Intervention Effects Of Daidzein In The Hypercholesterolemic Adults

Daidzein, one of major isoflavones, can be metabolized to equol by gut bacteria in aproportion of the population. Several clinical studies have concluded that isoflavonesmay produce better clinical effects in equol-producers than in non-equol producers.Previous studies often used soy or isoflavone extract to assess the interaction of equolstatus and isoflavone effects. However, the other major isoflavone component, genistein,which cannot produce equol, may confound the contributions of equol status as a resultof the effects of isoflavones. Genistein alone could play a protective role inpostmenopausal symptoms, osteoporosis, and cardiovascular health in humans. Thus,either in equol or non-equol producers, the effects of isoflavones containing genisteinwere dependent on if genistein was the main component of isoflavones supplementation.However, the effects of isoflavones may be also be due to daidzein or equol, since theyalso make up or are produced as a result of isoflavone supplementation. Importantly, noprevious clinical trials have used daidzein as the only isoflavone source. Additionally,clinical studies have seldom used isoflavones with daidzein as the major component ofthe supplement and previous studies have not reported the influence of equol status onthe effects of isoflavones.High circulating triglyceride and LDL-cholesterol concentrations, and low HDL-cholesterol concentrations are significant risk factors for cardiovascular diseases. In thelast decade, several systematic reviews and meta-analyses have assessed the effects ofisoflavones on lipid profiles in humans, and led to various conclusions. The effects ofisoflavones on lipid profiles is not yet clear due to the fact that different isoflavones wereused in previous studies, with differing durations of administration. In addition, uric acidwas an independent risk factor of cardiovascular diseases. The decrements of uric acidmaybe contribute to the prevention or treatment of cardiovascular diseases. In theChinese population, serum uric acid levels were lower in the equol producers than in the non-equol producers.To evaluate the effects of daidzein and equol status, we wanted to use daidzein asthe only isoflavone source. We therefore performed a clinical trial using daidzein alone toassess the effects of daidzein supplement on cardiovascular risk factors and theinteractions with equol status.Materials and Methods(1) Two hundred and ten patients with hypercholesterolemia were recruited into thisclinical trial. The subjects with a fasting total cholesterol concentrations high than5.18mmol/L were considered as hypercholesterolemic.(2) This study was a randomized, double-blind, placebo-controlled trial. Twohundred and ten eligible patients (108men and102women) were randomly assigned tothe soy isolated protein group (5g/d) with0mg daidzein (Placebo),40mg (DAI40), or80mg (DAI80) groups. The total intervention duration was6mo. This trial was registeredat Chinese clinical trial registry as ChiCTR-TRC-10001048.(3) All subjects were asked to complete a3d record of their food intake and aquestionnaire regarding lifestyle, disease history, medication, and nutrient supplements.(4) Before the start of the trial, subjects were asked to consume150g tofu for3consecutive days and then a first (day4) urine sample was collected. Urinary metabolitesof isoflavones were extracted using a method involving beta-glucuronidase andsulphatase deconjugation, and then daidzein and equol concentrations were assayed byHPLC. The subjects with urinary equol concentrations higher than0.242mg/L (1000nmol/L) and the log10transformed urinary S-equol:daidzein ratio higher than-1.75wereidentified as equol producers. Other subjects not falling within these criteria wereidentified as non-equol producers.(5) Assessment of serum fasting lipid profiles and glucose was performed usingroutine methods. Serum uric acid concentrations were assayed by a direct enzymemethod. Serum lipoprotein(a)concentrations were determined by turbidimetricimmunoassay. Blood glycated hemoglobin levels were determined by a latexagglutination inhibition assay. Serum insulin was measured by anelectrochemiluminescence immunoassay.(6) All statistical analyses were performed by using SPSS for Windows software. Differences in sex, equol status, and other categorical data among the3treatment groupswere assessed by the chi-square method. Differences in measurement data among the3treatment groups at baseline and at the end of the trial were evaluated by one-wayANOVA. The effects of the interventions on cardiovascular risk factors and the dailynutrients intakes of participants were assessed by one-factor ANCOVA, with the changeat6mo from baseline considered the dependent variable and the baseline valueconsidered the covariate. Multiple comparison tests were performed using the Bonferronimethod. Data were also classified by sex, menopausal status, and equol status in eachgroup in order to assess the effects of these parameters on the daidzein effects. All Pvalues reported were2sided and <0.05were considered significant.Results(1) A total of177subjects (91men and86women) were included in the finalanalysis. No adverse reactions occurred during this trial. The overall subject compliancelevel of this trial was excellent. Baseline characteristics of subjects in3groups weresimilar. The distribution of equol status were not different among groups.(2) There were no significant differences in the daily mean dietary nutrient intakeamong the3groups at baseline and after6mo of supplementation. Since subjects wereasked to avoid intake of soy and soy products during the study, the intakes of soy proteinand isoflavones significantly decreased during treatment from baseline in each group.(3) Daidzein supplementation for6mo significantly decreased serum triglycerideand uric acid concentrations, but not in a dose-dependent manner. Compared to theplacebo group, triglycerides were significantly decreased in the DAI40and DAI80groups (P <0.05). However, there was no significant difference between the DAI40andDAI80groups. In participants with hypertriglyceridemia (baseline serum triglyceridesconcentration higher than1.71mmol/L), triglycerides significantly decreased by0.62±0.71mmol/L (n=27) and0.69±0.71mmol/L (n=21) in the DAI40and DAI80groupsafter treatment, in comparison to the placebo group (n=22, P <0.05).(4) The reductions of serum uric acid concentrations were different among the3treatment groups (P <0.05). After6mo of treatment, the reduction of serum uric acidconcentration was greater in the DAI80groups than that in the placebo group (P <0.05).There was no significant difference between the DAI40and the placebo, or the DAI40 and DAI80groups in terms of the reduction of uric acid.(5) There was no significant difference in serum total, HDL-, and LDL-cholesterol,apolipoprotein AI and B, lipoprotein(a), glucose, insulin and blood glycated hemoglobinamong groups after the treatment.(6) There were more equol producers in women than in men (69%and51%respectively, P <0.05) at baseline. Equol status did not influence the effects of daidzeinon the blood lipid, glucose, insulin, glycated hemoglobin, or uric acid concentrations inhypercholesterolemic subjects. Equol status of some indibiduals had been changed after6month of daidzein supplement.Conclusion(1) Daidzein supplementation for6mo decreased triglyceride and uric acid levelseffectively in hypercholesterolemia adults， but not in a dose-dependent manner.Daidzein had on effects of the other lipids, glucose and insulin.(2) Equol ststus did not influence the effects of daidzein supplement inhypercholesterolemia adults. Equol status of some indibiduals had been change d after6month of daidzein supplement.