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5-hydroxytryptophol as a marker for recent alcohol intake.

AIMS: To review the mechanism behind the alcohol-induced shift in serotonin metabolism, and the use of urinary 5-hydroxytryptophol (5-HTOL) as a biochemical marker of acute alcohol consumption. BACKGROUND: The serotonin metabolite 5-HTOL is a normal, minor constituent of urine and is excreted mainly in conjugated form with glucuronic acid. The formation of 5-HTOL increases dramatically after alcohol intake, due to a metabolic interaction, and the elevated urinary excretion remains for some time (>5-15 hours depending on dose) after ethanol has been eliminated. This biochemical effect can be used for detection of recent alcohol intake. RESULTS: 5-HTOL is determined by the gas chromatography-mass spectrometry (GC-MS) or liquid chromatography and mass spectrometry (LC-MS) techniques. A new ELISA method for 5-HTOL glucuronide provides a promising clinical assay. The most robust way to use the marker is by measuring the ratio of 5-HTOL to 5-hydroxyindoleacetic acid, because this compensates for urine dilution and dietary intake of serotonin. 5-HTOL is a very sensitive and specific indicator of recent alcohol consumption and, as such, a valuable complement to self-report. In clinical use, 5-HTOL is effective for monitoring lapses into drinking during out-patient treatment and for objective evaluation of treatment efforts. Other applications include detection of high-risk patients in elective surgery, monitoring of disulfiram treatment and a method to rule out artefactual ethanol formation in forensic toxicology. 5-HTOL can also be used as a sensitive reference method for validation of self-report data in clinical alcohol research. CONCLUSIONS: An elevated urinary 5-HTOL level can serve as a sensitive and reliable marker for recent alcohol intake with a number of clinical and forensic applications.

5-Hydroxytryptophan↗

Comparison of self-reported alcohol intake with the urinary excretion of 5-hydroxytryptophol:5-hydroxyindole-3-acetic acid, a biomarker of recent alcohol intake.

Under-reporting of alcohol intake has been frequently reported. However, due to the lack of an objective reference method, e.g. a biomarker, information about the extent of under-reporting of alcohol intake obtained with dietary assessment instruments is not available. The objective of this study was to compare reported alcohol intake data derived from a 24 h recall with a biomarker of recent alcohol intake, the urinary excretion of 5-hydroxytryptophol (5-HTOL):5-hydroxyindole-3-acetic acid (5-HIAA). Embedded into the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, Germany, a validation study that collected 24 h recall data and 24 h urine samples was conducted. Cohort study participants (n 107) volunteered to participate in this validation study. Among them were five subjects who reported no consumption of alcoholic beverages but had a 5-HTOL:5-HIAA ratio that indicated recent alcohol intake when the clinical cut-off point was taken as a judging criterion. After exclusion of these under-reporters, the Pearson's correlation coefficient between reported alcohol intake and the 5-HTOL:5-HIAA ratio was 0.92 (P<0.0001). Except for low alcohol intake of <0.1 g/kg body mass, a significant increase in 5-HTOL:5-HIAA excretion was observed with increasing amounts of alcohol intake. In conclusion, the 5-HTOL:5-HIAA excretion ratio appears to be a valuable quantitative biomarker of recent alcohol consumption. Denial of alcohol intake can be detected, but for the quantification of under-reporting of alcohol intake 24 h reference data are not yet available. With these data at hand, however, 5-HTOL:5-HIAA could become a biomarker for validation purposes in nutritional epidemiology.

5-Hydroxytryptophan↗

Estimation of the methylating capacity in the pineal gland of the rat with special reference to the methylation of N-acetylserotonin and 5-hydroxytryptophol separately.

In the present paper, an extension is presented of an earlier described method, by which the methylating capacity of the pineal gland can be determined. Supplementary to the earlier method, the synthesis of melatonin and 5-methoxytryptophol can now be qualified and quantified separately.

Acetylserotonin O-Methyltransferase↗

5-Hydroxytryptophol in human cerebrospinal fluid: quantitative determination by gas chromatography-mass spectrometry using a deuterated internal standard.

Procedures for the quantification of 5-hydroxyindole-3-ethanol, or 5-hydroxy-tryptophol (5-HTOL), in human cerebrospinal fluid are described. 5-HTOL was determined as its di-pentafluorpropionyl derivative. Deuterium labelled 5-hydroxyindole-3-ethanol-a,a,b,b-d4 (5-HTOL-d4) was used as internal standard. Mass fragmentography was performed by double ion monitoring each for 5-HTOL and 5-HTOL-d4 and their ratios were determined for specificity. Assay sensitivities of 0.15 ng/ml were achieved using 2.0 ml of cerebrospinal fluid. Free 5-HTOL concentrations in human cerebrospinal fluid were determined to be 0.73 +/- 0.44 ng/ml (mean +/- S.D.) (range 0.33-2.11 ng/ml) from 15 patients with various neurological disorders, and 0.85 +/- 0.30 ng/ml (range 0.48-1.32 ng/ml) from 9 subjects who complained of low back pain but did not show signs of neurological illnesses.

Chromatography, Gas↗

Mass fragmentography of 5-hydroxytryptophol and 5-methoxytryptophol in human cerebrospinal fluid.

A specific and very sensitive method for the determination of 5-hydroxy-tryptophol (5-HTOL) and 5-methoxytryptophol (5-MTOL) in extracts from human cerebrospinal fluid (CSF) involving the use of mass fragmentography and pentafluoropriopionyl derivatives is described. 5-HTOL and 5-MTOL were determined in human CSF of three patients with leukaemia and from nine patients with neurological disorders. The concentration of free 5-HOT in CSF was in the range of 0.1-33 ng/ml and that of 5-MTOL was 0.3-13.9 ng/ml. For the first time the presence of these compounds in human material has been shown. The concentration of these two alcohols in CSF is markedly lower than the concentration of 5-hydroxyindoleacetic acid. These results suggest that human cerebral 5-hydroxytryptamine is preferentially metabolized to 5-HTOL-hydroxyindoleacetic acid rather than to 5-HTOL and 5-MTOL.

Adolescent↗

Anxiolytic-like actions of melatonin, 5-metoxytryptophol, 5-hydroxytryptophol and benzodiazepines on a conflict procedure.

Male Wistar rats (120-230 g) were used in these experiments. Some rats were deprived of water for 48 h before testing in a conflict procedure. Then, after 20 licks from a water bottle with a metal drinking tube, the animal received an electric shock (0.5 mA/500 msec). The effects of two classical anxiolytic drugs, DIAZ (1.0, 2.0 and 4.0 mg/Kg b.wt), and CDP (5.0 and 10.0 mg/Kg b.wt) were compared to those produced by MEL (0.1, 0.2, 0.5, 1.0 and 2.0 mg/Kg b.wt), 5-MTOPHOL (1.0 and 2.0 mg/Kg b.wt), 5-HTOPHOL (1.0 and 2.0 mg/Kg b.wt) and vehicle solution. Anxiolytic drugs as well as MEL produced a dose-dependent increase in the number of shocks received. The results suggest that the three pineal indoles are involved in the modulation of the stress responses. MEL showed a higher potency than the other indoles.

Animals↗