Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes.

BACKGROUND: Plasma lipoproteins may be classified by their apolipoprotein composition. The lipoprotein subclass containing apolipoproteins B and C (LpB:C) is considered the most atherogenic. OBJECTIVE: We evaluated the acute effects of individual fatty acids on apolipoprotein B (apo B)-containing lipoproteins in adults with type 2 diabetes (n = 15). DESIGN: We administered 3 meals in a randomized, double-blind, crossover design. Treatments contained skim milk and 50 g fat from high-oleic acid safflower and canola oils (monounsaturated fatty acid; MUFA), MUFA + 3.5 g alpha-linolenic acid (ALA; MUFA + ALA) from high-ALA canola oil, or MUFA + 4.0 g both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; MUFA + EPA/DHA) from sardine oil. Apo B, LpB, LpB:C, LpB:E + LpB:C:E, and LpA-II:B:C:D:E were measured at baseline and 2 and 4 h after the meal. Flow-mediated dilation was measured at baseline and 4 h after the meal. RESULTS: The treatments significantly increased apo B and LpB postprandially (P < 0.03 for both), but the magnitude of the changes did not differ significantly between the treatments. The postprandial change in LpB:C was 23% lower after MUFA + EPA/DHA than after MUFA (treatment x time interaction, P < 0.0001). MUFA + ALA attenuated the increase in LpA-II:B:C:D:E in those with high triacylglycerols (>/=1.69 mmol/L) but was the only treatment to significantly increase this particle in those with low triacylglycerols (treatment x group interaction, P < 0.0001). Examination of change scores did not reveal the source of the interaction of treatment and time (P < 0.007) for LpB:E + LpB:C:E. Furthermore, the subjects with the largest increases in LpB:C exhibited the largest impairment in endothelial function. CONCLUSIONS: The results suggest that unsaturated fatty acids differentially affect concentrations of apo B-containing lipoprotein subclasses. A rise in LpB:C adversely affects endothelial function. Meals containing MUFA + EPA/DHA attenuated the postprandial rise in LpB:C and the impairment of endothelial function.

An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans.

Human, animal, and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 (n-3) polyunsaturated fatty acids (PUFA) on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). Subjects (n = 23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1) Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA), 13% monounsaturated fatty acids (MUFA), 9% PUFA (7.7% LA, 0.8% ALA)]), 2) Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]), and 3) alpha-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of ALA. NTx levels were significantly lower following the ALA diet (13.20 +/- 1.21 nM BCE), relative to the AAD (15.59 +/- 1.21 nM BCE) (p < 0.05). Mean NTx level following the LA diet was 13.80 +/- 1.21 nM BCE. There was no change in levels of BSAP across the three diets. Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFalpha for all three diets. The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation.

Lipid response to a low-fat diet with or without soy is modified by C-reactive protein status in moderately hypercholesterolemic adults.

Recent evidence suggests that individuals with high concentrations of C-reactive protein (CRP), a marker of inflammation, are less responsive to cholesterol-lowering diets. CRP concentrations are increased by oral estrogen; however, the effect of soy phytoestrogens on inflammation has not been studied comprehensively, especially in women receiving hormone replacement therapy (HRT). This study was conducted to determine whether adding soy to a low-fat, high-fiber diet affects CRP and interleukin (IL)-6, and to examine the association between CRP levels and lipid response in moderately hypercholesterolemic adults (men = 18, postmenopausal women = 14; 6 receiving HRT). After a 3-wk run-in period with consumption of a Step I diet (27% total fat, 7% saturated fat, 275 mg cholesterol), participants were randomly assigned to diets containing 25 g/d soy protein (+ 90 mg/d isoflavones) or 25 g/d milk protein for 6 wk in a crossover design. Lipids and lipoproteins, CRP, and IL-6 were measured at the end of each diet and participants were categorized into high (>3.5 mg/L) or low CRP groups based on a median split. The addition of soy or milk protein to the Step I diet did not affect lipids or inflammatory markers. Regardless of protein source, those with low CRP exhibited significant decreases in LDL cholesterol (-3.5%) and the LDL:HDL cholesterol ratio (-4.8%), whereas those with high CRP had significant increases in LDL cholesterol (+4.8%), the LDL:HDL cholesterol ratio (+5.2%), apolipoprotein B (+3.8%), and lipoprotein(a) (+13.5%) compared with the run-in diet. These results suggest that inflammation may not only attenuate lipid responses, but also aggravate dyslipidemia in hypercholesterolemic subjects consuming a cholesterol-lowering diet.

Effects of including soy protein in a blood cholesterol-lowering diet on markers of cardiac risk in men and in postmenopausal women with and without hormone replacement therapy.

BACKGROUND: Increased consumption of soy foods has been associated with reduction in low density lipoprotein cholesterol (LDL-C) in both clinical and observational studies. However, it is not clear whether adding soy to a low-fat diet has additional lipid-lowering benefits, and few previous studies have examined these effects in women using hormone replacement therapy (HRT+). METHODS: We tested whether adding soy protein to a low-fat, high-fiber, Step I diet improved cardiac risk markers in 18 postmenopausal women and 14 men with hypercholesterolemia and examined whether concurrent use of HRT altered diet responsiveness. Diets were matched for macronutrient content, and all food was provided. After 3 weeks on the Step I diet, subjects were randomized to diets (6 weeks) containing 25 g/day protein isolate from soy or cow's milk, with crossover. The soy treatment contained 90 mg/day isoflavones. Lipids, vascular cell adhesion molecule-1 (VCAM-1), p-selectin, and urinary isoflavonoids were measured at the end of each diet. RESULTS: In men and HRT- women only, there were significant reductions in LDL-C (-17.3%), high-density lipoprotein cholesterol (HDL-C) (-15.3%), and triglycerides (-11.5%) during the Step I diet, and soy had no additional effects. At study entry, HRT+ women had lower LDL-C and higher triglycerides than men. Their LDL-C was unchanged, and triglycerides were significantly reduced (-15.1%) by the Step I diets. Isoflavonoid excretion was unrelated to diet response or HRT status. CONCLUSIONS: In men and HRT- women, the diets significantly lowered LDL-C, independent of soy intake. In HRT+ women, the diets improved triglycerides without lowering HDL-C.

Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer.

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, legumes, oils, and nuts.