arccess2011
Dołączył: 12 Lis 2010
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 Wysłany: Wto 7:40, 23 Lis 2010 Temat postu: Both stimulatory and inhibitory effects of dietary |
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Introduction
Two critical neurotransmitters, serotonin (5-hydroxytryptamine; 5-HT) and dopamine,are synthesized from the amino acids tryptophan and tyrosine, respectively.1,2 Serotonin synthesis in vivo is accomplished by a two-step process converting tryptophan to 5-hydroxytryptophan (5-HTP), facilitated by the enzyme tryptophan hydroxylase, and 5-HTP is then decarboxylated by dihydroxyphenalanine (DOPA) decarboxylase to form serotonin. Tyrosine is converted to dopamine by the combined action of tyrosine hydroxylase to form DOPA and DOPA decarboxylase to form dopamine. The synthesis
of serotonin is commonly stimulated by dietary delivery of L-5-hydroxytryptophan (5-HTP)3 and dopamine synthesis is stimulated by dietary administration of either tyrosine or L-dihydroxyphenylalanine (L-DOPA).4 Protein-containing foods such as meat and dairy products are good natural sources of both tyrosine and tryptophan.Both 5-HTP and tyrosine are available in the United States as dietary supplements.
These agents are utilized as natural supplements to augment brain levels of either serotonin or dopamine. This study investigates the effects of 5-HTP
and tyrosine ingestion on urinary excretion of serotonin and dopamine in a large sample of humans ingesting 5-HTP and tyrosine. Curiously,[link widoczny dla zalogowanych], the urinary excretion of these compounds after ingestion of 5-HTP or tyrosine has only been reported in human trials involving very small patient cohorts and the results
involve anomalous responses.5�7 Therefore, this study was designed to critically test the hypothesis that increased ingestion of 5-HTP or tyrosine elevates urinary excretion of serotonin and dopamine, respectively. The purpose of the study was to determine if urinary excretion of serotonin or dopamine refl ect
the adequacy of supplementation with 5 HTP or tyrosine.
Methodology
The study included 824 individuals ingesting 5-HTP, tyrosine,both 5-HTP and tyrosine, or neither.Multiple urine samples were obtained from all of these individuals and most received multiple doses of supplements to enable comparisons between doses of supplements and urinary excretion of mature neurotransmitters, as well as the relationship between changes in doses and changes in urinary neurotransmitter excretion. The primary rationale for using the dietary supplements was weight loss although a signifi cant number of patients were treated for diseases other than obesity that were caused by, or associated with, serotonin and/or dopamine dysfunction.The participants resided throughout the United States. The dose range for 5-HTP ranged from 0 to 2700 mg per day. Tyrosine was taken in doses of 0 to 17,000 mg per day. The supplements were taken in divided doses two, three,or four times a day depending on the dosing of amino acid precursors administered.Urine samples were collected six hours prior to bedtime with 4:00 PM being the most frequent collection time point.The samples were obtained in 6 N HCl to preserve dopamine and serotonin.The urine samples were collected after a minimum of one week at a specifi c dose of the precursor being consumed.Samples were shipped to DBS Laboratories (Duluth, MN,USA) under the direction of one of the authors (Dr Thomas Uncini, a hospital-based dual board certifi ed laboratory pathologist).
Urinary dopamine and serotonin were assayed utilizing commercially available radioimmunoassay kits (3 CAT RIA IB88501 and IB89527; Immuno Biological Laboratories, Inc.,[link widoczny dla zalogowanych],Minneapolis, MN, USA). The DBS Laboratories are accredited as a high complexity laboratory by Clinical Laboratory Improvement Amendments (CLIA) to perform these assays.Statistical evaluations utilized either two-way ANOVA to compare dose-response curves or regression analyses to establish correlations between precursor doses and urinary urinary sertotonin excretion was not statistically signifi cant (r 0.040; p 0.09). All of these individuals also were consuming tyrosine, therefore we sought an interaction with tyrosine as well,[link widoczny dla zalogowanych], but there was none (p 0.50). Surprisingly,the data from these experiments indicate only a marginal relationship between administration of a serotonin precursor and urinary excretion of serotonin.
We then sought a more convincing relationship by analyzing the effect of 5-HTP dosing alterations on changes in urinary serotonin excretion in individual patients. These experiments were conceived to ascertain whether individuals exhibited dramatically different basal levels of urinary serotonin excretion but consistently responded to changes in precursor administration with increased excretion of the serotonin.Figure 2 depicts a statistically signifi cant relationship between changes in 5-HTP administration and alterations in urinary effl ux of serotonin (p _ 0.0001; r 0.145).These data indicate a relationship between ingested 5-HTP and urinary serotonin excretion, but this effect remains modest based on the regression coeffi cient.
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