5-HTP: What Is It and Does It Work?


Touted as one of the new panaceas for better health, can 5-HTP really live up to everything its proponents claim?

5-hydroxytryptophan ( 5-HTP), is being touted for boosting motivation and learning, enhancing mood, reducing stress, cutting bodyfat, relieving depression, controlling pain and improving sleep. Like most supposedly new panaceas, 5-HTP has been hanging around for decades, so studies on it abound. It shouldn't be too hard to discover whether or not the claims hold water.

Your Body Makes 5-HTP

Your body converts the amino acid L-tryptophan from food into 5-HTP, some of which then converts to the neurotransmitter serotonin, more properly called 5-hydroxytryptamine ( 5-HT). 5-HTP is biologically inactive until it converts to serotonin.( 1) So all the claims being made depend on the way it affects serotonin metabolism. Oral supplements of 5-HTP do indeed cause large increases in brain serotonin levels.( 2, 3, 4)

A Sketch of Brain Function

Without delving too deep into complexity, we can describe a lot of brain activity as the interaction of four major neurotransmitters - dopamine, acetylcholine, noradrenalin, and serotonin. In general terms, three of the neurotransmitters increase bodily activity. Noradrenalin forms part of your fight or flee reaction system. Dopamine is your main get-up-and-go neurotransmitter. Acetylcholine is intimately involved in alertness, learning and memory.

Serotonin, however, generally works in opposition to the other three neurotransmitters. It reduces activity. To allow you to fall asleep, the lower part of the brain, just above your neck, releases a flood of serotonin to quiet down the brain. That's why supplementary L-tryptophan, the precursor of serotonin, is sometimes effective as a sedative. In halfway normal brains like yours and mine, the four neurotransmitters work in harmony, variously opposing or complementing each other's activity.

The Serotonin Deficiency Argument

From all the popular articles and a lot of scientific papers I read on 5-HTP, market moguls pushing this potion have no idea what they're doing. One claim is that many people become serotonin deficient.( 5, 6) This notion arose from work of Poldinger and colleagues. They tested 5-HTP against the anti-depressant fluvoxamine, which affects serotonin metabolism, and found it to be equally effective in reducing some of the symptoms of depression.( 7) Fluvoxamine is a pretty poor anti-depressant so these findings were no great shakes.

There are no studies showing serotonin deficiency in healthy people. Just the opposite. Multiple studies of both animal and human subjects, show that serotonin levels do not decline throughout life. If anything they increase.( 8) Extreme low levels of serotonin metabolism do occur in some rare diseases, such as myoclonus epilepsy, but they are not helped by 5-HTP supplements.( 9)

5-HTP Acts Differently Than Fluoxetine

Fluoxetine (Prozac(R)) is a type of anti-depressant called selective-serotonin-reuptake-inhibitors (SSRI). When you take fluoxetine, you change the balance of intracellular and extracellular by holding more of the serotonin outside the nerve cells. The overall amount of serotonin in the brain does not change. When you take 5-HTP, however, you increase the total amount of brain serotonin. 5-HTP has no direct effect on other neurotransmitters.( 2, 10) It just loads your brain with serotonin. In contrast, fluoxetine causes a general stimulation of your get-up-and-go neurotransmitters, noradrenalin, dopamine and acetylcholine, and then dampens their overactivity by its stronger action on serotonin.

5-HTP works entirely differently. By increasing only serotonin, it down-regulates total brain function. From this action, we can predict that 5-HTP would be effective as a sleep aid, but ineffective for can't-get-out-of-bed, woe-is-me depressions, which are the most common forms.

Unfortunately, studies of 5-HTP treatment of depression rarely sort out anxious, agitated patients from vegetative, woe-is-me types. But when you examine their data closely, it's simple to see that 5-HTP is virtually useless for woe-is-me.( 4, 7)

In the amounts of up to 100 milligrams now being sold as supplements, it doesn't matter, because that much 5-HTP will not affect anything. Marketers seem to think that 20 mg of 5-HTP is equivalent to a 20 mg pill of fluoxetine. No way! About 99% of 5-HTP is converted to serotonin before it reaches the brain, and virtually none of that serotonin gets across the blood/brain barrier, because the serotonin molecule is too big. So it would take at least, 500 mg and up of oral 5-HTP to have appreciable action on brain function.

I wouldn't advise taking such amounts. Those unfortunates who have the rare disease called hindgut carcinoid syndrome, in which a serotonin-secreting tumor loads their body with serotonin, have the worst diarrhea known to man. And animals given high doses of 5-HTP, quickly emulate the human sufferers.( 1)

The Serotonin Syndrome

Since SSRI have become the prescriptions of choice, a new man-made disease has entered the literature serotonin syndrome. The main cause is almost certainly interference with serotonin metabolism.( 11)

One symptom of this disorder is memory impairment and reduced learning ability. This is exactly the opposite to the improved brain function now being claimed for 5-HTP supplements. For twenty years we have known that stimulation of brain serotonin activity with a variety of drugs impairs memory and reduces learning in both animals and human subjects.( 12-15) We also know that drugs which reduce brain serotonin activity, enhance learning and memory.( 16, 17)

Before some alert reader jumps on me, it's true that Prozac(R) and some other SSRI anti-depressants initially enhance memory and learning.( 18-20) These drugs increase extracellular serotonin by blocking it's re-uptake into nerves. They don't increase nerve use of serotonin, they deplete the nerves of it. So its likely that SSRI initially reduce brain serotonin activity, while at the same time dampening their stimulation of the other three neurotransmitters with the excess of serotonin they hold outside the nerves throughout the brain.( 21)

5-HTP floods the brain with serotonin which is then free to be taken up by nerve terminals. So it increases nerve serotonin activity big time, and down-regulates brain function. The evidence indicates that this action of 5-HTP is useful for sleep and for the anxious, agitated form of depression, and perhaps for the fibromyalgia and migraines that sometimes form part of this syndrome.( 22) But for the general blahs that beset most of us from time to time, for fat loss, motivation, learning, memory and mood, 5-HTP supplementation may just be an insidious way to gradually lose your mind.

(1.) Bourin M, et al. 5-HTP induced diarrhea as a carcinoid syndrome model in mice. Fundament Clin Pharmacol, 1996;10:450-457.

(2.) Li XM, et al. On the in-vivo modulation of dopamine release by fluoxetine and 5 hydroxy-L-tryptophan in conscious rats. J Pharm Pharmacol, 1996;48:825-828.

(3.) Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol, 1996;398:373-379.

(4.) Zmilacher K, et al. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Neuropsychobiology, 1988;33:20-28.

(5.) South J. Oxitriptan; Prozac's true alternative. JAS Bulletin, October 1996, 1.

(6.) Life Enhancement News, 1996;28:12-15.

(7.) Poldinger W, et al. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopharmacol, 1991;24:53-81.

(8.) McEntee WJ, Crook TH. Serotonin, memory, and the aging brain. Psychopharmacol, 1991;103:143-149.

(9.) Pranzatelli MR, et al. A controlled trial of 5-hydroxy-L-tryptophan for ataxia in progressive myoclonus epilepsy. Clin Neural Neurosurg, 1996;98:161-164.

(10.) Physicians Desk Reference, 50th Edition. Montvale NJ: Medical Economics, 1996.

(11.) Martin TG. Serotonin syndrome. Ann Emerg Med, 1996;28:520-526.

(12.) Lawlor BA et al. Hyperresponsivity to the serotonin agonist m-chlorophenyl-piperazine in Alzheimer's disease. Arch Gen Psychiatry, 1989a;46:542-549.

(13.) Lawlor BA et al. A preliminary study of the effects of intravenous m-chlorophenyl-piperazine, a serotonin agonist, in elderly subjects. Biol Psych, 1989b;25:679-686.

(14.) Ramirez TM et al. The effects of serotonergic intrahippocampal neonatal grafts on learning and memory in the Stone 14-unit T-maze. Sac Neurosci Abstr, 1989; 15:465.

(15.) Winter JC, Petti DT. The effects of 8-hydroxy-2-(di-n-propylamino) tetralin and other serotonergic agonists on performance in a radial maze: a possible role for 5-HT receptors in memory. Pharmacol Biochem Behav, 1987;27:625-628.

(16.) Altman HJ, Normile HJ. What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile dementia. Neurobiol Aging, 1988;9:627-638.

(17.) McEntee WJ, Mair RG. Memory enhancement in Korskof psychosis with clonidine: further evidence for a noradrenergic deficit. Ann Neurol, 1980;7:466-470.

(18.) Martin PR et al. Effective pharmacotherapy of alcoholic amnestic disorder with fluoxamine. Arch Gen Psychiatry, 1989;46:617-621.

(19.) Flood JF, Cherkin A. Fluoxetine enhances memory processing in mice. Psychopharmacology, 1987;93:36-43.

(20.) Weingartner H et al. Effects of serotonin on memory impairments produced by ethanol. Science, 1983;221:472-474.

(21.) Altman HJ, Stone WS, Ogren SO. Evidence for a possible functional interaction between serotonergic and cholinergic mechanisms in memory retrieval. Behav Neural Biol, 1987;48:49-62.

(22.) Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy. Adv Exp Med Biol, 1996;398:373-9.

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