Boosting Serotonin for Better Mood: A Comparison of Tryptophan and 5-HTP for Depression

The cause of depression has been a topic of debate for years, but one widely accepted theory is an imbalance of neurotransmitters in the central nervous system. Among these neurotransmitters, serotonin is considered crucial, and the Serotonin Hypothesis is well-regarded. It is believed that three neurotransmitters (dopamine, norepinephrine, and serotonin) influence depression, with serotonin being the primary one. The mainstream prescription antidepressants like SSRIs mainly target serotonin reuptake, while SNRI drugs affect serotonin and norepinephrine reuptake.

Biosynthesis Pathway of Serotonin

Although the gut and other tissues can produce serotonin, they cannot pass through the blood-brain barrier. Therefore, serotonin, as a neurotransmitter, must be synthesized in the central nervous system. After protein-rich foods are digested and metabolized into amino acids, tryptophan can enter the central nervous system through carriers (but it competes with other LNAA). Under the action of enzymes, serotonin is first metabolized into 5-HTP, a process that involves various co-factors. The body can also directly supplement 5-HTP, which can pass through the blood-brain barrier more efficiently than supplementing tryptophan, as it is closer to being converted into serotonin in the central nervous system and requires different co-factors.

The principle of SSRI medication is to block serotonin reuptake, thereby increasing serotonin levels in the central nervous system, which is believed to be beneficial for depression. Similarly, the herb St. John’s Wort can also inhibit serotonin reuptake, making it widely used as a natural supplement. Another approach to boost serotonin is by increasing the production of 5-HTP or tryptophan through supplementation. However, if the bottleneck in serotonin production lies in the co-factors rather than the raw materials, supplementing various co-factors like B3, B6, etc., may be more effective in increasing serotonin levels.

In this article, we’ll first introduce two supplements known to enhance serotonin in the central nervous system: tryptophan and 5-HTP.

Trytophan and 5-HTP

Supplementing with tryptophan can increase serotonin in the central nervous system and improve depression symptoms. In a clinical trial conducted in 2014 [1], 25 healthy participants were compared after consuming a low-tryptophan diet for four days and a high-tryptophan diet for another four days. The high-tryptophan diet showed a significant positive impact on mood.

Another study in 2016 [2] found that tryptophan can improve social behavior in patients with social behavior disorders, enhancing their social self-control. Even in healthy individuals, tryptophan supplementation appears to promote social behavior.

As early as 1982, an RCT involving 115 patients with depression already demonstrated the helpfulness of tryptophan in treating depression symptoms [3]. The trial confirmed that tryptophan has an equally effective therapeutic effect as the tricyclic antidepressant.

5-HTP, an intermediate metabolite for serotonin, can also help improve depression symptoms. The first clinical trial on 5-HTP for treating depression, conducted in 1972 with 107 patients with depression [4], demonstrated that taking 50mg-300mg of 5-HTP daily could improve depressive symptoms within just two weeks, and no significant side effects were observed.

A clinical trial found that 5-HTP’s effects were faster than SSRIs. Out of 59 depressed patients taking 150mg-300mg of 5-HTP daily for three weeks, 22% showed significant improvement, 45.8% had moderate improvement, and 80% experienced positive effects within one week. [5]

So, how does the effectiveness of 5-HTP compare to prescription SSRIs? In a Swiss clinical study from 1991 [6], 36 depressed patients were divided into two groups: one received 3 doses of 100mg 5-HTP daily, and the other received 3 doses of 150mg fluvoxamine (an SSRI) daily. Both interventions showed similar effectiveness. After 4 weeks, 15 out of 36 5-HTP participants and 18 out of 36 SSRI participants showed improvement. At 6 weeks, both groups had a 50% improvement rate, indicating comparable effectiveness. Side effects were also assessed, with 5-HTP showing slightly fewer side effects than SSRIs, but the difference was not statistically significant.

Over the past years, 5-HTP has been the subject of more than 60 clinical trials in the United States, Europe, and Japan [7]. Test dosages ranged from 50mg to 600mg per day, with some individual tests using doses as high as 3,250mg per day, and no serious side effects were reported. The long history of 5-HTP as a nutraceutical for depression proves its safety. Side effects, such as nausea, are typically observed in the early stages of supplementation and may be easier to adapt to when starting at a lower dose (50mg) [8].

Which is better: Trytophan or 5-HTP

So, which is better to take, tryptophan, or 5-HTP? Tryptophan needs to compete with other large neutral amino acids (LNAA) to enter the central nervous system, which means that much of the ingested tryptophan may not reach the brain. On the other hand, 5-HTP can pass through the blood-brain barrier, resulting in a higher bioavailability in the central nervous system.

Additionally, tryptophan in the central nervous system needs to be converted to 5-HTP before producing serotonin, making 5-HTP more directly involved in serotonin synthesis, whereas tryptophan requires an extra step. This might explain why 5-HTP has shown faster effectiveness in some studies [9].

Summary

Both tryptophan and 5-HTP work along the same pathway, so choosing one is sufficient.

5-HTP shows faster effects and can provide short-term relief for depression symptoms, but it is not advisable to use it for extended periods. A better strategy would be to use 5-HTP while finding more effective treatments for depression and gradually reduce and eventually stop 5-HTP supplementation.

It’s crucial not to assume that depression is cured solely by taking 5-HTP. However, like SSRIs and other medications, 5-HTP may not be effective for every individual with depression.

Vegetarians may find tryptophan supplementation more beneficial as their diets might have lower tryptophan content, and supplementing with tryptophan could support overall health.