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Friday, September 23 2016

Warning: This newsletter may put you to sleep

There are many factors that influence both depression and sleep.  In a previous newsletter I talked about the dangers of GMO foods, and how Glyphosate (Roundup) has been shown to influence the Shikimate pathway of our gut bacteria and their production of amino acids such as Tryptophan and Tyrosine that are precursors to Serotonin and Dopamine.  Other newsletters on Heart Rate Variability and stress pointed to the effects of the imbalance of the sympathetic and parasympathetic nervous system and how cortisol fluctuations could influence hormones and sleep cycles.  All of those factors are important but this newsletter will focus on Tryptophan, about why it is such an important amino acid, why it is poorly utilized and what can be done to improve optimal levels.


The Serotonin pathway and Kynurenine pathway

Tryptophan is an amino acid that gets converted to a neurotransmitter serotonin and this has been linked to restful sleep, and in the case of low levels, depression and even problems such as obsessive compulsive issues.  There are a few biochemical steps that take place in order for this to happen.  Tryptophan first gets converted to 5-HTP or (5-hydroxytryptophan) and this in turn is converted in our bodies to serotonin.  If you or someone you know has tried either taking tryptophan or 5-HTP as a supplement, they may or may not have had success in achieving restful sleep or avoiding SSRI (selective serotonin reuptake inhibitor) antidepressant medications.  The following information may explain why. 

The above diagram shows how tryptophan can either be converted along the Serotonin  pathway, or take another route called the Kynurenine pathway.  The Kynurenine pathway has its purpose because it leads to the production of vitamin B3 (niacin).  In fact, it is estimated that well over 90% of all tryptophan may well go this route.  In 1969, an early researcher of this information Gregory Oxenkrug, suggested that the best way to deal with depression was not to focus on optimizing serotonin levels but to focus on the cause of why someone might shunt more tryptophan down the kynurenine pathway than was needed.   Not all of tryptophan along the Kynurenine pathway winds up as vitamin B3.  When excessive amounts of tryptophan go down the Kynurenine pathway excess amounts of an inflammatory chemical Quinolinic acid rise.


One of the reasons for the body to shunt tryptophan to the kynurenine pathway is the overproduction of the stress hormone cortisol.  Cortisol increases hepatic tryptophan 2,3 dioxygenase (T.D.O) activity in the liver.  T.D.O is a potent catabolic enzyme of tryptophan, leading to tryptophan depletion, and to a decrease in serotonin synthesis.  It is also referred to as tryptophan pyrrolase.


The other most common reason is the presence of inflammation in the body.  Inflammation from food sensitivities, chronic infections, or exposure to substances in our environment such as pesticides and other chemicals increase a chemical called indolamine 2,3 dioxyanase (I.D.O.)  I.D.O., burns up 5-HTP and tryptophan before it can be transported across the blood-brain barrier causing a release of some toxic byproducts such as Quinolinic acid.  For people with inflammation who take tryptophan and 5-HTP and as a result experience malaise or a lack of wellbeing, then this is a confirmation that the person has inflammation. 

Final thoughts

There are nutrients that help convert tryptophan to 5-HTP, and 5-HTP to serotonin.  Notably they are zinc, iron, calcium, magnesium, folic acid, vitamin C, and B6.  Those supplements may help in elevating serotonin. There is also another nutrient that is needed to help convert tryptophan to 5 HTP.  It is also important for converting other amino acids into neurotransmitters. This nutrient is BH4.  BH4 is tetrahydrobiopterin, and is made by our bodies from BH2, methyl folate, and SAMe.  BH4 is a critical enzyme that can be low in people who are genetically challenged with methylation ability, or have problems with breaking down ammonia in the urea cycle.  This can result in elevated nitrogen based free radicals such as the unhealthy form of nitric oxide, iNOS, also known as inducible nitric oxide synthase, causing inflammation!

Depression and sleep disturbances are clearly not just a disturbance in the serotonin pathway.  It is imperative to look at the liver, the inflammatory state of the patient, the level of stress they are under, and all the co-factors of serotonin synthesis to see the greatest results.   Therefore it would be useful to do various lab tests to evaluate levels of toxicity, vitamin and mineral deficiencies and stress levels for yourself if you wanted to get a more complete understanding of how you may enjoy a more restful sleep, reduce bouts of depression or obsessive compulsive disorders.  A more natural approach can help you avoid medications such as SSRI's and their serious side effects.

Posted by: Dr. Paul Goldstein AT 10:50 am   |  Permalink   |  0 Comments  |  Email

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