Pharmacokinetic Comparison of Soy Isoflavone Extracts in Human Plasma

The soy isoflavones daidzein and genistein produce several biological activities related to health benefits. A number of isoflavone extracts are commercially available, but there is little information concerning the specific isoflavone content of these products or differences in their bioavailability and pharmacokinetics. This study describes the development and validation of an analytical method to detect and quantify daidzein, genistein, and equol in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was applied in a crossover, randomized, bioavailability study. Twelve healthy volunteers were administered the same total isoflavones dose from two isoflavone supplement preparations (Super-Absorbable Soy Isoflavones (Life Extension, USA) and Fitoladius (Merck, Spain)). The pharmacokinetic parameters (AUC_0–24/dose and <i>C</i>_max/dose) of the isoflavones from the two preparations differed significantly. Such differences in bioavailability and kinetics may have relevant effects on the health benefits derived from their intake

Mean (SD) MDMA/MDA concentrations (µg/L) in MDMA and the combined pindolol+MDMA condition.

<p>Mean (SD) MDMA/MDA concentrations (µg/L) in MDMA and the combined pindolol+MDMA condition.</p

Mean (SE) of dependent variables of the WLT and main effects of Treatment Condition and Task Variable* (Trial); ns = not significant, na = not applicable.

<p>Mean (SE) of dependent variables of the WLT and main effects of Treatment Condition and Task Variable* (Trial); ns =  not significant, na =  not applicable.</p

Schematic representation of a test day; BP = Blood Pressure, HR = Heart Rate; * T3 = first dose of 40 IU.

<p>Schematic representation of a test day; BP =  Blood Pressure, HR =  Heart Rate; * T3 =  first dose of 40 IU.</p

Mean (SE) of subscales of the POMS and main effect (GLM) of Treatment Condition; T = Time of measurement (B = baseline; Peak = drug peak moment); Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.

<p>Mean (SE) of subscales of the POMS and main effect (GLM) of Treatment Condition; T =  Time of measurement (B =  baseline; Peak =  drug peak moment); Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.</p

Oxytocin (pg/mL) and cortisol (nM or nmol/L) serum concentrations * B = Baseline; Start of test battery = 45′post-oxytocin administration, 90′post-MDMA administration, 150′post-pindolol administration; End of test battery = 120′post-oxytocin administration (first dose), 165′post-MDMA administration, 225′ post-pindolol administration; Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.

<p>Oxytocin (pg/mL) and cortisol (nM or nmol/L) serum concentrations * B =  Baseline; Start of test battery = 45′post-oxytocin administration, 90′post-MDMA administration, 150′post-pindolol administration; End of test battery = 120′post-oxytocin administration (first dose), 165′post-MDMA administration, 225′ post-pindolol administration; Statistically significant treatment-placebo contrasts are flagged with an ‘a’, MDMA vs pindolol + MDMA contrasts with a ‘b’.</p

Influence of gender and genetics (<i>COMT, 5-HTTLPR</i>) on the temporal course of systolic blood pressure (upper-left panel), heart rate (lower-left panel), and oral temperature (right-end panel) (mean ± SEM); women n = 12 <i>vs.</i> men n = 15; COMT, <i>val/val</i> n = 8 <i>vs. met/*</i> n = 18; 5-HTTLPR, <i>l/*</i> n = 18 <i>vs. s/s</i> n = 9).

<p>*<i>p</i><0.05, **<i>p</i><0.01. Graph A corresponds to gender differences in OT, graph B corresponds to differences in OT as a function of 5-HTTLPR polymorphisms (<i>l/l</i> n = 11 <i>vs. s/s</i> n = 9). Subjects <i>l/s</i> (n = 7) are not represented for graph clarity, but data almost fully overlaps with the <i>s/s</i> trace.</p

Anthropometric data of included volunteers and MDMA doses according to gender and genotypes (mean ± SD [min, max]).

<p>MDMA, ±3,4-methylenedioxymethamphetamine; CYP2D6, cytochrome P450 2D6; FA: functional alleles COMT, catechol-O-methyltransferase; 5-HTTLPR, gene-linked polymorphic region. BMI: body mass index; <i>p.o: per os. *p</i><0.05<i>; **p</i><0.01.</p

Gender differences in physiological and subjective effects after MDMA administration (mean ± SD; women n = 12 <i>vs.</i> men n = 15) (only significant effects included).

<p>AUC: area under the effect-time curve; Emax: peak effect; Tmax: time of peak effect. VAS: visual analogue scale. ARCI: Addiction Research Center Inventory, PCAG: pentobarbital-chlorpromazine-alcohol group. VESSPA: Evaluation of the Subjective Effects of Substances with Abuse Potential.</p>*<p>p<0.05,</p>**<p>p<0.01.</p

Genetic differences in physiological and subjective effects after MDMA administration (mean ± SD; women n = 12 vs. men n = 15) (only significant effects included).

<p>AUC: area under the effect-time curve; Emax: peak effect; COMT, catechol-O-methyltransferase; SBP: systolic blood pressure; DBP: diastolic blood pressure. 5-HTTLPR, gene-linked polymorphic region VESSPA: Evaluation of the Subjective Effects of Substances with Abuse Potential.</p>*<p>p<0.05;</p>**<p>p<0.01. N = [COMT, valval n = 8 vs. met/* n = 18; 5-HTTLPR, l/* n = 18 vs. s/s n = 9.</p