sleep, mood, and stress - A review of benefits and side effects, safety, risks
by Ray Sahelian,
March 1 2014
L Tryptophan is an essential amino
acid found in foods that contain protein such as turkey.
It is able to convert into 5-HTP
(5-hydroxy-tryptophan), and then to serotonin. Serotonin is involved in mood,
appetite, sleep and impulse control.
Serotonin taken orally as a pill is not able to
easily cross the blood brain barrier, hence either tryptophan or
5-hydroxy-trytophan are good natural options since they convert into serotonin
after going into the brain.
The figure below shows l-tryptophan converting into 5-HTP, which then readily converts into serotonin. Once serotonin is made, the pineal gland is able to convert it at night into melatonin, the sleep-inducing hormone.
L-Tryptophan --> 5-Hydroxytryptophan 5-HTP --> Serotonin --> N-Acetyl-serotonin --> Melatonin
Vitamin B6 is involved in the metabolism of tryptophan to serotonin. Note: L-Tryptophan is also metabolized to a
different pathway, not all of it is converted into 5-HTP.
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Suggested use: Take one tryptophan capsule in the evening, preferably on an
empty stomach, or as recommended by your health care provider. Tryptophan powder
is sold, but it is difficult to make an accurate measurement of the appropriate
dosage. I prefer to use a capsule and know exactly how much I'm taking.
NOTE: There are some companies selling tryptophan for very cheap. They may use a low quality source or mix it with 5-HTP. This tryptophan source is of the highest quality and purity and possibly the best raw material source available.
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Can tryptophan be of benefit for anxiety and panic disorder related symptoms?
Some people find this amino acid supplement to be useful for anxiety reduction, however, how well it helps to reduce panic disorder is still not clear.
Email - I have been suffering from anxiety / depression for about 5 months. My symptoms have included panic attacks, unidentified fears, existential anxiety, self-consciousness, low moods, persistent thoughts, sense of burning inside my chest, general anxiety, etc. I started taking L-Tryptophan 4 weeks ago and my symptoms seem to be getting less intense.
Depression and low mood
Is tryptophan helpful for depression?
Some people who have a shortage of serotonin may benefit from it for depression, others may be helped by St. John's wort, still others by 5-HTP or SAM-e or pharmaceutical drugs.
How does tryptophan compare to 5-HTP as far as sleep?
This is a good question. Some people prefer tryptophan for sleep while others prefer 5thp, and still others prefer melatonin. The best way to find out is to try each product by itself for 2 nights in a row with a break for 2 or 3 nights between each supplement trial.
The anorectic effect of increasing doses of L-tryptophan in obese patients.
Eat Weight Disorder. 1997.
Treatments that raise the level of tryptophan in the brain can rapidly alter the rate at which it is converted to serotonin. This paper compares the effect of 1, 2 and 3 g L-tryptophan administered 1 h before a plated meal on total food intake and carbohydrate and protein consumption in 10 obese subjects versus a lactose placebo in another 10 obese subjects. There was a progressive decrease in carbohydrate consumption in function of the tryptophan dose. These results provide further support for the view that serotoninergic mechanisms play a role in the regulation of human food intake.
What is generally the dose of tryptophan that is taken to see the positive effects?
Most people find 500 mg or 1000 mg taken in the evening to be helpful.
I have trouble swallowing pills, can the capsules
be opened and the contents added to yogurt or juice?
This product works better when taken on an empty stomach, so the contents can be mixed with water or small amount of juice and preferably without yogurt or food.
The unfortunate history, safety and risks,
caution and danger in past
During the 1980s consumers were using tryptophan for sleep and as an antidepressant. It was available without a prescription until 1989 when the FDA prohibited its over-the-counter sale because a manufacturer in Japan shipped a contaminated batch to the U.S. This caused a serious illness called eosinophilia myalgia syndrome in about 1,000 individuals. Around 1995, tryptophan gradually became available by prescription through compounding pharmacies, and then since about the year 2000 it slowly and cautiously was placed on the over the counter market through a few vitamin companies.
effects, caution, safety, toxicity
A common tryptophan side effect from high dose use is drowsiness so it may be a good idea to take this amino acid supplement in the evening and not while driving or operating heavy machinery. Dry mouth is a less common tryptophan side effect. Other less common l-tryptophan side effects include nausea, dizziness, and loss of appetite.
A beneficial l-tryptophan side effect is drowsiness since that is the desired effect of many users who take this supplement for sleep. Confusion or disorientation is rare.
I read on a website that patients
with asthma or systemic lupus erythematosus should not take tryptophan
supplements, why is this?
I have not seen any studies regarding the interaction of this amino acid supplement and airway disease such as asthma or an autoimmune condition such as lupus. However, there is a possibility that elevating serotonin levels may trigger airway disease. I will await the results of studies focusing on this issue before coming to a firmer conclusion. A search on Medline for "tryptophan asthma" and "autoimmune or lupus" reveals no human clinical trials.
I have taken tryptophan some time
ago, and it caused me to have nightmares. Is this common?
Yes, melatonin, 5-HTP and the amino acid supplement are known to make dreams more vivid.
with SSRI medications used for depression
Can tryptophan be dangerous with low or moderate dose of SSRI drugs such as Prozac or Zoloft or Paxil. I would take it only under my doctors supervision. I just wanted your opinion.
When taken in low dosages of 200 to 500 mg, most people are not likely to have any major untoward effects when combined with low dosages of SSRI antidepressants. However, each case is unique and some people may be very sensitive to such combinations.
J Nutr. 2013. Supplementing healthy women with up to 5.0 g/d of L-tryptophan has no adverse effects. Because of the frequent use of L-tryptophan (L-Trp) in dietary supplements, determination of the no-observed-adverse-effect-level is desirable for public health purposes. We therefore assessed the no-observed-adverse-effect-level for L-Trp and attempted to identify a surrogate biomarker for excess L-Trp in healthy humans. A randomized, double-blind, placebo-controlled, crossover intervention study was performed in 17 apparently healthy Japanese women aged 18-26 y with a BMI of ≈ 20 kg/m(2). The participants were randomly assigned to receive placebo (0 g/d) or 1.0, 2.0, 3.0, 4.0, or 5.0 g/d of L-Trp for 21 d each with a 5-wk washout period between trials. Food intake, body weight, general biomarkers in blood and urine, and amino acid composition in blood and urine were not affected by any dose of L-Trp. Administration of up to 5.0 g/d L-Trp had no effect on a profile of mood states category measurement. The urinary excretion of nicotinamide and its catabolites increased in proportion to the ingested amounts of L-Trp, indicating that participants could normally metabolize this amino acid. The urinary excretion of L-tryptophan metabolites, including kynurenine (Kyn), anthranilic acid, kynurenic acid, 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid, and quinolinic acid (QA), all of which are intermediates of the L-TRP→Kyn→QA pathway, was in proportion to L-Trp loading. The response of 3-HK was the most characteristic of these L-Trp metabolites. This finding suggests that the urinary excretion of 3-HK is a good surrogate biomarker for excess L-Trp ingestion.
Social behaviour and mood in everyday life: the effects of tryptophan in quarrelsome individuals.
J Psychiatry Neurosci. 2006.
We conducted a double-blind crossover study, in which participants took tryptophan at 3 grams a day and placebo for 15 days each and recorded how they behaved, felt and perceived others during everyday social interactions. Treatment significantly decreased quarrelsome behaviours and increased agreeable behaviours. Men also behaved less dominantly, whereas both men and women perceived others as more dominant.
turkey, and sleep, food content
Does eating turkey make a person sleepy due to the tryptophan in turkey meat? Would eating foods high in tryptophan induce sleep?
Turkey has an amino acid called tryptophan that is involved in sleep and mood balance. However, turkey has no more tryptophan than chicken or beef. The cause of sleepiness at Thanksgiving is more likely due to consuming lots of food and drink rather than the tryptophan content in turkey. When this amino acid is ingested as part of a protein food, there are a number of additional amino acids in the protein that compete with crossing the blood brain barrier. Hence, taking a supplement on an empty stomach is much more direct and effective than trying to consume this amino acid through food or turkey. Any food with protein will have tryptophan, and turkey, meat, chicken, fish, dairy, eggs, all have this substance.
with St. John's wort
Is St John's wort herb okay to take with tryptophan pill? I read these interact.
Much depends on the dosage used and the person taking them. It is best to learn how each one works by itself before combining. Some people take the St. John's wort in the morning and the tryptophan pill in the evening. Use low dosages at first to know how your body reacts.
Tryptophan Research studies
Effect of orally administered L-tryptophan on serotonin, melatonin, and the innate immune response in the rat.
Mol Cell Biochem. 2004.
Tryptophan taken orally can convert into serotonin and melatonin
Tryptophan was given to a group of rats at 8 am in the morning, and to another group of rats at 8 PM at night. Four hours after administration, researchers measured the blood and brain fluid levels of serotonin and melatonin. During daytime administration, tryptophan raised the levels of serotonin. Interestingly, when tryptophan was given at night, serotonin levels did not increase, but melatonin levels increased significantly. Therefore, the serotonin that was generated by tryptophan administration was being converted into melatonin.
My comments: First, this study confirms again that levels of 5-HTP, serotonin, and melatonin can be influenced by supplements. Second, it shows that the timing of a supplement can make a difference on how it is metabolized.
Pyridoxine, regardless of serotonin levels, increases production of
5-hydroxytryptophan in rat brain.
Arch Med Res. 2004.
The aim of this study was to evaluate effects of pyridoxine and butylated hydroxytoluene (BHT) on lipid peroxidation and on levels of 5-hydroxy-tryptophan and serotonin. Thirty rats (30 days of age) were used in the survey, measuring levels of lipid peroxidation (TBARS), hemoglobin, 5-hydroxy tryptophan, and serotonin (5-HT) after intraperitoneal injections of pyridoxine HCl during 20 days and a single dose of BHT. Levels of TBARS and 5-HTP increased considerably in all vitamin- and/or BHT-treated groups, and serotonin increased partially only in B(6) with or without BHT-treated groups compared with control group. Results suggest that pyridoxine plays a role in tryptophan metabolism, increasing production of 5-hydroxy tryptophan.
Tryptophan administration increase contractility and change the
ultrastructure of mice duodenum.
Amino Acids. 2004.
Serotonin has been shown to induce contractions in rat duodenum and ileum. We planned to investigate the in vivo effects of Tryptophan administration on duodenal contractility. Two equal groups of adult male Swiss-albino mice were used in the experiments. Controls and tryptophan treated. Duodenum tissues contractility responses to different concentration of KCl and acetylcholine (ACh) were recorded on polygraph. Body weights decreased and duodenal contractile response of ACh increased significantly by tryptophan treatment. The duodenal ultrastructural changes in tryptophan group illustrated partially loss of apical surface and fusion in microvilli. Immunohistochemical detection showed that serotonin increased by tryptophan treatment. There is a relation between duodenal contractility increased by tryptophan treatment and changes in the duodenal tissue serotonin level and ultrastructure.
The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.
Psychol Med. 2003
Dieting in healthy women results in a decrease in the availability of tryptophan. This is associated with increases in the prolactin response to serotonin drug challenge suggesting a 'supersensitivity' of serotonin neuroendocrine responses. The aim of the study was to assess whether increased tryptophan intake during dieting would prevent the changes in tryptophan availability and serotonin neuroendocrine function. Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced tryptophan (1.8 g daily) or placebo in a double-blind, parallel group, design. Tryptophan supplementation failed to modify the dieting-induced reduction in fasting tryptophan availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional tryptophan did not show enhanced prolactin responses to intravenous tryptophan challenge. The decrease in tryptophan availability produced by dieting may be due to increased tryptophan metabolism rather than decreased tryptophan intake. While tryptophan treatment did not increase fasting tryptophan availability it may have modified the effect of dieting on brain serotonin function. Further studies will be needed to see if this effect of tryptophan has consequences for the effectiveness of dieting as means of weight control.
Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers.
Psychopharmacology (Berl). 2004
Acute tryptophan depletion is an established method for lowering 5-HT levels and an important tool to study the effects of reduced 5-HT on mood and cognition in human subjects. The University of Maastricht developed a new and inexpensive method for acute tryptophan depletion: a natural collagen protein (CP) mixture with low tryptophan content. The reductions in plasma trypotophan after taking this CP mixture were compared with the reductions achieved taking the traditional AA mixture, and effects on memory and reversal learning were studied. Fifteen healthy young volunteers participated in a double-blind, counterbalanced within-subject study. Reversal learning, verbal memory and pattern recognition were assessed at baseline and 3-4 h after taking the CP mixture. The new acute tryptophan depletion method significantly reduced plasma tryptophan by 74% and the ratio between tryptophan and the other large AAs by 82%. The placebo mixture did not change these measures. Delayed recognition reaction time on the verbal learning task was increased following acute tryptophan depletion. No other cognitive effects were found. The CP mixture was shown to be an efficient tool for lowering plasma tryptophan in humans. The validity of this method with regard to behavioral changes remains to be established in healthy, vulnerable and clinical populations.
In a study of 28 healthy young adults, researchers found that accompanying an evening meal with a milkshake containing a protein powder called alpha-lactalbumin -- which delivers a high concentration of tryptophan -- seemed to improve morning alertness among participants who had mild sleep problems. "Good" sleepers, on the other hand, showed no such benefit. Alpha-lactalbumin, or A-LAC, is a protein derived from the whey component of milk. It contains a high concentration of the essential amino acid tryptophan. The protein powder, marketed as BioPure, was supplied by Eden Prairie, Minnesota-based Davisco Foods International. Fourteen men and women with mild sleep problems, and 14 others without sleep complaints took part in two experiments on separate evenings -- one in which they consumed a tryptophan -fortified milkshake with dinner and later for a snack, and one in which they had "placebo" milkshakes that did not contain the A-LAC supplement. The next morning, participants took a computerized test that measured their mental reaction times, while electrodes placed on their scalps recorded their brain activity. Markus and his colleagues found that participants' blood levels of tryptophan were more than twice as high on the night they dined on the supplemented milkshakes compared with the placebo milkshakes. More importantly, men and women who normally had sleep problems performed better on the mental-alertness test on the morning after having the tryptophan containing milkshakes. On the other hand, tryptophan made no difference to the performance of the 14 participants with no sleep problems. American Journal of Clinical Nutrition, 2005.
My doctor tried me on 5-HTP but it made me overwhelmingly sleepy. He then tried tryptophan, to which I am responding with more energy, mental clarity, and a decrease of carbohydrate cravings. Since I thought 5-HTP was "downstream" from tryptophan on the way to becoming serotonin, what would cause this reaction?
There are several factors that could be involved, dosage, timing, with or without food, etc. Also, tryptophan does not completely metabolize into 5-HTP, some of it is channeled in different metabolic pathways. You may try to see if a lower dose of 5-HTP reduces sleepiness.
A few weeks ago I had emailed you regarding bad side effects of excessive
menstrual bleeding, poor control of depression when I added 5-htp and
tryptophan to my Effexor treatment. I spoke to the School of Pharmacy at my
local university and they advised that my heavy bleeding would have been
caused by taking 5HTP, Tryptophan AND Effexor. They said this combination was
too much and that I shouldn't be taking all 3. They said if I wanted to take
either 5HTP or Tryptophan with Effexor, Tryptophan seems to have the best
results for boosting depressive symptoms. Since I have been doing this
my period this month is fine and my depression is wonderful. Seems Tryptophan
with Effexor is better than 5HTP with Effexor for me. I'm only on low doses of
both to avoid excess serotonin though - 500 mg Tryptophan and 75 mg Effexor / day.
Just wanted to let you know that your product is in fact very good but I was
not using it in the right manner or amount. It's often a matter of trial and
error but thought this info may help somebody else. I don't wish my name to be
made public though if you choose to use this info. Thanks for your time and a
best tryptophan product.
Thank you for your informative web site. I saw your response on your web site about stopping the tryptophan frequently, and need more info: What happens if you don't stop periodically? How long should it be stopped for? I have never been told this before and wonder if that is why the tryptophan has stopped working for me?
As with many supplements, particularly amino acids, somehow the body and brain get used to the effects, so that is one reason to take breaks. Another reason is that we don't know too well what the long term effects are of taking a particular amino acid in high amounts. They may be beneficial, or harmful. As to the frequency of breaks or length of a break from tryptophan, this depends on each person and their individual physiology, but as a rough guideline a week off per month seems reasonable.
I have experienced the worst 8 months of my life
thanks to my first extreme bout of depression and anxiety at 38. I have been
unable to tolerate a number of SSRIs so I tried Kira the German St John's Wort
prescription. I am significantly better, however, I never quite went back to
normal. Because on five pills a day, under my doctors supervision, I have
experienced some side effects - electrical shocks in my hands and feet when
cool and thick, tingling sensations in my brain. It is all worth it though!
Could I perhaps decrease my dose and increase my dietary intake of tryptophan?
Could you please give a reliable web site that lists tryptophan content of
foods. I have searched and searched and found them all to be
different. Perhaps there is a good book that has nutritional content of
Tryptophan is found in foods that contain protein, however, since these foods also have other amino acids, they all compete to get in the brain and the tryptophan is not able to overwhelm the others to get in. Trying to increase brain tryptophan levels specifically through foods is not the best way to go. The best option to increase brain tryptophan levels is to take tryptophan pills or, since the real goal is to increase serotonin levels, taking 5-HTP is another option.
Q. Can you get enough tryptophan from food to fight
A. I don't think so. Tryptophan is needed by itself in the blood stream to easily cross the blood brain barrier and enter the brain and convert into serotonin. While tryptophan is found in food such as meat and poultry, there are tons of other amino acids present in these foods that would interefere with the pure tryptophan effect needed to fight depression.
Thanks for your informative website on alternative
medical treatments. I feel that it's very informative and helpful in deciding
the pros and cons of various treatments without the emotional "hype" that seems
to be common to other alternative treatment websites. I recently read that
tryptophan supplementation could have a carcinogenic effect on the liver, and
for this reason, 5htp is a better treatment option to increase serotonin levels
in the brain.
We have not seen any reports that tryptophan use leads to harm to the liver.
Q. I am a freelance journalist from Sweden. I am doing
research on 5-Htp and L Tryptophan and had a few questions that I hope you might
have the answers to. I have a lot of information about these products, but I get
mixed information from different doctors. When you have a chance, please let me
know what you think about the following questions:
1. Are 5-HTP and tryptophan safe before and during pregnancy?
2. Which of these two products are most effective to raise seratonin levels?
3. How can you know that you will get good 5-Htp or tryptophan product when there are so many products on the market?
4. How does these products compare with some of the "normal" medicines for depressions. Is the effect the same?
A. 1. 5-HTP and tryptophan supplements have not been adequately tested during pregnancy and for the time being we suggest not using them unless absolutely required. 2. 5-HTP has a more direct influence on serotonin than tryptophan. Tryptophan converts into 5-HTP which converts into serotonin. 3. It is nearly impossible for the consumer to know which product is good unless they have it tested themselves in a testing laboratory. 4. Some people respond to natural supplements better, others respond better to pharmaceutical antidepressants. For mild to moderate depression, without suicidal tendencies, we suggest using the natural options first.
I am a chronic sufferer of insomnia. Years ago
I tried tryptophan and it was very effective in making sleepy and keeping asleep
through the night.
However, after a few days I started getting stomach cramps and I discontinued use. Are stomach cramps possible from tryptophan use?
5-HTP causes stomach cramps more frequently than tryptophan, but tryptophan can cause GI symptoms, too. Lowering the dose could be of help or taking it with a small amount of food.
Would like to know the conversion ratio for L-Tryptophan
to 5-HTP please. I have been told anywhere from 5-1 to 10-1.
Tryptophan hydroxylase is the rate-limiting enzyme for serotonin production and involves the conversion of tryptophan to 5-HTP. The activity of this enzyme varies among individuals and can be influenced by a number of factors. Tryptophan is also metabolized to a different pathway, not all of it is converted into 5-HTP. Therefore it is difficult to give a precise number for the conversion ratio since it can vary significantly among different individuals and may be affected within the same person by a number of factors including diet, time of day, stress, medications, etc. But a rate of 5 to 1 or 10 to 1 seems reasonable since 50 mg of 5-HTP often has a similar affect as 500 mg of tryptophan in most people.
If tryptophan converts to melatonin, then why not
start with melatonin in the first place? I successfully manage my depression
with Sam E (200mg once a week), but have been having some trouble with sleep
recently. If I use tryptophan with Sam E, will I risk too much seratonin? Maybe
I should go straight to melatonin?
The effects of tryptophan slightly overlap with those of melatonin but they are not the same. There are no easy answers in regards to combining supplements since much depends on the dosage used, the timing of the supplements, and the individual person's overall health and biochemistry.
I am a medical doctor. I wrote you a while back
about my sleep disorders. RLS, PLMD, no deep sleep, REM sleep disorder. I
believe I had asked about l-tryptophan and deep sleep. I have been on a
"cocktail" of Clonazepam, Flexeril, and Vicodin for the RLS for many years (Vicodin
added later). Not an optimal combination, but it is what has worked for me.
Recently I began having RLS during the day. I recall taking the l-tryptophan
before it was banned, but do not remember why. I just know it helped. I decided
to try the l-tryptophan again, as my sleep neurologist wishes to put me on an
orphan drug, Xyrem. The Xyrem would help the deep sleep. I am a little
apprehensive. We have tried the dopamine agonists, Lyrica, Gabapentin, all of
them. Too many side effects. Not to mention that the neurologist scoffs at such
non-pharmaceutical treatments. The l-tryptophan has a quick onset, but seems to
only be effective for a couple of hours. As I know of long acting amino acids
like l-arginine, I tried to find such a form of the l-tryptophan and could not
come up with anything. I take it with juice (carb) as suggested, along with
magnesium and chromium picolinate. Are you aware of some sort of long acting l-tryptophan
I am not aware of long acting tryptophan supplements.
Some people misspell this amino acid as tryptophane or triptophan