Also see:
Enzyme to Know: Tryptophan Hydroxylase
Omega -3 “Deficiency” Decreases Serotonin Producing Enzyme
Linoleic Acid and Serotonin’s Role in Migraine
Gelatin > Whey
Thyroid peroxidase activity is inhibited by amino acids
Whey, Tryptophan, & Serotonin
Tryptophan, Fatigue, Training, and Performance
Carbohydrate Lowers Free Tryptophan
Protective Glycine
Intestinal Serotonin and Bone Loss
Hypothyroidism and Serotonin
Estrogen Increases Serotonin
Gelatin, Glycine, and Metabolism
Whey, Tryptophan, & Serotonin
Tryptophan, Sleep, and Depression
p-Chlorophenylalanine inhibits serotonin production in the brain via inhibition of tryptophan hydroxylase leading to a marked increases in sexual activity in male rats likely by increasing testosterone. This indicates that a serotonin deficiency (high libido, high testosterone) or a serotonin excess (low libido, low testosterone) could play a role in the sexual function in male humans.
Tryptophan is an amino acid that serves as the precursor from which serotonin is made. A tryptophan poor diet decreases serotonin production as does a diet that does not inflame the intestines where most serotonin is formed. Tryptophan is found in abundance in muscle meats, egg whites, whey protein, and organ meats. Reduction in consumption of these foods in favor of more gelatin rich proteins or proteins with less tryptophan (cheese, milk, shellfish, low fat fish, egg yolks, tougher/less expensive cuts of meat) may be beneficial to improve libido and testosterone levels.
Additionally, reducing all situations in which cortisol can by high would likely prove beneficial. Cortisol catabolizes skeletal muscle and increases tryptophan and thus the production of serotonin. Polyunstaurated fatty acids (PUFA) increase uptake and formation of serotonin in the brain so their avoidance is also recommended as is a reduction in substances that encourage the release of PUFA into the blood (estrogen, adrenaline, serotonin, hypothyroidism). Saturated fats (coconut oil, butter, ghee, dairy fats, pastured animal fats) do not increase serotonin formation or entry into the brain.
Science. 1969 Dec 12;166(3911):1433-5.
Compulsive sexual activity induced by p-chlorophenylalanine in normal and pinealectomized male rats.
Tagliamonte A, Tagliamonte P, Gessa GL, Brodie BB.
p-Chlorophenylalanine depletes brain serotonin and induces longlasting sexual excitation in male rats. The effect of p-chlorophenylalanine is potentiated by pargyline. Administration of 5-hydroxytryptophan to rats treated with p-chlorophenylalanine plus pargyline blocks the sexual excitation. p-Chlorophenylalanine also elicits sexual excitation in pinealectomized rats; this effect is not mediated by the lack of indole hormones in the pineal but may be the consequence of depletion of 5-hydroxytryptophan in the brain and the resulting imbalance between 5-hydroxytryptophan and catecholamine activity in the central nervous system.
Mol Pharmacol. 1967 May;3(3):274-8.
Tryptophan hydroxylase inhibition: the mechanism by which p-chlorophenylalanine depletes rat brain serotonin.
Jéquier E, Lovenberg W, Sjoerdsma A.
Administration of the specific serotonin depletor p-chlorophenylalanine to rats results in marked inhibition of tryptophan hydroxylase of the brain. The enzyme inhibition can be correlated with and is assumed to be responsible for brain serotonin depletion. Although p-chlorophenylalanine is a competitive inhibitor of tryptophan hydroxylase in vitro, it causes an irreversible inactivation of the enzyme in vivo. The findings also support the conclusion that tryptophan hydroxylation is the rate-limiting enzymic step in serotonin biosynthesis.
Nature. 1970 Aug 8;227(5258):616-7.
Essential role of testosterone in the sexual stimulation induced by p-chlorophenylalanine in male animals.
Gessa GL, Tagliamonte A, Brodie BB.
P-CHLOROPHENYLALANINE (PCPA), a compound that inhibits the synthesis of 5-hydroxytryptamine (5-HT) without affecting that of noradrenaline1, produces compulsive sexual activity in male animals. This effect was observed by Ferguson et al. in cats2, by Tagliamorite et al. in rats and rabbits3 and by Shillito in rats4. The compulsive sexual activity is not caused by a depletion of indole hormones in the pineal gland, for we found that PCPA elicited sexual stimulation in pinealectomized animals. Further, sexual stimulation induced by PCPA is inhibited by restoring brain 5-HT levels with 5-hydroxy-tryptophan3, a precursor of 5-HT. This effect thus seems to be associated with the depletion of brain 5-HT. Moreover, because sexual stimulation induced by PCPA is potentiated when catecholamine levels in brain are increased with pargyline, an inhibitor of monoamine oxidase, we postulated that both brain 5-HT and catecholamines control sexual behaviour in male animals, 5-HT inhibiting sexual behaviour and catecholamines stimulating it. Our results show that the effect of PCPA on sexual behaviour in male rats is not only prevented by castration but is strikingly potentiated by testosterone.
Monogr Neural Sci. 1976;3:94-101.
Sex, migraine and serotonin interrelationships.
Sicuteri F, Del Bene E, Fonda C.
Sexual deficiency or frank impotence in man could be due to an imbalance of monoamines, particularly 5-HT, at the mating center level. An absolute or relative excess of 5-HT seems to antagonize testosterone at the level of the mating center receptors in the brain. Plasma testosterone levels in so-called psychological impotence are normal. When the 5-HT concentration in sexually deficient men is sufficiently decreased with parachlorophenylalanine (PCPA) treatment and testosterone levels increased following its administration, a vivid sexual stimulation appears in about half of the untractable cases. Similar results are observed by substituting testosterone with monoamine oxydase inhibitor (MAOI) in PCPA-treated volunteers. Furthermore, MAOI-PCPA are administered to emphasize the brain shift between serotonin and catecholamines. Yet the PCPA-MAOI treatment avoids the prostate carcinogenic risk of testosterone administration in aging males, and seems to have euphorizing effects stronger than those expected only from MAOI therapy. Because of the several side effects of PCPA-MAOI testosterone, the present experiments should be interpreted very cautiously.
Br J Pharmacol. 1974 June; 51(2): 249–251.
Lack of copulatory behaviour in male castrated rats after p-chlorophenylalanine
M. Del Fiacco, W. Fratta, G.L. Gessa, and A. Tagliamonte
1 The effect of p-chlorophenylalanine (PCPA) on the copulatory behaviour of normal and castrated male rats with females in oestrus was studied.
2 Castration 2 months before the experiment completely prevented the increased copulatory behaviour produced by PCPA in normal rats.
3 The administration of testosterone restored the copulatory behaviour in the castrated rats indicating that testosterone is essential for this behaviour.
Pharmacol Biochem Behav. 1976 Sep;5(3):319-27.
Sexual behavior in castrated male rats treated with monoamine synthesis inhibitors and testosterone.
Södersten P, Larsson K.
Castrated male rats treated daily with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA, 20 mg/kg) started to display mounts, intromissions and ejaculations more rapidly in response to daily treatment with testosterone propionate (TP, 0.15 mg/kg) than NaCl-treated rats. Daily treatment with the catecholamine (CA) synthesis inhibitor alpha-methyl-p-tyrosine (alpha-MT, 20 mg/kg) had no effect on the behavioral response to subsequent TP treatment. The acceleration of TP-induced sexual behavior by PCPA pretreatment was inhibited by pretreatment with DL-5-HTP (20 mg/kg) but not with L-DOPA (12.5 mg/kg). Analyses of brain monoamines showed that the PCPA treatment reduced brain 5-HT levels and produced a marked inhibition of the 5-HT synthesis. The 5-HTP treatment restored brain 5-HT levels to normal. Daily treatment with PCPA also reduced brain CA levels and inhibited the CA synthesis but these biochemical effects were not related to the effects of PCPA on sexual behavior. Daily treatment with PCPA (40 mg/kg for 12 days) or treatment with 126 mg/kg PCPA for 3 days induced the complete pattern of sexual behavior in 5 of 9 and 19 of 30 castrated rats respectively without concurrent TP treatment. It is suggested that 5-HT exerts a modulating influence on sexual behavior in male rats.
Acta Vitaminol Enzymol. 1975;29(1-6):100-2.
The influence of tryptophan and parachlorophenylalanine on the sexual activity in man.
Sicuteri F, Del Bene E.
The effects on the sexual tone of parachlorophenylalanine, a selective inhibtor of 5-hydroxytryptamine synthesis, testosterone and placebo were evaluated in patients complaining of migraine-headache and sexual deficiency. The combined treatment with parachlorophenylalanine and testosterone significantly increases the sexual stimulus more than parachlorophenylalanine, testosterone and placebo, when given on their own. Conversely subjects with normal or excessive sexual activity, reported a decrease of sexual tone, during chronic treatment with tryptophan. The hypothesis of an implication of brain 5-HT in the mechanism of psychogenic sexual deficiency and the possibility of a therapeutic approach with drugs able to interfere with 5-HT turnover are discussed.
Br J Pharmacol. 1972 Sep;46(1):46-55.
Influence of age and of testosterone on the response of male rats to parachlorophenylalanine.
Bond VJ, Shillito EE, Vogt M.
1. Castrated male rats and male rats that had been castrated as well as adrenalectomized, showed hypersexual behaviour 24 h after treatment with parachlorophenylalanine (PCPA), as did intact rats.2. A dose of PCPA 100 mg/kg was sufficient to induce mounting behaviour; this dose lowered the cerebral 5-hydroxytryptamine (5-HT) to about 50% in 24 h and further to 40% in 72 hours.3. Groups of juvenile male rats treated chronically with PCPA 100 mg/kg or 50 mg/kg, or with testosterone propionate 1.25 mg, showed hair loss after three weeks of treatment (6 injections), because of increased social interaction.4. Groups of intact male rats 9-11 weeks old given testosterone propionate 1.25 mg subcutaneously, showed mounting behaviour 3-5 h after the injection which was indistinguishable from the behaviour seen 24 h after treatment with PCPA 100 mg/kg. The 5-HT content of the brain was not altered by testosterone.5. The number of rats which showed mounting after PCPA treatment did not change with age, but the younger rats made more mounts in the observation time than rats more than three months old.6. The age of castration (3 weeks or 4 months) did not influence the results.
Br J Pharmacol. 1970 February; 38(2): 305–315.
The effect of parachlorophenylalanine on social interaction of male rats
Elizabeth E. Shillito
1. Juvenile male rats treated with parachlorophenylalanine showed hair loss round the head and neck extending down the chest and abdomen.
2. Treated isolated rats did not have this loss of hair, while untreated animals living in the same cage as treated rats lost their hair. The loss therefore seems to be caused by increased social behaviour. This consists of a greater frequency of chasing each other, rolling over and social grooming.
3. Adult male rats show an increase in mounting after treatment with parachlorophenylalanine, and this change in behaviour was counteracted by treatment with 5-hydroxytryptophan.
4. It is concluded that 5-hydroxytryptamine inhibits sexual behaviour in male rats. The increase in social interaction seen in juvenile rats may be the behavioural precursor of adult sexual behaviour.
5. Atropine 2·5 mg/kg blocked all forms of social interaction in adult male rats, although other activity was not altered.
Br J Pharmacol. 1970 December; 40(4): 659–667.
The effect of parachlorophenylalanine on the behaviour of cats
Valerie J. Hoyland, Elizabeth E. Shillito, and Marthe Vogt
1. Male and female kittens and adult cats were given p-chlorophenylalanine orally.
2. After treatment, some of the male cats showed mounting behaviour and the kittens and non-oestrous females showed an increase in treading and rubbing which was similar to one aspect of pro-oestrus behaviour.
3. The treated animals also appeared to suffer from skin irritation and showed increased restlessness which accompanied sleep deprivation.
4. Injection of 5-hydroxytryptophan stopped abnormal sexual activity and restored normal sleep for about 5 hours.
5. It is concluded that 5-hydroxytryptamine-containing neurones inhibit sexual behaviour in cats and that this role can be seen in male and, to some extent, also in female animals.
Br J Pharmacol. 1971 February; 41(2): 404P.
Effect of parachlorophenylalanine on the behaviour of castrated male rats.
E E Shillito
JPET December 1966 vol. 154 no. 3 499-516
p-CHLOROPHENYLALANINE: A SPECIFIC DEPLETOR OF BRAIN SEROTONIN
B. Kenneth Koe and Albert Weissman
“p-Chlorophenylalanine has been found to be a potent and selective depletor of brain serotonin (5HT) in mice, rats and dogs.”
