Tryptophan to Serotonin Conversion
When neurons convert tryptophan into serotonin, they first use a vitamin B-3
dependent enzyme to convert tryptophan into 5-HTP. A vitamin B6-dependent enzyme is
then used to convert 5-HTP into serotonin. As Zmilacher et al note: "There are
several advantages of considering 5HTP as opposed to L-Tryptophan as being the major
determinant in elevating brain serotonin levels: 5-HTP is not degraded by the
tryptophan pyrrolase to kynurenine, the major pathway for peripheral degradation of
L-tryptophan (about 98%). Furthermore, 5-HTP easily crosses the blood-brain
barrier ..."(1). Additionally, it should be noted that 5-HTP is not incorporated
into proteins, as is tryptophan; nor is 5-HTP used to make vitamin B-3, as is
Thus, in comparison to tryptophan, 5-HTP is virtually a "guided missile"
directly targeted to increase brain serotonin. Indeed, some studies have shown
better results using 200-300 mg 5-HTP/day than other studies using
2000-3000 mg or more tryptophan/day.(17)
The enzyme L-aromatic amino acid decarboxylase (L-AAD) is found outside the brain, and its
activity is especially high in liver, kidney and intestinal lining. L-AAD can convert
5-HTP into serotonin, which cannot cross the blood-brain barrier. Thus, only 5-HTP
which actually makes it into the brain intact is usable to increase brain serotonin
For this reason, some
studies using 5-HTP have also employed compounds called "peripheral decarboxylase inhibitors" (PDI's) -- usually carbidopa or
benserazide. PDI's prevent L-AAD from converting 5-HTP to serotonin outside the
brain. Yet, many studies have successfully used 5-HTP without PDI's, (1,2,4,6,11)
which are prescription drugs and may cause negative side effects.(1) Thus,
Takahashi et al reported favorable response in 8 of 24 people treated with
300 mg 5-HTP daily without a PDI.(6)
A placebo-controlled, double-blind study reported in 1992 found excellent results using 900 mg 5-HTP daily without a
PDI, with minimal side effects.(11)
et al., treated an equal number of people using 5-HTP both with and without
a PDI. The study showed no difference between the two treatments. However, the 5-HTP + PDI group had over twice the side effects of the 5-HTP-only group,
including various emotional and bodily side-effects that showed up in none of the
Zmilacher et al concluded: " ... there was no evidence that the
administration of benserazide [a PDI] intensified the efficacy of 5-HTP [in their
clinical trial]. A review of the literature on this subject revealed
that L-5-HTP given alone was more effective (249 out of 389
patients, 64%) than the combination of L-5-HTP with a peripheral decarboxylase inhibitor (93 out of 176 patients, 52.9%)."(1)
The studies using 5-HTP infer that 5-HTP can naturally elevate
brain serotonin without any help from
SSRI drugs. Yet the study related by Risch and Nemeroff eloquently shows that the
success of SSRI drugs is crucially dependent upon the brain producing adequate serotonin
(from either tryptophan or 5-HTP), and that brain serotonin production is the controlling
or rate-limiting variable underlying the apparent success of SSRI's.
The recommended dose of 5HTP for most
people is 50-100 mg, three times a day, 20 minutes before meals.
to read more from Dr. Michael T. Murray, Author of
The Natural Way to Boost Serotonin.
for 6 steps to healthy sleep by Dr. David Williams.
Murray on 5HTP
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