Life Extension Magazine May 2006
Effects of omega-3 fatty acid supplementation and exercise on low-density lipoprotein and high-density lipoprotein subfractions.
The purpose of this study was to examine the effect of combining exercise with omega-3 fatty acids (n-3fa) supplementation on lipoprotein subfractions and associated enzymes. Subjects were 10 recreationally active males, aged 25 +/- 1.5 years (mean +/- SE), who supplemented n-3fa (60% eicosapentaenoic acid [EPA] and 40% docosahexaenoic [DHA]) at 4 g/d for 4 weeks. Before and after supplementation, subjects completed a 60-minute session of treadmill exercise at 60% Vo(2)max. Following a 24-hour diet and activity control period, blood was collected immediately before and after the exercise session to assess lipid variables: high-density lipoprotein cholesterol (HDL-C) and subfractions, low-density lipoprotein cholesterol (LDL-C) and subfractions and particle size, lecithin:cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity. Supplementation with n-3fa alone increased total HDL-C and HDL(2)-C, while exercise alone increased total HDL-C, HDL(3)-C, and total LDL-C. LDL subfractions, particle size, and LCAT and CETP activities were not affected by supplementation. Combination treatment resulted in an additive effect for HDL(3)-C only and also increased LDL(1)-C versus baseline. LCAT and CETP activities were not affected by treatments. These results suggest that n-3fa supplementation or an exercise session each affect total HDL-C and subfractions but not LDL-C or subfractions. In addition, the combination of n-3fa and exercise may have additional effects on total HDL-C and LDL-C subfractions as compared to either treatment alone in active young men.
Metabolism. 2004 Jun;53(6):749-54
Association between small dense low-density lipoprotein and postprandial accumulation of triglyceride-rich remnant-like particles in normotriglyceridemic patients with myocardial infarction.
BACKGROUND: Although the small dense low-density lipoprotein (sd-LDL) is associated with hypertriglyceridemia, more than 60% of myocardial infarction (MI) patients are normotriglyceridemic in the fasting state. This study was aimed to investigate the relationship between the low-density lipoprotein (LDL) phenotype and postprandial hyperlipemia (PPL) in MI patients. METHODS AND RESULTS: Oral fat tolerance tests were performed in 71 patients with acute MI and fasting triglyceride concentrations below 200 mg/dl. Postprandial changes in the LDL particle diameter (LDL-PD) and lipids over a 6-h period after a meal were compared among 4 groups of patients classified according to fasting triglyceride levels (A, B as <150, and C, D as > or =150) and postprandial triglyceride levels (A, C as <230 and B, D as > or =230). Although fasting concentrations of triglyceride and remnant-like particle (RLP)-triglyceride were significantly higher in group C than in group B, the areas under the curves of the RLPs were significantly higher in group B. The triglyceride-to-cholesterol ratio in the RLPs was significantly higher in the PPL group than in the nonPPL group postprandially. The prevalence of sd-LDL (LDL-PD < or =25.5 nm) was significantly higher in group D but similar between groups B and C (23%, 42%, 50% and 83% in groups A, B, C and D, respectively). CONCLUSION: These results suggest that postprandial accumulation of triglyceride-rich lipoproteins is strongly associated with sd-LDL in MI patients without hypertriglyceridemia.
Circ J. 2004 Dec;68(12):1165-72
Contribution of postprandial lipemia to the dietary fat-mediated changes in endogenous lipoprotein-cholesterol concentrations in humans.
BACKGROUND: Dietary fats alter LDL and HDL cholesterol while serving as precursors of postprandial triacylglycerol-rich lipoproteins (TRLs). OBJECTIVE: We hypothesized that the saturated fatty acid (SFA)-mediated increase and the polyunsaturated fatty acid (PUFA)-mediated decrease in endogenous lipoprotein cholesterol are promoted by postprandial TRLs. DESIGN: We performed a 16-d crossover diet study to examine the effect of PUFA-rich [ratio of PUFAs to SFAs (P:S) = 2.0] and SFA-rich (P:S = 0.25) diets on fasting and postprandial plasma lipid and lipoprotein-cholesterol concentrations in 16 normolipidemic subjects. RESULTS: Fasting plasma cholesterol decreased significantly after a PUFA-rich diet because of a decrease in LDL (-12.3%; P < 0.05) and HDL (-3.8%; NS), but did not change after an SFA-rich diet. The appearance of postprandial TRLs in plasma at 4 h was linked to a significant lowering of both LDL (-7.4%) and HDL (-4.8%) after a PUFA-rich diet; no such effect was observed after the SFA-rich diet. At 7 h, LDL and HDL cholesterol returned to near fasting concentrations without postprandial TRL accumulation after a PUFA-rich diet but with a significant postprandial TRL accumulation after an SFA-rich diet. Thus, the in vivo postprandial clearance of cholesterol in LDL+HDL was greater after a PUFA-rich diet than after an SFA-rich diet. The appearance of postprandial TRLs in plasma increased the cholesteryl ester transfer protein-mediated transfer of cholesteryl ester from LDL+HDL to TRLs in vitro without a significant influence from dietary fat. CONCLUSION: Dietary fat-mediated alterations in the rate of hepatic removal of postprandial TRLs, which carry cholesterol accepted from LDL+HDL via cholesteryl ester transfer protein in vivo, may contribute to the dietary fat-mediated change in endogenous lipoprotein cholesterol.
Am J Clin Nutr. 2004 Nov;80(5):1145-58
Lipoprotein(a): an elusive cardiovascular risk factor.
Lipoprotein (a) [Lp(a)], is present only in humans, Old World nonhuman primates, and the European hedgehog. Lp(a) has many properties in common with low-density lipoprotein (LDL) but contains a unique protein, apo(a), which is structurally different from other apolipoproteins. The size of the apo(a) gene is highly variable, resulting in the protein molecular weight ranging from 300 to 800 kDa; this large variation may be caused by neutral evolution in the absence of any selection advantage. Apo(a) influences to a major extent metabolic and physicochemical properties of Lp(a), and the size polymorphism of the apo(a) gene contributes to the pronounced heterogeneity of Lp(a). There is an inverse relationship between apo(a) size and Lp(a) levels; however, this pattern is complex. For a given apo(a) size, there is a considerable variation in Lp(a) levels across individuals, underscoring the importance to assess allele-specific Lp(a) levels. Further, Lp(a) levels differ between populations, and blacks have generally higher levels than Asians and whites, adjusting for apo(a) sizes. In addition to the apo(a) size polymorphism, an upstream pentanucleotide repeat (TTTTA(n)) affects Lp(a) levels. Several meta-analyses have provided support for an association between Lp(a) and coronary artery disease, and the levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with cardiovascular disease or with preclinical vascular changes. Further, there is an interaction between Lp(a) and other risk factors for cardiovascular disease. The physiological role of Lp(a) is unknown, although a majority of studies implicate Lp(a) as a risk factor.
Arterioscler Thromb Vasc Biol. 2004Dec;24(12):2219-26
Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation.
OBJECTIVE: The beneficial effect of dietary fish oil, rich in omega-3 polyunsaturated fatty acids (PUFAs), on cardiovascular disease is multifactorial and may partly rely on their anticoagulant action. We studied how fish oil intake influenced thrombin generation in plasma and which factors were involved herein. METHODS AND RESULTS: Twenty-five healthy males with borderline overweight received 3.0 g omega-3 PUFAs daily for 4 weeks. Fish oil intake reduced plasma triglycerides and lowered platelet integrin activation, as well as plasma levels of fibrinogen and factor V, but had no effect on vitamin K-dependent coagulation factors. Before fish oil intake, thrombin generation (reflecting the coagulant potential) considerably varied between plasmas from individual subjects, which were partly explained by variation in prothrombin, antithrombin, fibrinogen, and factor V levels. Fish oil intake reduced thrombin generation in the presence and absence of platelets. This reduction correlated with the fish oil effect on fibrinogen and factor V levels. Interestingly, the lowering effect of fish oil on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying a structural fibrinogen alpha-chain polymorphism. CONCLUSIONS: Dietary omega-3 PUFAs provoke a hypocoagulant, vitamin K-independent effect in humans, the degree of which may depend on fibrinogen level. Intake of fish oil reduced fibrinogen and factor V levels as well as thrombin generation in plasma. The effects on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying alpha-chain fibrinogen polymorphism. Thus, dietary fish oil can provoke a hypocoagulant effect depending on the fibrinogen level.
Arterioscler Thromb Vasc Biol. 2004Sep;24(9):1734-40
Glycemic and insulinemic meal responses modulate postprandial hepatic and intestinal lipoprotein accumulation in obese, insulin-resistant subjects.
BACKGROUND: Exacerbated postprandial lipemia is a risk factor for cardiovascular disease and is linked to insulin status. Limited data on the effect of dietary carbohydrate on postprandial lipoprotein accumulation are available. OBJECTIVE: We tested the hypothesis that dietary carbohydrates with different glucose availability alter postprandial lipoprotein metabolism differently in obese, insulin-resistant subjects. DESIGN: After an overnight fast, 9 subjects with central obesity and insulin resistance but normal triacylglycerolemia randomly ingested 2 test meals with comparable amounts of fat (28-29 g) and digestible carbohydrate (91-94 g) but with different quantities of slowly available glucose (SAG) in cereal products (17 or 2 g SAG/100 g for biscuits and wheat flakes, respectively). Blood samples were collected before and for 6 h after meal intakes. RESULTS: The postmeal 0-2-h areas under the curve (AUCs) for glycemia and insulinemia were significantly lower (P < 0.05) after the biscuit meal than after the flakes meal. Plasma triacylglycerol concentrations increased significantly after the flakes meal but not after the biscuit meal (1.5-fold higher 0-6-h AUC for the flakes meal). Apolipoprotein B-100 concentrations in the triacylglycerol-rich lipoprotein fraction increased significantly 2 h after the flakes meal but not after the biscuit meal (3-fold higher 0-6-h AUC for the flakes meal). Apolipoprotein B-48 concentrations increased (P < 0.05) 4 h after the flakes meal but not after the biscuit meal (2.3-fold higher 0-6-h AUC for the flakes meal). CONCLUSION: Mixed meals containing slowly digestible carbohydrate that induces low glycemic and insulinemic responses reduce the postprandial accumulation of both hepatically and intestinally derived triacylglycerol-rich lipoproteins in obese subjects with insulin resistance.
Am J Clin Nutr. 2004 Oct;80(4):896-902
Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform?
OBJECTIVES: The purpose of this study was to investigate the utility of the new National Cholesterol Education Program (NCEP) III guidelines in a group of young adults. BACKGROUND: These guidelines have been hailed as an improvement in their potential to identify individuals at risk for coronary heart disease (CHD) complications. Compared with the NCEP II, the new guidelines will increase the number of patients who qualify for medical management. However, the effectiveness of these guidelines to identify young adults at risk for a cardiac event is yet to be studied. METHODS: A retrospective review of clinical data from young adults (age <or=55 years for men and <or=65 years for women) hospitalized for acute myocardial infarction over a three-year period was conducted. Patients with a history of CHD or CHD equivalent were excluded. Using the NCEP III guidelines, we calculated a 10-year risk for coronary events on all patients. RESULTS: A total of 222 patients met criteria for inclusion. The mean age was 50 years and 25% were women. Mean lipid levels were all within the normal range; however, rates of smoking and obesity were high. When the 10-year risk of these patients was stratified by the number of risk factors and low-density lipoprotein cholesterol level, only 25% met criteria to qualify for pharmacotherapy. For women in this population, only 18% met criteria for treatment. CONCLUSIONS: The new guidelines offer multiple new features but have a tendency to underappreciate the risk for disease in young adults. To improve performance in young adults, statistical adjustments may be necessary.
J Am Coll Cardiol. 2003 May 7;41(9):1475-9
Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide: a randomized, controlled, crossover trial.
BACKGROUND: Although recent studies have indicated that nut consumption may improve levels of blood lipids, nuts are not generally recommended as snacks for hyperlipidemic subjects because of their high fat content. Furthermore, the effective dose is still unknown. METHODS AND RESULTS: The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean 423 kcal/d) supplements each for 1 month. Supplements provided 22.2% of energy and consisted of full-dose almonds (73+/-3 g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Fasting blood, expired air, blood pressure, and body weight measurements were obtained at weeks 0, 2, and 4. Mean body weights differed <300 g between treatments. The full-dose almonds produced the greatest reduction in levels of blood lipids. Significant reductions from baseline were seen on both half- and full-dose almonds for LDL cholesterol (4.4+/-1.7%, P=0.018, and 9.4+/-1.9%, P<0.001, respectively) and LDL:HDL cholesterol (7.8+/-2.2%, P=0.001, and 12.0+/-2.1%, P<0.001, respectively) and on full-dose almonds alone for lipoprotein(a) (7.8+/-3.5%, P=0.034) and oxidized LDL concentrations (14.0+/-3.8%, P<0.001), with no significant reductions on the control diet. No difference was seen in pulmonary nitric oxide between treatments. CONCLUSIONS: Almonds used as snacks in the diets of hyperlipidemic subjects significantly reduce coronary heart disease risk factors, probably in part because of the nonfat (protein and fiber) and monounsaturated fatty acid components of the nut.
Circulation. 2002 Sep 10;106(11):1327-32
Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions.
It has been estimated that approximately 37% of the US population judged to be at high risk for developing coronary artery disease (CAD), based on the National Cholesterol Education Program guidelines, have increased plasma lipoprotein(a) [Lp(a)], whereas Lp(a) is increased in only 14% of those judged to be at low risk. Therefore, the importance of establishing a better understanding of the relative contribution of Lp(a) to the risk burden for CAD and other forms of vascular disease, as well as the underlying mechanisms, is clearly evident. However, the structural complexity and size heterogeneity of Lp(a) have hindered the development of immunoassays to accurately measure Lp(a) concentrations in plasma. The large intermethod variation in Lp(a) values has made it difficult to compare data from different clinical studies and to achieve a uniform interpretation of clinical data. A workshop was recently convened by the National Heart, Lung, and Blood Institute (NHLBI) to evaluate our current understanding of Lp(a) as a risk factor for atherosclerotic disorders; to determine how future studies could be designed to more clearly define the extent to which, and mechanisms by which, Lp(a) participates in these processes; and to present the results of the NHLBI-supported program for the evaluation and standardization of Lp(a) immunoassays. This report includes the most recent data presented by the workshop participants and the resulting practical and research recommendations.
Clin Chem. 2003 Nov;49(11):1785-96