Functional foods and cardiovascular disease.

Functional foods are foods that, by virtue of physiologically active food components, provide health benefits beyond basic nutrition. Many functional foods have been found to be potentially beneficial in the prevention and treatment of cardiovascular disease, the leading cause of mortality in the United States. These foods include soybeans, oats, psyllium, flaxseed, garlic, tea, fish, grapes, nuts, and stanol- and sterol ester enhanced margarine. When eaten in adequate amounts on a consistent basis, these foods may aid in decreasing the risk of cardiovascular disease by several potential mechanisms: lowering blood lipid levels, improving arterial compliance, reducing low-density lipoprotein oxidation, decreasing plaque formation, scavenging free radicals, and inhibiting platelet aggregation.

Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian hormone deficiency in rats.

Soy protein, a rich source of isoflavones, fed immediately after an ovariectomy prevents bone loss in rats. Reports of the effectiveness of natural and synthetic isoflavones in preventing or treating osteoporosis led us to examine the effect of soy protein in reversing established bone loss. Seventy-two 95-d-old female Sprague-Dawley rats were assigned to 6 groups. The rats were either sham operated (SHAM; 2 groups) or ovariectomized (OVX; 4 groups) and then fed a casein-based, semipurified diet. Thirty-five days after surgery, 1 SHAM and 1 OVX group were killed to examine the occurrence of bone loss. Thereafter, the other SHAM and 1 OVX groups continued to receive the casein-based diet. Whereas the remaining 2 OVX groups received diets in which casein was replaced by soy protein with normal (OVX+SOY) or reduced (OVX+SOY-) isoflavone content for 65 days. The OVX control group had significantly lower femoral and fourth lumbar vertebral bone densities than the SHAM group. Femoral density of rats fed SOY or SOY- diets were not significantly different from SHAM or OVX controls. This suggests a slight reversal of cortical bone loss that may be partially due to higher femoral insulin-like growth factor I mRNA transcripts resulting from both the SOY and SOY- diets. The ovariectomy-induced increases in indexes of bone turnover were not ameliorated by either of the soy diets, suggesting that any positive effect of soy was achieved through enhanced bone formation rather than slowed bone resorption. Long-term consumption of soy or its isoflavones may be needed to produce small but continued increments in bone mass.

Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content.

Our previous studies showed that a soy-protein diet prevents ovariectomy-induced bone loss. The purpose of this study was to determine whether isoflavones in soy protein are responsible for this bone-protective effect. Forty-eight 95-d-old Sprague-Dawley rats were divided into 4 groups: sham-operated fed a casein-based diet (SHAM), ovariectomized fed a casein-based diet (OVX+CASEIN), ovariectomized fed soy protein with normal isoflavone content (OVX+SOY), and ovariectomized fed soy protein with reduced isoflavone content (OVX+SOY-). The OVX+SOY group had significantly greater femoral bone density (in g/cm3 bone vol) than the OVX+CASEIN group, whereas OVX+SOY- was similar to OVX+CASEIN (mean +/- SD; SHAM, 1.522 +/- 0.041; OVX+CASEIN, 1.449 +/- 0.044; OVX+SOY, 1.497 +/- 0.030; OVX+SOY-, 1.452 +/- 0.030). Ovariectomy resulted in greater bone turnover as indicated by higher serum alkaline phosphatase activity, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations, and urinary hydroxyproline. These increases were not affected by soy with either normal or reduced isoflavone content. Similarly, histomorphometry revealed a greater bone formation rate with ovariectomy, and this was not altered by the soy diets. The findings of this study suggest that isoflavones in soy protein are responsible for its bone-sparing effects. Further studies to evaluate the mechanism of action of isoflavones on bone are warranted.

Incorporation of n-3 fatty acids into WB-F344 cell phospholipids inhibits gap junctional intercellular communication.

In this investigation, we demonstrate that rat liver epithelial (WB-F344) cells grown in medium supplemented with n-3 fatty acids (FA) results in the inhibition of gap junctional intercellular communication (GJIC). Cells incubated for 48 hr in medium containing 50 microM alpha-linolenate (18:3n-3) resulted in a 60% inhibition of GJIC, compared to control cells, while treatment with gamma-linolenate (18:3n-6) had no effect. Supplementation with octadecatetraenoate (18:4n-3), eicosapentaenoate (20:5n-3), and docosahexaenoate (22:6n-3), inhibited GJIC by 42%, 28%, and 18%, respectively. Incubation with each of the n-3 FA markedly increased the total n-3 FA content of cellular phospholipids (PL). Growing cells in medium containing 50 microM arachidonate (20:4n-6) plus 50 microM 18:3n-3 partially attenuated the inhibition of GJIC induced by 18:3n-3. The mechanism by which n-3 FA inhibit GJIC remains to be determined.

Inhibition of gap junction-mediated intercellular communication by alpha-linolenate.

The purpose of this investigation was to assess whether alterations in the fatty acid composition of rat liver epithelial (WB-F344) cell phospholipids would modulate gap junction-mediated intercellular communication (GJIC). WB-F344 cells were grown to confluency in culture medium supplemented with one of seven different fatty acids at a concentration of 50 microM for 48 h. Only alpha-linoleate (18:3 n-3) significantly inhibited GJIC. Saturated fatty acids (12:0, 16:0, and 18:0), a monounsaturated fatty acid (18:1 n-9), and n-6 polyunsaturated fatty acids (18:2 and 20:4) did not affect GJIC. The alpha-linolenate-induced inhibition of GJIC was not due to the activation of protein kinase C or intracellular hydroperoxide production, two lipid-dependent parameters previously shown to inhibit GJIC. In addition, alpha-linolenate did not alter membrane fluidity. Although the mechanism by which alpha-linolenate inhibits GJIC is unclear, changes in the fatty acid composition of cell phospholipids may be of critical importance. Subsequent to supplementation with alpha-linolenate, WB-F344 cell phospholipids had reduced 20:4 n-6 and elevated n-3 fatty acids. The results of this investigation emphasize the importance of current research into the influence of lipids on cell function and identify a new mechanism by which gap junctions can be modulated.