Is L-tryptophan Safe?

  • By Performance Lab
  • 5 minute read
Is L-tryptophan Safe?

We've talked about L-tryptophan a fair bit—what it is, how it can help control your anxiety, and why it makes you sleepy, but there's one important factor we haven't hit on: Is it safe?

In the following article, we'll answer that very question.

So, with no further ado, let's dive in!

L-Tryptophan - An Essential Amino Acid

L-tryptophan is one of twenty amino acids that's needed by the body to synthesize proteins and other chemical compounds.

But unlike the other 11 amino acids, tryptophan belongs to the class of 9 amino acids that are essential, i.e. the body can't make them.Whether you fall into the group that takes tryptophan to improve energy levels or boost mood, or maybe you take it to check your anxiety and improve your sleep, it's a great supplement to keep on hand. As an amino acid, you'd probably think its safety is a no brainer, because, well, your body synthesizes amino acids anyway, so why would giving it more do any harm? Well, that's partly right.But just like anything else—be it natural or non—too much of a good thing is possible.

First off, let's give you a quick reminder of why people take tryptophan to begin with, then you can understand why it may not be so good for some people… The body metabolizes Tryptophan in two main pathways; which shows the effect it will elicit.

As the pathways are a little complicated, we'll save you from all the science-y jargon and just give you the main idea for each one in the next section.

The Two Pathways of L-Tryptophan

  1. Kynurenine pathway: tryptophan is metabolized into alanine and niacin
  2. Serotonin pathway: tryptophan is metabolized into 5-HTP, serotonin, and melatonin

The first pathway is a major energy-producing pathway, synthesizing NAD, the main energy storage molecule and accounts for 95% of dietary tryptophan degradation . The second pathway involves the conversion of tryptophan to serotonin, a major hormone involved in mood regulation.

Then there's melatonin, the hormone involved in a variety of processes including regulation of the sleep cycle, immune function, the endocrine system, reproduction, free radical scavenging, and regulating mental state and behaviour.

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And while you may think the latter pathway does more, this pathway only accounts for approximately 1% of dietary tryptophan degradation .Based on the percent of degradation, it's clear that food sources of tryptophan are a hit or miss, and they don't have the greatest reliability if you're looking to it for affecting mood and sleep. Remember why? Because tryptophan competes with other amino acids to get on the transport protein that shuttles them to the brain.

Suppose there's a lot of competition (i.e. high amounts of larger amino acids like BCAAs, tyrosine, phenylalanine, and methionine). In that case, chances are slim that tryptophan is going to catch a ride . With supplements, however, you're getting the pure form of tryptophan, meaning you're in the clear to jump on the transport protein and enter the brain without having to fight off valine, isoleucine, methionine, or any other amino acid bullies.

How Much L-Tryptophan is Too Much?

The good news is that you may not want to overdo it on the turkey. Still, with L-tryptophan supplementation, you're likely in the clear assuming you keep it to a reasonable dosage and don't have any underlying conditions. 

Tryptophan supplementation is considered safe in mild to moderate doses. However, some side effects have been reported, including :

  • Nausea and vomiting (mild)
  • Drowsiness
  • Headache
  • Light-headedness

What Else You Might Find

Excessive consumption of L-tryptophan has been linked to eosinophilia-myalgia syndrome (EMS). This very rare multi-system condition causes inflammation in areas of the body like the muscles, skin, and lungs. 

This condition causes high levels of eosinophils, a type of white blood cell, to build up within the body and can lead to severe complications. It arises in two phases: acute and chronic. The acute phase includes myalgias (severe muscle pain), fevers, rash, arthralgias, weight gain, edema, and dyspnea. The chronic phase includes muscle cramps and pain, weakness, weight loss, fatigue, neuropathy, and skin changes . Doesn't sound too pleasant, does it?

So How Safe is Safe?

While L-tryptophan is safe for most people supplementing with moderate doses, if you're pregnant, you may want to reconsider.Supplementing with L-tryptophan may be contraindicated in pregnancy because of potential effects on the fetus and potential to suppress the central nervous system.

There isn't enough information available on the safety of L-tryptophan when breastfeeding, so it's best to steer clear of it to avoid any complications . A rodent study also suggests that tryptophan supplementation during pregnancy increases fetal levels of hypothalamic serotonin and serum progesterone and prolactin.

Additionally, there is an increased risk of developing pituitary prolactinomas and mammary adenomas .

If you're on meds or other supplements, you'll want to sit this one out

Just like the title suggests, L-tryptophan can be a bit problematic if you're on prescription medication .

This is especially true if you're taking any CNS depressants (i.e. sedatives) like clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), or zolpidem (Ambien).

Taking tryptophan along with sedatives can exacerbate the effect and cause excessive drowsiness.But it's not just sedatives you have to be wary of.Cough medications, anti-depressants, MAOIs, and any other drugs that increase brain concentrations of serotonin can react negatively with L-tryptophan.

Ever thought too much serotonin in your brain could be a problem? If you take tryptophan with these drugs, it can.Excessive amounts of serotonin flooding the brain can cause heart problems, shivering, and induce anxiety.

But is there anything else you should be wary of? Find out in the next section.

L-Tryptophan - What Else You Need to Know

Taking L-tryptophan alongside herbs with sedative properties, which includes things like hops, Jamaican dogwood, kava, catnip, skullcap, and valerian, may increase drowsiness.

This also applies to supplements with serotonergic properties like 5-HTP and SAMe, as the effect of L-tryptophan on increasing serotonin levels may increase both the effects and side effects of the supplements.And specifically, combining L-tryptophan with St. John's Wort may increase the risk of developing serotonin syndrome, a condition that results from too much serotonin circulating in the body. With all of that said, if you're thinking about taking L-tryptophan and you may have a pre-existing condition that tryptophan could interfere with, speak with your doctor before self-prescribing.

And either way, always use moderate doses to avoid any complications.

References

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  2. AA Badawy. Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention. Egypt J Basic Clin Pharmacol. 2019; 9: 10.
  3. E Höglund, O Overli, S Winberg. Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review. Front. Endocrinol. 2019 April; 10: 158.
  4. JD Fernstrom. Effects and Side Effects Associated with the Non-Nutritional Use of Tryptophan by Humans. The Journal of Nutrition. Dec 2012; 142(12): 2236S–2244S.
  5. DJ Groskreutz, J Mandel. Pulmonary Vasculitis. Pulmonary Vascular Disease. Elsevier BV; 2006.
  6. PJ DiSaia, G Chaushuri, LC Giudice, TR Moore, LH Smith, MM Porto. Women's Health Review: A Clinical Update in Obstetrics–Gynecology. Elsevier Health Sciences; 2012.
  7. C Santana, L Martin, F Valladares, L Diaz-Flores, C Santana-Herrera, A Milena, M Rodríguez Díaz. Tryptophan ingestion by pregnant rats induces pituitary and mammary tumours in the adult female offspring. Human Reproduction. Aug 1999; 14(8): 2155–2161.
  8. L-Tryptophan. MedLine Plus. January 02, 2020.