The promise of
benefiting brain and behavior with dietary alterations has intrigued
clinicians and researchers for decades. In particular, evidence
supporting the effectiveness of amino acid supplementation with
l-tryptophan (TRP) for behavioral conditions like aggression and
obsessive-compulsive disorder is mounting.
TRP is an
essential amino acid and the precursor to the neurotransmitter
serotonin. Although the liver metabolizes over ninety percent of plasma
TRP, a certain amount leaves the liver and enters the brain. There,
tryptophan hydroxylase converts TRP to 5-hydroxytryptophan (5-HTP),
which 5-hydroxytryptophan decarboxylase turns to 5-hydroxytryptamine
(5-HT), or serotonin.
Researchers
began intensively focusing on the effects of TRP supplementation in the
1970’s. Drs. Richard and Judith Wurtman at the Massachusetts Institute
of Technology noted that reductions in brain serotonin played a pivotal
role in the development of mood and behavioral disorders. Serotonin
affects several central nervous system functions, including sleep,
mood, aggression, pain, anxiety, memory, eating behavior, temperature
regulation, hormonal regulation, and motor behavior. The Wurtmans and
others postulated and proved that dietary supplementation of serotonin
precursors such as tryptophan could improve mood and behavior
significantly. More recently, studies on orally administered 5-HTP show
that this serotonin precursor also benefits the psyche.
TRP
occurs in low concentration (<1%) in most protein sources. In order
to gain access to the brain, it must compete with other large neutral
amino acids (LNAA) via a common transport mechanism. Low-protein diets
sway the ratio of TRP to LNAA in favor of TRP, so that more TRP is
transported into the brain. Dietary supplementation of TRP can likewise
increase the ratio of TRP to other LNAA’s, and afford TRP an advantage
when vying for entry into the brain. Tryptophan hydroxylase, the
rate-limiting enzyme that converts TRP to serotonin, is normally only
half-saturated with TRP, so that increased intake of TRP modifies the
plasma TRP/LNAA ratio, manipulating brain levels of TRP and
subsequently driving serotonin synthesis and metabolism.
Over the
past few decades, research has shown that TRP may be helpful for both
humans and animals with depression, aggression, and obsessive
compulsive disorders. In one study, Rhesus monkeys demonstrating
compulsive self-injurious behaviors improved significantly after
receiving three weeks of dietary TRP supplementation; cerebrospinal
fluid from these individuals revealed significant increased in
5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite.
Serotonin precursors
may aid in treating obesity via appetite suppression, since brain
serotonin affects satiety and macronutrient (protein vs. carbohydrate)
selection. Administration of 5-HTP causes transient increases in plasma
serotonin concentration; large doses of 5-HTP cause short-term
decreases in food intake, particularly of carbohydrate-rich food.
The
serotonergic system plays a significant role in obsessive-compulsive
behaviors. For example, feather picking behavior is linked to low 5HT
neurotransmission in the forebrain. Avian studies have demonstrated
that chronic increases of TRP in the diet significantly decrease
feather picking behavior. A 2004 study in Applied Animal Behaviour
Science noted that TRP administration significantly increased the ratio
of TRP to LNAA in the plasma of the birds. TRP supplementation
significantly escalated the turnover of serotonin in the hippocampus
and archistriatum in the brain, as well as elsewhere in the forebrain.
A 2000
study published in the Journal of the American Veterinary Medical
Association (JAVMA) evaluated the effect of high- and low-protein
diets, both with and without TRP supplementation, on canine behavior.
The authors looked specifically at the effects of dietary protein on
dogs with canine aggression, territorial aggression, and hyperactivity.
Because of serotonin’s effects on mood, they hypothesized that
low-protein diets and diets supplemented with TRP would reduce not only
aggression, but also excitability and reactivity. Although the diets
did not influence fearfulness, hyperactivity, or excitability, dogs fed
low protein diets plus TRP were less territorially aggressive, and dogs
on either high-protein diets supplemented with TRP or low protein diets
with or without TRP supplementation displayed less dominance
aggression. Similar reductions in aggression have been noted in other
studies on chickens and primates.
Amino
acid supplements comprise just one type of a general class of compounds
known as “nutraceuticals”, which are substances, orally administered,
that promote good health. Nutraceuticals are neither foods nor drugs.
Although the Food and Drug Administration Center for Veterinary
Medicine (FDA-CVM) is responsible for enforcing all aspects of the
Food, Drug and Cosmetic Act that apply to foods and drugs for animal
use, the agency has assigned most nutraceuticals to a status of low
regulatory importance. Thus, nutraceuticals marketed for animal use
continue to be widely available despite concerns regarding the safety
and efficacy of these products. In a 2001 JAVMA article on the
“Evaluation of nutraceuticals, dietary supplements, and functional food
ingredients for companion animals”, John E. Bauer recommends that
veterinarians consider four important characteristics of nutraceuticals
when discussing the use of these products with their clients: Product
quality, Efficacy, Tolerance, and Safety (PETS). For product quality,
Bauer states that veterinarians should obtain information on the
quality, purity, and ingredients as well as quality-control procedures
in place during processing. They should also ask the manufacturer to
supply any supportive documentation of product efficacy.
Will the animal be
able to tolerate the product, or will the supplement cause bad odor,
nausea, anorexia, or interactions with drugs. Finally, is the product
safe, especially when given over long period of time?
Notwithstanding
the widespread popularity among humans in favor of TRP and 5-HTP for
mood disorders and weight control, some veterinary practitioners remain
concerned about potential toxicity of TRP, 5-HTP, their possible
contaminants, and even amino acid supplementation in general.
Production of synthetic TRP as a serotonergic agent halted abruptly in
1989 after an outbreak of eosinophilia-myalgia syndrome in humans was
linked with TRP intake. The toxic products eventually linked to one
Japanese manufacturer, but the exact cause and contaminants responsible
for the outbreak still remain unclear. As with all supplement
recommendations made for animal patients, veterinarians recommending
TRP or 5-HTP should proceed cautiously, monitor their patients closely,
and report adverse outcomes.
Copyright, 2007. Narda G. Robinson,
DO, DVM, MS. All rights reserved.
reprinted with kind permission from Narda
G. Robinson, DO, DVM, MS
Director, CSU Center for Comparative and Integrative Medicine Colorado
State University Veterinary Teaching Hospital
email: Narda.Robinson@colostate.edu Website:
www.csuvets.colostate.edu/pain
