Altering the Brain's Chemistry

Written by By Donald Brown, N.D., Alan R. Gaby, M.D., and Ronald Reichert, N.D.

Doctors suggest using nutritional treatments to elevate mood and relieve depression symptoms as alternative to antidepressant drugs.

Depression is one of the most frequent psychological problems encountered in medical practice. Some studies say 13 to 20 percent of American adults exhibit some depressive symptoms. The mortality rate among those who are depressed is four times greater than those without depression - major depression accounts for 60 percent of all suicides.

Yet, despite this professional recognition and the fact that depression is a treatable condition, only about a third of depressed patients receive appropriate intervention.

While the exact etiology of depression is unknown, numerous factors appear to contribute. These include genetics, life/event sensitization and biochemical changes.

Family, twin and adoption studies demonstrate that predisposition toward depression can be inherited. In addition, stressful life events can contribute to depression; most studies concur that the likelihood of a depressive episode is five to six times greater six months after events such as early parental loss, job loss or divorce. The link between depression and stressful life events has been conceptualized in the form of the sensitization model, which proposes that prior exposure to stressful life events sensitizes the brain's limbic system to the degree that subsequently less stress is needed to produce a mood disorder. Many of the current biochemical theories of depression focus on the biogenic amines, which are a group of chemical compounds important in neurotransmission--most importantly norepinephrine, serotonin and, to a lesser extent, dopamine, acetylcholine and epinephrine.

Antidepressant medications, which address the brain's biochemistry, include monoamine oxidase (MAO) inhibitors, tricyclic antidepressants and selective serotonin reuptake inhibitors. MAOs increase norepinephrine levels, while tricyclics essentially enhance norepinephrine transmission. Serotonin, in particular, has been the subject of intense research during the past 25 years, indicating its importance in the pathophysiology of depression. Basically, a functional deficiency in serotonin results in depression.

Amino Acid Supplements for Treating Depression

The nutritional treatment of depression includes dietary modifications, supportive treatment with vitamins and minerals, and supplementation with specific amino acids, which are precursors to neurotransmitters. Dietary modification and vitamin and mineral supplementation in some cases reduce the severity of depression or result in an improvement in general well-being. However, these interventions are usually considered adjunctive, since they are not typically effective by themselves as a treatment for clinical depression. On the other hand, supplementation with the amino acids L-tyrosine and D,L-phenylalanine can in many cases be used as an alternative to antidepressant drugs. Another particularly effective treatment is the amino acid L-tryptophan.

L-Tyrosine is the precursor to the biogenic amine norepinephrine and may therefore be valuable to the subset of people who fail to respond to all medications except amphetamines. Such people excrete much less than the usual amounts of 3-methoxy-4-hydroxyphenylglycol, the byproduct of norepinephrine breakdown, suggesting a deficiency of brain norepinephrine.

One clinical study detailed two patients with long-standing depression who failed to respond to MAO inhibitor and tricyclic drugs as well as electroconvulsive therapy. One patient required 20 mg/day of dextroamphetamine to remain depression-free, and the other required 15 mg/day of D,L-amphetamine. Within two weeks of starting L-tyrosine, 100 mg/kg once a day before breakfast, the first patient was able to eliminate all dextroamphetamine, and the second was able to reduce the intake of D,L-amphetamine to 5 mg/day. In another case report, a 30-year-old female with a two-year history of depression showed marked improvement after two weeks of treatment with L-tyrosine, 100 mg/kg/day in three divided doses. No side effects were seen.

L-Phenylalanine, the naturally occurring form of phenylalanine, is converted in the body to L-tyrosine. D-phenylalanine, which does not normally occur in the body or in food, is metabolized to phenylethylamine (PEA), an amphetaminelike compound that occurs normally in the human brain and has been shown to have mood-elevating effects. Decreased urinary levels of PEA (suggesting a deficiency) have been found in some depressed patients. Although PEA can be synthesized from L-phenylalanine, a large proportion of this amino acid is preferentially converted to L-tyrosine. D-phenylalanine is therefore the preferred substrate for increasing the synthesis of PEA--although L-phenylalanine would also have a mild antidepressant effect because of its conversion to L-tyrosine and its partial conversion to PEA. Because D-phenylalanine is not widely available, the mixture D,L-phenylalanine is often used when an antidepressant effect is desired.

Studies of D,L-phenylalanine's efficacy show that it has promise as an antidepressant. Additional research is needed to determine the optimal dosage and which types of patients are most likely to respond to treatment.