Metabolism and Absorption of 5-HTP

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What is 5-HTP?

 

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.

 

Side effects are more marked with higher doses, and may be reduced by the use

of enteric-coated, pH sensitive capsules or tablets.

 

 

 

 

 

 

 

 

 

 

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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