Posted by Larry Hoover on May 22, 2003, at 13:54:42
In reply to Re: L-Tryptophan HEALTH WARNINGS, posted by Chris O on May 22, 2003, at 10:55:04
> I'm no expert on amino acid supplementation, but I did have a scary experience with l-typtophan this year. I bought it from a company called Lidtke, who, I guess, is selling it illegally on some health food store shelves. Of course, on their website they have lots of marketing info about how their l-tryp is "pure and uncontaminated", etc. Well, a day after I took 1,000mg of the Lidtke l-tryp, I had strange muscle spasms in my arms, legs, and calves. These lasted for about a week. I have never felt anything like this in my life. I went to see a doctor because I knew these symptoms mimicked those of EMS. He was young, did not appear conservative to me, and seemed to know a good deal about EMS. He informed me that there is too much unknown about taking individual amino acid supplements and that it was not only people who took the genetically-modified Japanese version of l-tryp in 1989 who got EMS. I guess people who have gotten those symptoms off other single amino acid supplements too. Bottom line for me is that I would love to take something l-tryp if it was well studied, validated, "safe", but despite my distaste for the pharmaceutical industry and the conventional medical industry, I don't think l-tryp is a viable alternative to meds yet. I wish it was.
I'd like to expand on my position, if I may.
By no means was I intending to suggest that l-tryptophan supplementation is completely safe. There are far too many variables, including genetic factors, for me to ever suggest something like that.
What got me about the original posting was the generalization from a specific form of contamination to the general utility of l-tryptophan use. Moreover, the analogy between MSG sensitivity and the risk of sensitivity to tryptophan is less than apt; glutamate is a neurotransmitter, whereas tryptophan is not.
Your personal reaction must serve as a precautionary consideration, however, there is no way to determine whether your reaction is idiosyncratic, or due to the properties of the supplement you consumed. Despite the similarity of symptoms you experienced to those of EMS, there has never been a reported incidence of EMS *even from the most heavily contaminated batches of l-tryptophan* which followed a single dose of 1 gram. There just couldn't possibly have been enough 1,1'-ethylidenebis[L-tryptophan] in the small sample you consumed, nor sufficient time for your immune system to have reacted to the contaminant, thereby producing symptomatic EMS.
One of the most conservative medical teams doing systematic reviews of various treatment strategies is the Cochrane team. Although they conclude that there is insufficient evidence for a clear benefit of l-tryptophan supplementation, there is sufficient evidence to suggest a positive effect over placebo. In broad strokes, that is evidence that it *will* work for some people.
Cochrane Database Syst Rev 2002;(1):CD003198
Cochrane Database Syst Rev. 2001;(3):CD003198.
Tryptophan and 5-hydroxytryptophan for depression.
Shaw K, Turner J, Del Mar C.
School of Population Health, University of Queensland, Public Health Building, Herston Rd, Herston, Queensland, Australia, 4006. email@example.com
BACKGROUND: 5 Hydroxytryptophan (5-HTP) and tryptophan are so-called natural alternatives to traditional antidepressants, used to treat unipolar depression and dysthymia. OBJECTIVES: To determine whether 5-HTP and tryptophan are more effective than placebo, and whether they are safe to use to treat depressive disorders in adults. SEARCH STRATEGY: Trials were searched in computerized general (Medline, Psychlit, and Embase) and specialized databases (Cochrane Controlled Clinical Trials Register, Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trial Register); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. SELECTION CRITERIA: Trials were included if they were randomized, included patients with unipolar depression or dysthymia, compared preparations of 5-HTP or tryptophan with placebo, and included clinical outcomes assessed by scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the three reviewers, onto data collection forms. Inclusion criteria were applied to all potential studies independently and a coefficient of agreement (Kappa) was calculated for them. Disagreement was resolved by reaching consensus. Trial quality was scored according to risk of bias. Analysis for 5-HTP and tryptophan were combined due to the small number of included trials. MAIN RESULTS: 108 trials were located using the specified search strategy. Of these, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive. REVIEWER'S CONCLUSIONS: A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.
Fortschr Med 1998 Nov 20;116(32):40-2
[Treatment of depression and sleep disorders. Significance of serotonin and L-tryptophan in pathophysiology and therapy]
[Article in German]
Riemann D, Vorderholzer U.
Abteilung fur Psychiatrie und Psychotherapie, Universitat Freiburg.
Since the nineteen-sixties, L-tryptophan has been used to treat depression and sleep-disorders. It appears to be suitable for the the treatment of mild forms of depression and of special forms, such as depressive mood associated with the climacteric. In a subgroup of patients, L-tryptophan can help re-establish a physiological sleep pattern in patients with chronic sleep problems. In the case of dependence on hypnotics, L-tryptophan can ease withdrawal symptoms. Recently published studies have shown that acute L-tryptophan depletion can lead to impairment of sleep continuity, and, in patients with an appropriate predisposition, to brief reversible depressive moods. In 1989, oral preparations of L-tryptophan were reported to precipitate the eosinophilia-myalgia syndrome (EMS). However, the real culprit proved to be contaminations of the basic substance of L-tryptophan which are no longer present in measurable amounts in the preparations now available on the market. Today, improved purification and analytic methods ensure the harmlessness of L-tryptophan preparations. In comparison with synthetic antidepressants and hypnotics, L-tryptophan is characterized by a particular low level of side-effects.
J Rheumatol Suppl 1996 Oct;46:81-8; discussion 89-91
J Rheumatol Suppl. 1996 Oct;46:44-58; discussion 58-9.
J Rheumatol Suppl. 1996 Oct;46:60-72.
Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome.
Kilbourne EM, Philen RM, Kamb ML, Falk H.
Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, Georgia 30333, USA.
Evidence from an array of scientific studies strongly supports the conclusion that ingestion of products containing L-tryptophan (LT) produced by Showa Denko KK caused the 1989 epidemic of eosinophilia-myalgia syndrome (EMS) in the United State. In case-control studies of EMS, LT exposure was essentially universal among cases but rare among controls. Of 6 manufacturers of LT, only LT manufactured by Showa Denko KK was clearly associated with illness. The data meet other Hill criteria for inferring a causal relationship. Consistent findings were found in multiple independently conducted studies. There was a dose-response effect, with risk of illness increasing as a function of the amount of tryptophan consumed. The extremely small p values observed in the multiple independently conducted studies effectively rule out the possibility that the tryptophan-EMS association was the result of chance. Moreover, no potential confounding factor or bias explains the association. The incidence of EMS in the United States diminished abruptly once LT containing products were recalled.
EBT, a tryptophan contaminant associated with eosinophilia myalgia syndrome, is incorporated into proteins during translation as an amino acid analog.
Buss WC, Stepanek J, Bankhurst AD, Mayeno AN, Pastuszyn A, Peabody D.
Department of Pharmacology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
The tryptophan dimer 1,1'-ethylidenebis[L-tryptophan] was identified as a contaminant of tryptophan preparations associated with Eosinophilia-Myalgia Syndrome. In this paper, we describe experiments examining the hypothesis that 1,1'-ethylidenebis[L-tryptophan] acts as an amino acid analog replacing L-tryptophan during the synthesis of proteins. We propose further that proteins containing 1,1'-ethylidenebis[L-tryptophan] are rejected in an autoimmune process identified clinically as Eosinophilia-Myalgia Syndrome. Rabbit reticulocyte lysates containing an estimated 1 microM L-tryptophan were used to assay the ability of 1,1'-ethylidenebis[L-tryptophan] to compete with 3H-L-tryptophan for incorporation into proteins translated from BMV RNA. 1,1'-Ethylidenebis[L-tryptophan] in concentrations of 40, 80 and 110 microM reduced lysate 3H-L-tryptophan incorporation to 81%, 76% and 75% of control incorporation obtained in the absence of 1,1'-ethylidenebis[L-tryptophan]. In the presence of 20 microM L-tryptophan, 110 microM 1,1'-ethylidenebis[L-tryptophan] reduced 3H-L-tryptophan incorporation to 56% of control incorporation. In contrast, ethyl-L-tryptophan did not significantly reduce 3H-L-tryptophan incorporation. In the presence of 110 microM 1,1'-ethylidenebis[L-tryptophan] and 20 microM L-tryptophan, 3H-L-leucine incorporation was not significantly reduced compared to incorporation in the absence of 1,1'-ethylidenebis[L-tryptophan], demonstrating that proteins were translated to full length during elongation. These findings suggest that 1,1'-ethylidenebis[L-tryptophan], but not ethyl-L-tryptophan, reduced 3H-L-tryptophan incorporation into proteins by substituting for L-tryptophan rather than by causing premature termination or significant slowing of nascent protein chains.