Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P < .001) and IGFBP-3 (P = .01) and the LF diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals.

Effects of furanocoumarins from apiaceous vegetables on the catalytic activity of recombinant human cytochrome P-450 1A2.

Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are potent inhibitors of several CYPs, we characterized the effects of three furanocoumarins from apiaceous vegetables on human CYP1A2 (hCYP1A2). We assessed hCYP1A2 methoxyresorufin O-demethylase (MROD) activity using microsomes from Saccharomyces cerevisiae expressing hCYP1A2. Isopimpinellin exhibited mechanism-based inactivation (MBI) of hCYP1A2 (K(i) = 1.2 µM, k (inact) = 0.34 min⁻¹, and partition ratio = 8). Imperatorin and trioxsalen were characterized as mixed inhibitors with K(i) values of 0.007 and 0.10 µM, respectively. These results indicate that even if present at low levels in apiaceous vegetables, imperatorin, trioxsalen and isopimpinellin may contribute significantly to CYP1A2 inhibition and potentially decreased procarcinogen activation. Moreover, the in vivo effect of isopimpinellin on CYP1A2 may be longer lasting compared to reversible inhibitors.

Effect of dietary fat and omega-3 fatty acids on urinary eicosanoids and sex hormone concentrations in postmenopausal women: a randomized controlled feeding trial.

Substantial evidence relates increased sex hormone concentrations with increased breast cancer risk. Varying omega-3 (n-3) fatty acid (FA) intake may lead to alterations in eicosanoid balance and changes in circulating sex hormones that reduce risk. To clarify effects of dietary fat and n-3 FA intake on breast cancer risk markers, circulating sex hormones and urinary eicosanoids were measured in response to controlled feeding of diets designed to increase plasma concentrations of n-3 FA. A controlled cross-over feeding trial in postmenopausal women was conducted using 3 diets: high fat (HF; 40% energy from fat), low fat (LF; 20% energy from fat), and low fat plus n-3 FA (LFn3; 20% of energy from fat plus 3% of energy from n-3 FA) in 8-wk feeding periods. Plasma phospholipid fatty acid n-3 increased with the LFn3 relative to HF and LF (P < 0.0001). Plasma estradiol increased by 51% with HF (P = 0.03). Urinary prostaglandin E metabolite increased with HF relative to LF (P = 0.02) and urinary 11-dehydro-thromboxane B(2) increased with HF (P = 0.01). These results do not support a role of n-3 FA in the reduction of sex hormone levels.