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 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.

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).  According to Wurtman, food-induced changes in energy and mood can be explained by the effect of foods on neurotransmitter levels. She suggested choosing foods on the basis of their content of principle amino acids and carbohydrate/protein ratios. Tryptophan uptake in the brain is enhanced if it is ingested alone along with sugar and not with other competing amino acids.

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, for example, 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 90’s. 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.

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Human Brain in Health and Disease

Neuroscience Notes

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