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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Cosupplementation of Isoflavones, Prenylflavonoids, and Lignans Alters Human Exposure to Phytoestrogen-Derived 17β-Estradiol Equivalents^1–3,

⁴ Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering, and ⁵ Laboratory of Pharmacognosy and Phytochemistry, Faculty of Pharmaceutical Sciences, Ghent University, B-9000 Ghent, Belgium; ⁶ Department of Uro-Gynaecology, and ⁷ Laboratory of Experimental Cancer Research, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, B-9000 Ghent, Belgium

The microbial metabolism of dietary phytoestrogens varies considerably among individuals and influences the final exposure to bioactive compounds. In view of the increasing number of food supplements combining several classes of phytoestrogens, the microbial potential to activate various proestrogens within an individual was evaluated in 3 randomized dietary crossovers. Treatment allocation was based on participants' eligibility (>45% in vitro bioactivation of 2 separate proestrogens by fecal cultures; n = 40/100). After a run-in of 4 d, participants were given soy-, hop-, and/or flax-based food supplements dosed either separately (SOY: 2.83 mg daidzein aglycone equivalents/supplement, HOP: 1.20 mg isoxanthohumol (IX)/supplement, or FLAX: 2.08 mg secoisolariciresinol (SECO) aglycone equivalents/supplement; reference intervention) or simultaneously (MIX; test intervention) 3 times/d for 5 d, followed by a wash-out period (7 d) and the second intervention. Before and after each (co)supplementation, spot urine and serum were collected. In total, 22 equol, 19 8-prenylnaringenin (8-PN), and 21 enterolactone (ENL) producers completed the SOY+MIX, HOP+MIX, and FLAX+MIX trials, respectively. The microbial bioactivation of daidzein, IX, and SECO, generally decreased upon coincubation in vitro (equol: 4.4%, P = 0.164; 8-PN: 20.5%, P < 0.001; ENL: 44.3%, P < 0.001) and cosupplementation in vivo (equol: 28.3%, P = 0.009; 8-PN: 35.4%, P = 0.107; ENL: 35.9%, P = 0.003). Although the bioavailabilities of total isoflavones, prenylflavonoids, and lignans were not significantly affected upon coadministration, participants were exposed to lower phytoestrogen-derived 17β-estradiol equivalents. In conclusion, the bioavailability of phytoestrogens, especially when given in mixtures, is subject to high interindividual variation. These findings support the importance of personalized screening when assessing the efficacy of such products and mixtures.

^* To whom correspondence should be addressed. E-mail: arne.heyerick{at}ugent.be.

Manuscript received 30 July 2009. Initial review completed 24 August 2009. Revision accepted 16 October 2009.

Published online 28 October 2009.

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