5-HTP & depression

I learned recently that 5-HTP is an intermediate between the amino acid tryptophan (oh ye of post-Thanksgiving turkey dinner sleepiness fame) & the neurotransmitter serotonin, whose activity is targeted by a lot of antidepressants. Thus, 5-HTP is alternative to antidepressants–& from my standpoint, a superior one. This is important to me given my history of problems with depression. Since I’m also insulin resistant (prediabetic), the metabolism of carbs & their intimate relationship with tryptophan & hence serotonin levels is crucial.

When I overhauled my diet to a low glycemic/moderate carb diet a couple of years ago, I discovered that I was just as prone to fall into depression if I went too low in carbs as I did when I was my carb intake was too high. I don’t seem to be having that problem so much now, as I go to a lower carb diet. Maybe I’ve adapted. But I’m now also supplementing with 5-HTP.

Here’s how I understand the mechanism relating carbs & insulin to tryptophan > 5-HTP > serotonin to mood disorders like depression (& probably other things like road rage, anxiety, etc.).

Low serotonin levels frequently (especially in insulin resistant people whose blood sugars are all over the map) lead to carb cravings because intake of carbs brings (as most of us here will know) increase in insulin secretion. The insulin works not only to control blood glucose (as best it can), but also to cause various amino acids to be absorbed into body tissues — except apparently tryptophan isn’t absorbed as much. This then leads to tryptophan to have less competition from other amino acids for riding the carrier molecule they use to get through the blood-brain barrier, where the tryptophan is synthesized into 5-HTP & from 5-HTP into serotonin. The effect of eating carbs for the depressed person is, thus, to increase serotonin levels into the brain — but at a cost (higher blood sugars, higher blood insulin, increase in insulin resistance & obesity, etc.).

The reason it might be better to supplement with 5-HTP than tryptophan is because: (1) tryptophan is also used in the body to synthesize other products, which might not hold as much advantage for mood issues, whereas (I think) 5-HTP is used mainly to synthesize serotonin; & (2) 5-HTP has a much easier time getting through the blood/brain barrier than tryptophan — apparently doesn’t require the carrier molecule that tryptophan does (in which tryptophan competes with other amino acids).

My source for this info is the book Hunger Free Forever: The New Science of Appetite Control by Michael T. Murray, N.D. and Michael R. Lyon, M.D. Murray has also written a book specifically about 5-HTP. I’ll see if I can find actual scientific cites. In any case, so far it’s working well for me.

Update 12 May 2008: I finally got around to finding a reference. Here is is, with its abstract.

  • Birdsall TC.. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80.(Full article with references is available at http://www.thorne.com/altmedrev/.fulltext/3/4/271.pdf.)

    5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

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