Large inter-individual variation in isoflavone plasma concentration limits use of isoflavone intake data for risk assessment.

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%, R(2)>0.87) for daidzein, genistein, equol (only for producers) and total isoflavones; for glycitein the association was weaker (15±1%, R(2)=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.

No effect of fish oil supplementation on serum inflammatory markers and their interrelationships: a randomized controlled trial in healthy, middle-aged individuals.

BACKGROUND: A high intake of n-3 polyunsaturated fatty acids (PUFAs), mainly present in fish, may be associated with decreased inflammation. Previous intervention studies on fish PUFA and inflammatory markers in healthy individuals did not analyze a broad spectrum of inflammatory cytokines, chemokines and cell adhesion molecules, or their interrelationships. Therefore, we determined the effects of fish oil supplementation on 19 serum inflammatory markers and their interrelationships in healthy, middle-aged individuals. METHODS: Individuals (n=77) aged 50-70 years completed a randomized, double-blind placebo-controlled intervention study. Participants received 3.5 g/day fish oil (1.5 g/day total n-3 PUFA) (n=39) or placebo (high oleic sunflower oil) (n=38) for 12 weeks. Serum concentrations of 19 inflammatory markers were determined using a multiplex immunoassay before and after intervention. Changes in concentrations were analyzed using analysis of covariance and differences in patterns in inflammatory markers between the fish oil and placebo group were analyzed by principal component analysis. RESULTS: Fish oil supplementation did not significantly affect serum concentrations of cytokines, chemokines or cell adhesion molecules as compared with placebo. However, there was a trend for all inflammatory markers to increase after fish oil supplementation. PCA did not result in markedly distinctive patterns of inflammatory markers for the fish oil and placebo group. CONCLUSION: In conclusion, this 12-week randomized, double-blind placebo-controlled intervention trial did not show that 1.5 g/day n-3 PUFA significantly affected the serum inflammatory response in healthy individuals, nor did patterns of inflammatory markers. Thus, a healthy middle-aged population may not benefit from fish oil as an anti-inflammatory agent.

Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects.

OBJECTIVE: High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of cardiovascular risk. We hypothesised that n-3 fatty acids reduce underlying inflammatory processes and consequently CRP concentrations in healthy middle-aged subjects. DESIGN: Placebo-controlled, double-blind study. SUBJECTS: A total of 43 men and 41 postmenopausal women aged 50-70 y. Before and after intervention, we measured serum CRP concentrations with an enzyme immunoassay. INTERVENTIONS: Capsules with either 3.5 g/day fish oil (1.5 g/day n-3 fatty acids) or placebo for 12 weeks. RESULTS: The median CRP change in the fish oil group did not significantly differ from that in the placebo group (0.01 vs -0.17 mg/l, P = 0.057). CONCLUSION: The currently available data--including ours--do not support that beneficial effects on CRP are involved in a mechanism explaining the protective effect on heart disease risk of n-3 fatty acids as present in fish.