Tryptophan is the sole precursor of serotonin. L-Tryptophan’s role in brain serotonin synthesis is critical for mood, behavior and cognition.
Serotonin is often referred to as the “happiness molecule”. Low serotonin levels can result in pain, insomnia, depression, seasonal affective disorder, and chronic fatigue.
For your body to manufacture serotonin, it needs an adequate supply of the natural amino acid Tryptophan. As a nootropic supplement, Tryptophan is used for anxiety, ADHD, depression, insomnia, memory loss, pain, and eating disorders.[i]
A lack of bioavailable Tryptophan in your body can have a big impact on your life.
- Anxiety & Mood. Tryptophan is an essential amino acid needed to synthesize serotonin which plays a role in mood, sleep, learning and even appetite control.
- ADHD. Low levels of Tryptophan and serotonin imbalances in the brain are associated with ADHD. Studies have found that children with ADHD have 50% lower than average levels of Tryptophan.[ii]
- Neurotransmitters. Low levels of Tryptophan can result in short- and long-term memory loss. Supplementing with Tryptophan has been found to improve memory in healthy adults.
Table of Contents
Tryptophan is an essential amino acid and precursor to serotonin, melatonin and niacin (Vitamin B3) in your body.
The enzyme Tryptophan hydroxylase converts Tryptophan into 5-HTP (5-hydroxytryptophan).
The decarboxylation of 5-HTP to serotonin is dependent on the presence of Vitamin B6, also called pyridoxal 5’-phosphate (P5P).
The further conversion of serotonin into melatonin requires the presence of SAM-e (S-Adenosyl-L-methionine).
Tryptophan is found in foods like oats, bananas, dried prunes, milk, tuna, cheese, bread, chicken, turkey, peanuts and chocolate.
Eating food containing Tryptophan will increase levels of this amino acid in your body. But not necessarily boost serotonin levels in your brain. Here’s why…
Tryptophan is one of 8 essential amino acids and has the lowest concentration in the body of all the amino acids. Tryptophan requires and competes for active transport to the brain. And competes for the same receptors as the other amino acids.
Research has also found that serotonin levels are enhanced by carbohydrates in your meals because insulin release accelerates the serum removal of some of the amino acids that Tryptophan is competing with.
And if your meal has a higher percentage of proteins, it also slows serotonin elevation in your brain.[iii]
Since Tryptophan from food has issues working its way to your brain to make serotonin, why not skip that step and supplement with 5-HTP instead? Tryptophan and 5-HTP both penetrate the blood-brain barrier. And 5-HTP is the intermediate step in serotonin synthesis.
See my post on 5-HTP for more on why supplementing with 5-HTP instead of Tryptophan is not such a good idea.
How does Tryptophan work in the Brain?
Tryptophan boosts brain health and function in several ways. But two in particular stand out.
- Tryptophan boosts memory. Tryptophan’s main nootropic mechanism of action is as a precursor to the neurotransmitter serotonin. Other neurotransmitters such as melatonin and beta-endorphin increase following Tryptophan supplementation.[iv]
Research shows that Tryptophan and serotonin play a significant role in memory. Enhanced brain serotonin has been shown to improve cognitive performance in animals and humans. And decreasing levels of serotonin through Tryptophan depletion impairs cognition.
A study done in Pakistan assessed memory in rats following Tryptophan administration. The rats received Tryptophan doses of 50 and 100 mg/kg of body weight for 6 weeks. The study showed significant improvement in memory of rats following both doses of Tryptophan.[v]
- Tryptophan enhances mood. As a precursor to serotonin, Tryptophan can have a significant effect on mood. Supplementing with Tryptophan has been found to increase not only serotonin, but growth hormone and prolactin as well.
Researchers infused 11 healthy male subjects with doses of 5, 7.5 and 10 grams of Tryptophan. And then monitored their hormonal and behavioral responses.
Tryptophan produced significant effects on mental and physical sedation but did not increase levels of tranquilization. Tryptophan provided a calming effect without knocking these guys out even at high doses.[vi]
How things go bad
As we get older, our brain chemistry and energy metabolism changes.
↓ Tryptophan levels decline
↓ Tryptophan hydroxylase levels decline
↑ Stress, insulin resistance and age increase
↓ Magnesium and Vitamin B6 levels decline
↓ Neurotransmitter levels decline
↓ Concentration, working memory and executive function decline
↓ Appetite regulation, energy and alertness decline
All of these changes can happen at an age. And are influenced by declining Tryptophan levels. Very little dietary Tryptophan is available for protein and serotonin synthesis. And for many people this can be a problem.
Anxiety, depression, ADHD, memory loss, binge eating and a host of other mental and physical issues have been correlated with low Tryptophan levels.
Just living in our modern society seems to leave us irritable, stressed-out, and anxious. Worst case is problems sleeping, depression, aggressive behavior, reduced motivation, pain and even suicidal thinking.
And all have been traced to not enough serotonin in our brain.[vii]
Serotonin, the happiness molecule relies on an adequate supply of Tryptophan for synthesis. Researchers now recognize that the role serotonin plays in psychiatric and behavior disturbances comes from Tryptophan depletion.[viii]
Tryptophan hydroxylase is the rate-limiting enzyme needed for serotonin production. And is involved in the conversion of Tryptophan to 5-HTP (5-Hydroxytryptophan) needed to make serotonin.
This enzyme (Tryptophan hydroxylase) can be inhibited by stress, insulin resistance, magnesium or Vitamin B6 deficiency, or increasing age.
Tryptophan and 5-HTP can penetrate the blood-brain barrier. But Tryptophan requires active transport and competes for the same receptors with other amino acids including tyrosine, phenylalanine, valine, leucine, and isoleucine.[ix]
To complicate things even more, serotonin levels are enhanced by carbohydrates in our diet because insulin release accelerates serum removal of the amino acids competing for Tryptophan transport. And high levels of protein in our diet slows increase in serotonin.[x]
So now you know why it’s helpful to add supplemental L-Tryptophan to your nootropic stack.
How does Tryptophan feel?
Many try L-Tryptophan the first time to cure insomnia or as an alternative to prescription sleep meds.
Dosing L-Tryptophan in the evening will typically ensure you’ll feel great the next day. You should have more energy for working out.
Anxiety levels should decrease. Happiness levels should rise. Tryptophan could help with memory. Music will sound better. Feelings of self-esteem will improve.
Some neurohackers report being able to taper off prescription antidepressant meds by supplementing with L-Tryptophan.
Tryptophan Clinical Research
5-HTP and Tryptophan are natural alternatives for the treatment of depression. And often used as alternatives to prescription antidepressant treatments because they don’t come with the side effects associated with antidepressant drugs.
But as neurohackers we don’t have a lot of research to help us decide if supplementing with Tryptophan makes sense. (If we base our decisions on clinical trials).
Much of the research looks at finding out if low levels of Tryptophan are associated with depression and poor cognition. But there is very little clinical evidence that supplementing with Tryptophan will help reverse low Tryptophan levels. And if adding this nootropic to our stack will boost mood and cognition.
Researchers at the University of Queensland in Australia decided to comb through the research to find out if clinical trials supported the natural health claims of using 5-HTP and/or Tryptophan for depression.
The team located 108 trials of which only 2 studies involving a total of 64 people had sufficient data to qualify. The team concluded that the very limited data showed 5-HTP and Tryptophan better that placebo for alleviating depression. But that larger and more studies were needed before their widespread use could be recommended.[xi]
Low Tryptophan = Depression and Poor Cognition
20 patients in remission or partial remission from depression were studied in a double-blind, crossover design trial. Tryptophan was artificially depleted in these patients so scientists could look at the effects on cognition and mood.
The research team found what we see in real life. Lower levels of Tryptophan had a negative effect on mood, their ability to process positive information, and attention.[xii]
Tryptophan Helps Manage Depression
Serotonin has been recognized as the neurotransmitter that is key to managing depression for the last 30 years. Most of the prescription drug therapies for depression work by raising serotonin levels at the relevant synapses.
We also know that Tryptophan is the immediate precursor to serotonin in the brain. So researchers, using a “what came first, the chicken or the egg” approach decided to find out if low serotonin levels or low Tryptophan levels were to blame for depression symptoms.
Researchers in China analyzed levels of Tyrosine, Tryptophan and serotonin in patients with major depressive disorder. And found that all three were decreased in depressed patients. (Note that Tyrosine is a precursor to dopamine in the brain).[xiii]
The Center for Addiction and Health in Toronto conducted a randomized, double-blind, placebo-controlled trial with 30 depressed individuals. Treatment was fluoxetine (Prozac®) 20 mg per day, 2-4 grams of Tryptophan per day or a placebo for 8 weeks.
Mood was assessed using the Hamilton Depression Rating Scale and the Beck Depression Index during the trial. During the 1st week there was a significant decrease in depression in those who used fluoxetine or Tryptophan.
At 4 weeks the research team recorded a disruption in sleep patterns for those using fluoxetine or a placebo. But not the Tryptophan group.
The team concluded that combining 20 mg of fluoxetine with 2 g of Tryptophan was a safe protocol for treating depression. Patients experienced a rapid decrease in depressive symptoms. And the combination had a protective effect on sleep patterns.[xiv]
DO NOT TRY THIS AT HOME. The trials combining Tryptophan with SSRI’s, SNRI’s and MAOI’s are all done under professional supervision. But remember, Tryptophan is a precursor to serotonin. And antidepressant meds also boost serotonin in the brain. When combined, serotonin levels are boosted even more.
Herein lies the problem. If you increase serotonin too much, you put yourself in real danger of Serotonin Syndrome. Which can lead to all kinds of nasty side effects. Including death.[xv]
DO NOT combine Tryptophan with antidepressant meds unless you are doing so under the careful supervision of a doctor. It is much too dangerous attempting this on your own.
Tryptophan Boosts Exercise Performance
Ever wondered why you cut a workout session short even though physical fatigue wasn’t an issue? Researchers found it could be due to low Tryptophan levels. And its effects on serotonin in your brain.
20 healthy young men aged 21 years used a cycle ergometer at about 50% of their physical capacity for 10 minutes followed by maximum intensity exercise for another 30 minutes. This sequence was repeated 3-times, and after the 4th series, each participant continued at the highest speed they could sustain for 20 minutes.
This protocol was performed twice: once with and once without Tryptophan. Researchers found peak power output during the last 20 minutes were higher on trials performed with Tryptophan than those who performed on a placebo.[xvi]
Another trial in Spain recruited 12 healthy sportsmen who ran on a treadmill until exhaustion. Once while supplementing with Tryptophan and once with a placebo.
Total exercise time, perceived exertion rate, maximum heart rate, peak oxygen consumption, pulse recovery rate, and excess post-exercise oxygen consumption were determined during the two trials.
Total exercise time was nearly 50% greater after receiving Tryptophan than after receiving a placebo. Perceived exertion rate was lower when using Tryptophan.
The researchers concluded that the longer exercise time could be due to increased pain tolerance as a result of Tryptophan supplementation.[xvii]
Tryptophan Relieves Symptoms of Seasonal Affective Disorder
Seasonal Affective Disorder (SAD) is a form of depression experienced by many during the winter months. Symptoms include difficulty waking, decreased energy, weight gain, carbohydrate craving, difficulty concentrating, decreased libido, withdrawal, anxiety, depression and irritability.
The first order of treatment is often light therapy. But many do not respond to light therapy typically because of a mutation in the melanopsin gene and the associated signaling pathway between the retina and the pineal gland.[xviii]
The pineal gland in your brain is your source of melatonin which influences sleep cycles. Melatonin is synthesized from serotonin which is synthesized from Tryptophan.[xix]
So if light therapy doesn’t work, possibly supplementing with Tryptophan to stimulate production of serotonin and melatonin could be effective.
Researchers at the University of British Columbia in Vancouver, Canada set out to find if Tryptophan could help those with Seasonal Affective Disorder (SAD) where light therapy failed.
Patients were treated for 2 weeks using light therapy. Those who did not respond to light therapy were treated with 1 g Tryptophan 3-times per day for 2 weeks while continuing light therapy.
The addition of Tryptophan resulted in a significant reduction in depression. 64% of the patients in this study showed very good clinical responses to the combined treatment with minimal side effects.[xx]
Tryptophan Recommended Dosage
Recommended dosage of Tryptophan is 500 – 1,000 mg per day for cognitive benefit.
The University of Michigan Health Department recommends much higher doses for:
- Lowering appetite and cravings: .5 – 2 grams per day
- Depression or Anxiety: 2 – 6 grams per day (with medical supervision)
- Chronic pain or migraines: 2 – 4 grams per day in divided doses
- Sleep disorders or insomnia: 1 – 2 grams at bedtime[xxi]
Tryptophan is a precursor to the neurotransmitter serotonin in the brain. Tryptophan hydroxylase is the rate-limiting enzyme needed for serotonin production. And requires magnesium and Vitamin B6 to synthesize serotonin.
Tryptophan is also a precursor to the synthesis of Vitamin B3 (niacin). So if you don’t have enough niacin in your body, supplementing with L-Tryptophan will not efficiently produce serotonin because it’s being used to produce niacin. Which also depletes stores of the vitamin cofactors B1, B2 and B6.
So supplement L-Tryptophan with a B-Vitamin complex that includes Vitamins B3 and B6, and magnesium.
Note that some of the clinical trials used in this post use much higher doses of Tryptophan. Which is not recommended and usually not necessary.
Too much Tryptophan will make you sleepy. And could produce excess levels of 5-HTP and serotonin which can lead to Serotonin Syndrome.
Tryptophan Side Effects
Tryptophan is a normal part of your diet and considered non-toxic and safe at recommended doses.
But in the unlikely event that you already have adequate levels of Tryptophan in your body, supplementing with more could cause problems. As can dosing more that the recommended amount.
Tryptophan could cause stomach upset, loss of appetite, nausea, heartburn, drowsiness, headaches, dry mouth and sexual problems.
Start at the lowest dose to see how your body reacts. When first starting with L-Tryptophan take your dose in the evening to avoid possible drowsiness issues.
Caution: Low to moderate doses of Tryptophan (30 mg per pound of body weight), or about 4.5 grams for the average 165 lb. adult is considered safe and free of side effects. However, most don’t need to dose at nearly these levels.
DO NOT use L-Tryptophan if you are taking antidepressant medications including SSRI’s. Because these drugs delay normal degradation of serotonin in brain synapses leaving more serotonin circulating in your brain.
Too much Tryptophan in combination with these drugs can produce Serotonin Syndrome which can lead to delirium, involuntary muscle contractions, high fever, and coma. And worse case and a very real scenario is death.[xxii]
Type of Tryptophan to buy
L-Tryptophan is available in tablet and capsule form usually 500 – 1,000 mg.
You also get Tryptophan in foods you eat including chocolate, oats, bananas, dried dates, milk, cottage cheese, meat, fish, turkey, and peanuts.
Approximately 300 mg of Tryptophan is available in three ounces of turkey, lamb, beef, tuna, or peanuts. Fortunately, relative to other amino acids, small amounts are needed for a therapeutic effect.
And you get 250 mg L-Tryptophan (as TryptoPure®) in Performance Lab® Sleep which also contains 100 mg magnesium (as Magnesium Bisglycinate, Magnesium Taurate, & NutriGenesis® Magnesium) and 500 mg Montmorency Tart Cherry (as CherryPURE®).
TryptoPure® is made by Ajinomoto Co. Inc. of Japan who have developed a new fermentation process for producing highly effective, bio-identical amino acids.
But there are all kinds of reasons why your body may not be making good use of the Tryptophan you’re getting from food. See “Tryptophan Benefits” for more on why it may be a good idea for you add Tryptophan to your stack.
Nootropics Expert Recommendation
Tryptophan 500 – 1,000 mg per day
I recommend using Tryptophan as a nootropic supplement.
Your body does get some Tryptophan from the food you eat. But this amino acid is competing with other amino acids for transport to your brain. It’s competing for the same receptors. And carbohydrates vs. proteins in your meals can affect Tryptophan’s ability to synthesize serotonin in your brain.
Supplementing with L-Tryptophan will make more of this amino acid available to synthesize serotonin and melatonin.
L-Tryptophan is especially helpful for those with low serotonin levels. Boosting this crucial neurotransmitter can help alleviate insomnia, pain, depression and anxiety.
Start with 500 mg of L-Tryptophan per day and take it in the evening. See how your body reacts and how you feel the next day. Increase the dose to no more than 2 grams per day as needed. And watch for side effects.
L-Tryptophan requires adequate levels of Vitamin B3, B6 and magnesium for serotonin synthesis. So add a good B-Complex vitamin and magnesium to your stack when using L-Tryptophan.
And if you’re dealing with insomnia, consider trying Performance Lab® Sleep which contains 250 mg L-Tryptophan (as TryptoPure®).
[i] Sidransky H. Tryptophan: Biochemical and Health Implications. CRC Press; Boca Raton, FL: 2002.
[ii] Johansson J., et. Al “Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study” Behavior and Brain Function. 2011; 7: 40. (source)
[iii] Lieberman H.R., Caballero B., Finer N. “The composition of lunch determines afternoon plasma tryptophan ratios in humans.” Journal of Neural Transmission. 1986;65(3-4):211-7. (source)
[iv] den Boer J.A., Westenberg H.G. “Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder.” Psychiatry Research. 1990 Mar;31(3):267-78. (source)
[v] Khaliq S., Haider S., Ahmed S.P., Perveen T., Haleem D.J. “Relationship of brain tryptophan and serotonin in improving cognitive performance in rats.” Pakistan Journal of Pharmaceutical Sciences. 2006 Jan;19(1):11-5. (source)
[vi] Winokur A., Lindberg N.D., Lucki I., Phillips J., Amsterdam J.D. “Hormonal and behavioral effects associated with intravenous L-tryptophan administration.” Psychopharmacology (Berlin). 1986;88(2):213-9. (source)
[vii] Sandyk R. “L-tryptophan in neuropsychiatric disorders: a review.”International Journal of Neuroscience. 1992 Nov-Dec;67(1-4):127-44. (source)
[viii] Bell C., Abrams J., Nutt D. “Tryptophan depletion and its implications for psychiatry.” British Journal of Psychiatry. 2001 May;178:399-405. (source)
[ix] Caballero B., Finer N., Wurtman R.J. “Plasma amino acids and insulin levels in obesity: response to carbohydrate intake and tryptophan supplements.” Metabolism. 1988 Jul;37(7):672-6. (source)
[x] Lieberman H.R., Caballero B., Finer N. “The composition of lunch determines afternoon plasma tryptophan ratios in humans.” Journal of Neural Transmission. 1986;65(3-4):211-7. (source)
[xi] Shaw K., Turner J., Del Mar C. “Tryptophan and 5-hydroxytryptophan for depression.” Cochrane Database of Systematic Revues. 2002;(1):CD003198. (source)
[xii] Booij L., Van der Does A.J., Haffmans P.M., Riedel W.J., Fekkes D, Blom M.J. “The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients.”Journal of Psychopharmacology. 2005 May;19(3):267-75. (source)
[xiii] Sa M., Ying L., Tang A.G., Xiao L.D., Ren Y.P. “Simultaneous determination of tyrosine, tryptophan and 5-hydroxytryptamine in serum of MDD patients by high performance liquid chromatography with fluorescence detection.” International Journal of Clinical Chemistry. 2012 Jun 14;413(11-12):973-7. (source)
[xiv] Levitan R.D., Shen J.H., Jindal R., Driver H.S., Kennedy S.H., Shapiro C.M. “Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.” Journal of Psychiatry and Neuroscience. 2000 Sep;25(4):337-46. (source)
[xv] Fernstrom J.D. “Effects and side effects associated with the non-nutritional use of tryptophan by humans.” Journal of Nutrition. 2012 Dec;142(12):2236S-2244S (source)
[xvi] Javierre C., Segura R., Ventura J.L., Suárez A., Rosés J.M. “L-tryptophan supplementation can decrease fatigue perception during an aerobic exercise with supramaximal intercalated anaerobic bouts in young healthy men.” International Journal of Neuroscience. 2010 May;120(5):319-27. (source)
[xvii] Segura R., Ventura J.L. “Effect of L-tryptophan supplementation on exercise performance.” International Journal of Sports Medicine. 1988 Oct;9(5):301-5. (source)
[xviii] Roecklein K., Wong P., Ernecoff N., Miller M., Donofry S., Kamarck M., Wood-Vasey W.M., Franzen P. “The post illumination pupil response is reduced in seasonal affective disorder.” Psychiatry Research. 2013 Nov 30;210(1):150-8. (source)
[xix] McGrath R.E., Buckwald B., Resnick E.V. “The effect of L-tryptophan on seasonal affective disorder.” Journal of Clinical Psychiatry. 1990 Apr;51(4):162-3. (source)
[xx] Lam R.W., Levitan R.D., Tam E.M., Yatham L.N., Lamoureux S., Zis A.P. “L-tryptophan augmentation of light therapy in patients with seasonal affective disorder.” Canadian Journal of Psychiatry. 1997 Apr;42(3):303-6. (source)
[xxi] “L-Tryptophan” University of Michigan Health System (source)
[xxii] Fernstrom J.D. “Effects and side effects associated with the non-nutritional use of tryptophan by humans.” Journal of Nutrition. 2012 Dec;142(12):2236S-2244S (source)
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To your knowledge are there any contraindications of taking Tryptophan (even small doses) on a daily and long-term basis?
Thanks for your time!
David Tomen says
John, there is no problem using L-Tryptophan long-term. The only thing you cannot use it with is any drug that increases the use of serotonin (i.e. SSRIs) because it could cause Serotonin Syndrome.
I’m taking Niacin-3g based on BillW’s and Dr. Bob’s recommendation. It has improved my mood and a great side effect is my cholesterol #’s improved. (my Dr. added a blood test for the liver and the 3g is safe for me-YMMV)
It also helped me sleep after stopping long term use of Ambien. I usually take it late afternoon.
My current sleep stack is
Magnesium glycinate 400mg
My sleep is better once I get to sleep but it still takes me a couple hours to get to sleep.
Do you have any suggestions for timing of when I take the stack?
Also, with the high Niacin dose I take, is there any issues with this stack?
David Tomen says
John, there are no problems with your stack including niacin. I use my stack about 90 minutes before bed and it works for me. But I also had to add Charlotte’s Web Calm gummies (https://bit.ly/3dH6Ndx) because they help me get to sleep fast and sleep through the night.
Hello and thank you for this article. I have long battled insomnia and tried many things with little success, but not Tryptophan. I’m interested in trying it along with theanine and GABA (would like to keep the stack simple but as effective as possible). I think anxiety around sleep is part of the issue. Otherwise, apart from chronic insomnia, I live a very healthy life.
Is there a risk of dopamine and serotonin imbalance by taking just Tryptophan?
Any concerns with Tryptophan along with theanine and GABA?
I also take creatine in the morning.
David Tomen says
There is no problem using Tryptophan along with theanine and GABA. And if you keep your dose to 500 mg you should not cause a serotonin/dopamine imbalance.
Very helpful article. Is it theoretically possible for l-Tryptophan to destabilise mood in any of the Bipolar Spectrum illnesses, particularly if used as an adjunct to mood stabilising medication (e.g. Lamotrigine)?
Appreciate your time!
David Tomen says
John, I suppose it is theoretically possible. Lamotrigine is a sodium channel-blocking drug so it does not directly affect serotonin. But anything that upsets the balance that prevents bipolar symptoms will likely have some kind of effect. Sometimes not a pleasant effect.