What is 5-HTP?

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What is 5-HTP?

JoAnn Guest

Nov 03, 2003 17:08 PST

 

What is 5-HTP?

http://www.willner.com/References/webref58.htm

 

5-HTP (5-hydroxytryptophan) is a naturally-occurring metabolite of

the

essential amino acid tryptophan. 5-HTP for use in dietary

supplements is

derived from the seeds of the Griffonia simplicifolia plant.

 

Metabolism and absorption of 5-HTP

 

5-HTP (5-hydroxytryptophan) is formed by the addition of a hydroxyl

group (-OH) to the 5 carbon of the indole ring of tryptophan.

Conversion

of tryptophan to 5-hydroxytryptophan is catalyzed by the enzyme

tryptophan hydroxylase.1 5-HTP functions as the precursor for

serotonin,

and is converted to serotonin in a pyridoxal phosphate (vitamin B6)

dependent reaction catalyzed by the enzyme L-amino acid

decarboxylase.2

 

Synthesis of serotonin in the brain requires an adequate supply of

either tryptophan or 5-HTP as precursors. The supply of tryptophan

available for conversion to 5-HTP depends on a number of factors,

including nutritional status and competition between tryptophan and

other amino acids for transport across the blood brain barrier.

 

Disturbances in the serotonin metabolic pathway may disrupt central

nervous system functions which utilize serotonin as a

neurotransmitter.2

Administration of 5-HTP bypasses the conversion of tryptophan to 5-

HTP.

5-HTP readily crosses the blood brain barrier and becomes available

for

serotonin synthesis. Serotonergic neurons (nerve cells stimulated by

serotonin) regulate sleep, appetite, nociception (the perception of

pain), and aggressive behavior.2

 

Serotonin is metabolized to 5-HIAA (5-hydroxyindolacetic acid) which

is

its primary breakdown product.3 The concentration of 5-HIAA in

cerebrospinal fluid is used as an indicator of serotonin turnover in

the

CNS serotonin level. Psychiatric patients have been found to have

low

levels of 5-HIAA in the CNS fluid, suggesting serotonin deficiency.3

 

5-HTP is readily absorbed by the mucosal cells of the

gastrointestinal

tract. The delivery of 5-HTP into general circulation is enhanced by

the

concomitant administration of an L-amino acid decarboxylase

inhibitor

such as carbidopa, which reduces the conversion of 5-HTP to

serotonin in

the gut and in liver. In one study using five subjects, systemic

absorption of 5-HTP in combination with carbidopa averaged 69.2

percent.4 Another absorption study found that carbidopa enhanced the

increase in serum 5-HTP concentration 5 to 15 fold.5 In this study,

a

single dose of 5-HTP increased the plasma level of 5-HTP only

slightly,

whereas 5-HIAA increased 9-20 fold. This suggests that the gut

mucosa

has a storage capacity for 5-HTP, and that plasma increases occur

after

maximum capacity is reached.5

 

Observed Effects of 5-HTP Administration

 

Improves Well-Being in Depressed Persons

 

Serotonin in the central nervous system is recognized as a causative

factor in some depressed persons.6,7 A comprehensive review of seven

open and seven controlled clinical studies found that oral

consumption

of 5-HTP improved mental and emotional status in 60 to 70 percent of

depressed people. The results varied from " modest " to " marked. " 8

Dosages

ranged from 50 to 300 mg daily.

 

The accumulated evidence is inconclusive as to whether 5-HTP is more

effective combined with decarboxylase inhibitors than when taken

alone.

Many of the early trials used the combination, and this has been a

frequently used therapeutic strategy for reducing conversion of 5-

HTP to

serotonin outside the CNS. It is generally accepted that a large

portion

of absorbed 5-HTP is metabolized to serotonin in peripheral tissues

before it can enter the brain.8

 

Peripheral conversion of 5-HTP to serotonin would theoretically

limit

the usefulness of oral 5-HTP for improving CNS functions and mental

health. However, trials in which 5-HTP was given alone do show

benefits.

A small open trial in which 25 people were given 5-HTP either alone

or

with a decarboxylase inhibitor found no difference in

effectiveness.9

Thirteen of the patients had " very good " or " good " improvement, 8

had

" moderate, " and in 4 out of the twenty-five the results were judged

to

be " poor. "

 

A more recent randomized double-blind study compared the efficacy of

oral 5-HTP (100 mg T.I.D., without a decarboxylase inhibitor) to

that of

fluvoxamine, a selective serotonin reuptake inhibitor.10 (SSRIs

block

the reabsorption of serotonin by postsynaptic receptors, thus

increasing

the available supply of serotonin in the synaptic cleft.) The two

were

found to be equally effective, and 5-HTP was better tolerated. It

should

be noted that 5-HTP was given in the form of enteric-coated pH-

sensitive

capsules which dissolve in the small intestine, thus preventing

conversion of 5-HTP to serotonin in the stomach.

 

In contrast to MAO inhibitors and SSRIs, medications which act by

blocking normal physiologic functions, 5-HTP supports normal

function in

its role as a serotonin precursor. Correcting serotonin deficiency

has

been called a " functional-dimensional approach " in the treatment of

depression.10 (continued on reverse)

 

Improves Sleep Quality

 

Studies have shown that 5-HTP influences the quality of sleep by

increasing REM (rapid eye movement) sleep. Administration of 5-HTP

in

the evening prior to bedtime has been shown to increase the duration

of

REM sleep and decrease the amount of non-REM sleep.11,12

 

Helps Prevent Migraine Headaches

 

Serotonin is known to play an important role in the pathophysiology

of

migraine headaches.13 Serotonin regulates a key pain control system

which is activated during a migraine attack.14 In a placebo-

controlled,

double-blind cross-over study 31 people with migraine took 400 mg of

5-HTP per day. By the second month, 5-HTP reduced the frequency and

severity of attacks by more than 50 percent in 52 percent of the

subjects, although the results were not statistically significant.13

In

a larger study using 124 migraine sufferers, 5-HTP for migraine

prevention was compared to methysergide.14 Seventy-one percent of

the

subjects taking 5-HTP (600 mg per day) experienced significant

reduction

of intensity and duration of attacks, compared to seventy-five

percent

of those taking the drug. Side effects were less frequent in the 5-

HTP

group.

 

Improves Clinical Parameters in Fibromyalgia

 

Disturbances in serotonin-controlled nervous system function are

believed to be a factor in fibromyalgia.15 In a 90 day open trial,

50

people with primary fibromyalgia received 100 mg of 5-HTP three

times

daily.16 Nearly 50 percent showed " good " or " fair improvements in

clinical parameters such as the number of tender points, anxiety,

fatigue and sleep quality. A placebo controlled, double-blind study

on

50 patients produced similar significant improvements.17

 

5-HTP–A Free-radical Scavenger

 

The OH group which is added to tryptophan in the formation of 5-HTP

gives 5-HTP antioxidant properties.18 (Compounds such as vitamin E

and

flavonoids derive their free-radical quenching ability from OH

groups,

which donate electrons to oxidants.) 5-HTP quenches a variety of

free-radicals. This is in contrast to tryptophan, which is sensitive

to

oxidation.

 

Adverse effects of 5-HTP

 

Oral administration of 5-HTP in clinical studies has resulted in

gastrointestinal disturbances such as nausea, vomiting and diarrhea.

According to a review by Byerley, et. al. these effects are

tolerated by

most patients and tend to lessen over time.8 Side effects are more

marked with higher doses, and may be reduced by the use of

enteric-coated, pH sensitive capsules or tablets.8,10

 

 

 

Scientific References:

 

1. Pike, R.L., Brown, M.L. Nutrition: An Integrated Approach. NY:

Macmillan Pub. Co.; 1986:626-28.

 

2. Peters, J.C. Tryptophan nutrition and metabolism: An overview.

Advances in Experimental Medicine and Biology 1991;294:345-349.

 

3. van Pragg, H.M. Central monoamine metabolism in depressions. I.

Serotonin and related compounds. Comprehensive Psychiatry

1980;21(1):30-43.

 

4. Magnussen, I., Neilsen-Kudsk, F. Bioavailability and related

pharmacokinetics in man of orally administered L-5-hydroxytryptophan

in

steady state. Acta pharmacol. et toxicol. 1980;46:257-62.

 

5. Magnussen, I., Jensen, T.S., Rand, J.H., Van Woert, M.H. Plasma

accumulation and metabolism of orally administered single dose

L-5-hydroxytryptophan in man. Acta pharmacol. et toxicol.

1981;49:184-89.

 

6. van Pragg, H.M. Korf, J. 5-hydroxytryptophan as an

antidepressant.

Journal of Nervous and Mental Disease 1974;158(5):331-37.

 

7. van Pragg, H.M. Management of depression with serotonin

precursors.

Biological Psychiatry 1981;16(3):291-310.

 

8. Byerley, W.F. et. al. 5-Hydroxytryptophan: A review of its

antidepressant efficacy and adverse effects. Journal of Clinical

Psychopharmacology 1987;7(3):127-37.

 

9. Zmilacher, K. Battegay, R., Gastpar, M. L-5-hydroxytryptophan

alone

and in combination with a peripheral decarboxylase inhibitor in the

treatment of depression. Neuropsychobiology 1988;20:28-35.

 

10. Pšldinger, W., Calanchini, B., Schwarz, W. A functional-

dimensional

approach to depression: Serotonin deficiency as a target syndrome in

a

comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology

1991;24:53-81.

 

11. Zarcone, V.P. Hoddes, E., Smythe, H. Oral 5-hydroxytryptophan

effects on sleep. in Serotonin and Behavior, edited by Barchas, J.,

Usidin, E., NY: Academic Press; 1973:499-505.

 

12. Wyatt, R.J., et. al. Effects of 5-hydroxytryptophan on the sleep

of

normal human subjects. Electroencephalography and Clinical

Neurophysiology 1971;30:505-09.

 

13. De Benedittis, G., Massei, R. 5-HT precursors in migraine

prophylaxis: A double-blind cross-over study with L-5-

hydroxytryptophan

versus placebo. The Clinical Journal of Pain 1986;2:123-129.

 

14. Titus, F., D‡valos, A., Alom, J., Codina, A. 5-hydroxytryptophan

versus methysergide in the prophylaxis of migraine. Eur. Neurol.

1986;25:327-29.

 

15. Nicolodi, M., Sicuteri, F. Fibromyalgia and migraine, two faces

of

the same mechanism. Recent Advances in Tryptophan Research, Vol.

398,

edited by Filippini, G.A., et. al., NY: Plenum Press; 1996:373-79.

 

16. Puttini, P.S., Caruso, I. Primary fibromyalgia syndrome and

5-hydroxy-L-tryptophan: a 90 day open study. The Journal of

International Medical Research 1992;20:182-89.

 

17. Caruso, I., Puttini, P.S., Cazzola, M., Azzolini, V. Double-

blind

study of 5-hydroxytryptophan versus placebo in the treatment of

primary

fibromyalgia syndrome. The Journal of International Medical Research

1990;18:201-09.

 

18. Simic, M.G. Al-Sheikhly, M. Jovanovic, S.V. Inhibition of free

radical processes by antioxidantsÐtryptophan and 5-hydroxytrytophan.

Bibl Nutra Dieta 1989;43:288-96.

 

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