Tryptophan: Metabolism for Mood, Sleep, Gut Health & Energy (a scientist’s view)

 

Let's talk about tryptophan

This is one of my favorite small molecules.  You may be familiar about tryptophan because of Thanksgiving turkey with the idea that many people fall asleep after eating turkey, but there is a whole lot more to tryptophan!  

• One reason people connect falling asleep after eating turkey is because turkey has a lot of tryptophan and importantly, melatonin is generated from tryptophan.  So eating more tryptophan should make more melatonin.  This is partially true, but lets dive into the metabolism of tryptophan.
• Melatonin is one of the metabolites that helps us sleep at night, but tryptophan makes many other molecules that are needed for our health, which is why it is an essential nutrient.
• The metabolism of tryptophan to both serotonin and melatonin begins with breakdown to 5-hydroxytryptophan.  This pathway is shown below to illustrate the process.  
• There is a lot about tryptophan and our metabolism that we will discuss.

What is Tryptophan?

It is an essential amino acid and that means we need to obtain it from the foods we eat.

• One primary source of tryptophan is chicken and beef.  
• However, it is found in many other foods including legumes and vegetables. In fact, pumpkin seeds have a relatively high amount of tryptophan making them an excellent snack especially during the fall when pumpkin seeds are plentiful.    
• Amino acids, like tryptophan, are important for many functions in our bodies including protein synthesis.  
• Tryptophan is the precursor to a class of metabolites known as indoles, which are commonly connected to the microbiome present in our gut. 

Tryptophan and the Immune System

As an essential nutrient, tryptophan is needed for many biological processes.  

• Tryptophan's metabolism has been studied for many years and is connected to our immune system, energy, mood and sleep to name a few.  
• In our immune system, tryptophan is metabolized to a small molecule called kynurenine by the enzyme idoleamine-2,3-dioxygenase, for simplicity just called IDO.  
• The activation of this enzyme has a direct impact on our immune system.  When the enzyme is activated, our body has signaled a need for an immune response.  
• If we collected a blood sample, we could read out the increase in the immune activation by measuring an increase in kynurenine in relation to tryptophan.  
• Likewise, a decrease in our immune response such as an immunocompromised or weakened immune system might cause a decrease in IDO and would result in a decrease in kynurenine.  
• There has been research over the years looking at suppressing the immune system as a way to help treat cancer more effectively by inhibiting the immune response during chemotherapy.   
• Some of my research was conducted to monitor the immune system following organ transplantation.  We found that we could measure the activity of the immune system by measuring kyurenine and tryptophan in urine.  This test showed for the first time that the immune system could be measured using only urine and that the ratio of kynurenine to tryptophan could be used to identify the immune activation.    The figure below shows that patients who received an organ transplant (on the right) had an activated immune system compared to health subjects.  

Energy

Tryptophan is connected to energy metabolism because it is needed to make niacin (vitamin B3).  

• Vitamin Bs are essential to our overall energy metabolism and niacin is one of 8 essential vitamin Bs. 
• We make approximately 1 mg of niacin from 60 mg of tryptophan, but niacin can also be obtained from other dietary sources and over the counter supplements.  
• A healthy tryptophan intake along with efficient tryptophan metabolism is one way to ensure enough niacin is available for energy. 

Mood and Sleep 

Two of the most widely associated connections to tryptophan are mood and sleep.  These two processes are connected.  

• Serotonin is a key neurotransmitter (the name for a chemical that regulates some of our brain function) that is directly related to our feeling of happiness and general well being.  Depression and stress have been linked to low levels of serotonin.  A two-step enzymatic process is required to make serotonin from tryptophan and the rate of conversion from tryptophan to serotonin is about 3% (roughly 60 mg of tryptophan will make 2 mg of serotonin).  
• Subsequently, melatonin is synthesized from serotonin in a two-step process with the enzymes arylalkylamine-N-acetyltransferase (AANAT) and hydroxyl-indole-O-methyltransferase (HIOMT).
• Melatonin is a sleep inducing metabolite of tryptophan.  Many supplements are sold with melatonin as a key ingredient because it is non-habit forming and helps those suffering from sleep disorders.  
• However, one concern may be that when melatonin is taken regularly, the body stops producing it from serotonin, thus limiting that essential internal mechanism needed for sleep induction.  
• Melatonin is a diurnal metabolite meaning that our bodies are designed to produce it at night.  Taking more tryptophan during the day won’t necessarily increase the amount of melatonin, but taking more near bedtime would like result in more melatonin.  
• Monoamine oxidase (MAO) inhibitors (some antidepressants) reduce the breakdown of serotonin and one of the side effects of these drugs includes insomnia because less melatonin is made. 

Your gut microbiome and tryptophan 

One of the most interesting new areas in tryptophan research is our understanding of the role that our gut microbiota play in metabolizing tryptophan.  

• Bacteria living in our gut make up our microbiome, which has a population well over a trillion.  
• We need nutrients to survive and so do the bacteria that live inside our gut.
• In our microbiome, several bacterial species metabolize tryptophan such as Bactericides, Lactobacillus, and Acidophilus.  
• Your gut can also make serotonin from the bacteria that metabolize tryptophan to serotonin. 
• Having a healthy gut microbiome will have a positive effect on our overall well-being improving both our mood and sleep patterns as well a digestive health.  This is often referred to as the Gut-Brain Axis as shown below.  Disruptions in the gut can cause neurological issues due to changes in the nutrients that your gut provides or changes in bacterial populations.  

Indolamines 

• Serotonin is an indolamine and is in the same class as other indolamines such as dimethyltryptamine (DMT) and psilocybin, both of which are neurotransmitters and are also psychedelics.  
• DMT is famous for being in ayahuasca, which has been used in healing ceremonies for many years. 
• There is new evidence that suggests our gut could produce these psychedelic neurotransmitters along with the production of serotonin.  This is very early research, but intriguing if you consider your gut as a source of neurological nutrients.  
• Regulation of the microbiome could be used in mental health treatment, which has far reaching potential to remove or supplement classic pharmaceutical solutions. Understanding the role your gut plays in your mental health is very important.  How can this be done?  
• First measuring your microbiome present by sending in your stool for analysis.
• Second, collecting a blood sample from a dried blood spot would be needed to connect your gut microbe population with your circulating metabolites.  This is a very important step because without measuring circulating blood metabolites, it is difficult to connect your gut with your health especially if you take probiotics which would alter your microbiome.  
• Having a healthy gut microbiome can be one factor in improving our overall health associated with tryptophan metabolism.  

Increasing tryptophan in our diet

Finding ways to ensure enough tryptophan through diet can be important to your health.  

• Chicken, turkey and fish have a high amount of dietary tryptophan with most offering more than 100% of the recommended daily allowance. 
• Other foods such as beans (kidney, white, black) offer about 70% of the recommended daily allowance.  
• Seeds such as flax and chia are also rich in tryptophan.  
• Interestingly, both squash and pumpkin seeds are rich in tryptophan having about 60% of our recommended daily allowance in a small handful.  
• You may also want to include probiotics such as yogurt and digestive supplements that help to improve your overall digestive health to metabolize tryptophan in our gut.  
• Adding other supplements such as tryptophan and 5-hydroxytryptophan, which are metabolized to serotonin, could also help with mood and sleep.  

Take home

• Tryptophan is essential to our immune system, mood, sleep and gut health.
• You may want to talk to your physician about the best ways to increase tryptophan in combination with your overall health and well-being.
• Taking a supplement may be an important way to improve your health in relation to tryptophan
• Currently, there are clinical tests to measure the concentration of tryptophan and serotonin in your blood.  These tests are not commonly ordered, but if your physician suspects you may be deficient in tryptophan, it may be a good idea to have your levels tested.