The main objective is to assess whether a natural inhibitor of aldehyde dehydrogenase 2 (ALDH2) contained in a soy extract could interfere on alcohol metabolism and effects in humans.
Soybeans contain isoflavones, which are biologically active polyphenols known as antioxidants and phytoestrogens. These isoflavones include daidzin, daidzein, genistin and glycitin, and have been implicated in the beneficial effects of soy consumption. Daidzin and daidzein are isoflavones contained in soybean that can act as natural inhibitors of aldehyde dehydrogenase 2. Animal studies have demonstrated that some soy isoflavones can reduce the auto-administration of cocaine and suggest they might be useful to treat cocaine dependence. Aldehyde dehydrogenase inhibitors, as disulfiram, are currently used in humans to treat alcohol dependence because they interfere with ethanol metabolism (specifically in the transformation of acetaldehyde to acetate. Alcohol intake after disulfiram administration increases concentration of acetaldehyde in the blood (five to 10 times higher than that found during metabolism of the same amount of alcohol alone). The combination produced acute symptoms of a severe "hangover" (named disulfiram-like reaction), and the patient may experience symptoms as flushing of the skin, tachycardia, shortness of breath, nausea, vomiting, throbbing headache, visual disturbances, mental confusion, and in some cases severe reactions as postural syncope, and circulatory collapse. In addition, disulfiram have demonstrated clinical efficacy in cocaine dependence. The mechanism of action for that effects are related to its ability to decrease dopamine degradation by inhibiting the dopamine-beta-hydroxylase enzyme (metabolizes dopamine to norepinephrine), and increasing its concentrations in some areas of the brain. The aim of the study is to assess whether a soy extract containing isoflavones (daidzin, daidzein and genistein) could interfere on alcohol metabolism and produce adverse effects in humans.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
10
Parc de Salut Mar.
Barcelona, Barcelona, Spain
Area Under the Concentration-Time curve (AUC 2-10h)
Calculation of AUC for blood alcohol concentrations
Time frame: From 2h to 10h after the first administration
Change in signs and symptoms of disulfiram-like reaction
Vital signs (heart rate, blood pressure, respiration rate, oral and facial temperature) and adverse effects measured by visual analogue scales (nausea, vomiting, vertigo, dizziness, headache, breathing difficulty, facial flushing)
Time frame: From baseline to 10h after the first administration
Change in drunkenness and euphoria effects
Drunkenness and euphoria will be measured by a visual analogue scale (VAS).
Time frame: From baseline to 10h after the first administration
Area Under the Concentration-Time curve (AUC 0-10h)
Calculation of AUC of plasmatic concentrations of daidzein, genistein and equol
Time frame: From baseline to 24h after the first administration
Number of participants with Serious and non-serious adverse events
Collection of adverse events spontaneously reported by the participants and/or observed by the investigators.
Time frame: 3 days after each condition
Change in other subjective effects
Subjective effects will be measured with the Addiction Research Center Inventory (ARCI)
Time frame: From baseline to 10h after the first administration
Elimination half-life
Calculation of elimination half-life from blood ethanol concentrations
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Time frame: From 2h to 10h after the first administration
Elimination half-life
Calculation of elimination half-life of plasmatic concentrations of daidzein, genistein and equol
Time frame: From baseline to 24h after the first administration
Cumulative amount of drug excreted into urine up to collection time
Urine will be collected in the following periods:0-2h,2-8h,8-14h,14-24 h after administration. Concentrations of daidzein, genistein and equol will be measured
Time frame: From baseline to 24h after the first administration