One theory about migraines is that it is triggered by dropping serotonin levels. One medication, sumatriptan, acts by raising serotonin acting as a reuptake inhibitor. Since tryptophan is converted into serotonin, can tryptophan supplements aid in fighting migraines. Is there any study in this regard?

  • You said that "One theory about migraines is that it is triggered by dropping serotonin levels". If tryptophan is converted into serotonin, then surely this raises serotonin levels counteracting the drop in serotonin, therefore helping to fight migraines. Feb 3, 2019 at 7:10
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    I do think that is the reason, but I would need to look up studies on it to be certain. Because remember, even when the theoretical application of a concept makes sense, whether or not it is the primary mechanism for clinical effectiveness in vivo is a completely different thing. There are plenty of meds that medicine thought worked one way but after additional study, turned out to actuality work a completely different way.
    – DoctorWhom
    Feb 3, 2019 at 9:42
  • @DoctorWhom that is why I am posting the question. There are several issues, including permeability of BBB to tryptophan, etc. I am wondering if they have done clinical trials on this
    – user
    Feb 3, 2019 at 13:34
  • Yes, it is a good question. Sorry, my comment was aimed @ChrisRogers :)
    – DoctorWhom
    Feb 3, 2019 at 19:20
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    @DoctorWhom btw, great nickname!
    – user
    Feb 4, 2019 at 1:31

1 Answer 1


Sumatriptan activates vascular 5-HT1 receptors. This results in vasoconstriction, which is what is thought to help the migraines. This is the same idea for giving caffeine, which is also a vasoconstrictor. Taking tryptophan would likely be ineffective for a variety of reasons in terminating a migraine. First, it would have to be ingested and absorbed, which takes time, and then it would have to be metabolized to 5-HT (Serotonin). Even if tryptophan was absorbed in the stomach, it would be ineffective at terminating the migraine in a timely fashion and thus not well tolerated by a patient.

Second, there is little evidence that oral tryptophan supplementation increases serotonin levels (Cynober et al., 2016).

Cynober et al. (2016) states that the subjects urinated out the tryptophan in a "dose dependent fashion." Further, there was no significant change in their mood with tryptophan supplementation at any dose. This suggests that the tryptophan is not being metabolized into 5-HT. This makes sense, since tryptophan is in our diets, and it would be wild to think that our bodies didn't regulate 5-HT metabolism (that is to say that our bodies just automatically made 5-HT every time we ate something with tryptophan in it).

If patients do have a serotonin imbalance, it is likely involved in metabolism issues, say some mutation or problem with co-factors or enzymes. Therefore, tryptophan likely isn't a solution.


Cynober, L., Bier, D. M., Kadowaki, M., Morris Jr, S. M., Elango, R., & Smriga, M. (2016). Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly–3. The Journal of nutrition, 146(12), 2652S-2654S. doi: 10.3945/jn.115.228478

  • Thank you for the great answer. I read that 5-HTP can be more readily cross the BBB and they eliminate one step (psychologytoday.com/us/blog/integrative-mental-health-care/…). Would that be more effective in fighting migraines?
    – user
    Feb 6, 2019 at 0:13
  • So, while 5-HTP does appear to help with mood much more than L-tryptophan there is poor evidence to support 5-HTP yet for migraines (which isn't to say that it doesn't help). The way that Imitrex works is that it directly activates the 5-HT1 receptors and causes vasoconstriction. The way that 5-HTP would have to work is to either directly activate or inhibit receptors, or be metabolized into something that does. The OP was wondering -- I think -- if tryptophan could work like Imitrex, and I think the answer is probably no. Feb 6, 2019 at 0:38
  • This is a good paper with some thoughts about migraine pathophysiology. Kokavec, A. (2016). Migraine: A disorder of metabolism? Medical Hypotheses, 97, 117–130. doi.org/10.1016/j.mehy.2016.10.029 Feb 6, 2019 at 0:39
  • Unfortunately I do not have access to either of the papers you linked, but thanks for the answers
    – user
    Feb 6, 2019 at 0:51
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    @user - A pdf of Cynober et al. (2016) can be downloaded from academic.oup.com/jn/article-pdf/146/12/2652S/23968978/… Feb 7, 2019 at 7:49

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