Introduction.
5-HTP
( 5-hydroxytrptophan ) is the immediate precursor of the monoamine neurotransmitter
serotonin. Serotonin plays an important role in the regulation of mood,
appetite, and body temperature. Deficiencies of serotonin in the brain
have been linked to a number of disparate conditions, including: depression
(especially the agitated, anxious, irritable type), (1-6) anxiety, (7)
suicide, (8) alcoholism, (9) violent behavior, (8) PMS, (10) obesity,
(10,11) compulsive gambling, (12) insomnia, (13) carbohydrate craving,
(10) SAD (seasonal affective disorder), (10) and migraine headaches.
(14)
When nutrients are allowed to cross the blood-brain barrier they must
be 'ferried' by specialized transport molecules, much as passengers
being transported on a bus. This process creates a special 'bottleneck'
for serotonin. Serotonin itself cannot pass through the blood-brain
barrier, while its precursor, tryptophan, must share its transport 'bus'
with five other amino acids -- leucine, isoleucine, valine, tyrosine
and phenylalanine.
In any normal diet, animal protein-based or vegetarian, tryptophan is
the least plentiful of all 20 food amino acids. Thus, tryptophan is
typically outnumbered as much as 9:1 in its competition to secure its
transport through the blood-brain barrier into the brain. Eating a high-protein
diet in an attempt to increase dietary tryptophan (a typical diet provides
only 1-1.5 grams/day) only increases its competition even more. Ironically,
the only dietary strategy that increases brain tryptophan supply is
a high-carbohydrate, low-protein diet. When large amounts of carbohydrates
are eaten, the body secretes large amounts of the hormone insulin to
lower the resulting high blood sugar. In addition to lowering blood
sugar levels, insulin also clears most of the five amino acids that
compete with tryptophan for a 'ride' to the brain. The result is that
tryptophan has the 'bus' to itself, allowing plenty of tryptophan to
reach the brain. (10)
Tryptophan to Serotonin Conversion
When neurons convert tryptophan into serotonin, they must first use
a vitamin B3-dependent enzyme to convert tryptophan into 5-HTP. A vitamin
B6-dependent enzyme is then used to convert 5-HTP into serotonin. One
researcher noted, 'There are several advantages of considering L-5-HTP,
as opposed to L-tryptophan, as being the major determinant in elevating
brain serotonin levels: L-5-HTP is not degraded by tryptophan pyrrolase
to kynurenine, the major pathway for peripheral degradation of L-tryptophan
(about 98 percent). Furthermore, L-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 B3, as is tryptophan. Thus, in comparison to tryptophan, 5-HTP
is virtually a 'guided missile' that is directly targeted to increasing
brain serotonin levels. Strikingly, some studies have shown better results
using 200 to 300 mg of 5-HTP per day as an antidepressant than other
studies using 2000 to 3,000 mg or more of tryptophan per day. (17)
Tryptophan vs. 5-HTP
In the 1970s, the American health food industry began to provide an
alternative method of getting more tryptophan to the brain -- tryptophan
supplements. Many people found that 500 to 3,000 mg of supplementary
tryptophan daily provided practical relief from depression, PMS, insomnia
and obsessive-compulsive disorders. In 1989, the FDA removed tryptophan
from the American health food market due to a mysterious outbreak of
a rare but serious ailment -- eosinophilia myalgia (EMS). This EMS 'epidemic'
was later traced to a single batch of contaminated tryptophan from a
Japanese producer. Thirteen years later, although tryptophan has been
proven to be safe (and is currently available in baby food formulas,
intravenous feeding solutions, and veterinary products) the FDA still
shows no signs of allowing tryptophan back onto the market as a dietary
supplement.
Fortunately, a safe, natural and effective alternative to tryptophan
has been researched for over 30 years. This substance is L-5-Hydroxytryptophan
(5-HTP). 5-HTP is not produced by bacterial fermentation (as was the
tainted tryptophan) nor chemical synthesis, but is extracted from the
seeds of the Griffonia plant.
Appetitie Suppression:
A placebo-controlled, double-blind study reported in 1992 found
excellent results treating obesity using doses of 5-HTP as high as 900
mg daily, with minimal side effects (the greatest side effect being
diarrhea or upset stomach)! (11) Four other clinical trials in overweight
or obese humans have found 5-HTP to decrease food intake and consequently
cause weight loss. In a double-blind, placebo-controlled trial conducted
by researchers at the University of Rome, 20 obese women were given
300 mg 5-HTP or placebo three times daily for six weeks of unrestricted
diets followed by six weeks in which subjects were instructed to consume
1200 calories daily. The 5-HTP group experienced significant weight
loss during both periods, and caloric intake was markedly reduced (1879
vs. 3220 calories during spontaneous eating, with a further reduction
to 1268 calories during the second period). In another double blind,
placebo-controlled study on 20 overweight type II diabetes patients,
subjects given 5-HTP had significant reductions in energy intake and
body weight compared to placebo
Studies in rodents indicate that 5-HTP administration causes a significant
increase in the hormone leptin. Leptin plays an important role in the
regulation of appetite and other physiological processes, and various
factors can alter leptin secretion. 5-HTP administration results in
significant increases in insulin, corticosterone, and prolactin levels,
and all of these hormones can increase leptin levels. The present animal
research indicates that the effect of 5-HTP on leptin levels are insulin-dependent,
while the role that 5-HTP-induced increases in corticosterone plays
seems to be minor. Future research should further define the mechanisms
by which 5-HTP increases leptin levels.
Depression:
The majority of the research on 5-HTP has focused on its possible
use as a treatment for depression. In 2000, the clinical research was
thoroughly reviewed by Meyers. Many studies were conducted by a group
of European researchers in the 1970's and early 1980's. In one study
60% of depressed patients given 5-HTP (200-3000 mg/day) improved while
there were no improvements in the placebo group. Another double-blind
study with 200 mg/day of 5-HTP indicated that it was more effective
than placebo and almost as effective as the tricyclic antidepressant
clomipramine . In one study, the antidepressant effects of 5-HTP was
compared with fluvoxamine, a prescription Prozac-like drug used in Europe.
The 5-HTP patients showed slightly better treatment response than the
fluvoxamine group, yet had significantly fewer and less severe side
effects. The researchers note: 'Regarding tolerance and safety, however,
oxitriptan [5-HTP] proved superior to fluvoxamine as was apparent from
a marked difference in severity of untoward side effects between the
two compounds. The study presented here ...strongly confirm[s] the efficacy
of 5-HTP as an antidepressant.' (4)
The
many successful published studies using 5-HTP show that 5-HTP, by naturally
elevating brain serotonin, can alleviate the serotonin-deficiency syndrome
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 SSRIs. It
appears that the more logical and economically sound choice to alleviate
conditions that result from the serotonin deficiency syndrome is 5-HTP,
the immediate precursor of the deficient substance.
Insomnia:
Although 5-HTP is commonly used for this purpose, research in humans
is still largely lacking. An open study found that 600 mg 5-HTP in creased
REM sleep by20minutes in normal subjects, with a smaller effect with
200 mg. There are theoretical reasons for a benefit, as high amounts
of serotonin can cause tiredness (and other serotonergic agents such
as trazodone are used to treat insomnia), and 5-HTP also increases melatonin
levels by increasing serotonin, an effect that is more pronounced in
the dark. Preliminary human research and research with tryptophan indicates
that 5-HTP may be of use in patients with obstructive sleep apnea.
Other Possible Benefits:
5-HTP may be useful in the treatment of chronic headaches, which have
been linked to low serotonin levels. In a trial with 124 subjects, 5-HTP
decreased the number of migraine headaches, but the difference was not
statistically significant, while another study in 48 elementary and
junior high school students indicated that 5-HTP reduced headache frequency
by 70% compared to 11% for the placebo group. 5-HTP may also be useful
in patients with panic disorder as one placebo-controlled trial found
it to reduce the panic reaction to CO2 challenge in patients with panic
disorder.
Side effects and precautions:
In clinical trials, the most commonly reported side effects are
nausea and gastrointestinal distress, and less commonly headaches and
sleepiness. The nausea problem may be resolved by starting with a low
dose and moving up, and even when large doses are used (900 mg/day),
the problem diminishes with time.
Recommended
dosage:
4EVER™
HEALTH 5-HTP is highly bioavailable, and about 70% reaches the bloodstream.
The half-life of 5- HTP is short (approximately 90 minutes), so it should
be taken three or more times daily if possible. It can be taken with
or without food. The typical dosage is usually 50-100 mg three times
daily, or for insomnia, 100-300 mg is taken before bed. 4EVER™HEALTH
5-HTP - is available in a 90 capsule bottle.
References
1. K. Zmilacher, et al. L-5-Hydroxytryptophan Alone and in Combination
with a Peripheral Decarboxylase Inhibitor in the Treatment of Depression.
Neuropsychobiology. 1988; 20: 28-35.
2. W. Byerley, et al. 5-Hydroxytryptophan: A Review of Its Antidepressant
Efficacy and Adverse Effects. J Clin Psychopharmacol 1987; 7: 127-37.
3. S. Risch and C. Nemeroff. Neurochemical Alterations of Serotonergic
Neuronal Systems in Depression. J Clin Psychiatry. 1992; 53: 3-7.
4. W. Poeldinger, et al. 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.
5. H. van Praag. Management of Depression with Serotonin Precursors.
Biol Psychiatry. 1981; 16: 291-310.
6. S Takahashi, et al. Effect of L-5-Hydroxytryptophan on Brain Monoamine
Metabolism and Evaluation of Its Clinical Effect in Depressed Patients.
Psychiat Res 1975; 12: 177-87.
7. R. Kahn and H. Westenberg. L-5-Hydroxytryptophan in the Treatment
of Anxiety Disorders. J Affect Disord, 1985; 8: 197-200.
8. V. Linnoila and M. Virkkunen. Aggression, Suicidality, and Serotonin.
J Clin Psychiatry. 1992; 53: 46-51.
9. L. Buydens-Branchey, et al. Age of Alcoholism Onset. II. Relationship
to Susceptibility to Serotonin Precursor Availability. Arch Gen Psychiatry.
1989; 46: 231-36.
10. J. Wurtman. Carbohydrate Craving, Mood Changes and Obesity. J Clin
Psychiatry. 1988; 49: 37-39.
11. C. Cangiano, et al. Eating Behavior and Adherence to Dietary Prescriptions
in Obese Adult Subjects Treated with 5-Hydroxytryptophan. Am J Clin
Nutr 1992; 56: 863-7.
12. D. Murphy et al. Obssessive-Compulsive Disorder as a 5-HT Subsytem
-Related Behavioral Disorder. Bri J Psychiatry. 1989; 155: 15-24.
13. C. Maurizi. The Therapeutic Potential for Tryptophan and Melatonin:
Possible Roles in Depression, Sleep, Alzheimer's Disease and Abnormal
Aging. Med Hypoth. 1990; 31: 233-42.
14. G. DeBenedittis and R. Massei. 5-HT Precursors in Migraine Prophy
laxis: A Double-Blind Cross-Over Study with L-5-Hydroxytryptophan versus
Placebo. Clin J Pain. 1986; 3: 123-29.
15. J. Robertson and T. Monte. Natural Prozac-Learning to Release Your
Body's Own Anti-Depressants. San Francisco: Harper; 1997.
16. A. Gaby. B6-The Natural Healer. New Canaan: Keats: 1984.
17. H. van Praag. Studies of the Mechanism of Action of Serotonin Precursors
in Depression. Psychopharmacol Bull. 1984; 20: 599-602.
18. P. Hartvig et al. Pyridoxine Effect on Synthesis Rate of Serotonin
in the Monkey Brain Measured with Positron Emission Tomography. J Neural
Trans. 1995; 102: 91-7.
19. K. Dakshinamurti, et al. Influence of B Vitamins on Binding Properties
of Serotonin Receptors in CNS of Rats. Klin Wochenschr. 1990; 68: 142-45.
20. M. Jacobsen, et al. Cardiac Manifestations in Mid-gut Carcinoid
Disease. Eur Heart J. 1995; 16: 263-68.
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Physiological State and Stress Conditions. Jpn J Psychosom Med. 1979;
19: 283-93.
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and Related Compounds. Compreh Psychiatry. 1980; 21: 30-43.
23. T. Li Kam Wa, et al. Blood and Urine 5-Hydroxytryptamine [Serotonin]
Levels after Administration of Two 5-Hydroxytryptophan Precursors in
Normal Man. Bri J Clin Pharmacol. 1995; 39:327-29.
24. G. Huether, et al. The Metabolic Fate of Infused L-Tryptophan in
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109: 442-32.
25. K. Tornebrandt, et al. Heart Involvement in Metastatic Carcinoid
Disease. Clin Cardiol. 1986; 9 (1).
Nutrition Facts
Each Capsule Contains:
5-Hydroxytryptophan (Griffonia Seed Extract) · · ·
· 50 mg
Ingredients: Griffonia Seed Extract, Microcrystalline Cellulose,
Magnesium Stearate
Directions: Take one capsule daily with a meal
This product contains no yeast, wheat, soy, sugar, artificial
colors or preservatives.
Store in a cool, dry place. Keep out of reach of children.
