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Home > Health Conditions > Depression Formulas >
| 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. 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
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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
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
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.13 (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.
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Suggested Adult Use: Take one capsule two or three times daily with or
without food.
Notice: Not to be used concurrently with MAO inhibitors, selective
serotonin reuptake inhibitors (SSRIs) or other anti-depressant
medications. It should also not be used by individuals taking any of the
category of medications known as "triptans".
Free of "Peak X" as verified by assay.
Caution: Keep out of reach of children.
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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. Pöldinger, 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. Simic, M.G. Al-Sheikhly, M. Jovanovic, S.V. Inhibition of free
radical processes by antioxidants-tryptophan and 5-hydroxytrytophan.
Bibl Nutra Dieta 1989;43:288-96. |
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