Tryptamine Metabolism in Depression

Depression is one of the world’s most commonly diagnosed psychiatric conditions. It is a mood disorder that causes sufferers to lose interest in day-to-day activities and instills in them a persistent feeling of sadness. The disorder is also a major challenge to the medical community because it is a recurrent condition and has a link to increased risk of heart disease stroke and diabetes. Common symptoms of it include difficulty sleeping, lethargy, unexplained aches and pains, fatigue, and suicidal thoughts.


A Scientific Breakthrough

An effective treatment for depression has been elusive because science has yet to fully unlock the inner working of the human brain, but several studies have suggested that substances capable of forging new neural connections could provide a breakthrough.

Tryptamine Metabolism’s Role in Depression

Scientists have long known that people who suffer from depression, anxiety disorders and addiction often have reduced executive functions. These are the cognitive processes that control behavior.

It is known that the prefrontal cortex neurons of people suffering from depression do not connect as well as they should to other brain cells, which is why a great deal of breakthrough research has been done on tryptamine substances like classic psychedelics and the amino acid tryptophan.

In fact, a recent study shows that psilocybin (magic mushroom) therapy is four times more effective than antidepressant medicine. The following studies suggest how these particular tryptamines improve these neural connections.

The Serotonin Hypothesis

Serotonin, which is also known as 5-hydroxytryptamine, is a hormone that has been linked to mood swings and feelings of happiness. It does this by helping brain cells to communicate with one another, and it has been at the center of depression research for more than 50 years. The brain uses the amino acid tryptophan to make serotonin, and research suggests that increasing the amount of tryptophan in the diet using food rich in the amino acid could combat many of the most debilitating symptoms of depression. Research indicates that low brain serotonin levels may exacerbate anxiety and depression symptoms.

Dietary intervention is necessary because tryptophan is an essential amino acid. This also means it cannot be made by the body. Some of the most promising research in this area was conducted in 2014 by a team of scientists from the University of North Dakota and the Northland Community and Technical College in Minnesota. Previous research focused mainly on tryptophan powders and supplements, and the results were not nearly as promising. The most often cited work in this area was done in 1970 by scientists from London’s UCL Institute of Neurology and Royal Free Hospital.

There is ample evidence that tryptophan metabolism is altered in people with affective disorder. Thus, the therapeutic activity of MAOI compounds was previously found to be amplified by oral tryptophan, suggesting that affective disorders may be caused by insufficient 5HT in the brain.

Cortisol secretion rates are high in depressed patients, therefore, it was theorized by the Department of Chemical Pathology, Institute of Neurology, and other members of the psychiatric community that “there may be a metabolic link between increased adrenocortical activity and abnormal 5HT metabolism in depression raised plasma cortisol inducing pyrrolase which might directly divert tryptophan from 5HT formation or cause the formation of metabolites which decrease 5HT synthesis.” One study in London researched these metabolic processes and another tested the effects of consumed tryptophan in the diet.

London Study

In a London study, two groups of people were given tryptophan supplements orally. One of the groups was made up of people who had been diagnosed with depression and the other was a control group comprised of people who did not suffer from the condition.

The researchers determined how the subjects responded to the tryptophan supplements by analyzing their urine for the metabolites kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. They noticed that the subjects who suffered from depression excreted more of the metabolites. At the end of the study, the researchers noted that the relationship between the severity of depression and kynurenine excretion after the tryptophan dose differed for some subjects.

Thus, a patient not in the control group was severely agitated and depressed at the time of the initial test when kynurenine was excreted. After a long course of electroconvulsive therapy (a common treatment for severe depression) the levels dropped, and the patient was improved. Another patient showed similar trends, a good response to antidepressant medication being associated with markedly decreased kynurenine excretion.

Minnesota and North Dakota Study

The University of North Dakota and Northland Community and Technical College researchers chose 25 young adults to take part in the study. The subjects consumed a diet high in tryptophan four days and then went through a washout period lasting four weeks. They then spent four days eating a diet low in tryptophan. The subjects were examined throughout the study for mood changes, higher or lower levels of anxiety and signs of depression.

The researchers discovered that a diet naturally high in tryptophan lowered anxiety and irritability and greatly reduced the symptoms of depression. They also found that irritability, anxiety and depression increased when the subjects consumed food low in the essential amino acid. While these results differ from the findings of other researchers who used supplements instead of foods high in tryptophan, studies conducted in 1998 and 2008 also found a link between tryptophan-rich diets and reduced symptoms of depression.

While the work done during the study is certainly promising, it is far from conclusive. The researchers concede that a group of only 25 subjects is not large enough to draw any firm conclusions, and they also accept that a more comprehensive study featuring a control group taking a placebo would provide more valuable data.


Dietary Intervention

While it is clear that more work needs to be done before diets rich in tryptophan can be lauded as a breakthrough in the treatment of depression, that does not mean people who suffer from the condition should wait until more data is available before increasing the amount of the amino acid in their diets. However, a balanced approach should be taken as some of the foods rich in tryptophan, such as oily fish and eggs, could negatively affect health if consumed in excessive quantities.

Another area where more work needs to be done is looking into the role gut bacteria plays in increasing or lowering tryptophan levels. Laboratory experiments have revealed that germ free mice have more tryptophan in their blood but less serotonin. Examinations of people diagnosed with depression have revealed higher levels of the gut bacteria Alistipes, which scientists believe could reduce tryptophan levels.

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