Tryptophan and Appetite

Almost three decades ago, we were laughed out of a college course in behavioral sciences when we introduced the notion that there were specific and powerful neurobiological influences on eating and drinking behavior. We have come a long way since then.

In particular, we were influenced by the work of Judith and Richard Wurtman and John Fernstrom. Working together in the 1980s and ‘90s, they postulated that the neurotransmitter serotonin and its amino acid precursor tryptophan played a key role in eating behavior.

Our own unpublished work essentially replicated that of the Wurtmans. We looked at tryptophan, serotonin, and specific cravings in a small number of hamsters during estrus.

In our study, hamster chow with varying amounts of tryptophan, sweetened water, ethanol intake, locomotor activity, and weight were measured during estrus and across light and dark cycles. The effect of increasing the tryptophan content of the chow was reliably associated with reduced food intake (hypophagia) in general and with a decreased consumption of alcohol, even if the alcohol was sweetened.

It has since been hypothesized and studied in detail in clinical settings that when levels of brain serotonin, also known as 5-hydroxy-tryptophamine, in human subjects reach a certain point or threshold, putative cravings for carbohydrates appear to subside, while protein cravings increase. Heath et al. (2006) noted that serotonin and noradrenalin, another neurotransmitter, participate in establishing taste thresholds. The observation that females appear to have lower levels of brain serotonin than males seems to amplify any effect when a study is conducted with female animals or female human subjects.

So one would expect that men and women would experience different taste perceptions, and possibly present differences in appetite and eating disorders based on these fundamental observations. Indeed, if one uses satiety as the outcome of very complex neuroendocrine dynamics that involve these hormones as well as insulin, corticosterone, leptin, and others, the control of eating behavior among men and women becomes even more challenging.

The relatively recent use of selective serotonin re-uptake inhibitors (SSRIs) has certainly added fuel to the discussion about dietary applications and food product innovations. Diagnostic entities such as seasonal affective disorder, depression in general, premenstrual syndrome, and substance dependence have sparked provocative clinical research. Berlin et al. (2005) demonstrated that oral glucose has been shown to attenuate tobacco craving, a process which is hypothesized to be mediated by tryptophan (TRP), since there is a decrease in plasma TRP and a gender dependent increase in serum serotonin. These findings suggest that regulation of blood glucose, regulation of appetite, and regulation of plasma serotonin are intimately intertwined.

In July 2005, the Australian & New Zealand Journal of Psychiatry kicked-off an entire series of neuroendocrine and neuroimaging studies on dietary TRP depletion and serotoninergic explanations of depression, anxiety, and other disorders.

In July 2006, Heisler et al. (2006) reviewed what is known about the neural pathways through which central serotoninergic systems regulate food intake and body weight. The importance of the subtypes of "downstream" melanocortin receptors (MCRs) in the arcuate nucleus of the hypothalamus was discussed at length. It was argued that food intake and body weight are regulated by peripheral signals such as leptin and ghrelin, and centrally by serotonin via action at serotonin 1B receptors and then downstream through modulation of agonists and antagonists at the MCRs.

The clinical observations noted above in the context of our understanding of the underlying molecular neurochemistry validate opportunities for the food industry to include TRP-rich proteins, such as whey proteins found in milk, and serotonin (primarily produced in the gastrointestinal tract) or its metabolic precursor, 5-hydroxy-tryptophan, in our functional foods research agenda.

by Roger Clemens,
Dr.P.H., Contributing Editor
Special Projects Advisor,
ETHorn, La Mirada, Calif.
[email protected]

by Peter Pressman,
M.D., Contributing Editor
Attending Staff, Internal Medicine,
Cedars-Sinai Medical Center, Los Angeles, Calif.
[email protected]

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