Low fat-monounsaturated rich diets containing high-oleic peanuts improve serum lipoprotein profiles

Postmenopausal hypercholesterolemic women are at risk for cardiovascular disease and are encouraged to follow low-fat (LF) (≤30% energy) diets. However, these diets may have undesirable effects on high density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apo A-I) and triglycerides, whereas diets high in monounsaturated fats do not. Twenty postmenopausal hypercholesterolemic women previously consuming high-fat diets (34% energy) were placed on a low fat-monounsaturated rich diet (LFMR: 26%, 14% energy, respectively) for 6 mon. Sixteen women already eating LF diets (24% energy) were also followed to monitor variations in serum lipids due to seasonal variations. Twenty-five women successfully completed the study (LFMR=12, LF=13). Serum cholesterol decreased 10% (264 to 238 mg/dL, P≤0.01) and low density lipoprotein cholesterol (LDL-C) decreased 12% (182 to 161 mg/dL, P≤0.01) in the LFMR group, but did not change in the LF group. The reduction in serum cholesterol in the LFMR group was greater than estimated by predictive formulas. Serum triglycerides and apo A-I did not change in the LFMR group. A modest decrease in HDL-C, HDL₃-C, and apolipoprotein B (apo B) occurred in both groups, but only the LFMR group showed a trend toward beneficial changes in LDL-C/HDL-C and apo A-I/apo B ratios. Overall, the LFMR diet was well tolerated and resulted in an improved serum lipid and apolipoprotein profile. A portion of this material was presented earlier at the annual meeting of the American Oil Chemists’ Society and in abstract from (O’Byrne, D.J., Shireman, R.B., and Knauft, D., 1993. The effects of a low-fat/high-oleic acid diet on lipoproteins in postmenopausal hypercholesterolemic women. INFORM 4(4), 553, #SS7).     

Leptospirosis is Associated with Markedly Increased Triglycerides and Small Dense Low-Density Lipoprotein and Decreased High-Density Lipoprotein

The objective of the present study was to evaluate the effects of acute infection with Leptospira interrogans on lipids, lipoproteins and associated enzymes. Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins (apo) A-Ι, B, E, C-II, C-III and lipoprotein (a) [Lp(a)] were determined in patients with Leptospirosis on diagnosis and 4 months after recovery as well as in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP) and lipoprotein-associated phospholipase A₂ (Lp-PLA₂) as well as paraoxonase 1 (PON1) hydrolysing activity and levels of cytokines were determined. LDL subclass analysis was performed with Lipoprint LDL System. Eleven patients (10 men, mean age 49.5 ± 8.4 years) and 11 controls were included. TC, HDL-C, LDL-C, apoA-I, apoB and Lp(a) levels were lower at baseline, whereas TG and apoE levels were elevated compared with 4 months later. At baseline, higher levels of cytokines and cholesterol concentration of small dense LDL particles (sdLDL-C) were noticed, whereas LDL particle size was lower compared with follow-up. Activities of plasma Lp-PLA₂ and HDL-associated Lp-PLA₂ were lower at baseline compared with post treatment values, whereas PON1 activity was similar at baseline and 4 months later. 4 months after recovery, the levels of all lipid parameters evaluated did not differ compared with controls, except for HDL-C which remained lower. PON1 activity both at baseline and 4 months later was lower in patients compared with controls. Leptospirosis is associated with atherogenic changes of lipids, lipoproteins and associated enzymes.     

Associations between apolipoprotein E genotype and circulating F<Subscript>2</Subscript>-isoprostane levels in humans

Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three common alleles (ε2, ε3, and ε4). Population studies have shown that the risk of diseases characterized by oxidative damage, such as coronary heart disease and Alzheimer’s disease, is significantly higher in ɛ4 carriers. We evaluated the association between apoE genotypes and plasma F₂-isoprostane levels, an index of lipid peroxidation, in humans. Two hundred seventy-four healthy subjects (104 males, 170 females; 46.9±13.0 yr; 200 whites, 74 blacks; 81 nonsmokers, 64 passive smokers, and 129 active smokers) recruited for a randomized clinical antioxidant intervention trial were included in this analysis. ApoE genotype was determined by PCR and restriction enzyme digestion. Free plasma F₂-isoprostane was measured by GC-MS. Genotype groups were compared using multiple regression analysis with adjustment for sex, age, race, smoking status, body mass index, plasma ascorbic acid, and β-carotene. Subjects with ε3/ε4 and ε4/ε4 genotype (ε4-carriers) and with ε2/ε3 and ε3/ε3 (non-ε4-carriers) were pooled for analysis. In subjects with high cholesterol levels (total cholesterol above 200 mg/dl), plasma F₂-isoprostane levels were 29% higher in ε4 carriers than in non-ε4-carriers (P=0.0056). High-cholesterol subjects that are ε4 carriers have significantly higher levels of lipid peroxidation as assessed by circulating F₂-isoprostane levels.     

Influence of Simvastatin on apoB-100 Secretion in Non-Obese Subjects with Mild Hypercholesterolemia

Statins decrease apoB-100-containing lipoproteins by increasing their fractional catabolic rates through LDL receptor-mediated uptake. Their influence on hepatic secretion of these lipoproteins is controversial. The objective of the study was to examine the influence of simvastatin on the secretion of apoB-100-containing lipoproteins in fasting non-obese subjects. Turnover of apoB-100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was used to derive kinetic parameters. Eight male subjects (BMI 25 ± 3 kg/m²) with mild hypercholesterolemia (LDL cholesterol 135 ± 30 mg/dL) and normal triglycerides (111 ± 44 mg/dL) were examined under no treatment (A), under chronic treatment with simvastatin 40 mg/day (B) and after an acute-on-chronic dosage of 80 mg simvastatin under chronic simvastatin treatment (C). Lipoprotein concentrations changed as expected under 40 mg/day simvastatin. Fractional catabolic rates increased in IDL and LDL but not in VLDL fractions versus control [VLDL +35% in B (n.s.) and +21% in C (n.s.); IDL +169% in B (P = 0.08) and +187% in C (P = 0.032); LDL +87% in B (P = 0.025) and +133% in C (P = 0.025)]. Chronic (B) and acute-on-chronic simvastatin treatment (C) did not affect lipoprotein production rates [VLDL −8 and −13%, IDL +47 and +38%, and LDL +19 and +30% in B and C, respectively (all comparisons n.s.)]. The data indicate that simvastatin does not influence the secretion of apoB-100-containing lipoproteins in non-obese subjects with near-normal LDL cholesterol concentrations.     

<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine/Simvastatin Reduces Lipoprotein (a) Levels Compared with Simvastatin Monotherapy: A Randomized Double-Blind Placebo-Controlled Study

Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. l ‐Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of l ‐carnitine/simvastatin co‐administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low‐density lipoprotein cholesterol (LDL‐C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study. Subjects were randomly allocated to receive l ‐carnitine 2 g/day plus simvastatin 20 mg/day (N = 29) or placebo plus simvastatin 20 mg/day (N = 29) for a total of 12 weeks. Lp(a) was significantly reduced in the l ‐carnitine/simvastatin group [?19.4%, from 52 (20–171) to 42 (15–102) mg/dL; p = 0.01], but not in the placebo/simvastatin group [?6.7%, from 56 (26–108) to 52 (27–93) mg/dL, p = NS versus baseline and p = 0.016 for the comparison between groups]. Similar significant reductions in total cholesterol, LDL‐C, apolipoprotein (apo) B and TAG were observed in both groups. Co‐administration of l ‐carnitine with simvastatin was associated with a significant, albeit modest, reduction in Lp(a) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a) levels.     

Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats

The effects of the phenolic compounds butylated hydroxytoluene (BHT), sesamin (S), curcumin (CU), and ferulic acid (FA) on plasma, liver, and lung concentrations of α- and γ-tocopherols (T), on plasma and liver cholesterol, and on the fatty acid composition of liver lipids were studied in male Sprague-Dawley rats. Test compounds were given to rats ad libitum for 4 wk at 4 g/kg diet, in a diet low but adequate in vitamin E (36 mg/kg of γ-T and 25 mg/kg of α-T) and containing 2 g/kg of cholesterol. BHT significantly reduced feed intake (P<0.05) and body weight and increased feed conversion ratio; S and BHT caused a significant enlargement of the liver (P<0.001), whereas CU and FA did not affect any of these parameters. The amount of liver lipids was significantly lowered by BHT (P<0.01) while the other substances reduced liver lipid concentrations but not significantly. Regarding effects on tocopherol levels, (i) feeding of BHT resulted in a significant elevation (P<0.001) of α-T in plasma, liver, and lung, while γ-T values remained unchanged; (ii) rats provided with the S diet had substantially higher γ-T levels (P<0.001) in plasma, liver, and lung, whereas α-T levels were not affected; (iii) administration of CU raised the concentration of α-T in the lung (P<0.01) but did not affect the plasma or liver values of any of the tocopherols; and (iv) FA had no effect on the levels of either homolog in the plasma, liver, or lung. The level of an unknown substance in the liver was significantly reduced by dietary BHT (P<0.001). BHT was the only compound that tended to increase total cholesterol (TC) in plasma, due to an elevation of cholesterol in the very low density lipoprotein + low density lipoprotein (VLDL+LDL) fraction. S and FA tended to lower plasma total and VLDL+LDL cholesterol concentrations, but the effect for CU was statistically significant (P<0.05). FA increased plasma high density lipoprotein cholesterol while the other compounds reduced it numerially, but not significantly. BHT, CU, and S reduced cholesterol levels in the liver TC (P<0.001) and percentages of TC in liver lipids (P<0.05). With regard to the fatty acid composition of liver lipids, S increased the n-6/n-3 and the 18∶3/20∶5 polyunsaturated fatty acids (PUFA) ratios, and BHT lowered total monounsaturated fatty acids and increased total PUFA (n−6+n−3). The effects of CU and FA on fatty acids were not highly significant. These results suggest some in vivo interactions between these phenolic compounds and tocopherols that may increase the bioavailability of vitamin E and decrease cholesterol in rats.     

The hypertriglyceridemic waist phenotype is a predictor of elevated levels of small, dense LDL cholesterol

The hypertriglyceridemic waist (HTGW) phenotype (hypertriglyceridemia and increased waist circumference) has been proposed as an inexpensive tool to monitor individuals with the atherogenic metabolic triad, hyperinsulinemia, hyperapobetalipoproteinemia, and increased levels of small, dense LDL (sdLDL) particles. We assessed the association of the HTGW phenotype with the metabolic syndrome (MetSyn) and the atherogenic metabolic triad in inhabitants (n=260) of northwestern Greece attending the Outpatient Lipid Clinic of the University Hospital of loannina. The LDL subfractions were assessed using the Lipoprint LDL System. HTGW (+) individuals had a more adverse lipid and lipoprotein profile compared with HTGW (−) individuals. Moreover, HTGW (+) subjects had elevated levels of sdLDL-C, as well as decreased mean and peak LDL particle size compared with HTGW (−) subjects. To our knowledge, this is the first report documenting the sdLDL-C abnormality in HTGW (+) subjects. Among men (n=105), 52.3% of the MetSyn (+) individuals and 66.7% of the HTGW (+) individuals had the metabolic triad. Among women (n=155), the corresponding percentages were 42.3% and 50.0%. Only 22.2% and 10.6% of the Metsyn (−) subjects (men and women, respectively) and 19.6% and 15.2% of the HTGW (−) subjects (men and women, respectively) had the atherogenic metabolic triad. In conclusion, the HTGW (+) phenotype is associated with a hostile lipid profile that includes higher levels of sdLDL-C and decreased LDL particle size. The HTGW phenotype, compared with the MetSyn criteria, can provide an easy and inexpensive tool to monitor patients characterized by an adverse lipid and lipoprotein profile.     

Absorption and transport of deuterium-substituted 2R,4′R,8′R-α-tocopherol in human lipoproteins

Oral administration of a single dose of tri- or hexadeuterium substituted 2R,4′R,8′R-α-tocopheryl acetate (d₃- or d₆-α-T-Ac) to humans was used to follow the absorption and transport of vitamin E in plasma lipoproteins. Three hr after oral administration of d₃-α-T-Ac (15 mg) to 2 subjects, plasma levels of d₃-α-T were detectable; these increased up to 10 hr, reached a plateau at 24 hr, then decreased. Following administration of d₆-α-T-Ac (15–16 mg) to 2 subjects, the percentage of deuterated tocopherol relative to the total tocopherol in chylomicrons increased more rapidly than the corresponding percentage in whole plasma. Chylomicrons and plasma lipoproteins were isolated from 2 additional subjects following administration of d₃-α-T-Ac (140 or 60 mg). The percentage of deuterated tocopherol relative to the total tocopherol increased most rapidly in chylomicrons, then in very low density lipoproteins (VLDL), followed by essentially identical increases in low and high density lipoproteins (LDL and HDL, respectively) and lastly, in the red blood cells. This pattern of appearance of deuterated tocopherol is consistent with the concept that newly absorbed vitamin E is secreted by the intestine into chylomicrons; subsequently, chylomicron remnants are taken up by the liver from which the vitamin E is secreted in VLDL. The metabolism of VLDL in the circulation results in the simultaneous delivery of vitamin E into LDL and HDL.     

Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein receptors

It was previously reported that a protein-free microemulsion (LDE) with structure roughly resembling that of the lipid portion of low density lipoprotein (LDL) was presumably taken up by LDL receptors when injected into the bloodstream. In contact with plasma, LDE acquires apolipoproteins (apo) including apo E that would be the ligand for receptor binding. Currently, apo were associated to LDE by incubation with high density lipoprotein (HDL). LDE-apo uptake by mononuclear cells showed a saturation kinetics, with an apparent K _m of 13.1 ng protein/mL. LDE-apo is able to displace LDL uptake by mononuclear cells with a K _i of 11.5 ng protein/mL. LDE without apo is, however, unable to displace LDL. The uptake of ¹⁴C-HDL is not dislocated by increasing amounts of LDE-apo, indicating that HDL and LDE-apo do not bind to the same receptor sites. In human hyperlipidemias, LDE labeled with ¹⁴C-cholesteryl ester behaved kinetically as expected for native LDL. LDE plasma disappearance curve obtained from eight hypercholesterolemic patients was markedly slower than that from 10 control normolipidemic subjects [fractional clearance rate (FCR)=0.02±0.01 and 0.12±0.04 h⁻¹, respectively; P<0.0001]. On the other hand, in four severely hypertriglyceridemic patients, LDE FCR was not significantly different from the controls (0.07±0.03 h⁻¹). These results suggest that LDE can be a useful device to study lipoprotein metabolism.     

Response of hypercholesterolemic subjects to administration of tocotrienols

The cholesterol-suppressive actions of Palmvitee and γ-tocotrienol were assessed in hypercholesterolemic subjects after acclimation to the American Heart Association Step 1 dietary regimen for four and eight weeks, respectively. The four-week dietary regimen alone elicited a 5% decrease (P<0.05) in the cholesterol level of the 36 subjects. Subjects continuing on the dietary regimen for a second four-week period experienced an additional 2% decrease in their cholesterol levels. Dietary assessments based on unanticipated recalls of 24-h food intake records suggest that significant reductions in energy and fat, predominantly in saturated fat, intakes are responsible. The subjects experienced significant Palmvitee- and γ-tocotrienol-mediated decreases in cholesterol. The group of subjects acclimated to the dietary regimen for four weeks responded to Palmvitee (a blend of tocols providing 40 mg α-tocopherol, 48 mg α-tocotrienol, 112 mg γ-tocotrienol, and 60 mg δ-tocotrienol/day for four weeks) with a 10% decrease in cholesterol (P<0.05). Dietary assessments showed no further change in energy and fat intakes. α-Tocopherol attenuates the cholesterol-suppressive action of the tocotrienols. The second group of subjects, acclimated to the dietary regimen for eight weeks, received 200 mg-γ-tocotrienol/d for four weeks. The cholesterol-suppressive potency of this α-tocopherol-free preparation was calculated to be equivalent to that of the mixture of tocotrienols (220 mg) used in the prior study. Cholesterol levels of the 16 subjects in the second group decreased 13% (P<0.05) during the four-week trial. Plasma apolipoprotein B andex vivo generation of thromboxane B₂ were similarly responsive to the tocotrienol preparations, whereas neither preparation had an impact on high density lipoprotein cholesterol and apolipoprotein A-I levels. Based on a paper presented at the PORIM International Palm Oil Congress (PIPOC) held in Kuala Lumpur, Malaysia, September 1993.     

Phytosterol Intake and Dietary Fat Reduction are Independent and Additive in their Ability to Reduce Plasma LDL Cholesterol

We studied the interrelationship of diet and plant sterols (PS) on plasma lipids, lipoproteins and carotenoids. Mildly hypercholesterolemic men (n = 13) and postmenopausal women (n = 9) underwent four randomized, crossover, double-blind, controlled feeding periods of 23 days each. The design consisted of two levels of PS (0 and 3.3 g/day) and two background diets having fat content either typical of the American diet (total and saturated fat at 33.5 and 13.2% of energy, respectively), or a Step 1 type of diet (total and saturated fat at 26.4 and 7.7% of energy, respectively). Plasma total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A1 and Apo B were 4.3, 5.3, 4.5, 2.8 and 2.5% lower, respectively (P ≤ 0.0001; <0.0001, 0.0016, 0.0006, and 0.0069), with the Step 1 diet than with the typical American diet. Diet had no effect on TC/HDL cholesterol (P = 0.1062). Plant sterol intake lowered TC, LDL cholesterol, and Apo B by 9.0, 12.4 and 6.1% and TC/HDLC by 9.6% (P ≤ 0.0001 for all), respectively, without affecting HDL cholesterol and Apo A1 (P = 0.2831 and 0.732). The PS effect in lowering plasma TC and LDL cholesterol was independent of and additive to the effect due to dietary fat reduction. Responses of plasma carotenoids to PS intake were consistent with the literature. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture.     

Rosuvastatin Enhances the Catabolism of LDL apoB‐100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner

Dose‐associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B‐100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA‐I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB‐100 production rate (PR), as well as increase apoB‐100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB‐100 in TRL and LDL and apoA‐I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography‐mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA‐I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB‐100 FCR by 36 and 46 % (both ns) and LDL apoB‐100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA‐I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB‐100 PR or HDL apoA‐I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB‐100, with no significant effects on apoB‐100 production or HDL apoA‐I kinetics.     

Plant sterol esters lower plasma lipids and most carotenoids in mildly hypercholesterolemic adults

The ability of plant sterol esters (PSE) in salad dressing to modify plasma lipids and carotenoids was determined in 26 men and 27 women fed controlled, weight-maintaining, isocaloric diets. Diets contained typical American foods that provided 32% of energy from fat. Dressings contained 8 g (ranch) or 4 g (Italian) of fat per serving. PSF (3.6 g/d) were provided in two servings/d of one of the dressings. Diets with ranch or Italian dressing without and with PSE were fed for 3 wk/diet and crossed over randomly within dressings. Diets were adjusted to similar fat and fatty acid concentrations. Type of salad dressing did not affect plasma lipids, lipoproteins, carotenoids, or fat-soluble vitamins (P>0.05). Switching from a self-selected baseline diet to the control diet resulted in reduction in low density lipoprotein (LDL) cholesterol of 7.9%, a decrease in high density lipoprotein (HDL) cholesterol of 3.1%, and a decrease in triglycerides (TG) of 9.3%. Consumption of 3.6 g of PSE resulted in further decreases in LDL cholesterol (9.7%) and TG (7.3%) but no additional change in HDL cholesterol. Total plasma carotenoids decreased 9.6% with PSE. An automated stepwise procedure was developed to produce candidate mixed models relating plasma carotenoid response to PSE. These models adjusted for preintervention plasma carotenoid levels and effects of diets on blood lipids. There were significant decreases in β-carotene, α-carotene, and β-cryptoxanthin (females only) not associated with changes in plasma lipids. Plasma carotenoids on all diets remained within normal ranges. We conclude that low-fat foods, such as salad dressings, are effective carriers for PSE.     

The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans

Normal, healthy male volunteers (n=6) were fed diets [high docosahexaenoic acid-DHA] containing 6 g/d of DHA for 90 d. The stabilization (low-DHA) diet contained less than 50 mg/d of DHA. A control group (n=4) remained on the low-DHA diet for the duration of the study (120 d). Blood samples were drawn on study days 30 (end of the stabilization period), 75 (midpoint of the intervention period), and 120 (end of the intervention period). Adipose tissue (AT) samples were taken on days 30 and 120. The plasma cholesterol (C), low density lipoprotein (LDL)-C and apolipoproteins (apo) [Al, B, and lipoprotein (a)] were unchanged after 90 d, but the triglycerides (TAG) were reduced from a mean value of 76.67±24.32 to 63.83±16.99 mg/dL (n=6, P<0.007 using a paired t-test) and the high density lipoprotein (HDL)-C increased from 34.83±4.38 mg/dL to 37.83±3.32 mg/dL (n=6, P<0.017 using a paired t-test). The control group showed no significant reduction in plasma TAG levels. Apo-E, however, showed a marked increase in the volunteers’ plasma after 90 d on the high-DHA diet, from 7.06±4.47 mg/dL on study day 30 to 12.01±4.96 mg/dL on study day 120 (P<0.002 using a paired t-test). The control subjects showed no significant change in the apo-E in their plasma (8.46±2.90 on day 30 vs. 8.59±2.97 on day 120). The weight percentage of plasma DHA rose from 1.83±0.22 to 8.12±0.76 after 90 d on the high-DHA diet. Although these volunteers were eating a diet free of eicosapentaenoic acid (EPA), plasma EPA levels rose from 0.38±0.05 to 3.39±0.52 (wt%) after consuming the high-DHA diet. The fatty acid composition of plasma lipid fractions—cholesterol esters, TAG, and phospholipid—showed marked similarity in the enrichment of DHA, about 10%, after the subjects consumed the high-DHA diet. The DHA content of these plasma lipid fractions varied from less than 1% (TAG) to 3.5% (phospholipids) at baseline, study day 30. EPA also increased in all plasma lipid fractions after the subjects consumed the high-DHA diet. There were no changes in the plasma DHA or EPA levels in the control group. Consumption of DHA also caused an increase in AT levels of DHA, from 0.10±0.02 to 0.31±0.07 (wt%) (n=6, P<0.001 using a paired t-test), but the amount of EPA in their AT did not change. Thus, dietary DHA will lower plasma TAG without EPA, and DHA is retroconverted to EPA in significant amounts. Dietary DHA appears to enhance apo-E synthesis in the liver. It appears that DHA can be a safe and perhaps beneficial supplement to human diets.     

Alterations of the lipid profile after 7.5 years of low-dose antioxidant supplementation in the SU.VI.MAX study

Antioxidant micronutrients have been reported to be associated with an improvement in the blood profile, but the results are not consistent. The aim of the present study was to assess the effects of antioxidant supplementation on changes in the serum lipid profile of adult participants in the SU.VI.MAX study. French adults (n=12,741∶7,713 females aged 35–60 yr, and 5,028 males aged 45–60 yr) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg β-carotene, 100 μg selenium, and 20 mg zinc) or a matching placebo. Median follow-up time was 7.5 yr. After 7.5 yr, no effect of supplementation on total cholesterol was observed in men or women after adjusting for baseline total cholesterol levels and lipid-lowering medications. The prevalence of hypercholesterolemia (≥6.5 mmol/L) showed a trend toward being higher in women who received supplements compared with those who received the placebo (P=0.06). In both sexes, the group receiving supplements exhibited higher mean serum TG concentrations than did the placebo group (P=0.06 in men; P=0.05 in women). The prevalence of hypertriglyceridemia (≥2.3 mmol/L) was also significantly higher in men who received supplements (P=0.03), but not in women. Our results suggest than long-term daily supplementation with low doses of β-carotene, vitamins C and E, selenium, and zinc does not result in an improved lipid profile and could even adversely affect some blood lipids, possibly with a higher risk of hyperlipidemia in women.     

Plasma high density lipoprotein subgroup distribution in rats fed diets with varying amounts of sucrose and sunflower oil

The effect of varying the dietary sunflower oil/sucrose (SO/SU) ratio on rat plasma lipid concentration and lipoprotein distribution was studied. Four groups of 10 rats were fed for 4 weeks diets with varying SO/SU ratios. Lipoprotein components were then estimated in whole plasma and after cumulative density ultracentrifugation. Whole plasma triacylglycerol (TG), total cholesterol (TC) and free cholesterol (FC) decreased with increasing SO/SU ratio; the CE/FC ratio increased, because CE remained virtually unaltered. Plasma TG-lowering was due to a decrease in VLDL and LDL-TG. Protein, CE and FC in d=1.063–1.100 g/ml (HDL_2b) and d=1.100–1.125 g/ml (HDL_2a) lipoproteins decreased upon increasing the SO/SU ratio. In contrast, in d=1.125–1.200 g/ml (HDL₃) lipoproteins, there was a concomitant increase in these components. Although increasing the SO/SU ratio effected more protein and CE transportation in HDL₃ and less in HDL₂, the total amount of these components in high density lipoproteins (d=1.063–1.200 g/ml) remained constant. Apo A-I and apo C-III decreased in HDL₂ but increased in HDL₃ upon increasing the SO/SU ratio. Also, HDL₂ apo E, and the apo C-II/apo C-III and small apo B/large apo B ratios in VLDL and LDL were lowered by increasing the SO/SU ratio. The hepatic VLDL-TG output during isolated liver perfusion was lowest in rats fed the diet with the highest SO/SU ratio. In perfusate, like in plasma, the VLDL and LDL apo C-II/apo C-III ratio, as well as the small apo B/large apo B ratio, decreased upon increasing the dietary SO/SU ratio. The results indicate that there can be appreciable diet-dependent variations in plasma HDL subgroup distribution in spite of unchanged total HDL levels.     

Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor-related protein mRNA expression in healthy humans

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n=5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6±4 mg/d), followed by a 7-d cholesterol (a mean of 791±150 mg/d) supplementation. Controls (n=3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P<0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P<0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P<0.05) and LRP mRNA increased by 59% (P<0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r=+0.79, P=0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r=−0.70, P=0.05). Also, 70% of the variability in LRP mRNA (P<0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.     

Changes in Plasma LDL and HDL Composition in Patients Undergoing Cardiac Surgery

Changes of lipoprotein composition have been mainly reported in conditions of sepsis. This study characterized compositional changes in LDL and HDL during the acute phase response following cardiac surgery with cardiopulmonary bypass. Twenty-one patients undergoing cardiac surgery were included in this study. Blood samples were drawn before operation and on day 2 post-surgery. In parallel to plasma lipids and antioxidant status, lipoproteins were analyzed for lipid, apolipoprotein (apo), hydroperoxide and alpha-tocopherol content. Beyond decreases in lipid concentrations and antioxidant defenses, cardiac surgery induced substantial modifications in plasma lipoproteins. ApoB decrease in LDL fraction (−46%; P < 0.0001) reflected a marked reduction in the circulating particle number. LDL cholesteryl ester content relative to apoB concentration remained unchanged post-surgery while triglyceride (+113%; P < 0.001), free cholesterol (+22%; P < 0.05) and phospholipid (+23%; P < 0.025) were raised relative to apoB indicating increased particle size. In HDL, an abrupt rise of apoSAA (P < 0.05) was observed together with a decrease of apoA1 (−22%; P < 0.005). Cholesteryl ester content in HDL fraction decreased in parallel to apoA1 concentration while triglycerides, free cholesterol and phospholipids increased relative to apoA1. In contrast to unchanged alpha-tocopherol content, hydroperoxide content was increased in LDL and HDL. By comparison to sepsis, cardiac surgery induces a comparable reduction in circulating LDL but a more limited decrease in HDL particles. Furthermore, in contrast, cardiac surgery induces an increase in polar and non-polar lipids, as well as of particle size in both LDL and HDL. M. Hacquebard is recipient of a fellowship from the Danone Institute, Belgium.     

Studies on the transfer of tocopherol between lipoproteins

The net transfer of labeled α-tocopherol from donor to acceptor lipoproteins at physiological concentrations was investigated. Labeled lipoproteins were isolated i) followingin vitro addition of [3,4-³H]all rac-α-tocopherol to plasma, or ii) from plasma obtained 12–16 h after ingestion by normal subjects of an oral dose (100 mg each) of 2R,4′R,8′R-α-[5,7-(C²H₃)₂]tocopheryl acetate and 2S,4′R′,R-α-[5-C²H₃]tocopheryl acetate. A constant amount (on a protein basis) of labeled lipoprotein was incubated with an increasing amount of unlabeled acceptor lipoprotein for 2 h at 37°C. No discrimination between stereoisomers of α-tocopherol was detected. Labeled VLDL and labeled LDL (very low and low density lipoproteins, respectively) tended to retain their labeled tocopherol. Labeled high density lipoproteins (HDL) readily transferred the labeled tocopherol to VLDL (>60% transferred), while the transfer to LDL was dependent upon the ratio of labeled HDL/LDL with a lower net transfer at higher ratios. This dependency of the distribution of tocopherol upon the ratio of HDL/LDL was also observedin vivo. The tocopherol/mg HDL protein was measured in 11 subjects with varying HDL levels. As the %HDL in the plasma increased from 14 to 50%, the tocopherol/HDL protein also increased (r²=0.37,P<0.05).     

Evidence that leptin contributes to intestinal cholesterol absorption in obese (ob/ob) mice and wild-type mice

In the present study, the effect of leptin on intestinal cholesterol absorption was investigated in C57 BL/6 OlaHsd Lep^ob/Lep^ob obese (ob/ob) mice and lean C57 BL/6 (wild-type) mice. Animals were treated either with or without recombinant leptin for 2 wk. Cholesterol absorption was measured by the constant isotope feeding method and indirectly by the ratio of campesterol to cholesterol in serum. In ob/ob mice, cholesterol absorption was significantly higher compared to wild-type mice [83.4±2.3% (SD) vs. 77.6±1.5%, P<0.01]. Treatment with leptin significantly reduced cholesterol absorption in both ob/ob and wild-type mice by 8.5 (P<0.001) and 5.2% (P<0.05), respectively. Serum concentrations of campesterol and the ratio of campesterol to cholesterol in ob/ob mice were significantly higher compared to wild-type mice (2.2±0.3 mg/dL vs. 1.2±0.3 mg/dL, P<0.001; and 36.8±2.8 μg/mg vs. 28.0±3.3 μg/mg, P<0.001). After treatment of ob/ob mice with leptin, concentrations of campesterol and its ratio to cholesterol were significantly lower (2.2±0.3 mg/dL vs. 1.0±0.2 μg/mg, P<0.001; and 36.8±2.8 μg/mg vs. 13.2±2.2 μg/mg, P<0.001, respectively). In wild-type mice, the ratio of campesterol to cholesterol in serum was also significantly lower after treatment with leptin (28.0±3.3 μg/mg vs. 22.6±5.0 μg/mg, P<0.05). A significant positive correlation (r=0.701, P<0.01) between cholesterol absorption and the ratio of campesterol to cholesterol, in serum was found. It is concluded that leptin contributes to intestinal cholesterol absorption in ob/ob mice and lean wild-type mice.