- A. Geelen (1)
- P.C.H. Hollman (1)
- E. Kampman (2)
- D. Keukeleire de (1)
- C.M. Korse (2)
- J.W. Lampe (1)
- F.E. Leeuwen van (2)
- M.R. Mensink (1)
- M. Nielen van (1)
- S. Possemiers (1)
- M.A. Rookus (2)
- E.G. Schouten (1)
- K. Struijs (1)
- L.J. van't Veer (2)
- P. Veer van 't (1)
- V. Velpen van der (1)
- W. Verstraete (1)
- J.P. Vincken (1)
- D.W. Voskuil (2)
- A. Vrieling (2)
- B.J.M. Witteman (2)
Large inter-individual variation in isoflavone plasma concentration limits use of isoflavone intake data for risk assessement
Velpen, V. van der; Hollman, P.C.H. ; Nielen, M. van; Schouten, E.G. ; Mensink, M.R. ; Veer, P. van 't; Geelen, A. - \ 2014
European Journal of Clinical Nutrition 68 (2014). - ISSN 0954-3007 - p. 1141 - 1147.
randomized controlled-trials - soy isoflavones - premenopausal women - soybean isoflavones - equol production - gut microflora - healthy-adults - habitual diet - bioavailability - humans
Background/objectives: Isoflavones are present in soy foods and soy-based supplements. Despite low plasma isoflavone concentrations in the general Western population, concentrations in supplement users exceed those suggested to be beneficial for health in Asian populations, raising concerns for adverse effects. To aid risk assessment, quantification of the relation between isoflavone intake and plasma concentrations is essential. Subjects/methods: Plasma samples were collected from postmenopausal women in three placebo-controlled crossover studies with 8-week periods for supplements (two studies, ~100¿mg isoflavones/day, n=88) or 4-week periods for soy foods (one study, ~48¿mg isoflavones/day, n=15). Plasma isoflavone concentrations (daidzein, equol, genistein and glycitein) were quantified using high-performance liquid chromatography and electrochemical detection. The association between plasma concentrations and isoflavone intake, equol producer status, intake–producer interaction and background dietary intake was assessed based on the assumption of a log-linear relation. Results: Median plasma total isoflavone concentrations after the soy food and supplement interventions were respectively 2.16 and 3.47¿µmol/l for equol producers and 1.30 and 2.39¿µmol/l for non-producers. Regression analysis showed that doubling isoflavone intake increased plasma concentrations by 55–62% (±s.e. 1–2%, R2>0.87) for daidzein, genistein, equol (only for producers) and total isoflavones; for glycitein the association was weaker (15±1%, R2=0.48). Adjustments for energy, carbohydrate and fat intake did not affect these estimates. Inter-individual variation, estimated based on repeated measures in one of the studies, was 30–96%. Conclusions: Although the relation between isoflavone intake and plasma concentrations was adequately quantified, the use of isoflavone intake data for risk assessment needs caution due to large inter-individual variation in plasma concentrations.
Metabolism of the Lignan Macromolecule into Enterolignans in the Gastrointestinal Lumen As Determined in the Simulator of the Human Intestinal Microbial Ecosystem
Eeckhaut, E. ; Struijs, K. ; Possemiers, S. ; Vincken, J.P. ; Keukeleire, D. de; Verstraete, W. - \ 2008
Journal of Agricultural and Food Chemistry 56 (2008). - ISSN 0021-8561 - p. 4806 - 4812.
trap mass-spectrometry - secoisolariciresinol diglucoside - urinary-excretion - in-vitro - premenopausal women - equol production - gut microflora - enterolactone - isoflavones - bacteria
Estrogenic plant compounds from the human diet such as the lignan secoisolariciresinol diglucoside (SDG, 1) can exert biological activity in the human body upon ingestion and bioactivation to enterodiol (END, 5) and enterolactone (ENL, 6). Bioavailability of lignans is influenced by the food matrix and gut microbial action, of which the latter is subject to a large interindividual variation. In this study, the fate of the lignan precursor SDG, present in the lignan macromolecule of flax seed (Linum usitatissimum), was determined during an artificial stomach and small intestinal digestion and during metabolism by two different enterolignan phenotypes in a TWINSHIME environment (TWIN Simulator of the Human Intestinal Microbial Ecosystem). The lignan macromolecule acted as a delivery system of SDG in the large intestine. SDG was only hydrolyzed into secoisolariciresinol (SECO, 2) through microbial action in the ascending colon, after which it was bioactivated into enterolignans from the transverse colon onward. Single demethylation was a first step in the bioactivation, followed by dehydroxylation. Enterolignan phenotypes remained stable throughout the experimental period. The establishment of END and ENL production equilibria reflected the subdominance of ENL-producing bacteria in the gastrointestinal tract.
No Effect of Red Clover-Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer
Vrieling, A. ; Rookus, M.A. ; Kampman, E. ; Bonfrer, J.M.G. ; Bosma, A. ; Cats, A. ; Doorn, J. van; Korse, C.M. ; Witteman, B.J.M. ; Leeuwen, F.E. van; van't Veer, L.J. ; Voskuil, D.W. - \ 2008
Cancer Epidemiology Biomarkers and Prevention 17 (2008)10. - ISSN 1055-9965 - p. 2585 - 2593.
healthy postmenopausal women - hormone replacement therapy - randomized controlled-trial - igf-binding-proteins - factor-i - prostate-cancer - soy protein - premenopausal women - antioxidant status - dna microarray
Background: Increased insulin-like growth factor (IGF)-I and IGF-II concentrations are related to increased colorectal cancer risk. Isoflavones have been associated with reduced colorectal cancer risk, and may affect the IGF system because of their weak estrogenic activity. The aim of the study was to investigate the effect of isolated isoflavones on serum concentrations of IGF system components. Materials and Methods: We conducted a randomized, placebo-controlled, double-blinded, crossover trial in four hospitals in the Netherlands to investigate the effect of an 8-week supplementation with red clover¿derived isoflavones (84 mg/d) on serum IGF-I concentrations. In addition, serum concentrations of IGF-II and IGF binding proteins (IGFBP)-1, IGFBP-2, and IGFBP-3 were assessed. Normal colorectal tissue biopsies were obtained after the first intervention period and mRNA expression of IGF-I, IGF-II, IGFBP-3, and IGF-IR was evaluated. Our study population consisted of 34 postmenopausal women with a family history of colorectal cancer or a personal history of colorectal adenomas. Results: Isoflavone supplementation did not significantly affect serum concentrations of total IGF-I (mean relative within-person difference; IGF-I, ¿2.0%; 95% confidence interval, ¿8.0% to 3.9%). IGF-II and IGFBPs were also not significantly altered after isoflavone supplementation. Colorectal tissue mRNA expression of IGF system components did not significantly differ between individuals on isoflavone supplementation and those who received placebo. Conclusions: The results of our trial, supported by a qualitative review of soy trials published to date, suggest that isoflavones do not significantly affect circulating levels of IGF system components. Increased levels of IGF-I, as observed in most of these trials, are likely due to simultaneous protein suppl
Isolated Isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk
Vrieling, A. ; Rookus, M.A. ; Kampman, E. ; Bonfrer, J.M.G. ; Korse, C.M. ; Doorn, J. van; Lampe, J.W. ; Cats, A. ; Witteman, B.J.M. ; Leeuwen, F.E. van; van't Veer, L.J. ; Voskuil, D.W. - \ 2007
The Journal of Nutrition 137 (2007)2. - ISSN 0022-3166 - p. 379 - 383.
estrogen replacement therapy - red-clover - factor-i - postmenopausal women - binding protein-3 - soy protein - clinical characteristics - premenopausal women - antioxidant status - human health
Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: ¿1.3%, 95% CI ¿8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r = ¿0.49, P = 0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies