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 control (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 non-saponifiable 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.

Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets.

The effects of National Cholesterol Education Program (NCEP) Step 2 diets on plasma lipoprotein profiles in 72 men [mean (+/- SD) age: 44 +/- 15 y, range: 19-81 y] and 48 women (mean age: 50 +/- 21 y, range: 21-78 y) participating in five previously published studies were examined. Subjects were placed on a baseline diet similar to an average American diet (35-41% total fat, 13-16% saturated fat, 31-45 mg cholesterol/MJ) and then on an NCEP Step 2 diet (18-29% total fat, 4-7% saturated fat, 11-20 mg cholesterol/MJ) under isoenergetic conditions. All food and drink were provided. Compared with the baseline diet, consumption of the NCEP Step 2 diets was associated with significant decreases in concentrations of low-density-lipoprotein (LDL) cholesterol (-18.9% and -15.6%, respectively) and high-density-lipoprotein (HDL) cholesterol (-17.0% and -11.2%, respectively) in both men and women. Men with the apolipoprotein (apo) E 3,4 phenotype had a significantly greater decrease in LDL cholesterol (-24.2%) with the NCEP Step 2 diets than men with the apo E 3,3 phenotype (-17.7%). Men with the apo A-IV 1,2 phenotype tended to have less LDL cholesterol lowering (-12.8%) than men with the apo A-IV 1,1 phenotype (-19.6%), but this difference was not significant. No differences were seen by apo E and A-IV phenotype in women. A large variability in lipid response to the diet was observed, with changes in LDL cholesterol ranging from +3% to -55% in men and and from +13% to -39% in women. Forty-eight percent of the variability in LDL-cholesterol response (in mmol/L) to the diet could be accounted for by baseline LDL concentrations and age in men, and 13% by age in women.

A prospective study of the epidemiology of colitis and colon cancer in cotton-top tamarins (Saguinus oedipus).

BACKGROUND & AIMS: Spontaneous colitis and colon cancer in the cotton-top tamarin have been shown to resemble human ulcerative colitis and its associated cancer. The effect of environment and diet on the evolution of the disease was studied in animals from birth to 5 years of age. METHODS: Newborn tamarins were assigned to three groups reared in (1) a colony in which colitis was highly prevalent and fed a standard diet; (2) an isolation unit and fed a standard diet or one of two semipurified diets; and (3) a multispecies nursery, returned to the colony, and fed the same semipurified diets. Mucosal biopsy specimens from the descending colon were taken at 4-month intervals. RESULTS: Acute colitis and chronic mucosal changes were significantly higher in the colony than in the isolation unit. Diet had no effect on acute colitis, but chronic mucosal changes were significantly higher in animals fed a standard diet than semipurified diets. CONCLUSIONS: Data suggest that acute colitis was associated with environment. Factors in the environment, including a transmissible agent, are discussed. Chronic mucosal changes were modified by diet. Cancer was associated with acute colitis and chronic changes and seems to be associated with diet.

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)

Cholesterol metabolism in New World primates: comparative studies in two tamarin species (Saguinus oedipus and Saguinus fuscicollis) and the squirrel monkey (Saimiri sciureus).

1. Cholesterol metabolism has been characterized in three species of New World primates, the cotton-top tamarin, the saddle-back tamarin, and the squirrel monkey. 2. When fed a diet containing cholesterol, the three species exhibited differing responses of plasma cholesterol levels. 3. Dietary cholesterol absorption was determined and plasma cholesterol die-away kinetics were analyzed in terms of a two-pool model. 4. The results of the analyses of cholesterol turnover are consistent with the observed species-specific differences in plasma cholesterol values and cholesterol absorption. 5. Cholesterol metabolism differs between the two tamarin species, as well as between the tamarins and the squirrel monkey. 6. Implications of species-specific differences between tamarin species are discussed in terms of the use of tamarin species as animal models for comparative studies of cholesterol metabolism and the etiology of cancer and cardiovascular disease.

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)

Fecal bile acids and neutral sterols in the cotton-top tamarin (Saguinus oedipus).

1. The cotton-top tamarin (Saguinus oedipus), a small New World primate susceptible to spontaneous development of colon cancer, was studied for its fecal neutral sterol and bile salt composition. 2. Standardization procedures to establish the effect of exposure of the stool to room temperature air for various time-periods showed no significant effects on the neutral sterol and bile salt composition of the samples. 3. Microbial degradation of cholesterol and bile acids to secondary metabolites showed a progressive rise during the first year of life after which some degree of homeostasis was observed. 4. The proportion of cholesterol that remained unmetabolized by colonic microflora was in excess of 50%, an amount that was significantly higher than in man and other higher primates. 5. Ursodeoxycholic acid was identified as a significant (12%) component of fecal bile acids in this species. 6. Secondary bile acids formed by the action of enteric microflora were also significantly lower than levels found in man and other animals.

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)

Rice bran oil lowers serum total and low density lipoprotein cholesterol and apo B levels in nonhuman primates.

The hypolipidemic response of rice bran oil (RBO) was investigated in nonhuman primates fed semi-purified diets containing blends of oils which included RBO at 0-35% Kcals as dietary fat. The studies demonstrated the following: (a) the degree of reduction of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) was highly correlated with initial serum cholesterol levels of the monkey on the stabilization diet; (b) the content of rice bran oil in the diet was the predominant factor influencing serum TC, LDLC and apoB causing up to a 40% reduction in LDLC without affecting high density lipoprotein cholesterol (HDLC) when RBO was the sole dietary oil fed; (c) the cholesterol-lowering capabilities of RBO were not explained by its fatty acid composition. These studies suggest that RBO may be an additional vegetable oil which lowers serum cholesterol levels by unique mechanisms which will require further study.

Fatty acid content of marine oil capsules.

The use of dietary omega 3 fatty acid capsules has been associated with a decrease in plasma triglyceride levels. In addition, populations consuming diets rich in fish appear to have a decreased incidence of cardiovascular disease. Eicosapentaenoic acid (EPA, 20:5 omega 3) and docosahexaenoic acid (DHA, 22:6 omega 3) are major fatty acids in fish oils. It is believed that fish oils exert their biologic effect through these fatty acids. Many individuals are currently taking fish oil capsules to lower lipids, increase bleeding time, and possibly decrease cardiovascular risk. These capsules also have been classified as food additives with less stringent controls on content. We assessed the fatty acid, cholesterol, and vitamin A and E content of eight commercially available capsules along with cod liver oil. The content of EPA was found to range from 8.7-26.4% (wt %) with a mean of 17.3% (82.4% of labeled content), and that of DHA from 8.9-17.4% with a mean of 11.5% (90.0% of labeled content) as assessed by capillary column gas-liquid chromatography. The mean content of the polyunsaturated omega 3 fatty acids was 31.9%, and that of the omega 6 fatty acids was 1.4%. The content of saturated fatty acids was 32.0%, and that of monounsaturated fatty acids was 25.1%. Cholesterol content was low, with a range of 0.7-8.3 mg/g, the alpha-tocopherol range was 0.62-2.24 mg/g, and the range of retinyl esters was 0.4-298.4 micrograms/g. Cod liver oil had substantially more retinyl esters (2450.1 micrograms/g) than did fish oil capsules.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental maternal and neonatal folate status relationships in nonhuman primates.

The influence of maternal dietary folic acid intake on folate status was studied in Cebus albifrons monkeys by feeding 10 or 250 micrograms/100 kcal dietary folic acid during pregnancy and 4 wk postpartum. Maternal, infant, and nonpregnant hematologic indices; blood and liver folate concentrations; and urinary formiminoglutamic acid excretion all varied with dietary folate intake and pregnancy status as did milk folate concentration in lactating dams. Maternal folate status, determined by plasma, red blood cell, and milk folate concentrations, as well as urinary formiminoglutamic acid excretion, all were correlated significantly with liver folate concentrations in neonates (r = 0.740, r = 0.919, r = 0.936, and r = -0.851, respectively). Results in these primates showed that neonatal folate status was related significantly to the dietary folate intake and folate status of the mother during pregnancy and lactation.

Effect of long-term feeding of soy-based diets on the pancreas of Cebus monkeys.

Feeding soy-based protein containing trypsin inhibitor causes pancreatic hypertrophy in the rat, and long-term feeding (up to 2 years) has revealed a high incidence of adenoma following hypertrophy. It was therefore of interest to determine whether the ingestion of soy-based protein has any adverse effects on the primate pancreas. A resource of 27 Cebus albifrons monkeys, previously used to evaluate the protein quality of several soy and milk proteins, has been maintained on semi-synthetic diets for 3 to 4 years; the protein sources for the diets were casein, lactalbumin, soy isolate and soy concentrate. In general the monkeys were in good physical health and their weights were appropriate for age and sex. Serum biochemical and hematological profiles were normal and there were no major differences between the groups. A pancreatic biopsy from both the head and tail region of the pancreas was taken from each monkey. Visual observation of the pancreas revealed no overt pathology; two independent histological examinations indicated no diet-related differences between groups, and biochemical analyses of trypsin, chymotrypsin, protein, DNA and RNA revealed no differences. It is concluded that feeding low level trypsin inhibitor-containing diets for up to 4 years caused no adverse effects in the pancreas of the Cebus nonhuman primate.

Acute erythroid hypoplasia in malnourished infant squirrel monkeys fed isolated soy protein.

Infant squirrel monkeys fed low protein diets using an isolated soy protein develop an acute anemia. To investigate this syndrome, four groups of animals fed diets containing adequate or restricted amounts of casein or soy protein were studied from 1 through 16 weeks of age. The low protein groups, in which growth was prevented by adjustment of the protein content between 2 through 8 weeks, showed no difference in caloric intake or plasma albumin concentrations. However, the low soy group developed a severe anemia (hemoglobin 4 to 7 g/dl) after 4 to 6 weeks of dietary treatment. The anemia was characterized as normocytic, normochromic, and was associated with reduced reticulocyte concentrations. Bone marrow specimens showed an increased myeloid/erythroid ratio due primarily to an absolute erythroid hypoplasia. Juvenile animals fed similar low soy diets did not become anemic. The selective effect of this isolated soy protein, demonstrable only during the transitional period of early infancy, was attributed to the interaction of the malnourished animal with a component of the isolated soy protein per se. The potential role of soy glycoproteins is discussed.

Hematological development of the infant squirrel monkey (Saimiri sciureus).

Hematologic developmental norms from infant squirrel monkeys indicate a relative maturation of the hematopoietic system by 16 weeks. The elevated hemoglobin, hematocrit, red blood cell count, MCV and MCH at birth are followed by a decreasing hemoglobin (decreasing red blood cell count and MCV) until 4 weeks of age. A reticulocytosis then occurs until the hemoglobin level approximates adult concentrations by 16 weeks of age with gradual changes in this as well as hematocrit, red blood cell count, MCV and MCH thereafter. Total leukocytes and segmented neutrophils are elevated at birth and decrease rapidly in the first 2 weeks, reaching stabile values by 16 weeks. An opposite trend is seen with the lymphocyte population. Plasma protein and albumin concentrations show a nadir at 2 weeks of age with the albumin levels stabilizing by 10 weeks and the total protein concentration continuing to increase throughout the 1st year.