Melatonin, Tryptophan & 5-HTP

Melatonin and Tryptophan Offer Antiaging Effects

Melatonin has been the subject of study for the important role that it plays in the aging process. Not only has it been shown to relieve oxidative damage (a probable cause of age-associated brain dysfunction), as we age the production of melatonin decreases, potentially causing physiological alterations. In a new study, scheduled for publication in the Journal of Pineal Research, scientists at the University of the Balearic Islands, Mallorca, Spain, administered melatonin to old rats in order to measure the effects on the neurotransmitters serotonin, dopamine, and norepinephrine, and behavior. While an age-related decline was observed in neurotransmitter activity in control rats, in rats administered melatonin (1 mg/kg/day, diluted in drinking water) for 4 weeks, there was a significant reduction in the age-induced deficits in all three neurotransmitters studied.

Then, when the rats were administered tryptophan (240 mg/kg/day at night for 4 wk), melatonin’s biosynthesis precursor, similar improvements were found, comparable to those induced by melatonin. Using spatial memory test in radial-maze and motor coordination in rota-rod to measure behavior, the results corresponded well with the neurochemical findings that were significantly improved after chronic melatonin treatment. Altogether, these findings suggest that both melatonin and L-tryptophan exert a long-term effect on serotonin, dopamine, and norepinephrine neurotransmission by enhancing their synthesis in aged rats, which might improve the age-dependent deficits in cognition and motor coordination. It is possible that melatonin and tryptophan can have similar antiaging effects in humans.

  • Esteban S, Garau C, Aparicio S, Moranta D, Barceló P, Fiol MA, Rial R. Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain. J Pineal Res 2010 Jan 17. [Epub ahead of print]

Tryptophan May Help a Variety of Psychiatric Disorders and Symptoms

Serotonin has long been established to play an important role in psychopathology, where dysfunction in the serotonergic system has been associated with symptoms of depression, panic, aggression, and suicide. In a recent study, researchers at the University Medical Centre of Groningen in The Netherlands, summarized the evidence that low brain serotonin levels represent a metabolic imbalance that is evolutionarily conserved and not specific for any specific psychiatric diagnosis. The synthesis and release of serotonin in the brain is dependant on both its concentration as free serotonin in the blood and the brain and concomitantly on tryptophan hydroxylase, the enzyme that is involved in its synthesis and keeping its levels within range. This correspondence is evolutionarily conserved.

When tryptophan (the precursor of serotonin) degrades, the consequences can be lower blood levels and the reduced production and release of serotonin. This can be triggered by inflammation, pregnancy, and stress. Intriguingly, tryptophan serves not only as an important nutrient, but also as a signaling amino acid. In humans suffering from inflammatory or other somatic diseases, low tryptophan levels are frequently found, and this may manifest as disturbed social behavior, increased irritability and lack of impulse control, instead of depression. Curiously, under certain circumstances, this type of behavior can have survival value, and consequently, supplemental nutrients that increase brain levels of serotonin may help in a variety of psychiatric disorders and symptoms. Tryptophan supplements can do this, as can 5-HTP.

  • Russo S, Kema IP, Bosker F, Haavik J, Korf J. Tryptophan as an evolutionarily conserved signal to brain serotonin: molecular evidence and psychiatric implications. World J Biol Psychiatry 2009;10(4):258-68.

The Importance of Tryptophan for Natal Development

Developing rats in the uterus of mothers deprived of tryptophan were studied by researchers at University of Catania, Italy. There were two parts of the experiment, one in which the deprivation took place at day 1 after conception, and the other at day 14.5. The idea was to determine the role of the serotoninergic system in sexual differentiation in the animals. In both parts, at birth the rats showed a significant physical hypoevolution, and this condition worsened, during post-natal development. In the earlier deprivation, there was marked dwarfism and growth hormone concentrations were lower, independent of sex, than that in the control rats.

At 30 days post-natal age, female rats from the early deprivation showed a right-timed onset of puberty, yet testes descensus could not be observed in male rats. In fact, dwarf male rats evidenced hypotrophy of the whole reproductive apparatus. Furthermore, dwarf female rats showed a pronounced underdevelopment of their reproductive organs. In the later stage deprivation group, there was less of a pronounced dwarfism, with normal right-timed onset of puberty in both sexes. This evidence shows that the role of tryptophan in physical and sexual maturation is essential for rats of either sex.

  • Imbesi R, Mazzone V, Castrogiovanni P. Is tryptophan “more” essential than other essential aminoacids in development? A morphologic study. Anat Histol Embryol 2009 Oct;38(5):361-9.

The Importance of Tryptophan in Mother’s Milk

Human milk possesses bioactive factors that are vital to the health of newborns. These factors are even more important with preterm infants. One of the roles of these compounds is to help reduce oxidative stress resulting from exposure to too much oxygen, along with immature physiologic defenses. To identify the components in mother’s milk that contribute to its greater resistance to oxidative stress compared with infant formulae, researchers at Carleton University, Ottawa, Ontario, Canada prepared enzymatic hydrolysates of mother’s milk, which they then ultrafiltered, separated, and analyzed for antioxidant potential.

The antioxidant activity of nondigested milk, whole digested milk, and derived ultrafiltrates was measured respectively. A high performance liquid chromatography fraction was obtained and its constituents identified as tryptophan, peptides HNPI, and PLAPQA. While there was no scavenging activity for PLAPQA, HNPI was found to have moderate activity. However, tryptophan demonstrated very high activity. And when tryptophan was added to mother’s milk and two infant formulas, the result was to significantly increase antioxidant properties. In conclusion, tryptophan appears to be a powerful free-radical scavenger naturally present in mother’s milk.

  • Tsopmo A, Diehl-Jones BW, Aluko RE, Kitts DD, Elisia I, Friel JK. Tryptophan released from mother's milk has antioxidant properties. Pediatr Res 2009 Dec;66(6):614-8

Tryptophan and 5-HTP Help Protect the Liver

It has been made clear in the scientific literature that several indoleamines—tryptamines, such as serotonin, which are based around the indole ring structure—help scavenge free radicals. In new research conducted at the University of Zaragoza in Spain, scientists set out to evaluate the ability of tryptophan and 5-HTP to protect liver cell membranes against induced lipid peroxidation and increases in membrane rigidity.

The presence of 5-HTP, but not tryptophan, thwarted these changes. However, in the absence of oxidative stress, neither indoleamine lessened rigidity. In conclusion, the evidence suggests that hydroxylation, the process whereby tryptophan is converted into 5-HTP, determines the ability of tryptophan to preserve membrane fluidity in the presence of oxidative stress.

  • Reyes-Gonzales MC, Fuentes-Broto L, Martínez-Ballarín E, Miana-Mena FJ, Berzosa C, García-Gil FA, Aranda M, García JJ. Effects of tryptophan and 5-hydroxytryptophan on the hepatic cell membrane rigidity due to oxidative stress. J Membr Biol 2009 Oct;231(2-3):93-9. Epub 2009 Oct 22.

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