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
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.
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".
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.
*Above statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.
