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PubMed1980

The rapid onset of functional tolerance to ethanol--role of different neurotransmitters and synaptosomal membrane lipids.

The rapid onset of functional tolerance to ethanol was studied in young adult mice of the TO Swiss and C57 Black strains. Drugs known to alter the metabolism of catecholamines and 5-hydroxytryptamine in mouse brain were without effect on the development of tolerance to ethanol. Amino-oxyacetic acid, which potentiates gamma-aminobutyric acid (GABA), slightly inhibited the development of tolerance, whereas the GABA antagonist, picrotoxin, produced a small increase in tolerance. The effects of treatments which altered synaptosomal membrane lipid composition were also investigated. Prolonged treatment of mice with diazacholesterol, an inhibitor of cholesterol synthesis, reduced the cholesterol content of synaptosomal membranes and, while not altering the initial sensitivity of mice to ethanol, prevented the subsequent development of tolerance. In contrast, feeding mice a diet rich in saturated fats throughout their lives reduced the unsaturated fat content of synaptosomal membranes and appeared to reduce the initial sensitivity of mice to ethanol. These results are consistent with our previous hypothesis that a reduction in unsaturation of synaptosomal membrane lipids underlies the rapid onset of ethanol tolerance in mice. They also provide further evidence for the suggestion that GABAnergic synapses may be particularly important in this respect.

Animals↗

PubMed2005

Dietary fat intake and early mortality patterns--data from The Malmö Diet and Cancer Study.

OBJECTIVES: Most current dietary guidelines encourage limiting relative fat intake to <30% of total daily energy, with saturated and trans fatty acids contributing no more than 10%. We examined whether total fat intake, saturated fat, monounsaturated, or polyunsaturated fat intake are independent risk factors for prospective all-cause, cardiovascular and cancer mortality. DESIGN: Population-based, prospective cohort study. SETTING AND SUBJECTS: The Malmö Diet and Cancer Study was set in the city of Malmö, southern Sweden. A total of 28,098 middle-aged individuals participated in the study 1991-1996. MAIN OUTCOME MEASURES: Subjects were categorized by quartiles of relative fat intake, with the first quartile used as a reference point in estimating multivariate relative risks (RR; 95% CI, Cox's regression model). Adjustments were made for confounding by age and various lifestyle factors. RESULTS: Women in the fourth quartile of total fat intake had a significantly higher RR of cancer mortality (RR 1.46; CI 1.04-2.04). A significant downwards trend was observed for cardiovascular mortality amongst men from the first to the fourth quartile (P=0.028). No deteriorating effects of high saturated fat intake were observed for either sex for any cause of death. Beneficial effects of a relatively high intake of unsaturated fats were not uniform. CONCLUSIONS: With the exception of cancer mortality for women, individuals receiving more than 30% of their total daily energy from fat and more than 10% from saturated fat, did not have increased mortality. Current dietary guidelines concerning fat intake are thus generally not supported by our observational results.

Age Distribution↗

PubMed1990

Effects on plasma lipoproteins of monounsaturated, saturated, and polyunsaturated fatty acids in the diet of African green monkeys.

Work by other investigators has shown that an increase in dietary content of monounsaturated fatty acids can result in a decreased plasma low density lipoprotein (LDL) cholesterol concentration. This observation, combined with the epidemiologic evidence that monounsaturated fat-rich diets are associated with decreased rates of death from coronary heart disease, suggests that inclusion of increased amounts of mono-unsaturated fat in the diet may be beneficial. The present study was carried out in a primate model, the African green monkey, to evaluate the effects of dietary monounsaturated fat on plasma lipoprotein cholesterol endpoints. Two study periods were carried out in which the fatty acid compositions of the experimental diets were varied. All diets contained 35% of calories as fat. In the first experimental period, a mixture of fats was used to set the dietary fatty acid composition to be approximately 50-60% of the desired fatty acid, either saturated, monounsaturated, or polyunsaturated (n-6). In the second experimental period, pure fats were used (palm oil, oleic acid-rich safflower oil, and linoleic acid-rich safflower oil) to maximize the difference in fatty acid composition. The effects of the more exaggerated dietary fatty acid differences of period 2 were similar to those that have been reported in humans. For the group fed the diet enriched in monounsaturated fat compared to saturated fat, whole plasma and LDL cholesterol concentrations were significantly lower while high density lipoprotein (HDL) cholesterol concentrations were not affected. For the group fed the diet enriched in polyunsaturated fat compared to saturated fat, both LDL and HDL cholesterol concentrations were significantly lower than in the group fed saturated fat. LDL cholesterol concentrations were comparable in the monounsaturated and polyunsaturated fat groups and the percentage of cholesterol in LDL was lowest in the monounsaturated fat fed group. Trends were similar for the mixed fat diets, although no statistically significant differences in plasma lipoprotein endpoints could be attributed to monounsaturated fatty acids in this dietary comparison. Since effects on plasma lipoproteins similar to those seen in humans were identified in this primate model, relevant mechanisms for the effects of dietary fatty acids on lipoprotein endpoints related to coronary artery atherosclerosis, per se, can subsequently be examined.

Analysis of Variance↗

PubMed1998

Composition of dietary fat affects blood pressure and insulin responses to dietary obesity in the dog.

Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs before and after they became obese on either a saturated fat (LD, lard, n=8) or unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased significantly in both groups, although no differences occurred between diet groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial pressure than those receiving the CO diet (p<0.01; 15.9 +/- 2.1 vs. 9.8 +/- 3.3 mm Hg increase). The CO diet stimulated a greater increase in heart rate than the LD diet (p<0.05; 32.8 +/- 7.8 vs. 14.1 +/- 5.8 bpm increase). Ganglionic blockade with chlorisondamine caused an increase in HR in both lean groups and in the obese CO group, but not the obese LD group, consistent with a decrease in parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity enhanced the heart rate response to beta-adrenergic stimulation by isoproterenol in the LD, but not CO group. The LD diet increased circulating insulin and decreased insulin sensitivity, whereas the CO diet had no effect on either parameter. These findings suggest that the composition of dietary fat can modulate the autonomic and metabolic adaptations induced by dietary obesity.

Adrenergic beta-Agonists↗

PubMed1977

Diet and cholesteremia.

The statistical correlation between elevated serum cholesterol levels and increased risk of coronary heart disease has channeled thinking towards regarding dietary fat and cholesterol as the principal causes of hypercholesteremia. Since 1909 there have been a number of changes in nutrient availability in the United States. Protein availability is unchanged but the ratio of animal to vegetable protein rose from 1.06 in 1909 to 2.37 in 1972. Fat availability has risen by 26% with the ratio of animal to vegetable fat falling from 4.88 in 1909 to 1.64 in 1972. A review of available data indicates that amount and type of protein may affect cholesteremia and atherosclerosis in experimental animals. Soy protein is less cholesteremic than casein but the extent of difference can be affected by the type of carbohydrate. In a semipurified, cholesterol-free diet, saturated fat exerts an atherogenic effect but unsaturated fat does not. No atherogenicity is evident when saturated fat is added to laboratory ration. In the semipurified diet, fructose is more atherogenic than glucose, and casein is more atherogenic then soy protein. The latter difference can be virtually eliminated if alfalfa replaces cellulose as the dietary fiber. The data suggest that all elements of the diet interact and can affect cholesteremia and atherosclerosis. These effects must be considered in the planning of dietary intervention trials.

Animals↗

PubMed1987

The result of feeding palmitoyl glycerol on lymph and plasma lipids.

Palmitoyl glycerol is toxic when fed to mice, but the toxicity is alleviated by supplementing the toxic diet with 2-4% oleate or linoleate at the expense of sucrose. Lipid and fatty acid composition of lymph and plasma were studied in mice fed chow and palmitoyl glycerol diets to help explain the toxicity mechanism. When mice were fed chow, intestinal lymph contained a high proportion of saturated fatty acids; when they were given palmitoyl glycerol, the proportion approached 90% saturated fatty acids. The cholesteryl ester fraction was higher in lymph from mice fed a toxic diet than when the diet was fortified with supplemental safflower oil. However, there were no differences between diets in lipid composition of blood plasma. Similarly, except for plasma cholesterol esters, there were no differences in fatty acid composition between mice fed palmitoyl glycerol as the only fat or supplemented with a protective unsaturated fat. In the plasma, cholesteryl palmitate was elevated and cholesteryl oleate and cholesteryl linoleate were depressed when mice were given a toxic diet. Although a monoacylglycerol was toxic when fed, the percentages of monoacyglycerols in lymph or plasma were not materially elevated. The findings indicate that neither the total proportion of saturated fatty acids nor the amount of circulating monoacylglycerols was directly involved in the toxicity of palmitoyl glycerol.

Aging↗

PubMed1990

Susceptibility of RDM4 lymphoma cells to LAK-mediated lysis is decreased in tumor bearers fed fish oil high fat regimen.

RDM4 lymphoma cells were grown intraperitoneally in genetically compatible AKR mice fed either regular mouse chow, or diet supplemented with either saturated fat (hydrogenated beef tallow = HBT) or unsaturated fat (fish oil = FO). It was observed that the lymphoma cells number was significantly greater in FO-fed hosts and lower in HBT-fed hosts, than in the mice fed regular chow. The tumor bearers diet did not dramatically influence the rate of DNA synthesis of RDM4 cells, as measured by [3H]thymidine uptake in culture, a few hours after harvesting from the peritoneal cavity. It was repeatedly found that FO feeding of the tumor bearers elicited an increased resistance of RDM4 cells to lysis by LAK effectors, as appraised in vitro by 51Cr release test and in vivo by the "Winn assay". Different FO percentage of the diet (16%, 8%, 4%) resulted in comparable reduction of susceptibility of RDM4 cells to lysis by LAK effectors. Lipid analysis showed that RDM4 cells grown in mice fed FO diet or HBT diet differed markedly in their fatty acid composition and that their resistance to lysis by LAK cells correlated with the quantity of oxidizable fatty acids especially of the n-6 type.

Animals↗

PubMed2002

Replacement of dietary saturated fat with trans fat reduces serum paraoxonase activity in healthy men and women.

A high intake of saturated fat and of trans isomers of unsaturated fat is associated with increased risk of cardiovascular disease. Recently, we found that replacement of saturated fat by trans fat in a dietary controlled study with 32 men and women decreased serum high-density lipoprotein (HDL)-cholesterol and impaired endothelial function, suggesting that trans fats have stronger adverse effects than saturated fats. To investigate this further, we measured the activity of serum paraoxonase (PON1) in serum samples of the same volunteers after consumption of both diets. PON1 protects lipoproteins from oxidative damage, and higher PON1 activity appears to be related to lower cardiovascular disease risk. PON1 activity (mean +/- SD) was 195.9 +/- 108.9 U/L after 4 weeks of consuming a diet with 22.9% of energy (en%) from saturated fat and 184.5 +/- 99.3 U/L when 9.3 en% from saturated fat was replaced by trans fat (P =.006). Thus, replacement of dietary saturated fat by trans fat not only decreased serum HDL-cholesterol and impaired endothelial function, but also decreased the activity of serum paraoxonase. Whether the changes in serum paraoxonase activity caused the changes in endothelial function needs to be further investigated.

Adult↗

PubMed1983

Alimentary lipemia: plasma high-density lipoproteins and apolipoproteins CII and CIII in healthy subjects.

Three healthy male and three female inpatient volunteers consumed isocaloric diets for 4 wk. At weekly intervals, a fatty meal (100 g fat) was consumed by each fasting subject and blood drawn at 2 h intervals for 12 h. Of the four oral fat loads, two contained saturated fat (polyunsaturated/saturated fat ratio = 0.34) and two contained unsaturated fat (polyunsaturated/saturated fat = 2.21). The magnitude of alimentary lipemia, expressed as area under the plasma triglyceride curve, was 3- to 4-fold higher in males than females. Alimentary lipemia was inversely related to the subjects' fasting plasma high-density lipoprotein (HDL)-cholesterol, HDL apolipoprotein (apo) CIII and directly related to plasma triglycerides. The P/S ratios of the daily diet or the fat meal did not significantly influence the plasma triglyceride curve. After fat intake, mean (+/- SEM) plasma total apoCII and CIII fell to 54 +/- 20% and 73 +/- 5% of base-line, respectively, at 12 h in five of six subjects. After oral fat, an initial fall and a subsequent rise in apoCII and CIII in HDL was associated with reciprocal changes in apoC concentrations in very low-density lipoproteins. We speculate from the data that 1) plasma HDL and their apoC concentrations are important determinants of chylomicron clearance and 2) transfer of apoCs from HDL to triglyceride-rich lipoproteins in the early phase of fat absorption does not result in the total recycling of apoCs from these lipoproteins to HDL during the late phase of alimentary lipemia.

Adolescent↗

PubMed2000

Changes in plasma lipids and other cardiovascular risk factors during 3 energy-restricted diets differing in total fat and fatty acid composition.

BACKGROUND: The well-established relation between changes in dietary fatty acids and plasma lipids has been determined in energy-balance states. Whether this relation is altered in states of energy restriction and active weight loss is not clear. OBJECTIVE: The objective of this 12-wk study was to compare the time course of lipid changes and other cardiovascular risk factors in 3 energy-restricted diets (all 6500 kJ) with different total fat and fatty acid compositions. DESIGN: Sixty-two subjects with a body mass index (in kg/m(2)) >24 were stratified into 1 of 3 parallel dietary intervention groups: 1) a very-low-fat (VLF) diet (10% of energy from fat; 3% from saturated fat), 2) a high-saturated-fat (HSF) diet (32% of energy from fat; 17% from saturated fat), and 3) a high-unsaturated-fat (HUF) diet (32% of energy from fat; 6% from saturated fat). RESULTS: After 12 wk, LDL cholesterol decreased by 0. 66 +/- 0.11 (mean +/- SEM) and 0.68 +/- 0.12 mmol/L ( approximately 20%) with the VLF and HUF diets, respectively, compared with a decrease of only 0.24 +/- 0.11 mmol/L (7%) with the HSF diet (P < 0.02 between groups). Diet affected the time course of changes in HDL cholesterol with both high-fat diets, resulting in smaller reductions in HDL cholesterol at weeks 1 (P = 0.0004) and 4 (P = 0.02); however, these differences were no longer apparent by 12 wk. Overall weight loss was 8.6 +/- 0.4 kg (9.7%) and waist circumference decreased by 7.3 +/- 5 cm (8%) for the combined groups, with no significant differences between diets. CONCLUSIONS: Significantly greater decreases in LDL cholesterol during active weight loss are achieved with diets low in saturated fatty acids. Changes in HDL cholesterol between diets appear dependent on both the fat content of the diet and the duration of energy restriction.

Adult↗

PubMed2003

Plant-based foods and prevention of cardiovascular disease: an overview.

Evidence from prospective cohort studies indicates that a high consumption of plant-based foods such as fruit and vegetables, nuts, and whole grains is associated with a significantly lower risk of coronary artery disease and stroke. The protective effects of these foods are probably mediated through multiple beneficial nutrients contained in these foods, including mono- and polyunsaturated fatty acids, n-3 fatty acids, antioxidant vitamins, minerals, phytochemicals, fiber, and plant protein. In dietary practice, healthy plant-based diets do not necessarily have to be low in fat. Instead, these diets should include unsaturated fats as the predominant form of dietary fat (eg, fats from natural liquid vegetable oils and nuts), whole grains as the main form of carbohydrate, an abundance of fruit and vegetables, and adequate n-3 fatty acids. Such diets, which also have many other health benefits, deserve more emphasis in dietary recommendations to prevent chronic diseases.

Cardiovascular Diseases↗

PubMed1987

Digestibility of cocoa butter and corn oil and their influence on fatty acid distribution in rats.

The comparative bioavailability of cocoa butter (a predominantly saturated fat) and corn oil (a predominantly unsaturated fat) was determined in male Sprague-Dawley rats by analysis of total fecal lipids following ad libitum feeding of purified diets containing 5, 10 and 20% cocoa butter or corn oil for 2 wk. Fecal lipid elimination was significantly increased (P less than 0.05) in each cocoa butter group when compared with the corresponding corn oil group, resulting in lower digestibility coefficients for cocoa butter (59-72%) than for corn oil (93-97%). Body weight gain and food intake data were similar among all treatment groups. Fecal fatty acid profiles in rats fed corn oil diets consisted primarily of 27-34% palmitic acid (16:0), 22-32% stearic acid (18:0) and 25-37% oleic acid (18:1). Palmitic, oleic and linoleic acids were also the primary fatty acids stored in epididymal fat tissue from corn oil-fed rats. In contrast, fecal fatty acids in animals fed cocoa butter diets consisted of 31-37% palmitic acid and 58-64% stearic acid; oleic acid was the major fatty acid stored in epididymal fat tissue. These results indicate that the decreased digestibility of cocoa butter is largely a result of its fatty acid composition. This reduced bioavailability of cocoa butter may be at least partially responsible for its previously described neutral effect on serum cholesterol.

Adipose Tissue↗

PubMed1998

Effects of consumption of oat milk, soya milk, or cow's milk on plasma lipids and antioxidative capacity in healthy subjects.

A drink based on oats has been developed with new technology. In this study the effects of this oat milk, soya milk and cow's milk on plasma lipid, glucose, insulin, and antioxidant status (measured as the ability of serum to suppress the formation of the radical cation ABTS*+) were compared in 24 healthy men and women. Half of the subjects (group A) consumed 0.75-1 liters/day of oat milk and soya milk for 4 weeks each, and the other half (group B) consumed oat milk and cow's milk for two 4-week periods. In the combined groups A plus B the oat milk regimen resulted in decreased plasma cholesterol (4%) and low-density lipoprotein (LDL) cholesterol (9%) levels as compared with baseline, but no changes in high-density lipoprotein cholesterol (HDL) and triglyceride values were observed. Also soya milk consumption resulted in decreased LDL cholesterol concentrations. The only significant plasma lipid change observed during consumption of cow's milk was an increase in HDL cholesterol. No consistent changes in body weight, fasting blood glucose, serum insulin, and antioxidant status occurred after consumption of any milk regimen. A significant correlation between baseline antioxidant status and total plasma cholesterol was found (r = -0.56). It is proposed that the high content of beta-glucans in oat milk was responsible for the decreased plasma cholesterol and LDL cholesterol concentrations, but the effect could also be due to a replacement of saturated fat in the customary diet by unsaturated fat. It is concluded that oat milk can be used as an alternative to other milk drinks by subjects who would benefit from reduced LDL cholesterol values.

Adult↗

PubMed2004

[Nutrient content and health effects of nuts].

Nuts are foods with a high energy density, due in part to its small water content. They also present a low saturated fat content (<7%) but a high unsaturated fat contribution (40-60%). They represent one of the richest sources of dietary fiber, which is basically of the insoluble type. The effects of nut intake on health have been widely studied. Several prospective epidemiological studies performed on large cohorts have consistently shown that regular consumption of small amounts of nuts is negatively related to the risk of cardiovascular disease and to the risk of cardiovascular or all-cause mortality. From these studies can be concluded that regular consumption of small amounts of nuts leads to a 30-50% reduction in the risk of cardiovascular disease. Additionally, intervention studies have shown a positive effect of nut intake on lipid profile with significant reductions in total and LDL cholesterol levels and small or null effects on the HDL fraction. More recently, some studies have focused on the effect of nuts on body weight. At present, no evidences support a detrimental effect of nut consumption on body weight. On the contrary some weight loss studies suggest a beneficial effect of nut intake on body weight regulation.

Body Mass Index↗

PubMed1969

Differential responses to fasting and subsequent feeding by microsomal systems of rat liver: 6- and 9-desaturation of fatty acids.

Hepatic microsomal preparations from nonfasted, fasted, and fasted-fed rats were employed, together with cofactors, in studies of 9-desaturation of stearate-1-(14)C and 6-desaturation of linolenate-1-(14)C. Prior fasting sharply reduced 9-desaturation but did not affect 6-desaturation; feeding restored 9-desaturation. Position of desaturation was determined by permanganate-periodate oxidation and separation of the dicarboxylic acids. Feeding after fasting stimulated both desaturase systems but either dl-ethionine or actinomycin D prevented this. Dietary carbohydrate or saturated fat increased 9-desaturation and dietary protein increased 6-desaturation. Insulin treatment of nonfasted rats increased 9-desaturation but not 6-desaturation. High dietary unsaturated fat (20% safflower oil) stimulated 6-desaturation but inhibited the 9-desaturation response to feeding. The results indicate that the two desaturases are distinct and are inducible in response to different substances.

Animals↗

PubMedDate not supplied

Optimizing lipid levels through diet.

Medical nutrition therapy, consisting of a diet low in saturated fat, has an important role in reducing risks for cardiovascular disease and hyperlipidemia. Dietary factors that have a negative effect on blood lipid levels include dietary cholesterol, saturated fat, and trans fatty acids, whereas unsaturated fats, omega-3 fatty acids, and soluble fiber may help lower blood lipid levels. A two-step approach to medical nutrition therapy can help health professionals counsel people with high lipid levels to change their food choices and eating behaviors to lower their risk of heart disease. This approach involves teaching the patient how to substitute lower-fat foods, read labels, control portions, and use healthier cooking techniques. Medical nutrition therapy needs to be individualized to help lower the risk of heart disease.

Cardiovascular Diseases↗

PubMed1998

Case-control study of diet and prostate cancer in China.

INTRODUCTION: A higher incidence of prostate cancer is observed in the Western world than in Asian countries. Although it is relatively rare in China, an increased incidence has been reported in recent years. Studies in high-risk populations have suggested that dietary fat may play a role in enhancing the risk of developing prostate cancer. However, limited epidemiologic study has never examined the role of diet in low risk populations. METHODS: A case-control study was conducted in 12 cities in China to evaluate the relationship between dietary factors and prostate cancer risk. We conducted personal interviews with 133 histopathologically confirmed prostate cancer cases diagnosed between 1989 to 1992 and 265 neighborhood controls of similar age. RESULTS: Cases were more likely than controls to consume food with high fat and from animal sources (p < 0.01). The daily fat intake and the percentage of energy from fat were statistically significantly higher among cases than among controls (p < 0.01). The adjusted odds ratio for total fat between lowest quartiles and highest quartiles was OR = 3.6 (95 percent C.I. 1.8-7.2); for saturated fat, OR = 2.9 (95 percent C.I. 1.5-5.7); and for unsaturated fat, OR = 3.3 (95 percent C.I. 1.7-6.3). DISCUSSION: The data suggest that dietary fat, both saturated and unsaturated, are associated with an increased risk for prostate cancer in a low risk population.

Adult↗

PubMed1987

Regulation of indices of cholesterol synthesis in human mononuclear leukocytes by dietary cholesterol and fat saturation.

The responses of 2 indices of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase activity and incorporation of [14C]acetate into sterols, in mononuclear leukocytes freshly isolated from peripheral blood to variation in the ratio of saturated to unsaturated fat (S:U) and the amount of cholesterol absorbed from the diet were examined in 24 free-living men. Increasing S:U was associated with increasing plasma cholesterol level (r = 0.27, P = 0.03) and increasing reductase activity in leukocytes (r = 0.60, p less than 0.001). This finding is consistent with the hypothesis that saturated fat decreases the flux of cholesterol from plasma into cells thereby releasing reductase from product feedback inhibition. Reductase activity, after controlling for the effect of S:U, was negatively correlated with absorbed cholesterol from sources other than eggs (r = 0.42, P = 0.02). Surprisingly, change in reductase activity was positively correlated with change in absorbed cholesterol upon eating eggs (r = 0.49, P = 0.008). Sterol labeling was negatively correlated with absorbed cholesterol from all sources including eggs (r = -0.64, P less than 0.001) and was uncorrelated with S:U. Reductase activity and sterol labeling responded in parallel to cholesterol in foods other than eggs but not to egg feeding nor to S:U, thus it is unclear which test best reflects endogenous sterol synthesis in these cells.

Cholesterol↗