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Dietary fat, fat subtypes, and breast cancer in postmenopausal women: a prospective cohort study.

BACKGROUND: The intake of total dietary fat and of certain fat subtypes has been shown to be strongly associated with breast cancer in international comparisons and in animal experiments. However, observational epidemiologic studies have generally reported either weak positive or no associations. To extend the prospective epidemiologic evidence on this question, we examined the association between adult dietary intake of fat, fat subtypes, and breast cancer in a large, prospective cohort of postmenopausal women. METHODS: Participants were selected from a national breast cancer mammography screening program conducted from 1973 through 1981 at 29 centers throughout the United States. From 1987 through 1989, 40022 postmenopausal women satisfactorily completed a mailed, self-administered questionnaire that included a 60-item National Cancer Institute/Block food-frequency questionnaire. Women were then followed for an average of 5.3 years; 996 women developed breast cancer. Risk was assessed by use of Cox proportional hazard regression, with age as the underlying time metric. All statistical tests were two-sided. RESULTS: Compared with women in the lowest quintile (Q1) of percentage of energy from total fat, the adjusted risk ratio (RR) and 95% confidence interval (CI) for women in the highest quintile (Q5) was 1.07 (95% CI = 0.86-1.32). In analyses stratified by history of benign breast disease (BBD), a positive association was observed among only women with no history of BBD (RR (Q5 versus Q1) = 2.20; 95% CI = 1.41-3.42; test for trend, P =.0003). The increased risk in these women appeared to be attributable to unsaturated fat intake and oleic acid in particular. CONCLUSIONS: In this study, there was no overall association between fat intake during adulthood and breast cancer risk; however, among women with no history of BBD, there appeared to be a positive association between total and unsaturated fat intake and breast cancer risk.

Breast Neoplasms↗

Olive oil and reduced need for antihypertensive medications.

BACKGROUND: The blood pressure (BP) effects of changing the total fat intake and saturated-unsaturated fat ratio are still controversial, despite evidence that saturated fat-enriched diets are associated with higher BP levels. This double-blind, randomized crossover study evaluated a possible difference between antihypertensive effects of monounsaturated (MUFA) (extra-virgin olive oil) and polyunsaturated fatty acids (PUFA) (sunflower oil). METHODS: Twenty-three hypertensive patients were assigned randomly to MUFA or PUFA diet for 6 months and then crossed over to the other diet; effects were evaluated on the basis of daily antihypertensives needed. RESULTS: Diets high in MUFA and PUFA differed from the habitual diet for reduced total and saturated fats, whereas they differed from each other for MUFA (17.2% vs 10.5%) and PUFA content (3.8% vs 10.5%). Resting BP was significantly lower (P = .05 for systolic BP; P = .01 for diastolic BP) at the end of the MUFA diet compared with the PUFA diet. Blood pressure responses during sympathetic stimulation with the cold pressor test and isometric exercise were similar. Daily drug dosage was significantly reduced during the MUFA but not the PUFA diet (-48% vs - 4%, P<.005). All patients receiving the PUFA diet required antihypertensive treatment, whereas 8 of those receiving the MUFA diet needed no drug therapy. CONCLUSIONS: A slight reduction in saturated fat intake, along with the use of extra-virgin olive oil, markedly lowers daily antihypertensive dosage requirement, possibly through enhanced nitric oxide levels stimulated by polyphenols.

Adult↗

Dietary intake in sensitized children with recurrent wheeze and healthy controls: a nested case-control study.

BACKGROUND: The rising prevalence of asthma and allergic disease remains unexplained. Several risk factors have been implicated including diet, in particular poly-unsaturated fats and antioxidant intake. METHODS: A nested case-control study comparing the dietary intake of sensitized children with recurrent wheeze (age 3-5 years) and nonsensitized children who had never wheezed was carried out within an unselected population-based cohort. Cases and controls were matched for age, sex, parental atopy, indoor allergen exposure and pet ownership. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire and nutrient analysis program. RESULTS: Thirty-seven case-control pairs (23 male, mean age 4.4 years) participated. Daily total polyunsaturated fat intake was significantly higher in sensitized wheezers (g/day, geometric mean, 95% confidence intervals: 7.1, 6.4-7.9) compared with nonsensitized nonwheezy children (5.6, 5.0-6.3, P = 0.003). Daily omega-3 and omega-6 fat intakes were not significantly different between the two groups. No significant differences were found in intake of any antioxidant or antioxidant cofactors between the groups. CONCLUSIONS: Young sensitized wheezy children had a significantly higher total polyunsaturated fat intake compared with nonsensitized nonwheezy children. However, we were unable to distinguish a significant difference in specific poly-unsaturated fat intakes. Otherwise the children in both groups had a very similar nutritional intake.

Antioxidants↗

Influence of two dietary fats on the composition of emu oil and meat.

Male and female emus were fed a diet rich in saturated fat (beef tallow) or a diet rich in unsaturated fat (soybean oil) until they weighed about 35 kg. Samples of subcutaneous and retroperitoneal adipose tissues and samples of six major meat cuts were taken for determination of composition. Emus fed the two different diets grew at similar rates, but the male emus had a higher percentage of carcass fat. The adipose tissue cells from males were larger than those from females. All six meat cuts averaged 2.2% fat, with the regular filet having the most and the inside and outside drums the least. Cholesterol concentration of all sizes of meat cuts averaged 32.2 mg/100 g meat. Diet did not influence cholesterol content of the rendered oil. Fan filets had the greatest concentration of cholesterol, and the inside and outside drums had the least. Source of dietary fat had no effect on fat and cholesterol content of the meats. Meat from emus fed beef tallow was more tender and juicy. Fan filets were the most tender meat, had the least intense flavor, and were the most flavorful. Untrained panelists were able to discriminate between emu meat and beef. Source of dietary fat did not influence the fatty acid compositions of the meats. As expected, the soybean oil-fed emus produced oil that was more polyunsaturated than did the tallow-fed emus.

Adipose Tissue↗

Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.

Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P < 0.001) at 2 months; 4.4 +/- 0.15, 3.9 +/- 0.1, 3.4 +/- 0.15 (P < 0.001) at 4 months; 4.3 +/- 0.17, 4.0 +/- 0.13, 3.7 +/- 0.26 (P < 0.001) at 6 months; 4.8 +/- 0.28, 4.4 +/- 0.11, 3.8 +/- 0.05 (P < 0.001) at 9 months; and 4.7 +/- 0.11, 4.4 +/- 0.08, 4.1 +/- 0.19 (P < 0.001) at 12 months, for the E4, E3, and E2 groups, respectively. Increases in LDL cholesterol and LDL apoB behaved similarly. The total triglyceride, and total HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.

Aging↗

Association of prothrombin and protein S with plasma triglyceride-rich lipoproteins in humans after test meals rich in milk fat or soybean oil.

INTRODUCTION: Prothrombin can associate with rat chylomicrons in vitro. This enhances a platelet factor Xa mediated prothrombin activation when the chylomicron-prothrombin complex is exposed to platelets. Vitamin K-dependent pro- and anti-coagulation proteins are associated with TG-rich lipoproteins obtained from human plasma. In the present study, we examined the effects of saturated and unsaturated fat meals on the association of prothrombin and protein S with TG-rich lipoproteins in vivo. MATERIALS AND METHODS: Human EDTA plasma was separated from normal subjects after overnight fasting and 2.5 h after ingestion of either a saturated fat meal (butter and cream) or an unsaturated fat meal (soybean oil) containing 54-80 g fat (60.2 E%). The prothrombin and protein S in delipidated lipoproteins were determined by SDS-PAGE combined with Western blotting. RESULTS: Both prothrombin and protein S associated with TG-rich lipoproteins in fasting and in postprandial samples. The levels of prothrombin and protein S in postprandial TG-rich lipoproteins, especially after ingestion of a saturated fat meal, were higher than those in fasting TG-rich lipoproteins. CONCLUSIONS: The levels of both prothrombin and protein S in TG-rich lipoproteins in plasma increased after a single fat meal. This association is more pronounced after saturated fat meals and one may hypothesize that it can be linked to atherogenic properties of TG-rich lipoproteins.

Adult↗

Development of an animal model of chronic alcohol-induced pancreatitis in the rat.

This study was designed to develop an animal model of alcoholic pancreatitis and to test the hypothesis that the dose of ethanol and the type of dietary fat affect free radical formation and pancreatic pathology. Female Wistar rats were fed liquid diets rich in corn oil (unsaturated fat), with or without a standard or high dose of ethanol, and medium-chain triglycerides (saturated fat) with a high dose of ethanol for 8 wk enterally. The dose of ethanol was increased as tolerance developed, which allowed approximately twice as much alcohol to be delivered in the high-dose group. Serum pancreatic enzymes and histology were normal after 4 wk of diets rich in unsaturated fat, with or without the standard dose of ethanol. In contrast, enzyme levels were elevated significantly by the high ethanol dose. Increases were blunted significantly by dietary saturated fat. Fibrosis and collagen alpha1(I) expression in the pancreas were not detectable after 4 wk of enteral ethanol feeding; however, they were enhanced significantly by the high dose after 8 wk. Furthermore, radical adducts detected by electron spin resonance were minimal with the standard dose; however, the high dose increased carbon-centered radical adducts as well as 4-hydroxynonenal, an index of lipid peroxidation, significantly. Radical adducts were also blunted by approximately 70% by dietary saturated fat. The animal model presented here is the first to demonstrate chronic alcohol-induced pancreatitis in a reproducible manner. The key factors responsible for pathology are the amount of ethanol administered and the type of dietary fat.

Aldehydes↗

Dietary fat and experimental atherosclerosis.

This paper reviews studies relating to the effects of fat unsaturation and fatty acid composition on the development of experimental atherosclerosis in rabbits. The results derived from the feeding of various fats are similar whether one feeds cholesterol or an atherogenic, cholesterol-free semipurified diet. In general, the severity of atherosclerosis is inversely related to the level of fat unsaturation. Two exceptions are cocoa butter which is much less atherogenic than expected, most probably due to its high content of stearic acid, and peanut oil, while relatively unsaturated, is surprisingly atherogenic for rats, rabbits and monkeys. This latter effect is not related to the level (6%) of long-chain saturated fatty acids (arachidic, behenic, lignoceric) present in peanut oil, but rather to its triglyceride structure. Randomization of peanut oil, which modifies its triglyceride structure, significantly reduces its atherogenicity.

Animals↗

Toxicology of sulphiting agents. I: Animal studies.

Oral toxicity studies of sulphite in animals are briefly reviewed. On the basis of a chronic toxicity/carcinogenicity study of sodium metabisulphite in rats JECFA established an ADI of 0.7 mg SO2/kg using a safety factor of 100. The effects of sodium metabisulphite (1% Na2S2O5) on the composition of semi-purified rat diets during storage for at least three months have been studied. Under these conditions sulphite induced rancid off-flavours in diets containing unsaturated fats. The feeding of such stored sulphited-diets to rats resulted in growth retardation and diminished food efficiency. The extractability of the lipids from these diets was markedly reduced. Extraction with hexane, followed by ethanol extraction did not remove the toxic factor(s). It was suggested that sulphite in stored semi-purified diets may react with unsaturated fats leading to the formation of polymers of unsaturated fatty acids and/or other toxic substances. It is recommended that special attention is paid to the fatty acid composition of sulphited foods to be stored.

Animals↗

Dietary fat and the risk of breast cancer: a prospective study of 25,892 Norwegian women.

In this prospective study, the relationship between energy and fat consumption and the risk of breast cancer was examined. Between 1977 and 1983, 31,209 Norwegian women, 20 to 54 years of age attended a health screening. The attendees were given a food-frequency questionnaire to be completed at home, and this was returned by 25,892 (83%). During the 7 to 13 years of follow-up, 248 cases of breast cancer were identified for analysis by linkage to the Norwegian Cancer Registry. The relative risk of women who ate meat more than 5 times a week, as compared with those who consumed meat twice or less than twice a week, was 2.44. Consumers of 0.75 litres or more of full-fat milk daily had a relative risk of 2.91 compared with those who consumed 0.15 litres or less. A positive relationship was found between those reporting the highest quartile of mono-unsaturated fat consumption and the risk of breast cancer. The main foods contributing to the mono-unsaturated fat index were edible fats, meat and milk.

Adult↗

Substitution of saturated with monounsaturated fat in a 4-week diet affects body weight and composition of overweight and obese men.

A randomised crossover study of eight overweight or obese men (aged 24-49 years, BMI 25.5-31.3 kg/m(2)), who followed two diets for 4 weeks each, was performed to determine whether substitution of saturated fat with monounsaturated fat affects body weight and composition. Subjects were provided with all food and beverages as modules (selected ad libitum) of constant macronutrient composition, but differing energy content. The % total energy from saturated fat, monounsaturated fat and polyunsaturated fat was 24, 13 and 3 % respectively on the saturated fatty acid (SFA)-rich diet and 11, 22 and 7 % respectively on the monounsaturated fatty acid (MUFA)-rich diet. MUFA accounted for about 80 % of the unsaturated fats consumed on both diets. Body composition, blood pressure, energy expenditure (resting and postprandial metabolic rates, substrate oxidation rate, physical activity), serum lipids, the fatty acid profile of serum cholesteryl esters and plasma glucose and insulin concentrations were measured before and after each diet period. Significant (P< or =0.05) differences in total cholesterol and the fatty acid composition of serum cholesteryl esters provided evidence of dietary adherence. The men had a lower weight (-2.1 (SE 0.4) kg, P=0.0015) and fat mass (-2.6 (SE 0.6) kg, P=0.0034) at the end of the MUFA-rich diet as compared with values at the end of the SFA-rich diet. No significant differences were detected in energy or fat intake, energy expenditure, substrate oxidation rates or self-reported physical activity. Substituting dietary saturated with unsaturated fat, predominantly MUFA, can induce a small but significant loss of body weight and fat mass without a significant change in total energy or fat intake.

Absorptiometry, Photon↗

Effect of short-term dietary fat on cell growth in rat gastrointestinal mucosa and pancreas.

The effects of high fat diets on gastrointestinal and pancreatic cell growth were examined in order to determine whether short-term high fat consumption leads to pancreatic and colonic cell hyperplasia. Three groups of eight rats were fed defined diets for 4 wk. The controls were fed a 5% corn oil diet (unsaturated fat) while those fed high fat diets received either 27% lard (saturated fat) plus 3% corn oil or 30% corn oil. Body weight gain and total caloric intakes were equal. Both high fat diets produced significant decreases in proximal jejunal mass (p less than 0.05), while in the distal ileum and cecum, the only change was the development of mucosal cell hypoplasia in the group fed the high unsaturated fat diet (p less than 0.05). The high fat diets produced no change in cell growth or the incorporation of [3H]thymidine into DNA of stomach, pancreas, or colon but did result in a higher level of pancreatic lipase and lower levels of amylase activity. These results show that a short-term high fat intake leads to small intestinal hypoplasia without affecting pancreatic or colonic cell growth and therefore do not support the hypothesis that dietary fat promotes pancreatic and colonic carcinogenesis by producing cell hyperplasia.

Amylases↗

[Effects of dietary fats of vegetable and animal origin on lipid synthesis in pigs].

We have compared the effect of dietary fats, unsaturated (rapeseed oil: RO) or saturated (cow milk: CM), on growth performance, lipogenesis and fatty acid composition of backfat. Both group had the same food intake and growth performance. Nevertheless, the percentage of body fat increases with the diet RO (P < 0.05). Lipogenesis enzyme activities of backfat were greater with RO than with MC. Then, it appeared that pigs fed diets containing high level of unsaturated fat with long-chain fatty acids have both greater lipogenesis and carcass fatness as opposed to pigs fed diet containing saturated fat with medium-chain fatty acids. The fatty acids composition of lipids deposited with RO diet may alter the technological qualities of adipose tissues and that of meat.

Adipose Tissue↗

Effect of type of dietary fat, cholesterol and chenodeoxycholic acid on gallstone formation, bile acid kinetics and plasma lipids in squirrel monkeys.

To explore the effect of type of dietary fat, cholesterol and chenodeoxycholic acid on gallstone formation, bile formation, bile composition, bile acid kinetics and plasma lipids in squirrel monkeys, 39 monkeys were studied using seven different diets. Safflower oil, a highly unsaturated fat, added to a diet with cholesterol resulted in at least as high an incidence of cholesterol gallstones as butter added to the same diet. On the other hand, diets with high levels of saturated or unsaturated fat without cholesterol did not result in gallstone formation. Dietary chenodeoxycholic acid (0.1%) did not reduce the incidence of cholesterol gallstones, although the proportion of bile acids as chenodeoxycholic acid increased. Gallbladder biles from monkeys fed semipurified diets with cholesterol had a significantly higher lithogenic index than the comparable groups without cholesterol. Pool sizes of bile acids in all semipurified diet groups were reduced and the lithogenic indices were increased compared with the group fed a commercial feed. Dietary chenodeoxycholic acid caused a decrease in plasma cholesterol in butter groups and an increase in triglyceride concentrations in safflower groups. Diet infuences bile composition and bile acid kinetics, as well as the incidence of gallstones, in squirrel monkeys.

Animals↗

Diet and risk of ethanol-induced hepatotoxicity: carbohydrate-fat relationships in rats.

Nutritional status is a primary factor in the effects of xenobiotics and may be an important consideration in development of safety standards and assessment of risk. One important xenobiotic consumed daily by millions of people worldwide is alcohol. Some adverse effects of ethanol, such as alcohol liver disease, have been linked to diet. For example, ethanol-induced hepatotoxicity in animal models requires diets that have a high percentage of the total calories as unsaturated fat. However, little attention has been given to the role of carbohydrates (or carbohydrate to fat ratio) in the effects of this important xenobiotic on liver injury. In the present study, adult male Sprague-Dawley rats (8-10/group) were infused (intragastrically) diets high in unsaturated fat (25 or 45% total calories), sufficient protein (16%) and ethanol (38%) in the presence or absence of adequate carbohydrate (21 or 2.5%) for 42-55 days (d). Animals infused ethanol-containing diets adequate in carbohydrate developed steatosis, but had no other signs of hepatic pathology. However, rats infused with the carbohydrate-deficient diet had a 4-fold increase in serum ALT levels (p < 0.05), an unexpectedly high (34-fold) induction of hepatic microsomal CYP2E1 apoprotein (p < 0.001), and focal necrosis. The strong positive association between low dietary carbohydrate, enhanced CYP2E1 induction and hepatic necrosis suggests that in the presence of low carbohydrate intake, ethanol induction of CYP2E1 is enhanced to levels sufficient to cause necrosis, possibly through reactive oxygen species and other free radicals generated by CYP2E1 metabolism of ethanol and unsaturated fatty acids.

Alcohol Drinking↗

Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic coffee ingestion.

The effect of chronic coffee ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body weight at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body weight at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either in combination with coffee or not. Coffee was provided instead of drinking water. A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and coffee after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. In rat pancreas, the numbers of adenomas and carcinomas were significantly lower in the group maintained on the combination of a high-fat diet and coffee than in the high-fat group without coffee, while in the latter group the number of adenomas and carcinomas had significantly increased as compared to the low-fat controls. In hamsters, the number of ductal/ductular adenocarcinomas had significantly increased in the high-fat group as compared to the low-fat controls. The inhibitory effect of coffee on dietary fat-promoted pancreatic carcinogenesis was also noticed in this species but was less pronounced than in rats. It was concluded that chronic coffee consumption has an inhibitory effect on dietary fat-promoted pancreatic carcinogenesis in rats and hamsters. More research is needed to elucidate the mechanism by which coffee (constituents) modulates carcinogenesis.

Adenocarcinoma↗

Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion.

The effect of chronic ethanol ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body wt at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either separately or in combination with ethanol. Ethanol was provided in drinking water at a concentration of 10% (w/v). A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and received ethanol via their drinking water after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. Dietary fat was found to enhance pancreatic carcinogenesis in both rats and hamsters. In rats, ethanol slightly enhanced the multiplicity but not the incidence of malignant tumours, while in hamsters ethanol did not show any modulating effect on dietary fat-promoted carcinogenesis. It was concluded that dietary fat-promoted pancreatic carcinogenesis as observed in the animal models applied is not significantly modulated by chronic ethanol ingestion.

Animals↗