Lynne M. Ausman

Effects of different forms of dietary hydrogenated fats on serum lipoprotein cholesterol levels.

BACKGROUND Metabolic studies suggest that fatty acids containing at least one double bond in the trans configuration, which are found in hydrogenated fat, have a detrimental effect on serum lipoprotein cholesterol levels as compared with unsaturated fatty acids containing double bonds only in the cis configuration. We compared the effects of diets with a broad range of trans fatty acids on serum lipoprotein cholesterol levels. METHODS Eighteen women and 18 men consumed each of six diets in random order for 35-day periods. The foods were identical in each diet, and each diet provided 30 percent of calories as fat, with two thirds of the fat contributed as soybean oil (<0.5 g of trans fatty acid per 100 g of fat), semiliquid margarine (<0.5 g per 100 g), soft margarine (7.4 g per 100 g), shortening (9.9 g per 100 g), or stick margarine (20.1 g per 100 g). The effects of those diets on serum lipoprotein cholesterol, triglyceride, and apolipoprotein levels were compared with those of a diet enriched with butter, which has a high content of saturated fat. RESULTS The mean (+/-SD) serum low-density lipoprotein (LDL) cholesterol level was 177+/-32 mg per deciliter (4.58+/-0.85 mmol per liter) and the mean high-density lipoprotein (HDL) cholesterol level was 45+/-10 mg per deciliter (1.2+/-0.26 mmol per liter) after subjects consumed the butter-enriched diet. The LDL cholesterol level was reduced on average by 12 percent, 11 percent, 9 percent, 7 percent, and 5 percent, respectively, after subjects consumed the diets enriched with soybean oil, semiliquid margarine, soft margarine, shortening, and stick margarine; the HDL cholesterol level was reduced by 3 percent, 4 percent, 4 percent, 4 percent, and 6 percent, respectively. Ratios of total cholesterol to HDL cholesterol were lowest after the consumption of the soybean-oil diet and semiliquid-margarine diet and highest after the stick-margarine diet. CONCLUSIONS Our findings indicate that the consumption of products that are low in trans fatty acids and saturated fat has beneficial effects on serum lipoprotein cholesterol levels.

Oryzanol Decreases Cholesterol Absorption and Aortic Fatty Streaks in Hamsters

Oryzanol is a class of nonsaponifiable lipids of rice bran oil (RBO). More specifically, oryzanol is a group of ferulic acid esters of triterpene alcohol and plant sterols. In experiment 1, the mechanisms of the cholesterol-lowering action of oryzanol were investigated in 32 hamsters made hypercholesterolemic by feeding chow-based diets containing 5% coconut oil and 0.1% cholesterol with or without 1% oryzanol for 7 wk. Relative to the control animals, oryzanol treatment resulted in a significant reduction in plasma total cholesterol (TC) (28%, P<0.01) and the sum of IDL-C, LDL-C, and VLDL-C (NON-HDL-C) (34%, P<0.01). In addition, the oryzanol-treated animals also exhibited a 25% reduction in percent cholesterol absorption vs. control animals. Endogenous cholesterol synthesis, as measured by the liver and intestinal HMG-CoA reductase activities, showed no difference between the two groups. To determine whether a lower dose of oryzanol was also efficacious and to measure aortic fatty streaks, 19 hamsters in experiment 2 were divided into two groups and fed for 10 wk chow-based diets containing 0.05% cholesterol and 10% coconut oil (w/w) (control) and the control diet plus 0.5% oryzanol (oryzanol). Relative to the control, oryzanol-treated hamsters had reduced plasma TC (44%, P<0.001), NON-HDL-C (57%, P<0.01), and triglyceride (TG) (46%, P<0.05) concentrations. Despite a 12% decrease in high density lipoprotein cholesterol (HDL-C) (P<0.01), the oryzanol-treated animals maintained a more optimum NON-HDL-C/HDL-C profile (1.1±0.4) than the contorl (2.5±1.4; P<0.0075). Aortic fatty streak formation, so defined by the degree of accumulation of Oil Red O-stained macrophage-derived foam cells, was reduced 67% (P<0.01) in the oryzanol-treated animals. From these studies, it is concluded that a constituent of the nonsaponifiable lipids of RBO, oryzanol, is at least partially responsible for the cholesterol-lowering action of RBO. In addition, the cholesterol-lowering action of oryzanol was associated with significant reductions in aortic fatty streak formation.

Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program Step 2 diet.

The most stringent dietary recommendations of the National Cholesterol Education Program (NCEP) are to limit fat intake to < 30% of calories, saturated fat intake to < 7% of calories, and cholesterol intake to < 200 mg/d (Step 2 diet). There is debate as to whether the remaining fat in the diet should be relatively high in monounsaturated or polyunsaturated fatty acids. We examined this issue by testing the effects of diets meeting the aforementioned guidelines that were enriched in three different vegetable oils on plasma lipids in the fasting and postprandial states in a clinically relevant population. Female and male subjects (n = 15, mean age, 61 years) with low-density lipoprotein cholesterol (LDL-C) concentrations > 130 mg/dL were studied under strictly controlled conditions. Subjects were first placed on a diet similar to that currently consumed in the United States to stabilize plasma lipids with respect to identical fat and cholesterol intakes. The subjects then received diets meeting NCEP Step 2 criteria in which two thirds of the fat calories were given either as canola, corn, or olive oil in a randomized, double-blinded fashion for 32 days each. Plasma cholesterol concentrations declined after consumption of diets enriched in all the test oils; however, the declines were significantly greater for the canola (12%) and corn (13%) than for the olive (7%) oil-enriched diet. Mean plasma LDL-C concentrations declined after consumption of diets enriched in all the test oils (16%, 17%, and 13% for canola, corn, and olive oil, respectively), and the magnitude of the declines was statistically indistinguishable among the test oils. Mean plasma high-density lipoprotein cholesterol (HDL-C) concentrations declined after consumption of the baseline diet, and these declines were significant for the canola (7%) and corn (9%) oil-enriched diets. Changes in LDL apolipoprotein (apo)B concentrations paralleled those of LDL-C. Switching from the baseline to the vegetable oil--enriched diets had no significant effect on plasma triglyceride, apoA-I, and lipoprotein(a) concentrations or the total cholesterol to HDL-C ratio. LDL apoB to apoA-I ratios were significantly reduced when the subjects consumed the vegetable oil--enriched diets. Differences similar to those observed in the fasting state were observed in the postprandial state.(ABSTRACT TRUNCATED AT 400 WORDS)

Hydrogenation impairs the hypolipidemic effect of corn oil in humans. Hydrogenation, trans fatty acids, and plasma lipids.

The effects of plasma lipoproteins and apolipoproteins of replacing corn oil with corn-oil margarine in stick form as two thirds of the fat in the National Cholesterol Education Program (NCEP) Step 2 diet were assessed in 14 middle-aged and elderly women and men (age range, 44-78 years) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-C] range, 133-219 mg/dl [3.45-5.67 mmol/l] at screening). During each 32-day study phase, subjects received all their food and drink from a metabolic kitchen. Subjects were first studied while being fed a diet approximating the composition of the current US diet (baseline), which contained 35% of calories as fat (13% saturated fatty acids [SFAs], 12% monounsaturated fatty acids [MUFAs; 0.8% 18:1n-9 trans], and 8% polyunsaturated fatty acids [PUFAs]) and 128 mg cholesterol/1,000 kcal. This baseline phase was followed by a corn oil-enriched diet containing 30% fat (6% SFA, 11% MUFA [0.4% 18:1n-9 trans], and 10% PUFA) and 83 mg cholesterol/1,000 kcal, and then a corn-oil margarine-enriched diet containing 30% fat (8% SFA, 12% MUFA [4.2% 18:1n-9 trans], and 8% PUFA) and 77 mg cholesterol/1,000 kcal. All diets were isocaloric. Mean fasting LDL-C and apolipoprotein (apo) B levels were 153 mg/dl (3.96 mmol/l) and 101 mg/dl on the baseline diet, 17% and 20% lower (both p < 0.001) on the corn oil-enriched diet, and 10% and 10% lower (both p < 0.01) on the margarine-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein Response to Diets High in Soy or Animal Protein With and Without Isoflavones in Moderately Hypercholesterolemic Subjects

Objective—The objective of this study was to assess the independent effect of soy relative to common sources of animal protein and soy-derived isoflavones on blood lipids. Methods and Results—Forty-two subjects with LDL cholesterol levels ≥3.36 mmol/L were fed each of four diets in randomized order for 6 weeks per phase. Diets contained a minimum of 25 g animal protein or isolated soy protein/4.2 MJ, with each containing trace amounts or 50 mg of isoflavones/4.2 MJ. Soy protein had a modest effect on total, LDL and HDL cholesterol, and triglyceride concentrations (−2%, P =0.017; −2%, P =0.042; +3%;P =0.034, −11%, P <0.001, respectively). Soy protein had no significant effect on plasma lipids in individuals with LDL cholesterol <4.14 mmol/L and significantly reduced total and LDL cholesterol and triglyceride concentrations in individuals with LDL cholesterol ≥4.14 mmol/L (−4%, P =0.001; −5%, P =0.003; −15%, P <0.001, respectively). No significant effect of isoflavones on plasma lipid levels was observed either constituent to the soy protein or supplemental to the animal protein. Conclusions—Although potentially helpful when used to displace products containing animal fat from the diet, the regular intake of relatively high levels of soy protein (>50 g/day) had only a modest effect on blood cholesterol levels and only in subjects with elevated LDL cholesterol levels (≥4.14 mmol/L). Soy-derived isoflavones had no significant effect.

Rice bran oil consumption and plasma lipid levels in moderately hypercholesterolemic humans.

The effect of rice bran oil, and oil not commonly consumed in the United States, on plasma lipid and apolipoprotein concentrations was studied within the context of a National Cholesterol Education Panel (NCEP) Step 2 diet and compared with the effects of canola, corn, and olive oils. The study subjects were 15 middle-aged and elderly subjects (8 postmenopausal women and 7 men; age range, 44 to 78 years) with elevated low-density lipoprotein (LDL) cholesterol (C) concentrations (range, 133 to 219 mg/dL). Diets enriched in each of the test oils were consumed by each subject for 32-day periods in a double-blind fashion and were ordered in a Latin square design. All food and drink were provided by the metabolic research unit. Diet components were identical (17% of calories as protein, 53% as carbohydrate, 30% as fat [< 7% as saturated fat], and 80 mg cholesterol/1000 kcal) except that two thirds of the fat in each diet was contributed by rice bran, canola, corn, or olive oil. Mean +/- SD plasma total cholesterol concentrations were 192 +/- 19, 194 +/- 20, 194 +/- 19, and 205 +/- 19 mg/dL, and LDL-C concentrations were 109 +/- 30, 109 +/- 26, 108 +/- 31, and 112 +/- 29 mg/dL after consumption of the rice bran, canola, corn, and olive oil-enriched diets, respectively. Plasma cholesterol and LDL-C concentrations were similar and statistically indistinguishable when the subjects consumed the rice bran, canola, and corn oil-enriched diets and lower than when they consumed the olive oil-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats.

Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high‐fat diet (HFD)‐induced nonalcoholic steatohepatitis (NASH) promoted diethylnitrosamine (DEN)‐initiated hepatocarcinogenesis in a rat model. Using this model, we investigated the efficacy of an equivalent dosage of dietary LY from either a pure compound or a tomato extract (TE) against NASH‐promoted hepatocarcinogenesis. Six groups of rats were injected with DEN and then fed either Lieber‐DeCarli control diet or HFD with or without LY or TE for 6 weeks. Results showed that both LY and TE supplementations significantly decreased the number of altered hepatic foci expressing the placental form of glutathione S‐transferase in the livers of HFD‐fed rats. This was associated with significantly lower proliferating cell nuclear antigen positive hepatocytes and cyclinD1 protein, as well as decreased activation of extracellular signal‐regulated kinase and nuclear NF‐κB. Although both LY and TE supplementations reduced HFD‐induced lipid peroxidation in the livers, we observed significantly decreased cytochrome P450 2E1, inflammatory foci and mRNA expression of proinflammatory cytokines (TNF‐α, IL‐1β and IL‐12) in the HFD+TE fed group but increased nuclear NF‐E2‐related factor‐2 and heme oxygenase‐1 proteins in the HFD+LY fed group, relative to HFD feeding alone. These data indicate that LY and TE can inhibit NASH‐promoted hepatocarcinogenesis mainly as a result of reduced oxidative stress, which could be fulfilled through different mechanisms.

Short-term consumption of a low-fat diet beneficially affects plasma lipid concentrations only when accompanied by weight loss. Hypercholesterolemia, low-fat diet, and plasma lipids.

Study subjects (6 women and 5 men) over the age of 40 years with fasting low-density lipoprotein cholesterol concentrations > 130 mg/dL were studied during three 5-week diet phases and one 10-week phase: baseline (36% fat: 13% saturated fatty acids [SFA], 12% monounsaturated fatty acids [MUFA], 8% polyunsaturated fatty acids [PUFA], and 128 mg cholesterol/1000 kcal); reduced fat (29% fat: 7% SFA, 9% MUFA, 11% PUFA, and 85 mg cholesterol/1000 kcal); and two low fat (15% fat: 5% SFA, 5% MUFA, 3% PUFA, and 73 mg cholesterol/1000 kcal). Body weight was maintained during the first three 5-week phases (baseline, reduced fat, and low fat [-->energy]) and decreased during the last 10-week phase when the low-fat diet was provided such that the subjects determined, in part, their caloric intake (low fat [decreases energy]). Mean body weight declined by 0.62 +/- 0.47 kg/wk during the first 5 weeks and 0.43 +/- 0.43 kg/wk during the second 5 weeks of the 10-week low-fat (decreases energy) period. Relative to the baseline diet, plasma cholesterol concentrations decreased from 226 +/- 33 to 195 +/- 19 (-13%), 208 +/- 22 (-7%), and 190 +/- 19 (-15%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. Low-density lipoprotein cholesterol concentrations decreased from 158 +/- 28 to 128 +/- 16 (-18%), 134 +/- 17 (-14%), and 119 +/- 15 (-23%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. High-density lipoprotein cholesterol concentrations decreased from 48 +/- 11 to 42 +/- 9 (-10%), 35 +/- 7 (-25%), and 38 +/- 8 (-18%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. Triglyceride concentrations increased from 110 +/- 32 to 115 +/- 31 (8%), 188 +/- 76 (75%), and 130 +/- 32 (22%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. Maximal changes in plasma lipid concentrations were observed after the first 5 weeks of the low-fat (decreases energy) diet phase despite continued weight loss throughout the entire 10-week diet period.(ABSTRACT TRUNCATED AT 400 WORDS)

Hydrogenation Impairs the Hypolipidemic Effect of Corn Oil in Humans

The effects of plasma lipoproteins and apolipoproteins of replacing corn oil with corn-oil margarine in stick form as two thirds of the fat in the National Cholesterol Education Program (NCEP) Step 2 diet were assessed in 14 middle-aged and elderly women and men (age range, 44-78 years) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-C] range, 133-219 mg/dl [3.45-5.67 mmol/l] at screening). During each 32-day study phase, subjects received all their food and drink from a metabolic kitchen. Subjects were first studied while being fed a diet approximating the composition of the current US diet (baseline), which contained 35% of calories as fat (13% saturated fatty acids [SFAs], 12% monounsaturated fatty acids [MUFAs; 0.8% 18:1n-9 trans], and 8% polyunsaturated fatty acids [PUFAs]) and 128 mg cholesterol/1,000 kcal. This baseline phase was followed by a corn oil-enriched diet containing 30% fat (6% SFA, 11% MUFA [0.4% 18:1n-9 trans], and 10% PUFA) and 83 mg cholesterol/1,000 kcal, and then a corn-oil margarine-enriched diet containing 30% fat (8% SFA, 12% MUFA [4.2% 18:1n-9 trans], and 8% PUFA) and 77 mg cholesterol/1,000 kcal. All diets were isocaloric. Mean fasting LDL-C and apolipoprotein (apo) B levels were 153 mg/dl (3.96 mmol/l) and 101 mg/dl on the baseline diet, 17% and 20% lower (both p < 0.001) on the corn oil-enriched diet, and 10% and 10% lower (both p < 0.01) on the margarine-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term fatty acid stability in human serum cholesteryl ester, triglyceride, and phospholipid fractions

Fatty acid profiles of biological specimens from epidemiological/clinical studies can serve as biomarkers to assess potential relationships between diet and chronic disease risk. However, data are limited regarding fatty acid stability in archived specimens following long-term storage, a variable that could affect result validity. Our objective was to determine the effect of prolonged storage at −80°C on the fatty acid profiles of serum cholesteryl ester (CE), triglyceride (TG), and phospholipid (PL) fractions. This was accomplished by determining the fatty acid profile of frozen, archived, previously unthawed serum samples from 22 subjects who participated in a controlled feeding trial. Initial analysis was performed after trial completion and the repeat analysis after 8–10 years of storage using GC. No significant differences were observed among the majority of fatty acids regardless of lipid fraction. Reliability coefficients were high for the fatty acid classes (saturated fatty acid : 0.70, MUFA : 0.90, PUFA : 0.80). When differences were identified, they were limited to low abundance fatty acids (≤1.5 mol%). These differences were quantitatively small and likely attributable to technical improvements in GC methodology rather than sample degradation. Thus, our data demonstrate that storage at −80°C up to 10 years does not significantly influence serum CE, TG, or PL fatty acid profiles.