Tryptophan is an amino acid that produces serotonin, melatonin, and kynurenine. Tryptophan supplements help with depression, anxiety, and insomnia. However, there are also side effects and contraindications of these supplements. Read on to find out if tryptophan supplements are right for you and how they can improve your health.
What is Tryptophan?
There are different types of tryptophan:
- L-tryptophan is the natural version of the amino acid and a building block of the proteins in the body.
In humans, tryptophan is not stored for long periods and therefore has the lowest concentration in the body among all the amino acids. However, only small amounts of tryptophan are required and it’s usually not necessary in excess [R].
Some common foods that contain tryptophan include oats, bananas, dried prunes, milk, tuna fish, cheese, bread, chicken, turkey, peanuts, and chocolate [R].
Why is Tryptophan Important?
Tryptophan absorption into the brain is influenced by diet.
A high carbohydrate, low protein diet will release insulin, which ultimately increases the absorption of tryptophan into the brain and can, therefore, increase serotonin [R]. This is the mechanism by which eating carbs can increase serotonin.
BCAAs compete with tryptophan absorption into the brain. Eating a high protein diet (high BCAAs) will cause less tryptophan to enter the brain, thus reducing serotonin levels [R].
However, higher protein diets usually have higher tryptophan, which can cancel out the effect from the BCAAs.
Health Benefits of Tryptophan
1) Helps with Sleep and Insomnia
Tryptophan produces melatonin in the brain (pineal gland), the gut, the retina, and immune cells. Melatonin regulates the circadian rhythm and sleep patterns and is used as a supplement itself to help people sleep [R, R].
A blind randomized controlled study of 5 healthy volunteers (3 received the supplement for the first 10 nights and placebo the next 10, the other 2 had the reverse procedure) showed that L-tryptophan supplementation increased average total sleep. All of them noticed some form of drowsiness half hour before sleep [R].
A study on 7 insomniac patients showed that L-tryptophan supplementation increased total sleep (by 28%). The supplementation also decreased early-morning wakefulness by an average of 37 minutes [R].
Tryptophan supplementation even helped induce sleep in manic patients. A blind and controlled study of 10 patients with mania showed improvements in total sleep after L-tryptophan supplementation [R].
A dose-response study of 15 insomniac patients showed that ¼ gram of L-tryptophan increased stage 4 sleep (deep sleep). Normal dietary intake of tryptophan is usually around ½-1 gram of L-tryptophan, so even minimal amounts of tryptophan can increase deep sleep [R].
Tryptophan supplementation may also improve obstructive sleep apnea (airflow blockage during sleep). A study on 12 patients showed that L-tryptophan supplementation increased sleep in those with obstructive sleep apnea during non-rapid eye movement (REM) sleep. However, patients with central sleep apnea showed no improvements [R].
Tryptophan Benefits due to Serotonin
Serotonin is commonly used to fight depression, anxiety, and insomnia. Therefore, conversion of tryptophan to any of its other metabolites (e.g. kynurenine) can induce depression in some people [R].
2) May Help Depression
Depressed patients often have problems creating serotonin from tryptophan. Instead, they create other metabolites such as quinolinic acid, which can be toxic. For these patients, tryptophan supplementation may not help [R].
A randomized study of 25 young adults showed that high tryptophan diets increased mood and decreased depressive symptoms and anxiety [R].
The conflicting evidence of tryptophan studies shows that tryptophan might not treat depression by itself, but can complement other antidepressants (amitriptyline, clomipramine) [R].
A study (DB-RCT) of 24 patients showed that clomipramine (a drug for depression) and L-tryptophan were more effective in improving depressed mood, suicidal intent, and anxiety compared to clomipramine alone [R].
When tryptophan is converted to kynurenine and not serotonin, depression may worsen. Some kynurenine metabolites are toxic and animal models have shown increased depressive symptoms with increased kynurenine [R].
Another study shows that kynurenic acid (KYNA), a derivative of kynurenine, protects the brain while 3-hydroxykynurenine (3-HK) (also a kynurenine derivative) is toxic. High levels of 3-HK and low levels of KYNA can cause depression [R].
3) May Reduce Anxiety
Tryptophan supplements decreased anxiety symptoms in cats [R].
However, other studies show that in social anxiety disorder, serotonin is increased, and tryptophan supplementation could do more harm than good [R].
Interestingly, a study (DB-RCT) of 16 people trying to quit smoking showed that L-tryptophan and a high-carbohydrate diet along with regular smoke-ceasing therapies decreased anxiety and withdrawal symptoms. People given tryptophan supplements smoked fewer cigarettes compared to placebo [R].
4) Reduces Appetite
A study (DB-RCT) on 15 healthy volunteers showed that those receiving L-tryptophan supplementation ate 19 – 20% fewer calories and more proteins than carbohydrates [R].
A rat study showed that after 24 hours of fasting, the rats given L-tryptophan not only ate less on their first meal, but also their post-meal interval between the first and second meal was longer [R].
Moreover, reduced tryptophan levels and absorption into the brain might also be responsible for carbohydrate cravings [R].
5) Can Improve PMS (Premenstrual Dysphoria Symptoms)
The breakdown of tryptophan via the kynurenine pathway is affected by the phase of the menstrual cycle, which can also indirectly affect serotonin production. After ingesting tryptophan, kynurenine was 40% higher during the luteal phase than in the follicular phase [R].
- Mood swings
6) May Treat Mania
In a study (DB-RCT) of five patients with mania, L-tryptophan supplementation improved the treatment with chlorpromazine hydrochloride (CPZ) and reduced side effects [R].
In another study (DB-RCT) on 24 patients with acute mania, L-tryptophan supplementation decreased manic symptoms by 43% outperforming a previous treatment with lithium (41%). Those who stopped receiving tryptophan showed worsening of the symptoms [R].
7) Tryptophan Supplementation can Decrease Dementia Symptoms
A study of 24 patients with dementia showed that serotonin levels in the brain were significantly lower in dementia patients compared to healthy people [R].
The same study showed that patients with dementia had less tryptophan absorption than healthy individuals [R].
When patients with low tryptophan absorption were supplemented with tryptophan, only those who increased absorption showed mental improvement [R].
8) May Help Reduce Post-hypoxic Intention Myoclonus
Tryptophan or 5-HTP supplementation improves myoclonus. However, tryptophan or 5-HTP can also worsen the effects of myoclonus in some people [R].
Tryptophan Effects due to Kynurenine
A change in the kynurenine pathway can induce depression. Certain metabolites like 3-hydroxykynurenine are toxic to the brain and increased production of these molecules can cause depression [R].
Increased kynurenine production also means decreased serotonin production and therefore decreased melatonin production leading to improper circadian rhythms. Disturbances in melatonin production have also been linked to depression [R].
9) Can Help Protect the Eyes
10) Can Help Prevent Pellagra (Niacin Deficiency)
Pellagra is caused by insufficient niacin or tryptophan intake [R].
However, the recommended dosage of niacin is 16 mg/day for men and 14 mg/day for women, which is almost always reached through normal diets and eating habits [R].
Tryptophan Effects due to Other Hormones
11) Can Improve Exercise Performance
In a study (DB-RCT) of 20 patients, tryptophan supplementation led to substantial increases in beta-endorphin, a neurotransmitter/hormone that is released in response to physical processes such as pain [R, R].
The L-tryptophan supplements lowered the athletes’ perceived exertion, most likely due to the increased pain tolerance [R].
12) Helps Breastfeeding
A study (DB-RCT) of 5 patients showed that tryptophan supplementation increased prolactin, which helps postnatal women produce milk [R].
13) Tryptophan Supplementation Can Help Children Grow
Tryptophan supplementation also increases growth hormone, which stimulates growth in children [R].
Limitations of Tryptophan Supplementation
1) Contradictory Research
Although there is much research showcasing the beneficial effects of tryptophan supplementation, there is also a lot of contradictory work by other researchers. For instance, in a clinical trial done on 10 female mania patients, the L-tryptophan supplementation did not perform better than placebo [R].
A study (DB-RCT) of 6 depressed patients showed that L-tryptophan supplementation did not help and the patients needed further treatment before release [R].
Depression is caused by many different factors. Therefore, treatments using L-tryptophan can be ineffective when the depression is not due to low serotonin levels. One study proved this by splitting up depressed patients by tryptophan levels. Only the low-level tryptophan patients showed improvements [R, R].
The studies on exercise also have been contradictory. One study shows that exercise performance increased after L-tryptophan supplementation while another shows that L-tryptophan had no effect [R, R].
A meta-analysis of 108 clinical trials on L-tryptophan supplementation effects on depressed patients found that only two of the trials could be fully considered. Many of the trials were discarded due to no placebo control, a very small number of patients, or improper randomizing and controlling [R].
Some of the trials could not be considered because they did not look at tryptophan alone [R].
Negative Effects of Tryptophan Deficiency
Studies on the effects of tryptophan deficiency deplete this amino acid through a process called acute tryptophan depletion, where the patient is given a beverage of 15 different amino acids excluding tryptophan [R].
Drinking the beverage produces two effects:
- Stored tryptophan is decreased when the liver produces proteins [R].
- Other amino acids compete with tryptophan in crossing the blood-brain barrier thereby reducing the levels of tryptophan in the brain [R].
People suffering from a condition that is linked with tryptophan deficiency can be helped by taking tryptophan supplements if their condition is caused by tryptophan depletion.
1) Motion Sickness
A study of 39 people with migraines and 37 controls showed that tryptophan depletion intensifies dizziness, nausea, and the illusion of movement after induced motion sickness. The depletion caused the same symptoms in the controls as people with migraines [R].
2) Tryptophan Depletion Leads to Lowered Mood
Depression worsened in healthy males after tryptophan depletion [R].
3) Memory Decline
A study (DB-RCT) of 30 patients showed that patients with lowered tryptophan levels did worse in pattern recognition tests [R].
Another double-blind trial of 27 volunteers showed that tryptophan depletion impaired long-term memory in word recall and recognition tests [R].
Another study showed that women were more prone to these memory-damaging effects than men [R].
4) Major Depressive Disorder
A study (DB-RCT) of 21 patients on antidepressants showed that lowering tryptophan levels caused the patients to return to their depressed states more often [R].
5) Seasonal Affective Disorder (SAD)
SAD is a disorder where the patient experiences depression based on seasons, mainly during the winter.
A study on 11 SAD patients with depleted tryptophan found that seven out of the eight patients who relapsed in the summer subsequently developed SAD the following winter [R].
SAD is usually treated with light therapy but only up to ⅓ of patients improve [R].
In one study, when 14 patients with SAD were given L-tryptophan supplements along with light therapy, 64% showed very good clinical responses to combined treatment and minimal side effects [R].
6) Bipolar Disorder
A double-blind study of 7 bipolar patients on lithium treatment showed that after tryptophan depletion, manic symptoms reappeared [R].
7) Increased Food Intake in those with Bulimia Nervosa
Bulimia nervosa is a disorder of distorted body image with periods of excessive food intake followed by periods of self-induced vomiting, which is linked to changes in serotonin [R].
A study of 20 women showed that those with bulimia nervosa took in more calories (39% more) and showed increased agitation and mood irritability due to tryptophan depletion [R].
In a study done on 16 women with PMS, depletion of tryptophan led to severe premenstrual symptoms, especially irritability [R].
A double-blind study on 22 patients with panic disorder showed that after tryptophan depletion, the patients had more anxiety and panic attacks. The controls, however, did not panic after tryptophan depletion [R].
10) Aggressive and Impulsive Behavior
A study of 12 patients with previous aggressive behavior and 12 without showed that after tryptophan depletion, those with aggressive tendencies became agitated and exhibited hostile behavior. Non-aggressive patients, however, decreased their aggression [R].
Tryptophan depletion increases impulsivity leading to aggression [R].
Violent Behavior in Alcoholics
A study of 9 AD patients with or without a history of blacked-out violent impulsive behavior found that violent patients had lower tryptophan levels than the non-violent [R].
While drugs that enhance serotonin receptor activity reduce alcohol intake, decreased serotonin due to tryptophan depletion triggered violent behaviors in alcoholic people [R].
Rat studies showed that continued alcohol consumption desensitizes the serotonin systems in the brain’s reward system (nucleus accumbens) [R].
Tryptophan Side Effects
1) May Induce Nausea
Nausea is one of the most common side effects of tryptophan supplementation [R].
In one study, a patient has nausea after L-tryptophan supplementation; however, it stopped by lowering the dosage [R].
2) May Induce Distress in the Gut
Another common side effect of tryptophan or 5-HTP supplementation is distress in the gut [R].
3) Linked to Eosinophilia-Myalgia Syndrome (EMS)
Between 1988-1999, an EMS outbreak prompted the FDA to recall and cease over-the-counter tryptophan supplements. However, this was because one company in Japan that made synthetic tryptophan altered their creation process, which caused the outbreak. After this was caught and fixed, the FDA lifted the ban in 2001 [R].
4) May Decrease Tyrosine Absorption
Tryptophan and tyrosine use the same mechanisms to get into the brain. Therefore, excessive tryptophan supplementation decreases tyrosine absorption [R].
Tyrosine is also used for depression. Therefore, tryptophan supplementation could decrease the effectiveness of tyrosine therapy. For those taking tryptophan to fight depression, the supplement could hinder the results [R].
5) May Decrease Branched Chain Amino Acid (BCAA) Absorption
Tryptophan and BCAAs compete to cross the blood-brain barrier [R].
6) Other Side Effects
- Blurred Vision
- Poor Concentration
- Dizziness [R]
Mainly, tryptophan supplementation relieves many symptoms, such as anxiety, panic, and depression [R].
But, most people said that tryptophan helped with their insomnia [R].
Many users say that the supplement has changed their lives for the better. One user suffering from anxiety and panic attacks that had tried previous medications such as Paxil, Prozac, Celexa, and Clonazepam has scrapped all these for the L-tryptophan [R].
While the usual dosage of L-tryptophan is 500 mg, many people take more and supplement’s instructions recommend 3 pills before bedtime.
Less than 8 grams per day for 8 weeks shouldn’t produce any side effects. However, an upper limit for tryptophan supplementation is still uncertain [R].
1) Supplementation with Schizophrenic Drugs
2) Supplementation with Antidepressants
In one study, combining L-tryptophan with a monoamine-oxidase inhibitor (MAOI) improved the effects of L-tryptophan alone [R].
However, another study indicates that L-tryptophan with an MAOI can cause serotonin syndrome or dangerously high serotonin levels. Common symptoms of serotonin syndrome include [R]:
The use of L-tryptophan with MAOI has also led to extreme mania [R].
A double-blind study of 115 patients showed that L-tryptophan supplementation with amitriptyline was better than placebo, while other studies showed an improvement from L-tryptophan with nicotinamide or clomipramine [R, R, R].
3) Supplementation with Anti-cough Drugs
Tryptophan supplementation along with anti-cough drugs such as dihydrocodeine, noscapine, and dextromethorphan increased cough resistance [R].
Contraindications of Tryptophan
1) Should not be Taken by Those with Liver Diseases
A study of 40 patients and 14 healthy subjects showed that liver cirrhosis blocks tryptophan breakdown increasing its concentration in the blood by 3-fold [R].
2) Should not be Taken by Those with Kidney Diseases
A clinical study showed that those with kidney problems showed decreased levels of tryptophan in their blood [R].
3) Should not be Taken by Those with Social Anxiety Disorder
A study on 18 patients with social anxiety disorder showed increased serotonin compared to healthy individuals [R].
Genetic Mutations that Affect Tryptophan Breakdown
A study on the IL28B SNP proved that it controls the metabolizing rate of tryptophan. Patients with the C/C genotype at the IL28B SNP have the highest tryptophan breakdown rate while the T/T genotype have the lowest [R].
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