A New Use for the Amino Acid Phenylalanine
Catecholamines Kick Out the Demons of Depression
I am in that temper that if I were under water
I would scarcely kick to come to the top. - John Keats

Despair and hopelessness, so characteristic of serious depression, had engulfed the poet John Keats when he wrote those words to a friend in 1818. He could not have known then that a chemical called phenylalanine could provide a helpful "kick" for his own soul as well as for many other depressed souls in their struggle to remain afloat.

The demons of depression exact a terrible toll on human happiness and productivity - even on life itself. But the quest of science to understand the origins of this affliction, and to ameliorate it, continues to bear fruit. A recent study at the Yale University School of Medicine has shown a strong link between depression and the levels of catecholamines in our bodies.1

That in itself is not news, but there is an intriguing twist. It was found that people who suffer from bouts of clinical depression are biochemically different from people who are normal and healthy. People with a history of clinical depression, even when they are in remission and appear to be healthy, are still biochemically different. They are, in a sense, biochemical time bombs ready to go off into another depressive episode.

But what lights the fuse? Perhaps a better question is: Is there a way to dampen the fuse so it fizzles before anything goes boom? Neither question has a simple answer, but much research points to the critical role played by catecholamines.

What Are Catecholamines?
Catecholamines are biologically active compounds that serve a variety of functions. Dopamine, noradrenaline, and adrenaline are catecholamines. (Noradrenaline and adrenaline are also popularly referred to as norepinephrine and epinephrine.) Dopamine and noradrenaline are neurotransmitters - compounds that mediate the flow of impulses between neurons. Adrenaline is a neurotransmitter responsible for the well-known "fight or flight" response which prepares the body to cope with stress.

On its metabolic pathway, the amino acid phenylalanine converts to tyrosine, which transforms to dopamine. Dopamine is the immediate precursor of noradrenaline (see Figure 1). Dopamine deficiency is implicated in some forms of psychosis and abnormal movement disorders, such as Parkinson's disease.

Figure 1.
Metabollic pathway of phenylalanine, tyrosine, and the catecholamines.

Noradrenaline is released by certain neurons in the brain. A disturbance in its metabolism at important brain sites has been implicated in affective disorders. In other words, when noradrenaline is insufficiently present, a person's mood or energy levels may decline, even bottom out - for example, in depression.

These simple, structurally similar organic compounds play important roles in regulating the function of our nervous systems, both central and peripheral. Without these molecules, our bodies would be like the Internet if all the modems failed - dead. Normally our bodies synthesize catecholamines from nutrient molecules in our foods. Unfortunately, optimal levels of these nutrients cannot be obtained from food sources alone.

One way to ensure sufficient levels of these essential neurotransmitters is by consuming their nutrient precursors via supplementation. Phenylalanine can be taken as a nutrient supplement and neurotransmitter precursor to noradrenaline. Tyrosine does not provide the same uplifting benefits as phenylalanine, because the latter is required for the production of a metabolite, PEA, whose mood-elevating properties augment those of noradrenaline.

The Trouble with Catecholamine Deficiency
In the randomized, double-blind, crossover study mentioned above, Dr R M Berman and his colleagues at Yale administered a compound, alpha-methylparatyrosine, that inhibits the body's ability to synthesize catecholamines from their chemical precursors. The subjects had a history of clinical depression and had been in remission and medication-free for at least three months.

The results were dramatic: depleting the catecholamines produced marked symptoms of depression in the experimental group, as measured by the Hamilton Depression Rating Scale. The control group was almost totally unaffected. The authors concluded that ". . . catecholamine function may play a crucial role in mood regulation for subjects who are vulnerable to depression."

Several earlier short-term studies had shown that inhibition of catecholamine synthesis did not have any effect on the mood of normal, healthy people who had never suffered from clinical depression. They were clearly more resilient than those whose prior depression had made them vulnerable to a temporary depletion of these vital molecules.

This does not mean, however, that maintaining optimal levels of catecholamines is not important for normal, healthy people, nor that increased catecholamine levels cannot be perceived in such people. Catecholamines are very important for good mental health, especially as we grow older and our output of these neurotransmitters gradually declines. Most of the mental failings that often accompany aging, such as loss of memory, loss of mental alertness and energy, tendency toward depression, vulnerability to stress, and Alzheimer's and Parkinson's diseases, are associated with reduced levels of noradrenaline or dopamine.

There is a growing body of both anecdotal evidence and clinical observations showing that phenylalanine supplements can alleviate the symptoms of some forms of depression. It can also boost various aspects of mental function in healthy people who wish to maximize their ability to stay that way.2

In one such clinical study published in 1984, the authors concluded that "The results support the view that the brain is able to use dietary amino acids to enhance production of brain neuroamines capable of sustaining mood."3

It is worth mentioning again that obtaining optimal levels of these neuroamines is not generally feasible with the normal diet alone. Supplementation is required. For the replenishment of noradrenaline, a phenylalanine supplement would be effective.

The Orthomolecular Approach
Two of the goals of nutritional intervention, as mentioned above - to alleviate the symptoms of disease and to optimize a state of health - exemplify an approach to health care called orthomolecular medicine, or orthomolecular psychiatry when it's aimed at mental disorders. (The prefix ortho is from the Greek orthos = correct.)

The underlying idea is that many diseases result from imbalances in the concentrations of certain natural chemicals normally found in the body. These diseases can best be treated by administering one or more of those chemicals or their natural precursors (plus any relevant cofactors) so as to restore the correct balance and therefore restore health. The optimal concentrations of the chemicals needed in the body may differ greatly from the concentrations actually provided by a person's genetic makeup or normal diet, hence the need for nutrient supplementation.

The leading figure in the orthomolecular school of medicine was the late Linus Pauling, one of the greatest scientists who ever lived. Part of Pauling's legacy is the increasing acceptance of his conviction that the orthomolecular approach to therapy, prophylaxis, and health optimization is generally the best. In his own words, "Significant improvement in the mental health of many persons might be achieved by the provision of the optimum molecular concentrations of substances normally present in the human body."4

One way to put this approach into practice is with oral phenylalanine supplements.

And remember: if you start feeling down or depressed, it may not be all in your head. You may be able to kick-start your mental energy again just by putting the correct molecules in your stomach.


  1. Berman RM, Narasimhan M, Miller HL, Anand A, Cappiello A, Oren DA, Heninger GR, Charney DS. Transient depressive relapse induced by catecholamine depletion: potential phenotype vulnerability marker? Arch Gen Psychiatry 1999 May;56(5):395-403.
  2. Hendler SS. The Doctors' Vitamin and Mineral Encyclopedia. Simon and Schuster, New York, 1990:225-228.
  3. Kravitz HM, Sabelli HC, Fawcett J. Dietary supplements of phenylalanine and other amino acid precursors of brain neuroamines in the treatment of depressive disorders. J Am Osteopath Assoc 1984;84/1Suppl:119-123.
  4. Pauling L. Orthomolecular psychiatry: Varying the concentrations of substances normally present in the human body may control mental disease. J Nutr Environ Med 1995;5/2:187-198.

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