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Tocotrienols from rice bran oil have no effects on levels of LDL cholesterol and markers for cholesterol synthesis and absorption
Tuesday June 27, 2000: Poster Abstracts P: W12 Diet and Bioacfive Components of Food
114
0.01) and apt C l l (16.2 4- 3.6 vs 22.4 4- 4.4) and apt C l l l (93 -t- 13 vs 127 4- 20) were significantly lower on monounsaturated diet (p < 0.05). A p t C111 is known to mask apt E, the ligand for receptor-mediated clearance of VLDL. Conclusions: The monounsaturated fat diet improved clearance of postprandia particles due to reduction in apt C l l l and increase in apt E. The study suggests a mechanism that might explain the beneficial effect of a Mediterranean-type diet in the prevention of atherosclerosis I
Tu P22:W12 ] Macrophage-mediated oxidation of LDL may be counteracted by phenolic compounds contained in extra-virgin olive oil R. Maseila, R. Vail, B. Scazzocchio, R. Di Benedetto, M. De Vincenzi, C. Giovannini. Dept. of Metabolism and Pathological Biochemistry, lstituto
Superiore di Sanitd, Rome, Italy Phenolic antioxidants may play a key role in the prevention of cardiovascular disease. The aim of this study was to investigate the capability of phenolic compounds contained in extra-virgin olive oil in inhibiting the oxidation of LDL mediated by J774 A.I murine macrophage-like cell line. Cells (1.5 × 106/25 mm dish) were incubated with LDL (0.2 mg of protein/rot) in DMEM, phenol red-free, supplemented with 2 mM CuSO4, for 24 h at 37°C. To evaluate the effect of phenol compounds on cell-mediated oxidation of LDL, tyrosol, protocatechuic acid or oleuropein (range 0.25-1 mM) were added to the cells 2 h before. The extent of LDL oxidation was measured in the medium by TBARS assay. In addition, changes in electrophoretic mobility of LDL on agarose gel were evaluated. J774 A. 1 cells significantly increased the amount of TBARS when compared with the cell-free control (44.5 4- 7 vs 3.67 4- 1 nmol/mg of protein LDL, p < 0.001). Protocatechuic acid and oleuropein, at the lower concentration tested, completely inhibited TBARS formation, while tyrosol was lightly effective even at l mM concentration (34.5 4- 2.8 nmol/mg of protein LDL). In the presence of cells, the eleetrophoretic mobility of LDL was two times higher than native LDL. This increase was completely prevented by protocatechuic acid or oleuropein, but not by tyrosol. In conclusion the presence of protocatechuic acid and oleuropein may prevent the oxidation of LDL mediated by J774 A.1 cells. This finding might be related to the two hydroxyl groups on the phenol ring of those compounds. Our investigation suggest that dietary intake of extra virgin olive oil might contribute to lower the risk of coronary heart diseases.
Tu P23:W12 ] i
Influence of Apo A4 genotypes (ApoA4-347 mutation) on the lipid response to diet in familial hypercholesterolemia
R. Carmena-Ram6n, J.T. Real, M. Civera, J.E Ascaso, J.M. Ordovas I , R. Carmena. Departament of Endocrinology Hospital CEnico, Universidad
"~e ~ Spain; 1Lipid Metabolism Laboratory USDA, Tufts University, Boston, MA, USA Objective: To analyze the influence of Apo A4 genotypes (Gin360 -* His) on the lipid response to an hypocholesterolemic diet (NCEP-I) in familial hypercholesterolemia. Subjects and Methods: A total of 67 FH heterozygotes (43 women) were studied at baseline and after 3 months of consuming NCEP-1 diet. Lipids and lipoproteins were measured with standard methods and apo A4 genotype by PCR and restriction analysis. Results: Genotype 1/1 was found in 51 subjects while 16 subjects had genotype 1/2. No sex-related differences in response to diet were detected. Apo A4-2 allele was associated with lower LDLc (p = 0.049) and apo B levels (p = 0.027), independently of the response to diet. After diet, apo A4-2 carders showed lower reductions in apo B levels (6.2% p = 0.036) but not in LDLc. Conclusion: In FH subjects, presence of apo A4-2 allele is associated with lower lipid levels at baseline and after the NCEP-I diet period, indicating a beneficial interaction with LDL receptor alterations. 1
TuP24:W12 /d Tocotrienols from rice bran oil have no effects on levels of LDL cholesterol and markers for cholesterol synthesis and absorption D.A.J.M. Kerckhoffs I , R.P. Mensink 1, T.W.A. de Bruin 2, E.A. Trautwein 3 , F. Brouns l , GI Hornstra 1. 3Atpresent Unilever Research, Vlaardingen;
/Department of Human Biology, Maastricht University; 2Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands Objective: Tocotrienols from rice bran oil (T-RBO) have been reported to
lower LDL cholesterol by reducing HMG-CoA reductase activity, but results are controversial. We have therefore compared the effects of T-RBO with those of pravastatin (PRA, an HMG-CoA reductase inhibitor) on LDL cholesterol and markers (in terms of #mol/mmol of cholesterol) for cholesterol absorption and synthesis in hypercholesterolemic subjects. Methods: 33 men and 38 women followed a cholesterol-lowering diet for three weeks. For the next six weeks, subjects continued their diets and were randomly divided into three groups, consuming a placebo (PL) (n = 24), T-RBO (42 mg/day, n = 24) or PRA (40 mg/day, n = 23). In a subset of 50 persons, serum lathosterol as an indicator of cholesterol synthesis, and serum campesterol, a plant sterol, as a marker for intestinal cholesterol absorption, were determined by gas chromatography. Results: As compared to the PL-group, no favourable effects of T-RBO were observed on serum LDL cholesterol concentrations. Also, serum lathosterol and campesterol levels did not change. In the PRA-group, LDL cholesterol decreased by 32% (P < 0.001) and 28% (P < 0.001) as compared to the PL-group and T-RBO-group, respectively. Lathosterol was lowered with PRA by 50% (P < 0.001) compared to the PL-group, and by 57% (P < 0.001) compared to the T-RBO-group. Campesterol increased with PRA by 15% (P < 0.001) versus the PL-group. Conclusions: In contrast to PRA, T-RBO do not affect lipid metabolism as evidenced from unchanged concentrations of serum LDL cholesterol, lathosterol and campesterol. I
l TuP25:W1 2 I
Effect of dietary fatty acid modification on blood lipids, iipoproteius and lipoprotein subclasses in men
T. Tholstrup 1, B. SandstrOm I , M. Petersen 1, C.-E. H0y 2, P. Marckmann j .
Centre Advanced Food Studies; 1Research Dept. Human Nutrition, Royal Vet. Agric. Univ., Frb C.; 2Dept. Bioehem. Nutrition, Dan. Tech. Univ, Lyngby, Denmark Small, dense low density lipoproteins (LDL) (d > 1.044 mg/dl) are associated with increased atherogenic risk. The aim of the study was to investigate the effect of two modified test fats (A and B) on lipid profile in healthy men. Sixteen men (age 35-75 y) substituted 80 g of their normal dietary fat intake with test fat during two periods of 21 days in a double blind, randomized cross over study. Both test fats were low in cholesterol raising saturated fatty acids. Test fat A contained 5% w/w long chain n-3 fatty acids matched by oleic acid in test fat B. Before, during and between the study periods the participants' habitual diet was assessed by four days weighed food records. Fasting blood samples were drawn before and in the end of the study periods. Preliminary results show that plasma triglyceride (TG) was lower after fat A than B (P < 0.05), no other significant differences were observed. However, compared to baseline values test fat A decreased plasma triglyceride (TG) from 1.59 to 1.16 mmol/1 (P < 0.001), apolipoprotein-B in small dense LDL from 22.77 to 17.69 mg/dl (P < 0.01) and plasma cholesterol from 5.69 to 5.24 mmol/l (P < 0.01). LDL cholesterol and high density lipoprotein (HDL) cholesterol was unchanged. Compared to baseline values test fat B decreased plasma cholesterol from 5.80 to 5.32 mmol/1 (P < 0.001) and LDL cholesterol from 3.61 to 3.32 mmol/l (P < 0.01). There was no effect on TG, HDL cholesterol or small dense LDL. We conclude that compared to the habitual diet, both dietary regimes had a beneficial effect on lipid profile, with fish oil fat resulting in a considerable decrease in total TG and concentration of small dense LDL, whereas modified fat without fish oil decreased LDL cholesterol.
Supp. by FOTEK/Danish Research Agency I
I TuP26:W1 2 l i
Meal-induced factor VII activation and thrombin formation in atherosclerotic patients
P. Marckrnann ] , E.M. Bladbjerg 2 , A. Mtinster2, N. Keller3 , J. Jespersen 2 .
1Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Frederiksberg; 2Department of Thrombosis Research, University of Southern Denmark, Esbjerg; 3Department of Medicine, Ribe County Hospital, Esbjerg, Denmark Objective: To study whether meal-induced factor VII (FVII) activation leads to thrombin formation in atherosclerotic patients. Methods: Thirty patients with angiographically verified coronary artery disease consumed low-fat (5% of total dietary energy) breakfast (8.30 h) and lunch (11.00 h) and isoenergetic high-fat (40%) breakfast and lunch on two separate days in a randomized cross-over design. Blood samples were drawn at 8.15, 12.30, 14.00, 15.30, and 16.45 h. Plasma triglycerides, activated FVII (FVIIa), FVII protein (FVIIag), prothrombin fragment 1 + 2 (F1 + 2), and soluble fibrin were determined.
Xllth International Symposium on Atherosclerosis, Stockholm, Sweden, June 25-29, 2000
114
0.01) and apt C l l (16.2 4- 3.6 vs 22.4 4- 4.4) and apt C l l l (93 -t- 13 vs 127 4- 20) were significantly lower on monounsaturated diet (p < 0.05). A p t C111 is known to mask apt E, the ligand for receptor-mediated clearance of VLDL. Conclusions: The monounsaturated fat diet improved clearance of postprandia particles due to reduction in apt C l l l and increase in apt E. The study suggests a mechanism that might explain the beneficial effect of a Mediterranean-type diet in the prevention of atherosclerosis I
Tu P22:W12 ] Macrophage-mediated oxidation of LDL may be counteracted by phenolic compounds contained in extra-virgin olive oil R. Maseila, R. Vail, B. Scazzocchio, R. Di Benedetto, M. De Vincenzi, C. Giovannini. Dept. of Metabolism and Pathological Biochemistry, lstituto
Superiore di Sanitd, Rome, Italy Phenolic antioxidants may play a key role in the prevention of cardiovascular disease. The aim of this study was to investigate the capability of phenolic compounds contained in extra-virgin olive oil in inhibiting the oxidation of LDL mediated by J774 A.I murine macrophage-like cell line. Cells (1.5 × 106/25 mm dish) were incubated with LDL (0.2 mg of protein/rot) in DMEM, phenol red-free, supplemented with 2 mM CuSO4, for 24 h at 37°C. To evaluate the effect of phenol compounds on cell-mediated oxidation of LDL, tyrosol, protocatechuic acid or oleuropein (range 0.25-1 mM) were added to the cells 2 h before. The extent of LDL oxidation was measured in the medium by TBARS assay. In addition, changes in electrophoretic mobility of LDL on agarose gel were evaluated. J774 A. 1 cells significantly increased the amount of TBARS when compared with the cell-free control (44.5 4- 7 vs 3.67 4- 1 nmol/mg of protein LDL, p < 0.001). Protocatechuic acid and oleuropein, at the lower concentration tested, completely inhibited TBARS formation, while tyrosol was lightly effective even at l mM concentration (34.5 4- 2.8 nmol/mg of protein LDL). In the presence of cells, the eleetrophoretic mobility of LDL was two times higher than native LDL. This increase was completely prevented by protocatechuic acid or oleuropein, but not by tyrosol. In conclusion the presence of protocatechuic acid and oleuropein may prevent the oxidation of LDL mediated by J774 A.1 cells. This finding might be related to the two hydroxyl groups on the phenol ring of those compounds. Our investigation suggest that dietary intake of extra virgin olive oil might contribute to lower the risk of coronary heart diseases.
Tu P23:W12 ] i
Influence of Apo A4 genotypes (ApoA4-347 mutation) on the lipid response to diet in familial hypercholesterolemia
R. Carmena-Ram6n, J.T. Real, M. Civera, J.E Ascaso, J.M. Ordovas I , R. Carmena. Departament of Endocrinology Hospital CEnico, Universidad
"~e ~ Spain; 1Lipid Metabolism Laboratory USDA, Tufts University, Boston, MA, USA Objective: To analyze the influence of Apo A4 genotypes (Gin360 -* His) on the lipid response to an hypocholesterolemic diet (NCEP-I) in familial hypercholesterolemia. Subjects and Methods: A total of 67 FH heterozygotes (43 women) were studied at baseline and after 3 months of consuming NCEP-1 diet. Lipids and lipoproteins were measured with standard methods and apo A4 genotype by PCR and restriction analysis. Results: Genotype 1/1 was found in 51 subjects while 16 subjects had genotype 1/2. No sex-related differences in response to diet were detected. Apo A4-2 allele was associated with lower LDLc (p = 0.049) and apo B levels (p = 0.027), independently of the response to diet. After diet, apo A4-2 carders showed lower reductions in apo B levels (6.2% p = 0.036) but not in LDLc. Conclusion: In FH subjects, presence of apo A4-2 allele is associated with lower lipid levels at baseline and after the NCEP-I diet period, indicating a beneficial interaction with LDL receptor alterations. 1
TuP24:W12 /d Tocotrienols from rice bran oil have no effects on levels of LDL cholesterol and markers for cholesterol synthesis and absorption D.A.J.M. Kerckhoffs I , R.P. Mensink 1, T.W.A. de Bruin 2, E.A. Trautwein 3 , F. Brouns l , GI Hornstra 1. 3Atpresent Unilever Research, Vlaardingen;
/Department of Human Biology, Maastricht University; 2Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands Objective: Tocotrienols from rice bran oil (T-RBO) have been reported to
lower LDL cholesterol by reducing HMG-CoA reductase activity, but results are controversial. We have therefore compared the effects of T-RBO with those of pravastatin (PRA, an HMG-CoA reductase inhibitor) on LDL cholesterol and markers (in terms of #mol/mmol of cholesterol) for cholesterol absorption and synthesis in hypercholesterolemic subjects. Methods: 33 men and 38 women followed a cholesterol-lowering diet for three weeks. For the next six weeks, subjects continued their diets and were randomly divided into three groups, consuming a placebo (PL) (n = 24), T-RBO (42 mg/day, n = 24) or PRA (40 mg/day, n = 23). In a subset of 50 persons, serum lathosterol as an indicator of cholesterol synthesis, and serum campesterol, a plant sterol, as a marker for intestinal cholesterol absorption, were determined by gas chromatography. Results: As compared to the PL-group, no favourable effects of T-RBO were observed on serum LDL cholesterol concentrations. Also, serum lathosterol and campesterol levels did not change. In the PRA-group, LDL cholesterol decreased by 32% (P < 0.001) and 28% (P < 0.001) as compared to the PL-group and T-RBO-group, respectively. Lathosterol was lowered with PRA by 50% (P < 0.001) compared to the PL-group, and by 57% (P < 0.001) compared to the T-RBO-group. Campesterol increased with PRA by 15% (P < 0.001) versus the PL-group. Conclusions: In contrast to PRA, T-RBO do not affect lipid metabolism as evidenced from unchanged concentrations of serum LDL cholesterol, lathosterol and campesterol. I
l TuP25:W1 2 I
Effect of dietary fatty acid modification on blood lipids, iipoproteius and lipoprotein subclasses in men
T. Tholstrup 1, B. SandstrOm I , M. Petersen 1, C.-E. H0y 2, P. Marckmann j .
Centre Advanced Food Studies; 1Research Dept. Human Nutrition, Royal Vet. Agric. Univ., Frb C.; 2Dept. Bioehem. Nutrition, Dan. Tech. Univ, Lyngby, Denmark Small, dense low density lipoproteins (LDL) (d > 1.044 mg/dl) are associated with increased atherogenic risk. The aim of the study was to investigate the effect of two modified test fats (A and B) on lipid profile in healthy men. Sixteen men (age 35-75 y) substituted 80 g of their normal dietary fat intake with test fat during two periods of 21 days in a double blind, randomized cross over study. Both test fats were low in cholesterol raising saturated fatty acids. Test fat A contained 5% w/w long chain n-3 fatty acids matched by oleic acid in test fat B. Before, during and between the study periods the participants' habitual diet was assessed by four days weighed food records. Fasting blood samples were drawn before and in the end of the study periods. Preliminary results show that plasma triglyceride (TG) was lower after fat A than B (P < 0.05), no other significant differences were observed. However, compared to baseline values test fat A decreased plasma triglyceride (TG) from 1.59 to 1.16 mmol/1 (P < 0.001), apolipoprotein-B in small dense LDL from 22.77 to 17.69 mg/dl (P < 0.01) and plasma cholesterol from 5.69 to 5.24 mmol/l (P < 0.01). LDL cholesterol and high density lipoprotein (HDL) cholesterol was unchanged. Compared to baseline values test fat B decreased plasma cholesterol from 5.80 to 5.32 mmol/1 (P < 0.001) and LDL cholesterol from 3.61 to 3.32 mmol/l (P < 0.01). There was no effect on TG, HDL cholesterol or small dense LDL. We conclude that compared to the habitual diet, both dietary regimes had a beneficial effect on lipid profile, with fish oil fat resulting in a considerable decrease in total TG and concentration of small dense LDL, whereas modified fat without fish oil decreased LDL cholesterol.
Supp. by FOTEK/Danish Research Agency I
I TuP26:W1 2 l i
Meal-induced factor VII activation and thrombin formation in atherosclerotic patients
P. Marckrnann ] , E.M. Bladbjerg 2 , A. Mtinster2, N. Keller3 , J. Jespersen 2 .
1Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Frederiksberg; 2Department of Thrombosis Research, University of Southern Denmark, Esbjerg; 3Department of Medicine, Ribe County Hospital, Esbjerg, Denmark Objective: To study whether meal-induced factor VII (FVII) activation leads to thrombin formation in atherosclerotic patients. Methods: Thirty patients with angiographically verified coronary artery disease consumed low-fat (5% of total dietary energy) breakfast (8.30 h) and lunch (11.00 h) and isoenergetic high-fat (40%) breakfast and lunch on two separate days in a randomized cross-over design. Blood samples were drawn at 8.15, 12.30, 14.00, 15.30, and 16.45 h. Plasma triglycerides, activated FVII (FVIIa), FVII protein (FVIIag), prothrombin fragment 1 + 2 (F1 + 2), and soluble fibrin were determined.
Xllth International Symposium on Atherosclerosis, Stockholm, Sweden, June 25-29, 2000