If I don't put this up, I'll forget about it. This article [Robinson et al., 2003: (http://www.ncbi.nlm.nih.gov/pubmed/15028582)] discusses the fact that L-tryptophan can be converted enzymatically into various beta-carboline compounds, including tetrahydroharmane and harmane, following the conversion of tryptophan into tryptamine. Fekkes et al. (2001) [Fekkes et al., 2001: (http://www.ncbi.nlm.nih.gov/pubmed/11323106)] found that as little as 1.2 grams of free-form tryptophan elevated plasma levels of norharmane in humans. When the articles say these beta-carbolines are formed enzymatically, this means that the compounds are formed in tiny amounts from dietary tryptophan but could be expected to be formed from supplemental tryptophan in larger amounts, in the absence of any contamination of the supplemental tryptophan. Half of that issue of the Annals of the New York Academy of Sciences (http://www3.interscience.wiley.com/journal/118876207/issue) is devoted to harmane and norharmane as endogenous "clonidine-displacing substances," (as imidazoline receptor agonists, etc.) and they can have anxiolytic effects. But they're obviously really potent compounds, in my opinion, because they're formed in tiny amounts and are thought to meaningfully regulate imidazoline receptor and alpha2-adrenoreceptor activation. Beta-carboline compounds aren't associated with a lot of desirable effects in the literature, and they tend to just be really potent (pM-range Kd values for binding to benzodiazepine binding sites on GABA receptors, etc.).
In my opinion, these are disturbing articles and help to explain the ongoing association of free-form tryptophan ingestion with eosinophilic disorders, etc. [some occurred before or after the contamination of a batch of tryptophan with a beta-carboline compound that caused the eosinophilia myalgia disease (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=carboline+tryptophan+eosinophilia) that led to the banning of tryptophan from OTC sales] [Blauvelt et al., 1991: (http://www.ncbi.nlm.nih.gov/pubmed/1863073)]. In my opinion, it's pretty obvious that there's some problem with administering tryptophan in free form, because it's converted into beta-carboline compounds (which incidentally, along with kynurenine-pathway metabolites, can be really potent and might account for the growth hormone releasing effects of tryptophan). Also, kynurenine metabolites strongly regulate eosinophil function under normal circumstances [Odemuyiwa et al., 2004: (http://www.jimmunol.org/cgi/content/full/173/10/5909)(http://www.ncbi.nlm.nih.gov/pubmed/15528322?dopt=Abstract)] (in the absence of supplementation with tryptophan or any contaminant), and free form tryptophan ingestion has been associated, albeit in poorly-defined ways in any one individual, with a panoply of rheumatic disorders and other Th2-driven disorders (if a person's eosinophils are elevated in a blood panel, this suggests, most basically, some allergic disorder, but the abnormalities linked to tryptophan supplementation are much more complex). Researchers are arguing about which diseases are linked to it (diffuse fasciitis vs. scleroderma, etc.) (http://scholar.google.com/scholar?q=scleroderma+tryptophan&hl=en&lr=), but the point is that the endogenously-produced beta-carbolines and kynurenine metabolites, in my opinion, seem to be able to tip the scales of T-cell differentiation toward some of these pathological, Th2-cytokine-driven disorders, especially in people who might already have some susceptibility to those disorders. One can connect the dots, in my opinion. It's confusing and almost mind-bending to think about, but I don't see how one can explain away all of these separate facts in terms of one, isolated contamination.
I have no idea why free form tryptophan would cause more potent effects on eosinophils than tryptophan from food would, but foods don't contain all that much tryptophan. Additionally, free form tryptophan, like any free form amino acid, would be expected to provide some cell types, such as eosinophils, with much larger amounts of tryptophan than those cells would ever have access to in the face of increases in dietary tryptophan (i.e. tryptophan from foods). Food-derived tryptophan would be released very slowly, in comparison to free form tryptophan. Also, there's some unique aspect of the albumin-binding of tryptophan. I forget the details, but high-carbohydrate meals elevate plasma tryptophan more than other aromatic or other large neutral amino acids and supposedly also elevate free (unbound) tryptophan significantly (?). I forget the details, and this is just my opinion and sense of it (that an increase in free, unbound tryptophan in the blood could occur in response to supplementation and help to explain some of these supposed effects on the functions or Th2-differentiation-inducing capacities of eosinophils). I think it's just one of those things, one of those phenomena that's strange but that, in my opinion, could be associated with worrisome effects. I posted that information about free form tyrosine and phenylalanine and tryptophan, but there's, in my opinion, the most evidence suggesting that D-phenylalanine might have some therapeutic effects, but, even with that, there get to be all these issues with competition for uptake into the brain, etc.
[Incidentally, in a matter off-topic, D-phenylalanine is apparently not incorporated into proteins and not incorporated into aminoacyl-tRNAs (doesn't cause growth suppression in animals, like D-tyrosine). I couldn't find any article showing that it absolutely is never a substrate for aminoacyl-tRNA synthetases, though, so that would be the main concern I'd have with it. It looks like it probably isn't, but that's the type of thing one would want to talk with one's doctor about. I think that would have shown up, as it did with D-tyrosine administration, in animal experiments. D-phenylalanine substituted for L-phenylalanine dose-dependently, up to very high doses, and didn't produce the growth suppression that D-tyrosine did. That suggests that it probably isn't incorporated into proteins (and isn't normally a precursor of a D-phenylalanyl-containing aminoacyl-tRNA), and I found a couple of articles addressing the question directly. But apparently beta-phenylethylamine, derived in tiny amounts from D-phe, can be incorporated into proteins in tiny amounts (?). I forget the details, but that's the type of thing I would be concerned about and that one would want to keep in mind.]
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