Christoph Riegger

Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteers.

Genistein, an isoflavone and phytoestrogen predominantly found in soy, is considered a potentially safe therapeutic option to prevent postmenopausal bone loss. A novel purified product consisting of 99.4% synthetic genistein aglycone was investigated in a phase 1 clinical study to assess safety and tolerability in healthy volunteers as well as to obtain pharmacokinetic data. Single oral doses of 30, 60, 150, or 300 mg were administered to 40 healthy volunteers in this prospective, randomized, open-label and sequential-group study. Tolerability of the different genistein doses was very good. No clinically significant effects on vital signs, ECG, and clinical laboratory parameters were observed. Genistein was rapidly absorbed and the kinetic profiles revealed a one-peak plasma concentration-time course. Mean Cmax values of 252.0, 605.0, 1518.0, and 1808.0 ng/mL were observed after 4.0 to 6.0 hours. The mean terminal elimination half-lives were calculated to be7.7, 7.5, 8.1, and 10.2 hours resulting in mean AUCs0-∞ of 2761.8, 8022.3, 21655.0, and 27537.8 ngxhr/mL. Linear regression of the dosenormalized AUCs0-∞ was not significantly different from zero, whereas the analysis for Cmax showed significance. Based on consecutive administration of single oral doses of genistein, dose linearity was assumed for extent of absorption [AUC0-∞] for all doses (30–300 mg) and for rate of absorption (Cmax) up to 150 mg. At the highest dose the intestinal rate of absorption of genistein seemed to be limited. Genistein was safe and well tolerated in the dose range investigated and showed nearly dose-linear pharmacokinetic characteristics.

Contribution of the Ratio of Tocopherol Homologs to the Oxidative Stability of Commercial Vegetable Oils

The antioxidant activity of tocopherols in vegetable oils was shown to chiefly depend on the amount and the tocopherol homolog present. However, the most effective ratio of tocopherol homologs with regard to the antioxidant capacity has not been elucidated so far. The present study analyzed the effect of different tocopherol concentrations, homologs and ratios of homologs on markers of lipid oxidation in the most commonly consumed vegetable oils (canola, sunflower, soybean oil) stored in a 12 h light/dark cycle at 22 ± 2 °C for 56 days under retail/household conditions. After 56 days of storage, the α-tocopherol-rich canola and sunflower oil showed the strongest rise in lipid peroxides, yielding 25.1 ± 0.03 meq O2/kg (+25.3-fold) and 24.7 ± 0.05 meq O2/kg (+25.0-fold), respectively. ESR experiments, excluding effects of the oils’ matrices and other minor constituents, confirmed that a food representative tocopherol ratio of (γ + δ)/α = 4.77, as represented in soybean oil, led to a more pronounced delay of lipid oxidation than a lower ratio in canola (1.39) and sunflower oil (0.06). An optimum (γ + δ)/α -tocopherol ratio contributing to the oxidative quality of vegetable oils extending their shelf life has to be investigated.

Regioisomeric distribution of 9- and 13-hydroperoxy linoleic acid in vegetable oils during storage and heating

Abstract BACKGROUND The oxidative deterioration of vegetable oils is commonly measured by the peroxide value, thereby not considering the contribution of individual lipid hydroperoxide isomers, which might have different bioactive effects. Thus, the formation of 9‐ and 13‐hydroperoxy octadecadienoic acid (9‐HpODE and 13‐ HpODE), was quantified after short‐term heating and conditions representative of long‐term domestic storage in samples of linoleic acid, canola, sunflower and soybean oil, by means of stable isotope dilution analysis–liquid chromatography‐mass spectroscopy. RESULTS Although heating of pure linoleic acid at 180 °C for 30 min led to an almost complete loss of 9‐HpODE and 13‐HpODE, heating of canola, sunflower and soybean oil resulted in the formation of 5.74 ± 3.32, 2.00 ± 1.09, 16.0 ± 2.44 mmol L–1 13‐HpODE and 13.8 ± 8.21, 10.0 ± 6.74 and 45.2 ± 6.23 mmol L–1 9‐HpODE. An almost equimolar distribution of the 9‐ and 13‐HpODE was obtained during household‐representative storage conditions after 56 days, whereas, under heating conditions, an approximately 2.4‐, 2.8‐ and 5.0‐fold (P ≤ 0.001) higher concentration of 9‐HpODE than 13‐HpODE was detected in canola, soybean and sunflower oil, respectively. CONCLUSION A temperature‐dependent distribution of HpODE regioisomers could be shown in vegetable oils, suggesting their application as markers of lipid oxidation in oils used for short‐term heating.