To Supplement or Not to Supplement

Most modern antidepressants act on serotonin, one of the neurotransmitters in the brain. While depression is much more complicated than a simple "serotonin imbalance", increasing serotonin certainly seems to help in many cases of depression.

This is the intuition behind the popularity of L-tryptophan and 5-HTP, two dietary supplements that target the serotonin pathway. L-tryptophan is an amino acid found in various foods. The body converts it to an intermediate, 5-HTP, and finally to serotonin itself. It makes sense that supplementing either L-tryptophan or 5-HTP would increase serotonin in the body, and various studies have confirmed this to be true. So, is this a good solution to depression?


Studies have been contradictory and shown generally small effects - but this is true of almost all research into depression treatments. A review by the Cochrane Collaboration states that "the available evidence suggests these substances were better than placebo at alleviating depression...however, the evidence was of insufficient quality to be conclusive" and adds that "because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present."


Right now it is unclear whether L-tryptophan is more effective, less effective, or as effective as standard antidepressants. Aside from it being a gamble, one has to consider side effects and convenience. The side effects of conventional antidepressants are generally well-known. The side effects of L-tryptophan are still unclear. In 1989, thousands of people developed a dangerous immune condition called eosinophilia-myalgia syndrome from a contaminated batch of L-tryptophan. Since then manufacturing processes have improved, but there continue to be sporadic reports of a few L-tryptophan users developing this condition each year. There are also theoretical reasons to think L-tryptophan might contribute to liver disease, hypertension, and other serious conditions. In terms of convenience, most good studies of L-tryptophan supplementation have recommended doses between 3 and 6 g daily; since L-tryptophan usually comes in 500 mg capsules; a proper dose would require taking 6 to 12 capsules per day unless you can find a more efficient way to ingest the bulk powder (maybe a smoothie)?


The situation is similar with 5-HTP. Evidence is poor, with the Cochrane analysis showing a possible effect, and other studies failing to find one. There are some theoretical reasons to expect side effects, based upon excessive supplementation with one neurotransmitter causing deficiencies in others; for this reason, most 5-HTP supplements come with warnings suggesting not to use the substance for more than three months at a time. Both L-tryptophan and 5-HTP can cause drowsiness, nausea, and GI discomfort.


The question on most people's mind is - are these a good alternative to SSRIs? For most people, the answer is probably not. There's better evidence for SSRIs in treatment of depression. Although SSRIs have their share of side effects, they're generally well-known and unlikely to spring any surprises on you. And because SSRIs mostly work in the brain, compared to the effects of taking chemicals that increase serotonin everywhere, there's a theoretical reason to think they will have fewer long-term side effects in the cardiovascular, GI, and other systems. All of these substances are so poorly studied that for all we know this could be inaccurate, and their long term effects could be minimal,  whereas those of SSRI’s might end up being worse than we currently believe. But right now this is the state of our understanding.


Who might want to try L-tryptophan and 5-HTP? People who have tried antidepressants and found they didn't work. People who have too many side effects on antidepressants. People who have financial or other reasons to prefer non-prescription medication. People with relatively mild conditions who are willing to experiment and won't be too upset if the experiment fails.

A final consideration: both of these substances are used for sleep, with much better evidence than for depression. Although we always recommend people try non-chemical solutions to sleep problems first, L-tryptophan and 5-HTP are probably safer than most prescription sleeping pills. Although there are a few antidepressants that also help with sleep (for example mirtazapine), these tend to have their own set of side effects (for example, mirtazapine causes weight gain). An Individual who has problems with both mild depression and insomnia, and who wants to avoid weight gain, (both L-tryptophan and 5-HTP are sometimes marketed as weight loss supplements, though not especially effective ones) might be an ideal candidate for one of these supplements. We would recommend L-tryptophan as a first choice over 5-HTP; because its an earlier substrate in the metabolic pathway, your body has ultimate control over how much it converts to 5-HTP or serotonin.


If you're on any other medication, especially antidepressants, please don't try either of these supplements until you talk to your doctor and make sure there are no drug interactions.

Disclaimer: The posts on this blog are for informational purposes only and do not replace direct care from your mental health care provider. Contact your mental health care provider for specific questions or concerns about your own mental health. All posts are copyrighted, and the views expressed on this blog are representative of the opinions of Pacific Coast Psychiatric Associates (PCPA) as an organization.

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