Omega-3 Fatty Acids Effects on Inflammatory Biomarkers and Lipid Profiles among Diabetic and Cardiovascular Disease Patients: A Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis was to investigate omega-3 fatty acids' influence on 12 inflammatory biomarkers-LDL, HDL, total cholesterol, TG, HbA1c, Apo AI, Apo AII, Apo B, CRP, TNF-α, glucose, and fasting blood glucose among diabetic and cardiovascular disease (CVD) patients. We searched articles in six database engines, and 16 of the 696 articles reviewed met the inclusion criteria. Among these, lipid and inflammatory biomarkers investigated commonly included total cholesterol (11 studies), LDL, and TG (10 studies each). Overall, omega-3 was associated with a significant reduction in Apo AII among diabetic patients, as compared to different controls (-8.0 mg/dL 95% CI: -12.71, -3.29, p = 0.0009), triglycerides (-44.88 mg/dL 95% CI: -82.6, -7.16, p < 0.0001), HDL (-2.27 mg/dL 95% CI: -3.72, -0.83, p = 0.002), and increased fasting blood glucose (16.14 mg/dL 95% CI: 6.25, 26.04, p = 0.001). Omega-3 also was associated with increased LDL among CVD patients (2.10 mg/dL 95% CI: 1.00, 3.20, p = 0.0002). We conclude that omega-3 fatty acids may be associated with lower inflammatory biomarkers among diabetic and cardiovascular patients. Clinicians should be aware of these potential benefits; however, it is essential to recommend that patients consult with clinicians before any omega-3 intake.

[Gel electrophoresis analysis on plasma differential protein in patients with unstable angina of blood-stasis pattern].

OBJECTIVE: To seek the plasma differential proteins in patients with unstable angina of blood-stasis pattern (UA-BSS) for exploring the proteomic specialty in them by way of two-dimensional difference gel electrophoresis (DIGE) detection on plasma of patients and healthy persons. METHODS: Using DIGE and tandem mass spectrometry, comparative proteomic study was conducted on the plasma of 12 UA patients of qi-deficiency and blood-stasis pattern (UA-QBS), 12 UA patients of phlegm-stasis cross-blocking pattern (UA-PSS) and 12 healthy volunteers. RESULTS: Preliminary results showed that Haptoglobin beta chain, DBP, HBB, HBA, Transthyretin, ApoA- I, ApoA-IV were significantly differentially expressed in both patterns, while Haptoglobin alpha1 chain, alpha-1-acid glycoprotein, ApoC-III, ApoA-II, ApoC-II, ApoJ, and Haptoglobin alpha 2 chain were only seen differentially expressed in the UA-PSS patients, alpha1-antitrypsin, Fibrinogen gamma chain, and Fibrin beta were only seen differentially expressed in UA-QBS patients. CONCLUSION: The common proteomics characteristics of patients of QBS and PSS patterns may be correlated with inflammatory reaction and metabolic disturbance (including blood lipid and blood oxygen).

Effect of dietary unsaturated fatty acids on senile amyloidosis in senescence-accelerated mice.

Effects of dietary oils on aging were investigated in senescence-accelerated mice. For 26 weeks, mice were fed purified diets containing 4% olive oil, safflower oil, perilla oil, or fish oil. Serum total, high-density lipoprotein cholesterol, and apolipoprotein A-II (ApoA-II) were significantly lower in the fish oil group than in the perilla oil group, and these were significantly lower than in the olive oil or safflower oil group. The olive oil and safflower oil groups had significantly fewer ApoA-II amyloid fibril (AApoAII) deposits and anti-single-strand DNA (ssDNA) antibodies than the fish oil or perilla oil group, and the fish oil diet induced significantly more AApoAII deposits and anti-ssDNA antibodies than did the perilla oil diet. Survival decreased earlier in the fish oil group than in the other groups (as seen in the survival curve). The results suggest that greater the degree of unsaturation of dietary fatty acids, greater is the tendency for accelerated senescence.

Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity.

BACKGROUND: Disturbed HDL metabolism in insulin-resistant, obese subjects may account for an increased risk of cardiovascular disease. Fish oils and atorvastatin increase plasma HDL cholesterol, but the underlying mechanisms responsible for this change are not fully understood. OBJECTIVE: We studied the independent and combined effects of fish oils and atorvastatin on the metabolism of HDL apolipoprotein A-I (apo A-I) and HDL apo A-II in obese men. DESIGN: We conducted a 6-wk randomized, placebo-controlled, 2 x 2 factorial intervention study of the effects of fish oils (4 g/d) and atorvastatin (40 mg/d) on the kinetics of HDL apo A-I and HDL apo A-II in 48 obese men with dyslipidemia with intravenous administration of [d3]-leucine. Isotopic enrichments of apo A-I and apo A-II were measured with gas chromatography-mass spectrometry with kinetic parameters derived from a multicompartmental model (SAAM II). RESULTS: Fish oils and atorvastatin significantly decreased plasma triacylglycerols and increased HDL cholesterol and HDL2 cholesterol (P < 0.05 for main effects). A significant (P < 0.02) main effect of fish oils was observed in decreasing the fractional catabolic rate of HDL apo A-I and HDL apo A-II. This was coupled with a significant decrease in the corresponding production rates, accounting for a lack of treatment effect on plasma concentrations of apo A-I and apo A-II. Atorvastatin did not significantly alter the concentrations or kinetic parameters of HDL apo A-I and HDL apo A-II. None of the treatments altered insulin resistance. CONCLUSIONS: Fish oils, but not atorvastatin, influence HDL metabolism chiefly by decreasing both the catabolism and production of HDL apo A-I and HDL apo A-II in insulin-resistant obese men. Addition of atorvastatin to treatment with fish oils had no additional effect on HDL kinetics compared with fish oils alone.

Dietary exchange of an olive oil and sunflower oil blend for extra virgin olive oil decreases the estimate cardiovascular risk and LDL and apolipoprotein AII concentrations in postmenopausal women.

BACKGROUND: Dietary supplementation with Virgin olive oil is considered cardioprotective. Decreasing LDL and apolipoprotein (apo) AII-lipoproteins is also appropriate for CHD protection and treatment. AIM: To study the effects of an 8%En dietary exchange of linoleic acid for oleic acid on serum and lipoprotein levels and serum and LDL-TBARS in postmenopausal women consuming a diet rich in fat (46%En; saturated/monounsaturated/polyunsaturated profile: 1.1/1.9/1). EXPERIMENTAL DESIGN: 14 postmenopausal women (63 +/- 11 years) were assigned to exchange during 28-day dietary period the culinary oil used for years consisting in a blend of olive oil plus sunflower oil (SO) for extra virgin olive oil (EVOO). SO and EVOO represented 62% of the total lipid intake. DETERMINATIONS: Dietary intakes, serum Lp(a), and cholesterol, triglycerides, phospholipids, protein, apolipoproteins AI, AII, B were determined in serum and lipoproteins. RESULTS: The dietary intervention decreased serum total cholesterol (TC), phospholipids, apo AII (all, p < 0.001) and apo B (p < 0.01). Except for triglycerides, all components of the LDL fraction decreased (at least, p < 0.05). HDL-cholesterol was not affected but HDL-phospholipids and HDL-lipids decreased (at least, p < 0.01). VLDL-apo B and VLDL-proteins decreased (all, p < 0.001). Serum Lp(a), TBARS and LDL-TBARS were not affected by the dietary exchange. The estimate of 10-year cardiovascular risk decreased (p < 0.05). Apo AII (p = 0.061) and LDL-cholesterol (p < 0.05) underwent greater modifications in normocholesterolemics, while LDL-phospholipids (p = 0.094), experienced greater alterations in hypercholesterolemics. No significant interaction was observed between dietary exchange and age (> or <65 yrs). CONCLUSIONS: These findings suggest that the dietary exchange of an olive oil and sunflower oil blend for extra virgin olive decreases LDL and apo AII levels, and the estimate of 10-year cardiovascular risk.

Dietary fat saturation affects apolipoprotein AII levels and HDL composition in postmenopausal women.

Increased HDL-cholesterol levels have been associated with lower coronary heart disease (CHD) risk. However, HDL are heterogeneous lipoproteins, and particles enriched in apolipoprotein (Apo) AII have been associated with increased CHD risk. We examined the effect of dietary intervention on HDL composition in 14 postmenopausal women subjected to two consecutive diet periods, i.e., an oleic acid sunflower oil diet followed by a palmolein diet, each lasting 4 wk. The linoleic acid was kept at 4% total energy and the cholesterol intake at 400 mg/d. The palmolein diet increased serum total cholesterol (TC) (P < 0.001), phospholipids (P < 0.001), Apo AII (P < 0.001), HDL cholesterol (P < 0.05), HDL lipids (P < 0.05), HDL proteins (P < 0.01) and the HDL total mass (P < 0.05). The HDL cholesterol/Apo AI ratio was increased 22.0% (P < 0.05), whereas the HDL cholesterol/Apo AII and the Apo AI/Apo AII ratios were decreased 19.4% (P < 0.01) and 30.4%, (P < 0.001), respectively. When the effects of the dietary intervention were examined according to the cholesterolemia status (< or >6.2 mmol/L), the most significant changes (P < 0.001) were related to Apo AII levels. Moreover, a significant dietary oil by cholesterol level interaction was found for Apo AII and the HDL cholesterol/Apo AII ratio. In summary, a palmolein diet increased TC and HDL cholesterol compared with oleic acid sunflower oil diet; however, the increase in Apo AII but not in Apo AI suggests the impairment of reverse cholesterol transport and potentially an increase in CHD risk. This effect was more marked in women with serum TC > 6.2 mmol/L.

Dietary n-3 polyunsaturated fat increases the fractional catabolic rate of medium-sized HDL particles in African green monkeys.

We have previously described a novel pathway for the metabolism of HDL subfractions in which small [2 apolipoprotein (apoA-I) molecules per particle] HDL particles are converted in a unidirectional manner outside the plasma compartment to medium (3 apoA-I molecules per particle) or large (4 apoA-I molecules per particle) HDL particles, which are subsequently removed from the circulation by the liver (Colvin et al. 1999. J. Lipid Res. 40: 1782;-1792; Huggins et al. 2000. J. Lipid Res. 41: 384;-394). The purpose of the present study was to determine whether the reduction in concentration of medium HDL in African green monkeys consuming n-3 polyunsaturated versus saturated fat diets resulted from decreased in vivo production or increased catabolism. Tracer small LpA-I (HDL containing only apoA-I) were isolated, without ultracentrifugation, by gel filtration and immunoaffinity chromatography and radiolabeled. After injection, the specific activity of apoA-I in small, medium, and large HDL was determined, and the kinetic data were analyzed using our previously published multicompartmental model for HDL subfraction metabolism. We found a significant reduction of apoA-I concentration in medium HDL in the animals fed n-3 polyunsaturated fat (31.2 +/- 0.7 mg/dl) compared with animals fed saturated fat (85.4 +/- 11.9 mg/dl; P = 0.002). The production rates of apoA-I in small, medium, and large HDL were similar in both diet groups; however, there was a significant increase in the fractional catabolic rate of apoA-I in medium HDL in the animals fed n-3 polyunsaturated fat (2.188 +/- 0.501 pools/day) compared with animals fed saturated fat (0.714 +/- 0.191 pools/day; P = 0.02). We conclude that n-3 polyunsaturated fat reduces HDL cholesterol concentration by increasing the fractional catabolic rate of medium-sized HDL particles in African green monkeys.

Hypobetalipoproteinemia associated with apo B-48.4, a truncated protein only 14 amino acids longer than apo B-48.

Familial hypobetalipoproteinemia is an autosomal codominant trait that can be caused by mutations in the apo B gene. Here we report a novel apo B gene mutation causing hypobetalipoproteinemia, that is associated with the synthesis of a truncated apo B protein in a young healthy male subject and his mother. The mutation is an A deletion at position 6627 of the apo B cDNA leading to a truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the lipoprotein deficient plasma fraction. Affected family members present with elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles. Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein in the proband showed a normal response to an oral fat load compared to a group of eight matched healthy controls. In summary this novel mutation is associated with hypobetalipoproteinemia with a normal fat absorption as expected for a protein with a length similar to that of apo B-48.

Hepatic origin of cholesteryl oleate in coronary artery atherosclerosis in African green monkeys. Enrichment by dietary monounsaturated fat.

Relationships among plasma lipoprotein cholesterol, cholesterol secretion by the isolated, perfused liver, and coronary artery atherosclerosis were examined in African green monkeys fed diets containing cholesterol and 35% of calories as fat enriched in polyunsaturated, monounsaturated, or saturated fatty acids. The livers of animals fed monounsaturated fat had significantly higher cholesteryl ester concentrations (8.5 mg/g wet wt) than the livers of the other diet groups (3.65 and 3.37 mg/g wet wt for saturated and polyunsaturated fat groups, respectively) and this concentration was highly correlated with plasma cholesterol and apoB concentrations in each diet group. Cholesteryl oleate was 58 and 74. 5% of the liver cholesteryl ester in the saturated and monounsaturated fat groups. In each diet group, perfusate cholesteryl ester accumulation rate was highly correlated to liver and plasma cholesterol concentrations, and to plasma LDL cholesteryl ester content. Cholesteryl oleate was 48 and 67% of the cholesteryl esters that accumulated in perfusate in the saturated and monounsaturated fat animals, and this percentage was very highly correlated (r = -0.9) with plasma apoB concentration. Finally, in these two diet groups, liver perfusate cholesteryl ester accumulation rate was well correlated (r >/= 0.8) to coronary artery cholesteryl ester concentration, a measure of the extent of coronary artery atherosclerosis that occurred over the five years of diet induction in these animals. These data define an important role for the liver in the cholesteryl oleate enrichment of the plasma lipoproteins in the saturated and monounsaturated fat groups, and demonstrate strong relationships among hepatic cholesteryl ester concentration, cholesteryl ester secretion, and LDL particle cholesteryl ester content. The high correlation between liver cholesteryl ester secretion and coronary artery atherosclerosis provides the first direct demonstration of the high degree of importance of hepatic cholesteryl ester secretion in the development of this disease process. The remarkable degree of enrichment of cholesteryl oleate in plasma cholesteryl esters of the monounsaturated fat group may account for the relatively high amount of coronary artery atherosclerosis in this group.

Consistent relationship between selenium and apolipoprotein A-II concentrations in the sera of fasting middle-aged male abstainers and regular consumers of alcohol.

Several studies have suggested that selenium serum levels may be associated with serum lipids and apolipoproteins. In the present study, 99 clerical workers aged 40-49 yr were selected based on their drinking and smoking habits. The serum concentration of selenium was not affected by these lifestyle factors. The regular drinkers had raised serum high-density lipoprotein cholesterol, apo A-I, and apo A-II concentrations. Correlation analysis showed that serum selenium was positively and consistently associated with apo A-II regardless of alcohol consumption. Factor analysis revealed that serum selenium had no association with factors that represented each lipoprotein fraction (LDL, HDL, and VLDL). The present study indicates that serum selenium is positively correlated only with apo A-II levels.

Effects on health of dietary supplementation with 100 mg d-alpha-tocopheryl acetate, daily for 6 years.

To evaluate the clinical antioxidant effects of vitamin E, 161 healthy volunteers aged 39 to 56 years, were given 100 or 3 mg of d-alpha-tocopheryl acetate orally daily for 6 years using a randomized, double-blind design. Among the 147 volunteers who qualified for the analysis, seven of the 73 volunteers receiving 3 mg d-alpha-tocopheryl acetate daily and none of the 74 volunteers receiving 100 mg had coronary disorders including myocardial damage (P < 0.02). ST or T wave abnormalities on electrocardiograms were considered to indicate coronary disorders (four volunteers). The mean serum total tocopherol (TOC) concentration in the 100-mg group was significantly higher than that in the 3-mg group 6 months after the start of the study, and this raised value was maintained throughout the study; the level in the 3-mg group did not change significantly from the baseline value. The low-density lipoprotein cholesterol/total TOC ratio, a parameter of the inhibition of peroxidation of low-density lipoprotein cholesterol, was the only serum lipid parameter that was significantly different, at baseline, in the volunteers with coronary disorders compared with the others. These findings indicate that long-term supplementation with 100 mg tocopheryl acetate daily may prevent the early stages of coronary atherosclerosis by decreasing peroxidation of low-density lipoprotein cholesterol.

Effects of celiprolol vs. nifedipine on serum lipoproteins in patients with mild to moderate hypertension.

During a double-blind, randomized study in hypertensive patients, changes in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20-64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily), each time using a double-dummy technique. After 6 weeks, dosages of each drug could be doubled. After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks of treatment were different (p < 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol, and apoprotein AI, AII, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified. The present study showed that celiprolol was at least equivalent to nifedipine in terms of secondary effects on plasma lipids and lipoprotein.