors, and the body can also supplement 5-HTP directly, which can pass the blood-brain barrier more efficiently than tryptophan supplementation, and 5-HTP in the central nervous system will be Metabolized to serotonin in the next enzymatic reaction, the process also requires different amounts of cofactors.

SSRI drugs work by blocking the reabsorption of serotonin, thereby increasing the concentration of serotonin in the central nervous system, and more serotonin is thought to be helpful in depression. Of the herbs, St. John’s Wort also does a similar job of blocking serotonin reabsorption, which is why it has been widely used as a drug-like nutrient. In addition to affecting serotonin reabsorption, increasing serotonin output is another way to achieve related goals, either through increased 5-HTP or tryptophan supplementation. However, if the bottleneck of serotonin production is not the “raw material” but the “cofactor”, supplementation with various cofactors, such as B3 and B6, may be more effective in increasing serotonin.

In this article, we will first introduce two types of supplements that increase serotonin in the central nervous system: tryptophan and 5-HTP.

Tryptophan and 5-HTP.

Tryptophan supplementation can increase central nervous serotonin and improve depressive symptoms.A 2014 clinical trial [9], in which 25 healthy subjects, compared their consumption of a diet containing low tryptophan for four consecutive days, to a diet containing high tryptophan for four days, found that a diet high in tryptophan had a significant positive effect on mood. In a 2016 study [10], tryptophan was found to improve social behavior, and tryptophan supplementation may improve social self-control in patients with social behavior disorders; in healthy subjects, tryptophan supplementation also seemed to promote social behavior.

As early as 1982, double-blind controlled-group clinical trials have demonstrated the usefulness of tryptophan in the treatment of depressive symptoms [11], 115 depressed patients, divided into four groups, one group on tryptophan, a second group on tricyclic antidepressants (first-generation antidepressants, amitriptyline), a third group on tryptophan and tricyclic antidepressants, and a fourth control group on placebo. As a result, 29 of the placebo group dropped out of the trial, but there was no significant difference between tryptophan and tricyclic antidepressants in the treatment of depressive symptoms. The study confirmed that tryptophan was as effective as tricyclic antidepressants in treating depression. The trial used tryptophan alone, at a dose of 3g per day, but the researchers suggest that with tryptophan, you can start with 1g per day for 4 weeks, and if that doesn’t work, you’ll need to add an antidepressant as an intervention.

Tryptophan metabolism produces 5-HTP, so supplementation with 5-HTP can also increase central nervous serotonin, which can help to improve depressive symptoms. The first clinical trial of 5-HTP for depression was conducted in 1972 [12]. 74 (69%) of 107 depressed patients taking 50 mg-300 mg daily showed significant improvement in their symptoms.

In another clinical trial demonstrating the time required for 5-HTP to be effective [13], 59 depressed patients, taking 150 mg-300 mg of 5-HTP daily for 3 weeks, showed significant improvement in depressive symptoms in 13 (22%) patients and moderate improvement in 27 (45.8%) patients, while 32 of these 40 patients (80%) had an effect after 1 week of taking 5-HTP. Effect. Compared to SSRI drugs that take weeks to work, 5-HTP works significantly faster.

How does that compare to prescription SSRI drugs? In a 1991 Swiss clinical study [14], 36 patients with depression took 100 mg of 5-HTP three times a day, compared with 150 mg of an SSRI (fluvoxamine), also taken three times a day. Fifteen of the HTP subjects got better, compared to 18 of the 36 SSRI drug subjects; after 6 weeks, the 2 groups also had 50% improvement, so the study proved that 5-HTP was comparable to SSRI drugs. The study also tested for side effects, and 5-HTP had slightly fewer side effects than SSRIs. 34 subjects with 5-HTP tolerated it, compared to 29 subjects with SSRIs, but did not reach a statistical difference.

5-HTP has been tested in more than 60 clinical trials over the years in the United States, Europe, and Japan alone [15], with test doses ranging from 50 mg to 600 mg a day, with individual tests using doses as high as 3,250 mg a day, with no serious side effects.5-HTP has a long history of proven safety as a drug-like nutrient for depression. Side effects, such as symptoms of nausea reported by some patients, are usually experienced early in the course of use and may be easier to adapt to starting at a lower dose (50mg). [16]

So is it better to take tryptophan or 5-HTP? In addition, tryptophan needs to be converted to 5-HTP before it can produce serotonin in the central nervous system, so 5-HTP is “one step away”. “, whereas tryptophan requires an “extra step”, 5-HTP is more straightforward. This is probably why the study above proves 5-HTP’s quick effectiveness. But 5-HTP also has a downside, as the effect on serotonin is too direct and can lead to resistance, the same problem as with SSRI and SSNI drugs. [17]

Tryptophan and 5-HTP are both “the same way”, choose one is enough, among them 5-HTP fast effect, can relieve depression symptoms for a short time, but should not be taken for a long time. The strategy is to find a more effective treatment for depression during the period of taking 5-HTP, and then slowly reduce and finally stop taking 5-HTP. But 5-HTP, like SSRIs and other drugs, does not work for everyone with depression. Vegetarians may be better off taking tryptophan, as vegetarians may have less tryptophan in their daily diet, and supplementing with tryptophan may also be helpful for overall health.


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[16] Birdsall T. C. (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative medicine review : a journal of clinical therapeutic, 3(4), 271–280.

[17] Tristan (2016), L-Trytophan VS 5-HTP – Which one is better? Last viewed: October 15.2020