An Alternative to Tryptophan
5-HTP is also available over the counter. 5-HTP is extracted from griffonia seeds, which come from an African shrub-tree grown in Ghana and the Ivory Coast. There are several European pharmaceutical companies that extract 5-HTP from these seeds. For a complete discussion of the clinical uses of 5-HTP, cautions, side effects, and how to combine it with other nutrients to support mood, see 5-HTP (www.raysahelian.com/5-htp.html).

Mind Power Rx - formulated by Ray Sahelian, M.D.

Mind Power Rx is a sophisticated cognitive formula with a dozen herbs and nutrients. It combines a delicate balance of brain circulation agents and neurotransmitter precursors with powerful natural brain chemicals that support healthy:

• Memory and Mood
• Mental clarity
• Concentration 
• Alertness & Focus

Why buy all the individual herbs and nutrients separately -- at great expense -- when you can buy this excellent combination?

The herbs in Mind Power Rx include: Ashwagandha, Bacopa, Fo-Ti, Ginkgo biloba, Ginseng, Mucuna pruriens, and Reishi.  The nutrients and vitamins in Mind Power Rx include Acetyl-l-carnitine, Carnitine, Carnosine, Choline, DMAE, Inositol, Methylcobalamin, Pantothenic acid, Trimethylglycine, Tyrosine, and Vinpocetine.
To purchase Mind Power Rx or for more information see the link above in blue for Tryptophan and visit PhysicianFormulas.com

The unfortunate history of L Tryptophan
During the 1980s, consumers were using tryptophan for sleep and as an antidepressant. Tryptophan was available without prescription until 1989 when the FDA prohibited its over-the-counter sale because a tryptophan 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 tryptophan slowly and cautiously was placed on the over the counter market through a few small vitamin companies. No large vitamin companies are selling tryptophan at this time (2004).

Tryptophan Research Update
Effect of orally administered L-tryptophan on serotonin, melatonin, and the innate immune response in the rat.
Mol Cell Biochem. 2004 Dec;267(1-2):39-46.
To assess the effects of external administration of L- tryptophan on the synthesis of serotonin and melatonin as well as on the immune function of Wistar rats, 300 mg of the amino acid were administered either during daylight (08:00) or at night (20:00) for 5 days. Brain, plasma, and peritoneal macrophage samples were collected 4 h after the administration. The accumulation of 5-hydroxytryptophan ( 5HTP ) after decarboxylase inhibition was used to measure the rate of tryptophan hydroxylation in vivo. The results showed a diurnal increase in the brain 5HTP, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindolacetic acid (5-HIAA) of the animals which had received tryptophan at 08:00 and were killed 4 h later. In the animals which received tryptophan during the dark period, the 5-HT declined but the 5-HT/5-HIAA ratio remained unchanged. There was also a significant increase in nocturnal circulating melatonin levels. The results indicated that the synthesis of serotonin and melatonin, as well as the innate immune response, can be modulated by oral ingestion of tryptophan.

Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain.
Arch Med Res. 2004 Jul-Aug;35(4):271-4.
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. RESULTS: 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. CONCLUSIONS: 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 Oct;27(2):215-20. Epub 2004 Jun 21.
Serotonin is a metabolite of tryptophan. 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. tryptophan l tryptophan tryptophan food tryptophan turkey 5 hydroxy tryptophan.

The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function.
Psychol Med. 2003 Nov;33(8):1381-6.
Dieting in healthy women results in a decrease in the availability of tryptophan, the amino-acid precursor of serotonin, for brain serotonin synthesis. 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. RESULTS: 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. CONCLUSIONS: 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. l tryptophan tryptophan food tryptophan turkey 5 hydroxy tryptophan operon tryptophan cat tryptophan 5 hydroxy l tryptophan.

Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment.
Biol Psychiatry. 2003 Nov 1;54(9):906-14.
Tryptophan degradation into kynurenine (KYN) during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy. Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of tryptophan, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity. RESULTS: Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in tryptophan concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in tryptophan correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. CONCLUSIONS: The results suggest that reduced tryptophan availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated tryptophan depletion.

Acute administration of nutritionally sourced tryptophan increases fear recognition.
Psychopharmacology (Berl). 2003 Aug;169(1):104-7.
The serotonin precursor tryptophan has been widely used as a nutritional supplement and antidepressant. Recently, however, the use of tryptophan has been severely restricted due to its association with the eosinophilic myalgic syndrome, an autoimmune disorder probably caused by ingestion of a contaminant produced in certain tryptophan manufacturing processes. To determine the bioavailability of a nutritional source of tryptophan obtained from milk protein and to assess whether administration of this material produced neuroendocrine and neuropsychological effects consistent with increased brain serotonin activity. METHODS: We studied 24 healthy subjects who ingested approximately 1.8 g of nutritionally-sourced tryptophan or placebo in a double-blind, parallel group, design. We carried out venous sampling for amino acid and hormone estimation and performed a test of emotional processing using a facial expression recognition task. RESULTS: The nutritionally-sourced tryptophan caused a substantial increase in the availability of tryptophan in plasma. Relative to placebo the tryptophan material produced some evidence of an increase in plasma cortisol, and enhanced the perception of fearful and happy facial expressions. CONCLUSIONS: A nutritional source of tryptophan increased the availability of tryptophan for brain serotonin synthesis and produced endocrine and neuropsychological changes consistent with increased brain serotonin function. The effect of tryptophan on emotional processing may be relevant to its reported activity in primate studies of social behaviour.

Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals.
Psychopharmacology (Berl). 2002 Dec;164(4):385-91. Epub 2002 Oct 12.
Reduced serotonergic activity has been associated with impulsive behavior; however, intervention studies have been scarce. OBJECTIVES: To examine whether induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity. Twenty-four healthy young males ingested a mixture of the essential amino acids except for tryptophan in a balanced, randomized, double-blind, placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture. RESULTS: The intervention led to a dramatic fall in free and total plasma tryptophan, and the tryptophan  /large neutral amino acids ratio. This in turn has been shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive- or disinhibited response style on the continuous-performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli. CONCLUSIONS: These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients.

The anorectic effect of increasing doses of L-tryptophan in obese patients.
Eat Weight Disord. 1997 Dec;2(4):211-5.
Serotonin synthesis in neurons is initiated by hydroxylation of the essential amino acid tryptophan. 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: placebo 131 g; one g tryptophan 123 ; two g 114; three g 107. Protein consumption was less affected. These results provide further support for the view that serotoninergic mechanisms play a role in the regulation of human food intake. They are also consistent with the hypothesis that nutrients which increase serotonin availability selectively alter carbohydrate consumption. Further studies with modified molecules of naturally occurring tryptophan (hydroxytryptophan hydrochloride or diethylpropionate) may offer a potential field for the treatment of pathological ingestive behavior.

Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers.
Psychopharmacology (Berl). 2004 Jul 22
Disorders associated with low levels of serotonin (5-HT) are characterized by mood and cognitive disturbances. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.

Effect of supplemental tryptophan, vitamin E, and a herbal product on responses by pigs to vibration.
J Anim Sci. 2004 Aug;82(8):2410-20.
Economic losses related to increased stress during the transport of pigs are well documented. The effects of supplementing of tryptophan, vitamin E, or a herbal product via feed or drinking water were investigated in terms of effects on stress response in pigs during transport simulation. The study consisted of three analogous experiments. For the testing in each experiment, the pigs were allocated to one of two treatments, with and without supplementation of a product. The applied doses were tryptophan, vitamin E, and Sedafit. Sedafit is a commercial herbal product containing Valeriana officinalis L. and Passiflora incarnata L. as active components.  Pigs supplemented with tryptophan tended to spend more time lying down during the second hour of vibration. Vitamin E decreased the peak heart rate, ventricular ectopic beats, and ST elevation. In conclusion, tryptophan had a positive behavioral effect in this experiment, and vitamin E and Sedafit mediated an increase in some heart variables, suggesting sedative and antianxiety effects.

An evening milkshake spiked with the amino acid tryptophan may help clear the morning mental fog of the sleep-deprived, preliminary research suggests. 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, a protein building-block best known for its sleep-inducing effects. In the body, tryptophan serves as a precursor for the brain chemical serotonin, which, among other things, is thought to help regulate sleep. Tryptophan is found in foods such as beef, chicken, dairy products and, most famously, turkey -- which is often blamed for the near-coma that follows Thanksgiving dinner. In reality, however, the relatively low concentration of tryptophan in turkey and other foods is unlikely to affect the brain because it must compete with other amino acids and nutrients for absorption. In their study, Markus and his colleagues examined whether an A-LAC protein powder, with its high concentration of tryptophan, could increase the ratio of tryptophan to other amino acids in participants' blood -- and whether there would be any difference in their mental alertness the next morning. 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. SOURCE: American Journal of Clinical Nutrition, May 2005.

Tryptophan taken orally can convert into serotonin and melatonin
Tryptophan is an amino acid available in food. A few years ago tryptophan reappeared on the market as an over the counter supplement. The biochemistry of tryptophan is fascinating and quite important. It has been known for some time that in the body and brain, tryptophan gets converted into 5-hydroxy-tryptophan (5-HTP) which then converts into serotonin, a crucial brain chemical involved in mood, appetite, impulse control and sleep. Serotonin, in turn, is able to convert at night into melatonin.
     To confirm this knowledge, 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. Another study I came across in the January 2005 issue of the Journal of Pineal Research indicates that 5-HTP is a more potent antioxidant than Vitamin C.
     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. Since tryptophan, 5-HTP, and melatonin are available as supplements, I have had many questions over the years asking which one is best to take for depression, sleep, anxiety, or appetite control. This is difficult to answer since each person has a different biochemistry and would respond differently. The most reliable way to find out is by trial and error. There's really no practical blood study that can be done to determine which supplement someone will respond to, and in what dosage. As a rule, melatonin is most helpful for sleep and does not have a strong influence on mood or appetite. 5-HTP has a strong influence on mood, appetite and anxiety. Tryptophan has been used for depression and sleep.

Tryptophan Emails
Q. 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?
    A. 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 great product.

Q. Dear Dr. Sahelian, Thank you for your informative web site. I saw your response on your web site about stopping the tryptophan frequently, and need more info:

1. what happens if you don't stop periodically?
2. how long should tryptophan be taken before stopping?
3. 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?
     A. 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.

Q. Hello , I have been taking tryptophan for about a month and have started to respond to it. I have also gained some weight, is this common and will it go away with a little time?
     A. Tryptophan was reintroduced only recently in any significance, so we don't have as much experience with long term use.

Q. As with 5-HTP, do you recommend taking frequent breaks when taking L-Tryptophan? 
     A. Yes we do, definitely.

Q. Interesting reading, your website. Tryptophan, in my humble opinion, it is a great option for sleep (when taken with juice). Thanks for the info on your site.

Q. 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 listed.
A. 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.