Benefits
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 three times daily, 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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