I recently came across a really interesting article called “5-HTP efficacy and contraindications” on the NIH website. I found the article because I had been orally supplementing my diet with 200mg 5-HTP capsules, and I wanted to do some more research on what evidence there was for the efficacy of 5-HTP. I found the article to be really surprising, and I want to summarize it here. Of course if you have any questions, or want to know more about this, it’s better to just read the article itself rather than my summary here. Disclaimer: I am not a doctor or medical professional.
5-HTP is a precursor to the neurotransmitter serotonin. Serotonin is a critical neurotransmitter that plays a number of functions in the brain, among them contributing to feelings of well-being and happiness. Low serotonin levels have been linked with depression and other mood disorders (although not all cases of depression are caused by low serotonin levels). Serotonin does not cross the blood-brain barrier, which means that serotonin levels in the brain cannot be increased by direct supplementation. However, 5-HTP does cross the blood-brain barrier. In the brain 5-HTP is metabolized by an enzyme called AAAD into serotonin. Therefore oral supplementation of 5-HTP can increase latent serotonin levels in the brain. The pop science marketing of 5-HTP supplements suggest that by taking 5-HTP you can improve mood and happiness, and possibly even counteract the effects of depression, since taking 5-HTP can increase serotonin levels.
What the study I linked to shows is that not only is there poor evidence that 5-HTP supplementation alone can improve mood or combat depression, there’s actually a lot of circumstantial evidence to suggest that it can worsen those effects. That is what is meant by the medical term contraindication—that 5-HTP supplementation can potentially have a deleterious impact on mental health.
The article first summarizes some of the existing studies on 5-HTP supplementation. It points out that studies where 5-HTP was administered alone have not shown significant improvement for treating disorders like depression. Then it points out that in studies where 5-HTP supplementation has shown to be effective, that those studies were also controlling for dopamine levels with another drug like carbidopa. From what I gathered from the article, the current state of the art in medicine allows doctors to measure serotonin and dopamine levels and to control them carefully in a controlled setting. However, over the counter oral 5-HTP supplementation isn’t a controlled or monitored setting, and without the administration of a drug like carbidopa one isn’t controlling latent dopamine levels.
The article goes on to point out that there’s a lot of evidence to suggest that oral 5-HTP supplementation can actually cause dopamine levels to become imbalanced. The synthesis of 5-HTP into serotonin is catalyzed by the enzyme AAAD, and that same enzyme catalyzes L-DOPA into dopamine. Excess 5-HTP can compete with the L-DOPA reaction and therefore cause dopamine levels to be depressed. There’s evidence to show that other monoamine pairs can get out of balance when one monoamine precursor dominates another. Low dopamine levels are associated with a number of disorders, notably Parkinson’s disease. Low dopamine levels have also been implicated in depression. Therefore there is evidence to suggest that taking 5-HTP to increase serotonin levels can actually cause lowered dopamine levels, and therefore can potentially be implicated in worsening symptoms of depression.
On the basis of this article it doesn’t seem safe to me to take supplementary 5-HTP for extended periods of time, or possibly at all.