Neurotransmitters - Serotonin
Serotonin is similar to catecholamines. It is made from the amino acid,
tryptophan. Serotonin is converted to melatonin in the pineal gland. Tryptophan,
derived from food, is transported to the brain to make the neurotransmitter
serotonin. At the appropriate place inside a brain cell, two enzymes and vitamin
B6 transform tryptophan to serotonin. Serotonin is then transferred to the
sending end of the neuron (the terminal bouton of the axon), where it is used as
a molecular messenger to carry information across the synapse to the receiving
neuron. The serotonin synthesis equation is:
STEP 1. Tryptophan----> 5-Hydroxytryptophan
STEP 2. 5-Hydroxytryptophan (5HT)----> Serotonin
via enzyme 5HT-Decarboxylase
Serotonin production in the brain is sensitive to the supply of tryptophan in the diet.
The effects of serotonin were first observed in the digestive tract where it
causes contractions of the smooth muscle. Serotonin is released from blood
platelets and elevates blood pressure. Serotonin circuits arise from the brain
stem arousal complex and reach into all areas of the brain. Increased serotonin
circuit activity tends to activate abnormal behaviors. Too little serotonin is
associated with sleep disturbances, loss of appetite and depression. Some
antidepressant drugs increase serotonin activity and these drugs tend to
decrease appetite. Drugs which block serotonin tend to increase appetite.
Low levels of serotonin are found in aggressive rats and pathologically
violent people have lower levels of serotonin metabolites in their spinal fluid.
de Boer gave a serotonin autoreceptor (5-HT1a) blocker, S-15535, to aggressive
rats and found that serotonin levels rose and the violence of the rats
One nutrient, tryptophan, can be changed in a number of chemicals with
surprisingly divergent roles in the body. Many years ago, I was studying the
neurochemistry of indoleamines and found that trytophan could become the vitamin,
nicotinic acid, the neurotransmitter, serotonin, the hallucinogen,
dimethyltryptamine, or the hormone, melatonin.
Theories have linked the ingestion of foods containing tryptophan,
phenylalanine, and tyrosine with mood changes. Clues to the
amino-acid-neurotransmitter relationships were studied by Richard Wurtman and
his associates at MIT.
They showed, for
example, that the uptake of tryptophan was enhanced by sugar and decreased by
competition with other amino acids. Judith Wurtman suggested that serotonin
deficiency caused depression and was helped by eating high carbohydrate foods
(increasing tryptophan intake). The brain effects of food are more complex than
simple theories make it seem. Milk and wheat proteins can disrupt arousal,
attention and mood. Proteins adversely affect brain function through
immune-mediated mechanisms, before their content of amino acids has relevance.
Milk proteins, for example, can act as specific antigens and can also stimulate
immune responses by pushing immune cells toward hypersensitivity.
Drugs that increase serotonin levels have differing effects; fenfluramine was
marketed for many years as an appetite suppressant. Much publicity was given to
Redux or Fen Phen, the combination of two old weight loss drugs, fenfluramine
and phentermine in the early to mid 90s. Physicians, diet centers and clinics
advocated the use of this drug combination as a panacea for weight loss.
However, Redux caused pulmonary hypertension and heart valve defects in human
subjects and brain damage in animals.
The antidepressant drug, Prozac increases
serotonin activity. Its main action is to increase serotonin transmission in the
brain by inhibiting the reuptake of the neurotransmitter. Increased serotonin
activity in appetite regulating regions of the brain are associated with
decreased appetite. Prozac, however, is not always well-tolerated and may cause
agitation, aggression and suicidal impulses in some people. Meridia
(sibutramine) is a weight loss drug, similar to Prozac and was originally
developed as an antidepressant. Meridia has been linked to deaths from
cardiovascular causes. The drug was first withdrawn in Italy and fell under
scrutiny in other countries. Sibutramine increases blood pressure, heart rate
and may cause arrhythmias. Sibutramine should not be taken with other
antidepressants because of the risk of increased norepinephrine and serotonin
levels. Favorable pre-marketing studies showed modest weight loss benefits and
the manufacturer claimed that sibutramine was a safe and effective drug.
More recent data suggests that its modest benefits are not significant in light
of potentially serious adverse effects.