linoleic-acid and Hyperlipoproteinemia-Type-II

The cholesterol hypothesis implies that reducing the intake of saturated fatty acids and cholesterol and increasing that of polyunsaturated fatty acid are effective in lowering serum total cholesterol (TC), and thereby reducing the incidence of coronary heart disease (CHD). However, these dietary recommendations are essentially ineffective in reducing TC in the long run, but rather increase mortality rates from CHD and all causes. The reported "apparent relative risk of high TC in CHD mortality" (the ratio of mortality at the highest/lowest TC levels) varied several-fold among populations studied. The incidence of familial hypercholesterolemia (FH) in a population was proposed to be a critical factor in the observed variability, which could be accounted for by assuming that 1) the high CHD mortality rate in high-TC groups is mainly a reflection of the incidence and severity of FH, and 2) high TC is not a causative factor of CHD in non-FH cases. This interpretation is supported by recent observations that high TC is not positively associated with high CHD mortality rates among general populations more than 40-50 years of age. More importantly, higher TC values are associated with lower cancer and all-cause mortality rates among these populations, in which relative proportions of FH are likely to be low (circa 0.2%). Although the effectiveness of statins in preventing CHD has been accepted in Western countries, little benefit seems to result from efforts to limit dietary cholesterol intake or to TC values to less than approximately 260 mg/dl among the general population and the elderly. Instead, an unbalanced intake of omega6 over omega3 polyunsaturated fats favors the production of eicosanoids, the actions of which lead to the production of inflammatory and thrombotic lipid mediators and altered cellular signaling and gene expression, which are major risk factors for CHD, cancers, and shorter longevity. Based on the data reviewed here, it is urgent to change the direction of current cholesterol-related medication for the prevention of CHD, cancer, and all-cause mortality.

Topics: alpha-Linolenic Acid; Anticholesteremic Agents; Atherosclerosis; Coronary Disease; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Inflammation; Inflammation Mediators; Linoleic Acid; Neoplasms; Risk Factors; Thrombosis

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival (111 In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159+/-14 hours to a mean of 164+/-12 hours (p=0.025), whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL (p=0.003) in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9) platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandin I2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (-2.9%), low density lipoprotein cholesterol (-3.5%), and triglycerides (-12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.

Topics: Blood Platelets; Cell Survival; Combined Modality Therapy; Diet; Diet Records; Diet, Fat-Restricted; Double-Blind Method; Eicosapentaenoic Acid; Epoprostenol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Female; Fish Oils; gamma-Linolenic Acid; Humans; Hyperlipoproteinemia Type II; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Lipoproteins; Male; Malondialdehyde; Oenothera biennis; Plant Oils; Platelet Activation; Thromboxane B2

Serum paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that can inhibit low-density lipoprotein (LDL) oxidation in vitro. The role of PON1 in vivo still remains to be clarified. We investigated the effect of PON1 genotype (-107C > T and 192Q > R), concentration, paraoxonase activity, and arylesterase activity on the early phase of lipid peroxidation in plasma samples of 110 patients with heterozygous familial hypercholesterolemia. The degree of lipid oxidation was assessed by quantitation of oxidized-linoleic acid (the most abundant fatty acid present in LDL) using high performance liquid chromatography. We found a significant inverse correlation between paraoxonase activity and the oxidized-linoleic acid concentration (r = -0.22, P = 0.03), independent of baseline linoleic acid levels. These findings support an anti-oxidative role for PON1 in patients with FH, and thus may give insight into the functioning of PON1 in vivo.

Topics: Adult; Aryldialkylphosphatase; Cholesterol, LDL; Chromatography, High Pressure Liquid; Female; Humans; Hyperlipoproteinemia Type II; Linoleic Acid; Male; Middle Aged; Oxidation-Reduction

Intraindividual comparisons of diets supplemented with sunflowerseed oil (rich in linoleic acid, LA, C18:2n-6), linseed oil (enriched with alpha-linolenic acid, LNA, C18:3n-3) and canned mackerel (rich in eicosapentaenoic acid, EPA, C20:5n-3 and docosahexaenoic acid, DHA, C22:6n-3) were made in 30 patients with primary hyperlipoproteinemia (HLP) of phenotypes IIa (n = 9), IIb (n = 7), IV (n = 7) and V (n = 7). The lipid- and blood pressure-lowering effects of polyunsaturated fatty acids (PUFA), particularly those of the EPA- and DHA-rich diet, were confirmed irrespective of the type of HLP. Apolipoproteins A-I and B remained unchanged. The most remarkable finding was a substantial depression of free fatty acids (FFA) within a standardized glucose tolerance test (GTT) associated with the fall of serum triglycerides after diets enriched with n-6 and especially after those supplemented with n-3 PUFA. It was suggested that the decrease of FFA indicates reduced peripheral lipolysis, which might be a hitherto ignored factor involved in the triglyceride-lowering action of n-6 and, more pronounced, of n-3 PUFA.

Topics: Adult; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Hyperlipoproteinemia Type V; Hyperlipoproteinemias; Linoleic Acid; Linoleic Acids; Linolenic Acids; Linseed Oil; Lipids; Middle Aged; Plant Oils; Sunflower Oil; Triglycerides

Plasma apolipoprotein B (apo B) concentrations were determined in 178 randomly selected 40-49-year-old men from Eastern and Southwestern Finland and compared with the concentrations of plasma lipids and the fatty acid composition of plasma and adipose tissue determined previously from the same populations. The plasma apo B concentrations ranged from 50 to 209 mg/dl. Although men from the two regions had similar mean concentrations of plasma triglyceride, total cholesterol and high density lipoprotein (HDL)-cholesterol, men from Eastern Finland had significantly higher mean apo B levels (139 +/- 25 mg/dl) and a lower ratio of total cholesterol to apo B (1.85 +/- 0.25) than the Southwestern men (125 +/- 33 mg/dl and 2.05 +/- 0.40, respectively). In the whole population, apo B and total cholesterol had significant negative correlations with the percentages of linoleate in the fatty acids of plasma and adipose tissue, which are known to reflect the quality of dietary fat. As the percentages of linoleate have previously been shown to be lower in the Eastern population, part of the regional difference in apo B is obviously explained by differences in the quality of dietary fat. On the other hand, men (n = 59) who had high plasma apo B (greater than 130 mg/dl) but low density lipoprotein (LDL)-cholesterol within the reference values (less than 5.17 mmol/l) showed no correlation between linoleate and apo B. This suggests that other factors than dietary fat determine the concentration of apo B in this group of men.

Topics: Adipose Tissue; Apolipoproteins B; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats, Unsaturated; Finland; Humans; Hyperlipoproteinemia Type II; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Triglycerides

The effect of a virtually cholesterol-free, high-linoleic-acid vegetarian diet and a high-linoleic-acid "normal" diet with a moderate cholesterol content was tested in 39 children heterozygote for hypercholesterolemia type II-A. The diets were administered in an outpatient cross-over design of two periods of 10 weeks each and the serum lipoproteins were analyzed at the end of the two 10-week periods. The vegetarian diet induced a decrease in serum concentrations of LDL-II total and free cholesterol and of apo-B, by an average of 10%, whereas HDL cholesterol and apo-A-I decreased by 4%. The disproportionately large change in LDL compared to the small change in HDL was interpreted as an antiatherogenic effect of the vegetarian diet.

Topics: Adolescent; Apolipoproteins; Child; Child, Preschool; Cholesterol; Cholesterol, Dietary; Diet, Vegetarian; Dietary Fats; Humans; Hyperlipoproteinemia Type II; Linoleic Acid; Linoleic Acids; Lipoproteins