5-HTP vs L-Tryptophan

[-Aaron-]

The EMS epidemic took years to identify and was almost
missed. The only reason it was discovered was because the
disease had three concurrent characteristics: it was rare,
acute, and came on quickly. What would happen if all three
characteristics had not been in place? What if it took 20
years for onset or only impacted the next generation? What if
it produced only mild symptoms like frequent colds? What if
it created serious diseases that were common, like cancer,
heart-disease, obesity or diabetes? The epidemic might remain
undiscovered for decades.

What then of the thousands of products currently being fed to
US citizens that contain ingredients from genetic
modification? Might they be creating problems that don't have
all three characteristics? Are they contributing to the
doubling of food-related illnesses in the United States
between 1994 and 2001, corresponding to the time when many of
these products were introduced? We don't know, because no one
is looking. And even if we were, derivatives from the four
major GM crops, soy, corn, cottonseed, and canola, are found
in the majority of processed foods. Unlike L-tryptophan, if
common food ingredients were creating health problems,
identifying the source might be impossible.

In spite of these facts, and ignoring the thousands of victims
of GM L-tryptophan, U.S. regulators continue to make the
baseless statement that "millions of people have been eating
genetically engineered products for years and no one has
gotten hurt."

Dissatisfied with the way that the FDA is protecting their
health, more and more people have chosen to protect themselves
by avoiding GM foods altogether. Here too, the FDA stands in
the way. More than 90 percent of Americans want GM foods
labeled. Most industrialized nations require labeling. But the
FDA has an official mandate to promote biotechnology. They
know that more than half of those surveyed say they would
avoid GM foods if they were labeled. To protect industry
profits, the FDA ignores the desires of nine out of ten
Americans.

There is no indication that another EMS epidemic will emerge
from another GM food or supplement. But with obesity,
diabetes, migraines, allergies, and many other ailments
skyrocketing in the U.S., there is no guarantee that another
GM-related epidemic is not already upon us.

To learn more about the potential dangers of GM foods, to find
out how to shop GM-free, and to read the excellent report by
William Crist, visit
http://www.seedsofdeception.com/Publ...phan/index.cfm.

Spilling the Beans is a monthly column available at
www.responsibletechnology.org. Publishers and webmasters may
offer this article or monthly series to your readers at no
charge, by emailing column@responsibletechnology.org.
Individuals may read the column each month by subscribing to a
free newsletter at www.responsibletechnology.org.


References

[5] Barbara Deane, "Anatomy of an Epidemic," Reader's Digest,
April 1991
[6] P. Raphals, "Does medical mystery threaten biotech?"
Science, vol. 249, no. 619, 1990
[7] William E. Crist, The Toxic L-Tryptophan Epidemic, see
http://www.seedsofdeception.com/Publ...phan/index.cfm.
[8] Joshua H. Beisler, L-tryptophan Section from "Dietary
Supplements and Their Discontents: FDA Regulation and the
Dietary Supplement Health and Education Act of 1994,
Rutgers Law Journal, Winter 2000, see www.seedsofdeceptio-
n.com/utility/showArticle/?objectID=3D263.

=A9 Copyright 2005 by Jeffrey M. Smith. Permission is granted
to reproduce this in whole or in part.

[MBSowards]

I think here is the major problem in this thread.

Steve is saying that taking the recommended amount of these is fine for you.

Aaron is arguing that overdosing has adverse side effects.

So, to conclude:

Steve, overdosing on these could be bad and have adverse effects correct?

Aaron, do you have any research showing recommended amounts of these has adverse effects on health?

After these two questions are answered, assuming Steve believes overdosing is bad (I believe he's stated it in this topic even) and assuming that Aaron has no evidence of the harms of taking the recommended dose, you guys can quit arguing, because you're not even arguing about the same things.

[-Aaron-]

I think here is the major problem in this thread.

Steve is saying that taking the recommended amount of these is fine for you.

Aaron is arguing that overdosing has adverse side effects.

So, to conclude:

Steve, overdosing on these could be bad and have adverse effects correct?

Aaron, do you have any research showing recommended amounts of these has adverse effects on health?

After these two questions are answered, assuming Steve believes overdosing is bad (I believe he's stated it in this topic even) and assuming that Aaron has no evidence of the harms of taking the recommended dose, you guys can quit arguing, because you're not even arguing about the same things.

I have nothing with anything but overdosed patients...

The fact is, he attacked me personally and it's irritating the hell out of me.

[Phosphate bond]

It turns out that pro-inflammatory cytokines cause tryptophan to degrade in the blood. This occurs because these pro-inflammatory cytokines activate specific enzymes that deplete tryptophan in the bloodstream. The result of diminished blood levels of tryptophan is serotonin deficiency in the brain (and the onset of depression).

Pro-inflammatory cytokines are specialized biochemicals secreted by immune cells that are only supposed to be activated in response to acute infection or trauma. As people age, they often chronically overproduce pro-inflammatory cytokines, which subsequently cause inflammatory-related diseases such as arthritis,16-19 cancer,20,21 dementia and depression,22-26 and atherosclerosis.27-29

Health-conscious Americans are already taking nutrients (such as fish oil ,30-41 green tea,42-48 borage oil,49-51 curcumin,52-56 and flavonoids),57-61 which help suppress pro-inflammatory cytokines.

The new findings about cytokine-induced degradation of tryptophan explain how aging humans become depressed and why nutrients like fish oil alleviate depression.62-65

To give you an idea of how devastating inflammatory cytokines are to tryptophan levels, just look at what happens to people who are given a cytokine drug called interferon-alpha. When interferon-alpha is given to hepatitis C victims, one of the most dangerous side effects is the onset of depression so severe that users of this drug can become suicidal.63 It turns out that interferon drugs cause tryptophan-degrading enzymes to surge, thus depleting tryptophan in the blood and making less tryptophan available for conversion to serotonin in the brain.63,64,66 It would appear that supplemental tryptophan could enable those with hepatitis C to benefit from interferon drugs without encountering severe depression.

In a fascinating new study, scientists measured levels of tryptophan degradation metabolites in the brain. It turns out that people over age 50 had 30% more of these tryptophan degradation metabolites in their brains compared with people under age 50. The doctors who conducted this study stated that their research indicates a 95% probability that older people will have increased levels of these metabolites, reflecting excessive degradation of tryptophan in their brains.12

This finding further explains why depression is one of the most common mental health problems in adults age 60 and beyond and suggests that supplemental tryptophan, along with cytokine-suppressing agents, could help restore serotonin to more youthful levels and subsequently alleviate depression.

Basically the state of their body is "set-up" for increased de-amination (removal of NH4 group) of Tryptophan.

The idea behind fish oil with regards to this topic is that it helps the body retain less Bicarbonate (and therefore less C02) in the resting state. This improves aerobic metabolism of tissues in general. Remember that it is anaerobic metabolism that increases demands for gluconeogenesis (and therefore deamination of amino acids ).

Also consider why would the body decarboxylate (remove CO2) from an amino acid in the state I mentioned above? (it has too much CO2 already ). It is a negative feedback loop that makes a lot of sense when you think about it.

In general I think of "silent inflammation" as a poor energy state the body is stuck in that it is trying to compensate for. Excessive "de-amination" is one such way it does this (to make glucose).

[CognitiveNutrition]

Division of Natural Products, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, College Park, Maryland 20740-3835, USA. mitchell.smith@cfsan.fda.gov

In contrast to early epidemiological evidence offering links between eosinophilia-myalgia syndrome (EMS) and microimpurities of L-tryptophan-containing dietary supplements (LTCDS), this account shows why reliance on a finite impurity from one manufacturer is both unnecessary and insufficient to explain the etiology of EMS. Excessive histamine activity has induced blood eosinophilia and myalgia (Greek: mys, muscle + algos, pain). Termination of the multiple actions of histamine is dependent on particular amine oxidases and histamine-N-methyltransferase. Histamine metabolism is rapid when these degradative reactions are operative. The latent effects of incurred histamine can be potentiated and aggravating when these mechanisms are impaired. Overloads of tryptophan supplements cause - among other relevant side-effects - an increased formation of formate and indolyl metabolites, several of which inhibit the degradation of histamine. Moreover, (non-EMS) subjects with hypothalamic-pituitary- adrenal (HPA) axis dysregulation have also manifested greatly increased sensitivities to incurred tryptophan and histamine. A final common pathway for syndromes characterized by eosinophilia with myalgia is now evident.

And yet not 1 clinical study. Yes we all know overdoses of any supplement can cause a problem.

[CognitiveNutrition]

I think here is the major problem in this thread.

Steve is saying that taking the recommended amount of these is fine for you.

Aaron is arguing that overdosing has adverse side effects.

So, to conclude:

Steve, overdosing on these could be bad and have adverse effects correct?

Aaron, do you have any research showing recommended amounts of these has adverse effects on health?

After these two questions are answered, assuming Steve believes overdosing is bad (I believe he's stated it in this topic even) and assuming that Aaron has no evidence of the harms of taking the recommended dose, you guys can quit arguing, because you're not even arguing about the same things.

Overdosing on any supplement will produce unknown side effects not seen in clinical studies. So of course anything is possible. However note that we consume Tryptophan everyday in our diet.

[damned.]

The company Showa Denko, who made the Tryptophan that the outbreak of EMS was related to was also the cause of this:

http://en.wikipedia.org/wiki/Showa_D...namata_disease

Sounds like a great company!

[CognitiveNutrition]

The FDA?s Cruel Hoax
By William Faloon

Do you remember how popular tryptophan was in the 1980s? Back in those days, people seeking to lose weight, improve sleep, or alleviate depression used tryptophan to safely increase serotonin levels in their brain.

Serotonin is the natural compound that promotes feelings of well-being, satiety, and relaxation. A serotonin deficiency can result in sleep disturbance, anxiety, depression, and a propensity to overeat.

In 1989, the FDA restricted the importation of tryptophan. This forced American consumers to switch to expensive prescription drugs that produced only partial effects at best.

Tryptophan is an amino acid found naturally in the foods that we eat. The reason its sale was stopped was because of defective tryptophan made by a sub-standard company.

We believe that the FDA?s prejudicial position against tryptophan caused Americans to suffer widespread deficiencies of serotonin in their brains. A result of serotonin deficiency may be reflected in today?s epidemic of obesity, depression, anxiety, and insomnia.

Tryptophan Is Back!

Despite intense lobbying efforts by pharmaceutical companies, the FDA could not rationally continue to block the sale of tryptophan. After all, tryptophan is not only found in food, but the very tryptophan that the FDA restricted is still used in infant formulas and intravenous feeding solutions. If there were any danger to tryptophan, we would have known about it long ago.

Pharmaceutical-pure tryptophan can now be imported for use in dietary supplements. This means that aging Americans may be able to discard certain prescription drugs and once again treat their serotonin deficiency disorder with what Mother Nature intended all along? the amino acid tryptophan itself!

Why Aging People Need Tryptophan

Startling research findings reveal that brain serotonin levels decline sharply in most humans as they age!1-5 This helps explain why so many people suffer common age-related disorders such as depressed mood and sleep difficulties. Based on these discoveries, aging humans may improve their overall feeling of well being by restoring brain serotonin.

It was long ago established that tryptophan is the amino acid needed to produce serotonin in the brain. Regrettably, the amount of tryptophan in a typical diet is barely enough to meet basic metabolic requirements, let alone provide optimal brain serotonin levels.

Since tryptophan supplements were removed from the market, there have been increasing numbers of overweight and obese Americans. It would appear that serotonin deficiency may play an important role in the record number of Americans suffering from depression, insomnia, and excess weight gain.

Depressed People Are Often Tryptophan-Deficient

In people with major depression, blood levels of tryptophan are often significantly below normal.6-9 A number of studies indicate that normal mood depends in large part on adequate brain serotonin stores.7,10,11

Human studies have shown that reducing serotonin levels (by depriving the brain of tryptophan) can induce depression within hours and that supplementation with tryptophan can alleviate depressive symptoms.7,9,11

Why the Aging Process Causes Tryptophan Deficit

Depression is one of the most common health disorders affecting elderly people. Doctors still consider it to be a normal consequence of aging.

Recent studies, however, have identified specific age-related mechanisms that cause the degradation of tryptophan in elderly individuals.12-15 The encouraging news is that there are ways for people to counteract the loss of their precious mood-elevating tryptophan.

It turns out that pro-inflammatory cytokines cause tryptophan to degrade in the blood. This occurs because these pro-inflammatory cytokines activate specific enzymes that deplete tryptophan in the bloodstream. The result of diminished blood levels of tryptophan is serotonin deficiency in the brain (and the onset of depression).

Pro-inflammatory cytokines are specialized biochemicals secreted by immune cells that are only supposed to be activated in response to acute infection or trauma. As people age, they often chronically overproduce pro-inflammatory cytokines, which subsequently cause inflammatory-related diseases such as arthritis,16-19 cancer,20,21 dementia and depression,22-26 and atherosclerosis.27-29

Health-conscious Americans are already taking nutrients (such as fish oil,30-41 green tea,42-48 borage oil,49-51 curcumin,52-56 and flavonoids),57-61 which help suppress pro-inflammatory cytokines.

The new findings about cytokine-induced degradation of tryptophan explain how aging humans become depressed and why nutrients like fish oil alleviate depression.62-65

To give you an idea of how devastating inflammatory cytokines are to tryptophan levels, just look at what happens to people who are given a cytokine drug called interferon-alpha. When interferon-alpha is given to hepatitis C victims, one of the most dangerous side effects is the onset of depression so severe that users of this drug can become suicidal.63 It turns out that interferon drugs cause tryptophan-degrading enzymes to surge, thus depleting tryptophan in the blood and making less tryptophan available for conversion to serotonin in the brain.63,64,66 It would appear that supplemental tryptophan could enable those with hepatitis C to benefit from interferon drugs without encountering severe depression.

In a fascinating new study, scientists measured levels of tryptophan degradation metabolites in the brain. It turns out that people over age 50 had 30% more of these tryptophan degradation metabolites in their brains compared with people under age 50. The doctors who conducted this study stated that their research indicates a 95% probability that older people will have increased levels of these metabolites, reflecting excessive degradation of tryptophan in their brains.12

This finding further explains why depression is one of the most common mental health problems in adults age 60 and beyond and suggests that supplemental tryptophan, along with cytokine-suppressing agents, could help restore serotonin to more youthful levels and subsequently alleviate depression.

Tryptophan and Sleep

Poor sleep affects a significant percentage of older individuals. Trouble falling asleep, waking not rested, waking too early, and difficulty maintaining sleep are the chief sleep complaints in this age group. In response to complaints of poor sleep, more Americans are prescribed sleeping pills than ever before.

Before tryptophan was taken off the market, it was an enormously popular supplement used to alleviate chronic insomnia. Between 1962 and 1982, 40 controlled studies described the effects of tryptophan on human sleepiness and/or sleep.67 During the 1980s, placebo-controlled human studies documented the sleep-inducing effects of tryptophan.68-71

With the new knowledge that tryptophan-depleting enzymes increase as people age, there is now a biochemical basis to help explain why so many older individuals suffer sleep deprivation miseries. Serotonin enables one to calm down and relax. Without adequate serotonin to naturally tranquilize the brain, it becomes excruciatingly difficult for older people to get to sleep.

After low-cost tryptophan supplements were restricted, the door swung wide open for pharmaceutical companies to earn billions of dollars selling prescription benzodiazepine drugs such as *****? and Halcion?, as well as other sleep-inducing medications such as ******?.

Tryptophan Deficiency and Obesity

When the brain is flooded with serotonin, satiety normally occurs. A serotonin deficiency has been associated with the carbohydrate binging that contributes to the accumulation of excess body fat.72 Obese individuals have low blood tryptophan levels,73 which indicate that their overeating patterns may be related to a serotonin deficiency in the brain.

In a study of obese subjects, levels of tryptophan and the ratio of tryptophan to the other large neutral amino acids in the blood were measured over a 24-hour period. Compared with normal subjects, low tryptophan and a low ratio of tryptophan to other amino acids were seen in the obese study subjects throughout the 24-hour period.74 The significance of this low ratio of tryptophan is that the other amino acids compete with tryptophan for transport through the blood-brain barrier. If there are high levels of other amino acids in relation to tryptophan in the blood, relatively little tryptophan will enter the brain, causing a chronic serotonin deficiency. This explains the constant hunger that causes so many people to become and remain obese.

Why Diets So Often Fail to Induce Sustained Weight Loss

For those who try to lose weight by consuming fewer calories, the failure rate is well established. In a study that evaluated both depressed and non-depressed women, the effect of dieting was evaluated in relation to blood tryptophan levels. The results showed that in response to consuming a very low calorie diet (1,000 calories/day), blood tryptophan levels plummeted.75

This finding indicates that the intense hunger that occurs in response to reduced calorie intake is at least partially caused by the tryptophan deficiency that ensues. The implication is that it may be impossible for certain people to chronically reduce their calorie intake because a deficit of tryptophan/serotonin would cause unbearable chronic hunger.

Low Serotonin Induces Carbohydrate Craving

It is well known that carbohydrate binging plays a role in unwanted weight gain, yet Americans consume more carbohydrates than ever. Despite numerous books extolling the fat-loss benefits of ?low-carb? diets, few people are able to avoid excess carbohydrate ingestion over the long term.

One reason that people eat too many high-glycemic carbohydrates is the brain?s need to achieve ?feel good? levels of serotonin. While serotonin is made from the amino acid tryptophan, eating protein-rich foods does little good since other amino acids in the food compete for transport into the brain. When carbohydrates are ingested, the resulting insulin surge causes a depletion of these competing amino acids in the blood by increasing their uptake into muscle, thus sparing tryptophan to more readily transport into the brain for conversion to serotonin.

The need for tryptophan can most easily be understood by the carbohydrate binging that occurs when people become serotonin-deficient.

Why Dietary Tryptophan Is Inadequate

In any normal diet, be it omnivorous or vegetarian, protein-based tryptophan is the least plentiful of all amino acids.

A typical diet provides only 1,000 to 1,500 mg/day of tryptophan, yet there is much competition in the body for this scarce amino acid. Tryptophan is used to make various proteins that form structures of the body. In people with low-to-moderate intakes of vitamin B3 (niacin), tryptophan may be used to make B3 in the liver at the astounding ratio of 60 mg tryptophan to make just 1 mg of vitamin B3.76 This means that in vitamin B3-deficient people, virtually all dietary tryptophan may be used to synthesize B3, leaving none available for conversion to tranquilizing serotonin in the brain.

In people who are even marginally deficient in vitamin B6, tryptophan may be rapidly degraded into mildly toxic metabolites.77 Thus, the brain typically receives less than 1% of ingested tryptophan from dietary sources.

Dietary tryptophan contributes very little actual tryptophan to the brain, yet tryptophan is the only normal dietary raw material for serotonin synthesis in the brain. Is it any wonder that so many people today suffer from disorders (depression, insomnia, excess weight gain) associated with a serotonin deficiency.

[CognitiveNutrition]

A Financial Windfall for the Drug Companies

At the time that the FDA restricted tryptophan, it was one the most popular dietary supplements sold in the United States. Perhaps it is a coincidence, but since 1989, the percentages of overweight and obese adult Americans have soared. Could it be that a nationwide serotonin deficiency has led to the high-carbohydrate overeating syndrome that so many Americans suffer from today?

The removal of tryptophan created an economic windfall for the drug companies. Sales of drugs that interfere with the brain?s reuptake of serotonin (like Prozac?, and later Paxil? and Zoloft?) shot through the roof, earning tens of billions of dollars of profits for drug companies. While these drugs caused large numbers of unpleasant and possibly lethal side effects, the FDA withdrew none of them.

The ensuing epidemic of weight gain and sleeplessness resulted in dozens of anti-obesity and anti-insomnia drugs being approved by the FDA, some of which had horrendous side effects, and others that had virtually no efficacy.

Critics contend that the contaminated tryptophan coming from one sub-standard Japanese company provided a convenient excuse for the FDA to restrict the sale of all tryptophan dietary supplements. The FDA?s actions guaranteed that Americans would become tryptophan-deficient, and therefore turn to prescription drugs for relief from a host of disorders related to insufficient serotonin in the brain.

Pharmaceutical-Pure Tryptophan Now Available

Consumers now have access to pharmaceutical-pure tryptophan as an over-the-counter dietary supplement. According to the FDA, it is now the responsibility of the company who sells the tryptophan to ensure that it is not contaminated.

For 19 years, aging Americans have been forced to settle for less-than-optimal levels of tryptophan/serotonin in their bodies. Based on what has been published in the peer-reviewed scientific literature, it would appear that consumers have suffered enormously from a host of disorders related to lack of serotonin in the brain.

Pharmaceutical companies, on the other hand, have accumulated exorbitant wealth, as depressed, overweight, and sleep-deprived consumers were forced to experiment with costly and side effect-laden drugs in order to combat the effects of serotonin deficiency.

If tryptophan dietary supplements provide relief to those suffering from common age-related disorders such as anxiety, depressed mood, sleeplessness, and unwanted weight gain, the FDA?s nearly two-decade restriction on this natural agent may turn out to be one of the cruelest hoaxes of all time.

In this month?s issue, we provide an in-depth discussion on tryptophan, including suggested dosing, precautions to look out for, and optimal ways to safely benefit from it.

For longer life,

William Faloon

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[CognitiveNutrition]

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44. Haqqi TM, Anthony DD, Gupta S, et al. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci USA. 1999 Apr 13;96(8):4524-9.

45. Adcocks C, Collin P, Buttle DJ. Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro. J Nutr. 2002 Mar;132(3):341-6.

46. Yang F, de Villiers WJ, McClain CJ, Varilek GW. Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model. J Nutr. 1998 Dec;128(12):2334-40.

47. Chan MM, Fong D, Ho CT, Huang HI. Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem Pharmacol. 1997 Dec 15;54(12):1281-6.

48. Tipoe GL, Leung TM, Hung MW, Fung ML. Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection. Cardiovasc Hematol Disord Drug Targets. 2007 Jun;7(2):135-44.

49. Rothman D, DeLuca P, Zurier RB. Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum. 1995 Oct;25(2):87-96.

50. Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis Rheum. 1995 Aug;38(8):1107-14.

51. Kast RE. Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. Int Immunopharmacol. 2001 Nov;1(12):2197-9.

52. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8.

53. Antony S, Kuttan R, Kuttan G. Immunomodulatory activity of curcumin. Immunol Invest. 1999 Sep;28(5-6):291-303.

54. Zhang F, Altorki NK, Mestre JR, Subbaramaiah K, Dannenberg AJ. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis. 1999 Mar;20(3):445-51.

55. Jobin C, Bradham CA, Russo MP, et al. Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol. 1999 Sep 15;163(6):3474-83.

56. Pendurthi UR, Williams JT, Rao LV. Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3406-13.

57. O?Leary KA, de Pascual-Tereasa S, Needs PW, et al. Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mutat Res. 2004 Jul 13;551(1-2):245-54.

58. Manthey JA, Grohmann K, Guthrie N. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem. 2001 Feb;8(2):135-53.

59. Murakami A, Nakamura Y, Ohto Y, et al. Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti-inflammatory polymethoxyflavonoid. Biofactors. 2000;12(1-4):187-92.

60. Manthey JA, Grohmann K, Montanari A, Ash K, Manthey CL. Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-alpha expression by human monocytes. J Nat Prod. 1999 Mar;62(3):441-4.

61. Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397-440.

62. Oxenkrug GF. Genetic and Hormonal Regulation of Tryptophan Kynurenine Metabolism: Implications for Vascular Cognitive Impairment, Major Depressive Disorder, and Aging. Ann NY Acad Sci. 2007 Dec;1122:35-49.

63. Wichers M, Maes M. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol. 2002 Dec;5(4):375-88.

64. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production, tryptophan degradation, and mental depression?what is the link? Brain Behav Immun. 2002 Oct;16(5):590-5.

65. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61.

66. Wirleitner B, Neurauter G, Schrocksnadel K, Frick B, Fuchs D. Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects. Curr Med Chem. 2003 Aug;10(16):1581-91.

67. Hartmann E. Effects of L-tryptophan on sleepiness and on sleep. J Psychiatr Res. 1982;17(2):107-13.

68. Schneider-Helmert D, Spinweber CL. Evaluation of L-tryptophan for treatment of insomnia: a review. Psychopharmacology (Berl). 1986;89(1):1-7.

69. Korner E, Bertha G, Flooh E, et al. Sleep-inducing effect of L-tryptophane. Eur Neurol. 1986;25(Suppl 2):75-81.

70. Schmidt HS. L-tryptophan in the treatment of impaired respiration in sleep. Bull Eur Physiopathol Respir. 1983 Nov;19(6):625-9.

71. Demisch K, Bauer J, Georgi K, Demisch L. Treatment of severe chronic insomnia with L-tryptophan: results of a double-blind cross-over study. Pharmacopsychiatry. 1987 Nov;20(6):242-4.

72. Gendall KA, Joyce PR. Meal-induced changes in tryptophan:LNAA ratio: effects on craving and binge eating. Eat Behav. 2000 Sep;1(1):53-62.

73. Brandacher G, Hoeller E, Fuchs D, Weiss HG. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr Drug Metab. 2007 Apr;8(3):289-95.

74. Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003 May;77(5):1112-8.

75. Smith KA, Williams C, Cowen PJ. Impaired regulation of brain serotonin function during dieting in women recovered from depression. Br J Psychiatry. 2000 Jan;176:72-5.

76. Fukuwatari T, Ohta M, Kimtjra N, Sasaki R, Shibata K. Conversion ratio of tryptophan to niacin in Japanese women fed a purified diet conforming to the Japanese Dietary Reference Intakes. J Nutr Sci Vitaminol (Tokyo). 2004 Dec;50(6):385-91.

77. Guilarte TR, Wagner HN Jr. Increased concentrations of 3-hydroxykynurenine in vitamin B6 deficient neonatal rat brain. J Neurochem. 1987 Dec;49(6):1918-26.

LE Magazine April 2008

[CognitiveNutrition]

Why Aging People Become Depressed, Fatigued, and Overweight
By William Faloon

Serotonin is a compound in the brain that promotes feelings of personal security, relaxation, and confidence. A serotonin deficiency can result in sleep disturbance, anxiety, depression, and a propensity to overeat, particularly carbohydrates like simple sugars.

Startling research reveals that serotonin levels decline as we age!1-3 These findings provide a biochemical rationale to explain common age-related disorders such as depressed mood and sleep difficulties. Based on these discoveries, aging people may appreciably improve their health by restoring serotonin to youthful levels.

The amino acid tryptophan is needed to produce serotonin in the brain.4 While the amount of tryptophan in a typical diet meets basic metabolic requirements, it often fails to provide optimal brain serotonin levels.

Ever since the FDA restricted the importation of tryptophan for use in dietary supplements, there has been an upsurge in the percentage of overweight and obese Americans.

One could argue that a widespread serotonin deficiency is at least partially responsible for the record numbers of depressed, sleep-deprived, and overweight individuals.

Why Dietary Tryptophan Is Inadequate
Tryptophan is one of the eight essential amino acids found in the human diet. Essential amino acids are defined as those that cannot be made in the body and therefore must be obtained from food or supplements. (A ninth amino acid, histidine, is sometimes considered essential for children.)

Our bodies do need additional amino acids, but these other amino acids are made from the eight essential amino acids when we are in optimal health.

In any normal diet, be it omnivorous or vegetarian, tryptophan is the least plentiful of all amino acids. A typical diet provides only 1,000 to 1,500 mg/day of tryptophan, yet there is much competition in the body for this scarce tryptophan.

Tryptophan is used to make various protein structures of the body. In people with low-to-moderate intakes of vitamin B3(niacin), tryptophan may be used to make B3 in the liver at the astounding ratio of 60 mg tryptophan to make just 1 mg of vitamin B3.5

Yet even maintaining a minute amount of tryptophan provides little benefit in boosting serotonin in the brain due to competition with other amino acids for transport through the blood-brain barrier. Nutrients must be taken up through the blood-brain barrier by transport molecules. Tryptophan competes for these transport molecules with other amino acids.

The Human Body Requires the Following Eight Essential Amino Acids:
Tryptophan Threonine
Lysine Valine
Methionine Isoleucine
Phenylalanine Leucine

Essential amino acids cannot be made in the body and therefore must be obtained from food or supplements. (Children may require the amino acid histidine in addition to those listed above.)

As one can see, diet-derived tryptophan contributes very little actual tryptophan to the brain. As you will soon read, even eating tryptophan-containing foods like turkey may not always provide the body with enough of this essential amino acid. One reason is that aging people make enzymes that rapidly degrade tryptophan in the body.

Remember, tryptophan is the only normal dietary raw material for serotonin synthesis in the brain. Given all we now know about the difficulty in maintaining adequate tryptophan status, is it any wonder that so many aging humans suffer from disorders such as depression, insomnia, and excess weight gain associated with a serotonin deficiency?

How Tryptophan Functions in the Body

L-tryptophan converts into serotonin, primarily in the brain. Since serotonin is a neurotransmitter involved in controlling moods and appetite, tryptophan supplementation has been recommended for individuals suffering from a variety of conditions associated with decreased serotonin levels, including sleep disorders, depression and fibromyalgia, and eating disorders.6-8

It has been shown in human clinical studies that low levels of tryptophan contribute to insomnia.9 Increasing tryptophan may help to normalize sleep patterns.10-12 It is known that raising tryptophan levels in the body may decrease cravings and binge eating?especially for carbohydrates?and help people lose weight.13,14

L-tryptophan serves as a precursor not only to serotonin, but also melatonin and niacin. Serotonin is a major neurotransmitter involved in many ****tic and behavioral functions including mood, appetite and eating behavior, sleep, anxiety, and endocrine regulation.6,15-17

There are two possible sources for L-tryptophan: diet and tissue proteins, from which L-tryptophan has been recycled during protein turnover. Aging, chronic inflammatory diseases, and HIV infection are associated with tryptophan depletion, even in the absence of dietary tryptophan deficiency.

An adult male needs 250 mg a day of tryptophan just to maintain nitrogen balance.18 While a normal diet contains 1,000 to 1,500 mg of tryptophan per day,19 the enzymatic breakdown of tryptophan increases with age,20 and certain disease states can severely deplete tryptophan.

[CognitiveNutrition]

How Tryptophan is Metabolized in the Body

There are three potential fates for L-tryptophan once ingested:

Incorporation into body tissue proteins.

Conversion into serotonin (and melatonin).

Conversion into indoleamines, carbon dioxide, water, adenosine triphosphate (ATP), and niacin.21

For every nutrient absorbed into the body, there are specific enzymes that convert the nutrient into other substances. There are two specific enzymes that can deprive the body of sufficient amounts of tryptophan. These enzymes are called L-tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO).

The liver enzyme TDO is induced when plasma concentrations of L-tryptophan exceed those needed for conversion into serotonin and/or protein. This enzyme oxidizes surplus L-tryptophan into carbon dioxide, water, and ATP.22,23

The other tryptophan-degrading enzyme IDO is more insidious because it can degrade L-tryptophan even when circulating levels of L-tryptophan are low.23,24

This enzyme has been found outside the liver on macro****es and dendritic cells and is increased in pro-inflammatory states, HIV infection, and normal aging.25-30

Once the TDO or IDO enzymes act on tryptophan, it is no longer available for conversion to serotonin or incorporation into protein. Consuming large amounts of oral L-tryptophan will not generate more serotonin because more TDO will be induced to deplete the tryptophan.

Tryptophan and its metabolite 5-hydroxytryptophan (5-HTP) are taken up into the brain across the blood-brain barrier by a transport system that is active towards all the large neutral amino acids.31 The affinity of the various amino acids for the carrier is such that there is competition between the large neutral amino acids for entry into brain. In fact, the best predictor of a given meal?s effect on brain tryptophan-serotonin levels is the serum ratio of tryptophan to the pool of large neutral amino acids.32

What You Need to Know: Tryptophan
Serotonin is a brain biochemical that promotes restful sleep, well-being, and satiety. When serotonin levels are low, people often experience depression, anxiety, insomnia, and the urge to overeat.

The amino acid tryptophan is needed to produce serotonin in the body. While foods contain some tryptophan, the diet may not provide enough tryptophan to make adequate amounts of serotonin. Additionally, enzymes that are influenced by inflammation and aging can break down tryptophan before it converts to serotonin.

Individuals suffering from the adverse effects of low serotonin levels can now restore sleep, appetite control, and mood by supplementing with an advanced L-tryptophan formulation. This formula combines L-tryptophan with nutrients and herbs that help optimize its ability to convert to beneficial serotonin in order to counteract appetite and sleep disorders, and low mood.

More clinically relevant, however, is that serotonin levels are enhanced by carbohydrate ingestion.33 The reason is that the high amount of insulin released in response to carbohydrate ingestion accelerates the serum removal of valine, leucine, and isoleucine that compete against tryptophan for transport into the brain. Similarly, a higher percentage of protein in the diet slows serotonin elevation (by providing competing amino acids for the blood-brain barrier).34,35

Giving tryptophan with an inhibitor of the TDO enzyme would enable lower doses of tryptophan to be used. In the rat, high doses of pyridoxine (vitamin B6) can inhibit tryptophan catabolism in the liver and increase uptake of tryptophan into the brain.36 While the effect of high doses of pyridoxine on plasma tryptophan has not been studied in humans, pyridoxine should be given with tryptophan for another reason. When tryptophan was given to normal subjects for a week, levels of tryptophan metabolites in the plasma increased indicating that tryptophan was being broken down. This effect could be attenuated by pyridoxine (pyridoxine assists the breakdown of the tryptophan metabolite kynurenine, which can compete with tryptophan for uptake into the brain), suggesting that chronic tryptophan treatment increases pyridoxine requirements.37

Clinical Implications: Sleep Disorders
Tryptophan has been researched for sleep disorders for 30 years. Improvement of sleep normalcy has been noted38 at doses as low as 1,000 mg.19 Increased stage 4 sleep has been noted at even lower doses?as low as 250 mg tryptophan.19 Significant improvement in obstructive sleep apnea, but not central sleep apnea, has been noted at doses of 2,500 mg at bedtime, with those experiencing the most severe apnea demonstrating the best response.39 While many sedative medications have opioid-like effects, L-tryptophan administration does not limit cognitive performance or inhibit arousal from sleep.40

L-tryptophan depletion negatively impacts sleep. A significant decrease in serum tryptophan levels after a tryptophan-free amino acid drink was associated with an adverse effect upon sleep parameters (stage 1 and stage 2 time, and rapid eye movement sleep time).9 L-tryptophan is not associated with tolerance or difficulty with morning wakening and has been shown to be efficacious for sleep in several clinical trials of various designs and L-tryptophan dosages.

Depression
As previously mentioned, L-tryptophan is essential for the brain to synthesize serotonin, a neurotransmitter that has been shown to affect mood. Several studies have shown that acute tryptophan depletion can cause a depressive state in humans, especially patients who are in remission from depression.41,42 In a study of the effects of acute tryptophan depletion on healthy women and patients with bulimia nervosa, both groups were given amino acid mixtures to consume to decrease their plasma tryptophan levels. In both groups an increase in depression occurred.43


Plasma L-tryptophan levels can be raised through dietary intake of L-tryptophan, which raises serotonin levels in the brain, and thereby lessens the depressive state.44 In a study involving recovering alcoholic patients, it was found that the participants had severely depleted L-tryptophan levels accompanied by a high level of depressive state. When the patients were given supplemental doses of L-tryptophan over a short period of time, their depressive state lessened significantly.45 The tryptophan metabolite, 5-hydroxytryptophan (5-HTP), has shown significant clinical response for depression in 2-4 weeks, at doses of 50-300 mg three times daily.46-48

Premenstrual Syndrome
A daily dose of 6,000 mg of L-tryptophan significantly decreased mood swings, tension, and irritability in women with premenstrual syndrome.49 The meta-bolism of tryptophan is impacted by the different phases of a woman?s cycle,50 and therefore hormonal changes during the menstrual cycle may negatively affect the availability of tryptophan for conversion into serotonin.

Carbohydrate Cravings and Weight Loss
Some obese people consume carbohydrate-rich foods frequently and preferentially, because they have a persistently low plasma tryptophan ratio, as well as low tryptophan uptake into the brain.51 Remember that serotonin levels are enhanced by carbohydrate ingestion as insulin release accelerates the serum removal of other amino acids that compete for transport through the blood-brain barrier.

Increasing the L-tryptophan levels in blood plasma is also known to have an appetite-suppressing effect that mainly impacts carbohydrate consumption.52,53 Presumably the supplemental tryptophan would enhance the release of serotonin from brain neurons to diminish appetite for carbohydrates, which helps with loss of body weight. In addition, obese subjects are often insulin-resistant, and diminished insulin action may cause low plasma tryptophan ratios33 because of the peripheral effects of insulin on the uptake and utilization of other amino acids.

A study was done to measure L-tryptophan in the blood plasma of obese patients to assess the plasma tryptophan ratio to large neutral amino acids (tyrosine + phenylalanine + leucine + isoleucine + valine). The results showed the plasma tryptophan ratio was well below the normal ratio for humans.51 If elevation of the tryptophan in relation to large neutral amino acids occurs, more tryptophan is allowed into the brain to induce serotonin synthesis and influence functions of serotonin (mood, appetite, sleep, and hunger). This study helps show why obese people often have uncontrollable appetites, i.e., they have too little tryptophan in relation to other large neutral amino acids in their blood.

When these obese patients were given 1,000 mg, 2,000 mg, or 3,000 mg doses of L-tryptophan one hour before meals to raise the amount of tryptophan relative to the large neutral amino acids, a significant decrease in caloric consumption was observed. The majority of the reduction in caloric intake was due to the amount of carbohydrates, not protein, consumed. The only side effects observed were a mild decrease in mental alertness, mild dizziness, and mild drowsiness.54

In a double-blind, placebo-controlled study, obese patients on protein-rich diets who received tryptophan (750 mg twice daily orally) had significant weight loss, compared with a placebo group. A moderate dose of tryptophan supplementation did not cause any side effects such as mid-day sleepiness or fatigue.55 The effects of reducing tryptophan levels were also studied in a 7-year-old girl with severe anorexia. When tryptophan levels were reduced, spontaneous eating occurred for the first time in 4.5 years. The spontaneous eating ceased when the tryptophan intake was increased.56

How Aging Reduces Tryptophan-Serotonin Levels
As a result of normal aging, inflammatory cytokine levels increase. A little-known adverse effect is that inflammatory cytokines (such as tumor necrosis factor alpha and interferon alpha) cause induction of the tryptophan-degrading enzyme IDO (indoleamine 2,3-dioxygenase).

You might think that aging people could compensate for the tryptophan-degrading effects of IDO by consuming higher doses of tryptophan supplements. The problem is that in the presence of high blood levels of tryptophan, the other tryptophan-degrading enzyme TDO is also elevated.

So consuming large amounts of L-tryptophan (oral doses of 4,000 mg and greater) will not generate more serotonin because TDO will be induced. Yet if aging people fail to get more tryptophan into their bodies, brain serotonin levels will plummet because the higher IDO enzyme activity will degrade what little tryptophan remains in the blood.

[CognitiveNutrition]

Engineering Around This Problem
Fortunately, the new understanding of how tryptophan is degraded in aging humans provides a basis for engineering a natural solution around this epidemic problem.

First of all, we know from studies in patients with high levels of systemic inflammation that if sufficient niacinamide is given, the degradation of tryptophan in the body is significantly reduced.57,58 We also know that the amino acid lysine competes with tryptophan in the same oxidative degradation pathway. This means that in the presence of lysine, less tryptophan is oxidized.59

Tryptophan, however, can still be degraded by the IDO enzyme that increases as humans age. Nutrients such as curcumin inhibit interferon-induced nuclear factor-kappa-B and COX-2 expression and may limit the induction of IDO, thus making more tryptophan available for conversion to serotonin in the brain.60

It is thus possible for aging people to supplement with a modest dose of tryptophan (1,000-1,500 mg per day) and significantly decrease tryptophan oxidation/degradation, as long as lysine, niacinamide, and the proper cytokine-suppressing nutrients are taken with it to neutralize the effects of the IDO enzyme.

Cofactors that facilitate the conversion of tryptophan to serotonin in the brain are vitamin B6, magnesium, and vitamin C.60-62 These nutrients are already taken by most health-conscious people.

Dosage
An important factor in the decision to supplement with L-tryptophan is its excellent tolerability and the lack of development of tolerance during long-term use. Furthermore, L-tryptophan does not cause difficulties when trying to wake up the next morning.63

The minimal dose of L-tryptophan for effective treatment of insomnia may be at least 1,000 mg, and repeat administration of L-tryptophan may be required for improvement in chronic, well-established, sleep-onset insomnia or insomnia characterized by both sleep-onset and sleep-maintenance abnormalities.63 Low doses of L-tryptophan (250 to 500 mg) may not offer a significant benefit on sleep latency.64 For those with insomnia who wish to try L-tryptophan, a strong initial dose (1,000 to 4,000 mg) is recommended for the first week, followed by a lower maintenance dose (500 mg to 1,000 mg).

Evening oral doses of tryptophan as low as 250 mg have been shown to improve sleep quality, although the typical dosage range for sleep disorders and depression is 1,000-3,000 mg daily. Safe and effective dosages for other disorders range from 500 mg to 4,000 mg/day, while doses around 3,500 mg/day have been used short term as a smoking cessation intervention.65

Tryptophan is oxidized in the liver by tryptophan-2,3-dioxygenase (TDO), an enzyme that is induced both by glucocorticoids and by large doses of tryptophan itself. The enzyme activity of TDO increases after tryptophan administration66 and results in a relatively short half-life of tryptophan remaining in the plasma.67 Thus, tryptophan is often given in divided daily doses instead of a single dose. A single dose of 3,000 mg is sufficient to keep human brain serotonin synthesis maximized for about eight to twelve hours.68 Giving three daily doses of 2,000 mg will probably keep the rate-limiting tryptophan hydroxylase enzyme in the brain fully saturated for most of each 24-hour period, meaning that brain serotonin levels would be maintained at a constant optimal level.

Tryptophan Blackout Is Lifted!
American consumers can once again obtain tryptophan as a dietary supplement. Particularly compelling news is the discovery that aging people produce tryptophan-degrading enzymes, which can be neutralized by the simultaneous ingestion of nutrients that block pro-inflammatory cytokines and mitigate tryptophan depletion via other oxidative pathways.

A novel formula is now available that combines pharmaceutical-pure tryptophan with a blend of nutrients designed to nourish the brain with optimal levels of serotonin.

Based on hundreds of scientific studies, depletion of serotonin may contribute to age-related weight gain, depression, insomnia, anxiety, and loss of feeling of well-being.

By restoring serotonin to optimal levels, aging people can regain the neurotransmitter balance enjoyed in their youth. Those suffering from age-related weight gain or sleep difficulties could experience significant improvement by using tryptophan to increase their brain serotonin to youthful levels.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.

To learn who should not take high-dose tryptophan supplements, refer to the Tryptophan Precautions section on the following page.

Tryptophan Precautions
For many decades, tens of millions of people have safely used tryptophan supplements. The mechanisms by which tryptophan functions in the body, however, indicate that those taking certain prescription drugs should exercise caution when using tryptophan on a regular basis.

Although tryptophan has been shown to be safe when used alone, it can potentiate side effects of certain antidepressant drugs. Case reports of serotonin syndrome have noted a connection between tryptophan used concomitantly with monoamine oxidase (MAO) inhibitor drugs.69 A few popularly prescribed MAO-inhibiting drugs include Nardil? (phenelzine), Parnate? (tranylcyrpromine), and Marplan? (isocarboxazide). In studies measuring the antidepressant effects of an MAO-inhibitor drug alone compared with that of the MAO inhibitor plus tryptophan, the most common side effects of the combination were dizziness, nausea, and headache.70 The magnitude of these side effects was sufficient to limit the usefulness of the combination. However, the most serious complication in the use of the combination of tryptophan and MAO inhibitors is the serotonin syndrome. This syndrome is characterized by agitation, restlessness, shivering and tremor, confusion, delirium, tachycardia, diaphoresis, hypomania, myoclonus, hyperreflexia, and blood pressure fluctuations. Although no reports have been published, it is possible that tryptophan, when taken in combination with a selective serotonin-reuptake inhibitor (SSRI) drug such as Prozac?, Paxil?, Zoloft?, or Lexapro?, may also precipitate serotonin syndrome.71

The serotonin syndrome was first described in rats. When these animals were given tryptophan plus a monoamine oxidase inhibitor, or various other drugs including high doses of 5-hydroxytryptophan (5-HTP) (with a peripheral decarboxylase inhibitor drug), or serotonin-receptor agonists, the animals exhibited tremor, rigidity, hypertonicity, hind-limb abduction, rigidly arched tail, lateral head shaking, treading movements of the forelimbs, hyperreactivity, myoclonus, and even generalized seizures.72

The appearance of the serotonin syndrome in 38 patients in 12 reports has been reviewed.73 The majority of these cases were associated with patients taking a combination of tryptophan and an MAO-inhibitor drug, but the combination of serotonin-reuptake inhibitor and MAO-inhibitor drugs can also cause the serotonin syndrome. The incidence of the serotonin syndrome in patients is unknown, but some experts argue that it is under-reported, perhaps because it is not recognized, or possibly because it is confused with the neuroleptic malignant syndrome, which has some similarities in terms of symptoms.

The serotonin syndrome usually resolves within 24 hours of cessation of tryptophan treatment, with no residual symptoms. Although the animal model suggests that serotonin antagonists should be a useful treatment, this has not been tested in humans. Supportive measures have been used including cooling for hypothermia, intramuscular chlorpromazine as an antipyretic and sedative, artificial ventilation for respiratory insufficiency, anticonvulsants for seizures, clonazepam for myoclonus, and nifedipine for hypertension .73

Although the serotonin syndrome has been reported in patients taking tryptophan and an MAO-inhibitor drug, the incidence of this disorder is low. The total number of patients in the literature reporting symptoms of the serotonin syndrome after taking tryptophan and an MAO-inhibitor drug is less than 40. This is in spite of the fact that tryptophan has been on the market as an antidepressant in the United Kingdom for over 20 years, and psychiatrists in that country are more likely than psychiatrists in North America to use MAO-inhibitor drugs.

Moreover, in the clinical trials on the combination of tryptophan and an MAO-inhibitor drug, there is only one report of symptoms resembling the serotonin syndrome in spite of the very large doses of tryptophan used (up to 18,000 mg of tryptophan per day).74 There have been no reports of permanent effects after the serotonin syndrome was resolved in patients receiving tryptophan and an MAO-inhibitor drug, although deaths have been seen after the serotonin syndrome in patients who were given MAO-inhibitor and tricyclic antidepressant drugs.

Interaction with Herbs
Tryptophan may cause excessive sedation if it is taken with potentially sedating herbs such as catnip, kava kava, St. John?s wort, or valerian.75

Warnings and Contraindications
Patients with liver cirrhosis should avoid tryptophan supplementation. Cirrhotic liver disease patients present with reduced activity of tryptophan 2,3-dioxygenase (22%), with subsequent increased free tryptophan and half-life, and decreased clearance.76 Tryptophan is known to pass into the breast milk of new mothers, but its possible effects in infants are not known. Therefore, tryptophan should also be avoided during breast-feeding. Tryptophan may cause sedation, which may result in sleepiness or mental confusion during the daytime. Individuals who choose to take it should be careful when driving or performing other tasks that require alertness.

Toxicological studies
L-tryptophan has low oral toxicity. A rat carcinogenicity bioassay conducted by the US National Cancer Institute found no evidence of cancer causation.77

Side Effects
Potential side effects of L-tryptophan at high doses (100 mg/kg/day or 7,000 mg taken by a 150-pound person) include gastric irritation, vomiting, and head twitching.78 Less severe side effects include:

Blurry vision

Daytime drowsiness

Dry mouth

Headaches

Muscle incoordination

Nausea

Eosinophilia Myalgia Syndrome
In early 1990s, taking tryptophan was considered to be associated with a severe condition known as eosinophilia myalgia syndrome (EMS).65 Although the exact causes for the outbreak are still not completely known, it is believed that a defective manufacturing process used by one company either introduced contaminants or caused reactions that formed toxic substances within the tryptophan that was produced. However, an independent scientific committee on toxicity recently concluded that tryptophan has not resulted in a detectable increase in risk of EMS, and that pure tryptophan preparations are safe.

[CognitiveNutrition]

References
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2. Meltzer CC, Price JC, Mathis CA, et al. Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacology. 2004 Dec;29(12):2258-65.

3. Meltzer CC, Smith G, DeKosky ST, et al. Serotonin in aging, late-life depression, and Alzheimer?s disease: the emerging role of functional imaging. Neuropsychopharmacology. 1998 Jun;18(6):407-30.

4. Fernstrom JD, Wurtman RJ. Brain serotonin content: physiological dependence on plasma tryptophan levels. Science. 1971 Jul 9;173(992):149-52.

5. Fukuwatari T, Ohta M, Kimtjra N, Sasaki R, Shibata K. Conversion ratio of tryptophan to niacin in Japanese women fed a purified diet conforming to the Japanese Dietary Reference Intakes. J Nutr Sci Vitaminol (Tokyo). 2004 Dec;50(6):385-91.

6. Bell C, Abrams J, Nutt D. Tryptophan depletion and its implications for psychiatry. Br J Psychiatry. 2001 May;178:399-405.

7. Juhl JH. Fibromyalgia and the serotonin pathway. Altern Med Rev. 1998 Oct;3(5):367-75.

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[CognitiveNutrition]

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LE Magazine April 2008

[VegetaGD]

So in short, 50mg of enteric coated natures way 5-htp will not be harmful, and can actually benefit mood and sleep? Would it be better to dose with 1.5 g of tryptophan before bedtime?

[Mike83]

There is nothing wrong with L-Tryptophan!

[mullerhun]

hey!

so, at the end, is 5htp better for sleeping or L-tryptophan?
could i take both of them? (good idea?)

thx!!

[CognitiveNutrition]

hey!

so, at the end, is 5htp better for sleeping or L-tryptophan?
could i take both of them? (good idea?)

thx!!

Either should be fine. Both if you really need it I suppose.

[martymcfly]

loved the e fighting guys.

[martymcfly]

although CN was right, all supps cause problem at overdose. there was no agruement, but it was fun to read!

[Peppesbodega]

Any experiences with tryptophan?
Can You get a flushing sensation from it?
It is said to convert to niacin?
Overdose risks?

Anyone has good experiences with it?
Or is 5htp better?