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Optimal diets for prevention of coronary heart disease.

CONTEXT: Coronary heart disease (CHD) remains the leading cause of mortality in industrialized countries and is rapidly becoming a primary cause of death worldwide. Thus, identification of the dietary changes that most effectively prevent CHD is critical. OBJECTIVE: To review metabolic, epidemiologic, and clinical trial evidence regarding diet and CHD prevention. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE through May 2002 for epidemiologic and clinical investigations of major dietary factors (fat, cholesterol, omega-3 fatty acids, trans-fatty acids, carbohydrates, glycemic index, fiber, folate, specific foods, and dietary patterns) and CHD. We selected 147 original investigations and reviews of metabolic studies, epidemiologic studies, and dietary intervention trials of diet and CHD. DATA EXTRACTION: Data were examined for relevance and quality and extracted by 1 of the authors. DATA SYNTHESIS: Compelling evidence from metabolic studies, prospective cohort studies, and clinical trials in the past several decades indicates that at least 3 dietary strategies are effective in preventing CHD: substitute nonhydrogenated unsaturated fats for saturated and trans-fats; increase consumption of omega-3 fatty acids from fish, fish oil supplements, or plant sources; and consume a diet high in fruits, vegetables, nuts, and whole grains and low in refined grain products. However, simply lowering the percentage of energy from total fat in the diet is unlikely to improve lipid profile or reduce CHD incidence. Many issues remain unsettled, including the optimal amounts of monounsaturated and polyunsaturated fats, the optimal balance between omega-3 and omega-6 polyunsaturated fats, the amount and sources of protein, and the effects of individual phytochemicals, antioxidant vitamins, and minerals. CONCLUSIONS: Substantial evidence indicates that diets using nonhydrogenated unsaturated fats as the predominant form of dietary fat, whole grains as the main form of carbohydrates, an abundance of fruits and vegetables, and adequate omega-3 fatty acids can offer significant protection against CHD. Such diets, together with regular physical activity, avoidance of smoking, and maintenance of a healthy body weight, may prevent the majority of cardiovascular disease in Western populations.

Coronary Artery Disease↗

Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man.

Twenty patients consumed a liquid diet in which the predominant fatty acids were either saturated (Sat), monounsaturated (Mono), or polyunsaturated (Poly). The fats in these three diets comprised 40% of total calories and consisted of palm oil, high-oleic safflower oil, and high-linoleic safflower oil, respectively. During the third and fourth week of each dietary period, multiple samples of blood were taken and were analyzed for plasma total cholesterol (TC), triglycerides (TG), and cholesterol in lipoprotein fractions (VLDL-C, LDL-C, and HDL-C). Twelve of the patients had normal TG levels; in these patients, both Mono and Poly diets caused statistically significant and equal lowerings of plasma LDL-C, but the Poly diet lowered HDL-C levels more frequently than did the Mono diet. Neither diet changed the level of plasma TG. The proportions of total protein and the various lipid components in isolated fractions (VLDL, IDL, LDL, HDL) were not altered by the two diets. Eight patients had hypertriglyceridemia; these individuals showed considerable variability in response to Mono and Poly diets. Although there was a trend towards reductions in TC and LDL-C levels by both types of unsaturated fats, the changes were inconsistent; furthermore, HDL-C concentrations were low on the Sat diet and were unaffected by either the Mono or the Poly diet. The results of this study show that oleic acid is as effective as linoleic acid in lowering LDL-C levels in normo-triglyceridemic patients, and oleic acid seemingly reduces HDL-C levels less frequently than does linoleic acid. Neither type of unsaturated fat had striking effects on lipoprotein levels of hypertriglyceridemic patients.

Aged↗

Dietary hydrogenated fat increases high-density lipoprotein apoA-I catabolism and decreases low-density lipoprotein apoB-100 catabolism in hypercholesterolemic women.

OBJECTIVE: To determine mechanisms contributing to decreased high-density lipoprotein cholesterol (HDL-C) and increased low-density lipoprotein cholesterol (LDL-C) concentrations associated with hydrogenated fat intake, kinetic studies of apoA-I, apoB-100, and apoB-48 were conducted using stable isotopes. METHODS AND RESULTS: Eight postmenopausal hypercholesterolemic women were provided in random order with 3 diets for 5-week periods. Two-thirds of the fat was soybean oil (unsaturated fat), stick margarine (hydrogenated fat), or butter (saturated fat). Total and LDL-C levels were highest after the saturated diet (P<0.05; saturated versus unsaturated) whereas HDL-C levels were lowest after the hydrogenated diet (P<0.05; hydrogenated versus saturated). Plasma apoA-I levels and pool size (PS) were lower, whereas apoA-I fractional catabolic rate (FCR) was higher after the hydrogenated relative to the saturated diet (P<0.05). LDL apoB-100 levels and PS were significantly higher, whereas LDL apoB-100 FCR was lower with the saturated and hydrogenated relative to the unsaturated diet. There was no significant difference among diets in apoA-I or B-100 production rates or apoB-48 kinetic parameters. HDL-C concentrations were negatively associated with apoA-I FCR (r=-0.56, P=0.03) and LDL-C concentrations were negatively correlated with LDL apoB-100 FCR (r=-0.48, P=0.05). CONCLUSIONS: The mechanism for the adverse lipoprotein profile observed with hydrogenated fat intake is determined in part by increased apoA-I and decreased LDL apoB-100 catabolism.

Apolipoprotein A-I↗

Cholesterol-lowering potential in human subjects of fat from pigs fed rapeseed oil.

The possibility of achieving blood-lipid-lowering characteristics of pig fat by increasing the content of unsaturated fat in pig feed was evaluated. Three pig feeding regimens were applied: basal feed (no added fat or vitamin E), basal feed + rapeseed oil (60 g/kg feed), and basal feed + rapeseed oil (60 g/kg) + vitamin E (200 mg/kg). Meat and meat products from the three pig groups were incorporated into diets providing 86 g pig fat/10 MJ. The diets were served to twelve healthy human male subjects for 3 weeks each in a randomised crossover design. The diets prepared from pigs fed rapeseed oil had a lower content of saturated fatty acids (approximately 9 v. 11% of energy) and a higher content of polyunsaturated fatty acids (approximately 6 v. 4% of energy) than the diet prepared from pigs fed the basal feed. Diets based on fat from pigs fed the rapeseed oil resulted in significantly lower (approximately 4%, P = 0.019) total serum cholesterol concentration compared with the diet from pigs fed the basal feed. No differences were observed in LDL-, HDL- or VLDL-cholesterol, or in triacylglycerol or VLDL-triacylglycerol concentrations. Addition of vitamin E to the pig feed resulted in only a minor increase in vitamin E content in the human subjects' diet and the vitamin E content was low in all three pig diets. Plasma vitamin E concentration in the human subjects at the end of the period with diets from pigs fed rapeseed oil without vitamin E was significantly lower (P = 0.04) than in the other two diet periods. In conclusion, an increased content of rapeseed oil in pig feed changes the fatty acid composition of the pig fat in a way that has a potential to reduce blood cholesterol concentrations in human subjects. However, intake of pig fat with a higher content of unsaturated fatty acids needs to be matched by a higher dietary intake of vitamin E.

Adult↗

Sunflower, virgin-olive and fish oils differentially affect the progression of aortic lesions in rabbits with experimental atherosclerosis.

In this study we report the effects of sunflower, virgin olive and fish oils on the progression of aortic lesions. A total of 24 male New Zealand rabbits (six per each group) were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol, to induce atherosclerosis. An atherogenic control group (A) was killed after this period and three groups were fed for an additional period of 30 days with a diet composed of (1.75 g of supplemented oil and 98.25 of standard chow): sunflower oil (S), virgin olive oil (O) and fish oil (F). A control group (n=6) was fed with a standard chow diet for 80 days. LDL lipid composition and histological analysis of aortic atherosclerotic lesions were assayed. The atherogenic diet caused a significant increase of cholesterol levels in LDL and aorta tissue. Cholesterol ester content rose significantly in the aortic arch of groups S, O and F. Fatty streaks were found in all aortic sections, although only group S showed a significant progression of the lesion compared with group A. We conclude that the replacement of a high cholesterol-saturated fat diet by another cholesterol free-unsaturated fat diet does not regress atherosclerosis in rabbit. However, sunflower oil provokes a significant progression in lesion development, whereas diet enrichment with extra virgin olive oil and, to a lesser extent, fish oil, stops this progression.

Animals↗

Effects of dietary cholesterol and fat, sex and sire on lecithin-cholesterol acyltransferase activity in baboons.

We analyzed the effects of dietary cholesterol, type of dietary fat, sex and sire progeny family on lecithin-cholesterol acyltransferase activity in 80 adult baboons. The animals were the progeny of 80 dams and 6 sires and were randomly assigned at birth to breast feeding or to one of three formulas containing 0.02, 0.30 or 0.60 mg cholesterol/ml. After weaning at 4 months of age the animals were fed one of four diets that were either high or low in cholesterol with 40% of the calories from either saturated or unsaturated fat. The fractional and molar rates of lecithin-cholesterol acyltransferase activity were measured at 7-8 years of age by an HPLC method. Infant diet (breast vs. formula feeding or level of cholesterol in formula had no effect on enzyme activity later in life. The adult diets that were high in cholesterol decreased the fractional lecithin-cholesterol acyltransferase rate by 20% / compared to diets low in cholesterol (7.89 vs. 9.84%/h, P less than 0.002), but dietary cholesterol did not affect the molar activity. Animals fed the high cholesterol diets had higher unesterified cholesterol concentrations compared to those fed the low cholesterol diets (38.1 mg/dl vs. 31.6 mg/dl, P less than 0.0001). The molar lecithin-cholesterol acyltransferase rate was increased 13% by saturated compared to unsaturated fat (83.3 vs. 73.6 nmol/h per ml plasma, P less than 0.07), but no effect of dietary fat was observed on the fractional enzyme activity. Females compared to males had significantly higher fractional (10.9 vs. 7.14%/h, P less than 0.0001) and molar lecithin-cholesterol acyltransferase activities (99.3 vs. 61.7 nmol/h per ml plasma, P less than 0.0001). After adjustment for the effects of diet and sex we observed differences in the fractional activity (range, 7.2-10.8%/h, P less than 0.04) and in the molar rate (range, 63.6-99.8 nmol/h per ml plasma, P less than 0.07) among the six sire progeny groups. The differences among sire progeny groups are evidence for genetic differences in lecithin-cholesterol acyltransferase activities among the baboon families.

Animals↗

The in vitro preparation and histochemical properties of substances resembling ceroid.

Substances possessing the same histochemical properties as the ceroid in cirrhotic livers of rats fed choline-deficient diets have been prepared from various unsaturated fats, fatty acids and their esters by autoxidation but could not be obtained from hydrocarbons or saturated fats or fatty acids. The formation of ceroid-like substances occurred first on surfaces or at interfaces in the reaction mixtures. It was inhibited by antioxidants and was accelerated by the addition of tissues, blood cells, erythrocytic stroma, or hemoglobin, by emulsification, by increasing the surface exposed to the air, and by increasing the temperature. Histochemical studies provided much evidence that the following properties of ceroid might be attributed to the products of the autoxidation of unsaturated lipids: insolubility in organic solvents, sudanophilia, yellowing by concentrated nitric acid, positive periodic acid-Schiff's reaction, basophilia, acid fastness, positive hernofuscin reaction, and reduction of diammine silver carbonate and alkaline potassium permanganate. The normal reactivity of cells or tissues embedded in ceroid was effectively masked by the pigment, apparently, initially at least, by preventing the reagents' gaining access to them. It is suggested that the iron sometimes demonstrated in ceroid may be that of blood cells or tissue fragments incompletely masked by the ceroid. It is concluded that whenever conditions are such that unsaturated fats accumulate in tissues to such an extent that a relative lack of biological anti-oxidants results, autoxidation of the fats and their conversion to ceroid pigment are favored, and that ceroid and the lipofuscin pigment of vitamin E deficiency may be fundamentally similar.

Animals↗

Chromatographic determination of cis-trans monoethylenic unsaturation in fats and oils--A review.

Chromatographic procedures for the determination of geometric and positional monoethylenic fatty-acid isomers in fats and oils have been reviewed. For the determination of these isomers, the procedure involving prep GLC isolation of the monoethylenic ester fractions on polar stationary phases, further separation and determination of geometric isomers by prep Ag+/TLC, and determination of positional isomers by reductive ozonolysis, is considered to be the most suitable for the analysis of a wide range of oils. Although, in this review, emphasis has been placed on monoethylenic isomers, most of the techniques described are also applicable in the study of polyenoic isomers.

Adsorption↗

Effect of dietary unsaturated and saturated fats on azoxymethane-induced colon carcinogenesis in rats.

The effects of dietary unsaturated and saturated fats on chemically induced colon carcinogenesis were examined in male Donryu rats. The rats were fed two types of semipurified diets consisting of 5% linoleic acid or 4.7% stearic acid plus 0.3% essential fatty acid as dietary fats. The rats were treated with azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and sacrificed 15 weeks after the last injection of the carcinogen. The rats fed unsaturated fat diet demonstrated a significantly higher incidence of colon tumors [100%], more tumors per rat [2.68 +/- 1.60 (S.D.)], and greater malignant differentiation histologically than did those fed saturated fat diet [76%, 1.79 +/- 1.59, respectively]. Lipid analysis of colon tumors and colon mucosa showed that unsaturated fat diet altered the phosphatide fatty acyl composition of colon mucosa markedly and increased the content of arachidonic acid in the neutral lipid of colon tumors. The altered lipid composition of the mucosa may increase the sensitivity of the colon to the carcinogen, and the excess of arachidonic acid or its metabolites may be the primary agents of cocarcinogenesis of colon tumors. These findings suggest that dietary unsaturated fats have potent cocarcinogenic effects on colon carcinogenesis.

Animals↗

Effects of high fat diets on hibernation and adipose tissue in Turkish hamsters.

The effects of dietary fat saturation and fat content on hibernation and several properties of white and brown adipose tissue (WAT and BAT, respectively) were investigated in Turkish hamsters (Mesocricetus brandti). Male hamsters were housed in a long photoperiod (LD 16:8) at 23 degrees C and fed one of three diets: (1) chow (6.5% fat per weight), (2) chow + 13.5% vegetable oil (OIL, 20% fat per weight [largely unsaturated fat]) and (3) chow + 13.5% vegetable shortening [(SHORTENING, 20% fat per weight (largely saturated fat)]. Five weeks later body weights had stabilized and the animals were transferred to a short photoperiod (LD 8:16) at 3 degrees C. At the peak of the hibernation season (17 weeks) the animals were sacrificed within 24 h of arousal. Chow-fed hamsters had the greatest percentage of animals hibernating and days found torpid compared with the two fat-fed groups, with no differences found between the latter two groups for these measures. There were no differences between hibernating (HIB) and non-hibernating (NON-HIB) hamsters across or within the diet groups for any of the BAT measures [uncoupling protein content, mitochondrial mass, lipoprotein lipase (LPL) activity, and in vivo lipogenesis], nor were there significant effects of the diet on these measures. CHOW- and OIL-fed HIB hamsters showed decreases in body weight. All HIB groups had decreases in each carcass component, several fat pad weights, testes weight, and food intake. No consistent differences in WAT LPL activity or in vivo lipogenesis were found between HIB and NON-HIB hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Comparison of a vitamin E-rich diet and supplemental vitamin E on measures of vitamin E status and lipoprotein profile.

OBJECTIVE: To determine whether dietary modification rather than use of supplements can raise indices of vitamin E status to potentially cardioprotective levels. DESIGN: Eight week randomised controlled trial with parallel treatments to compare increased use of vitamin E-rich foods, supplementation with 200 IU of vitamin E, and a placebo. SETTING: Dunedin, New Zealand. SUBJECTS: Ninety subjects were recruited, of whom 82 non-smoking, free-living individuals aged 22-72 y with plasma cholesterol <7.5 mmol/l completed the trial. MAIN OUTCOME MEASURES: Dietary intakes, plasma alpha tocopherol, plasma alpha tocopherol/cholesterol ratio and lipoprotein cholesterol. RESULTS: Consumption of an additional 12 mg of vitamin E (alpha tocopherol equivalents) from dietary sources was primarily achieved through the replacement of saturated fat-rich foods with unsaturated fats rich in vitamin E, nuts and vegetables. This resulted in a 3.4 micromol/l increase in plasma alpha tocopherol at week 6 (95% CI 1.6-5.3), and 0.9 micromol/mmol in plasma alpha tocopherol/cholesterol at weeks 4 and 6 (95% CI 0.3-1.4 and 0.4-1.4, respectively) when compared with the placebo group. In the supplement group, plasma alpha tocopherol and plasma alpha tocopherol/cholesterol were significantly increased within 2 weeks and remained so throughout the 8 week intervention. CONCLUSION: Increasing dietary vitamin E intake can increase plasma alpha tocopherol levels, although factors other than dietary intake are also important determinants. The extent of dietary modification required to achieve potentially cardioprotective levels of plasma alpha tocopherol is difficult in practice. SPONSORSHIP: The study was supported through the Otago Medical Research Foundation Laurenson Award.

Adult↗

Cholesterol metabolism in adult baboons is influenced by infant diet.

We tested the hypothesis that preweaning diet alters cholesterol metabolism in adult baboons. Eighty baboons, progeny of 6 sires and 80 dams, were either breast-fed or fed one of three infant formulas containing 2, 30 or 60 mg cholesterol/100 mL. At 16 wk of age the baboons were weaned to one of four diets containing 1.0 or 0.01 mg cholesterol/kcal with 40% of energy from saturated [polyunsaturated fat/saturated fat [P/S) = 0.37] or unsaturated fat [P/S = 2.1] and maintained on these diets until they were necropsied as young adults at 7-8 yr of age. We observed no significant effects of formula cholesterol content on serum lipid or lipoprotein concentrations measured at 6-8 yr of age, but formula cholesterol intake influenced the cholesterol turnover rate and several variables of cholesterol metabolism in the adult. At 6-8 yr, baboons that were breast-fed during infancy, compared with those that were formula-fed, had lower high-density lipoprotein cholesterol (HDL-C) concentrations and higher ratios of very-low-density plus low-density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C. Breast-fed baboons, as adults, had lower cholesterol production rates, masses of the rapidly exchanging cholesterol compartment (pool A) and neutral steroid excretion rates than did those fed formula as infants. Breast and formula feeding differentially influenced the adult metabolic responses to dietary cholesterol or fat saturation. These results demonstrate that breast vs. formula feeding in infancy alters cholesterol metabolism and serum lipoprotein concentrations in adult baboons.

Aging↗

Assessment of the nutritional effects of olestra, a nonabsorbed fat replacement: introduction and overview.

Olestra is a mixture of polyesters formed from sucrose and fatty acids derived from edible fats and oils. It is not absorbed or digested and can serve as a zero-calorie replacement for dietary fat. Because olestra is lipophilic and not absorbed, it has the potential to interfere with the absorption of other dietary components, especially lipophilic ones, when it is in the digestive tract with those components. A series of studies were conducted in the domestic pig and in healthy adult humans to define the nature and extent of olestra's effect on fat-soluble vitamins, selected water-soluble micronutrients, and macronutrients, and to demonstrate that the effects of olestra on the absorption of fat-soluble vitamins can be offset by adding extra amounts of the affected vitamins to olestra foods. Before conducting the human and pig studies, the intake of olestra from the consumption of snack foods made with olestra was estimated for various subgroups. The potential for olestra to affect the absorption of nonessential but potentially beneficial dietary phytochemicals was also assessed. In addition, an assessment of how consumption patterns influence the effect of olestra on the absorption of the highly lipophilic carotenoids was made. Finally, the results from the pig and human studies were used to assess the potential for olestra to affect the nutritional status of subgroups of the population who have particularly high nutrient needs or unique dietary patterns that may lead to large olestra-to-nutrient intake ratios.

Adult↗

Effects of dietary carbohydrate and fat intake on glucose and lipoprotein metabolism in individuals with diabetes mellitus.

The dietary treatment of individuals with diabetes remains a controversial issue. The major emphasis in recent years has been on the reduction of total fat and saturated fat and replacement with complex carbohydrate. The rationale for this approach is based on the premise that such diets will reduce the risk of coronary artery disease (CAD) by reducing total and low-density lipoprotein cholesterol concentrations. In this article, we review the available data and conclude that there is little evidence to support the notion that low-fat high-carbohydrate diets per se lead to any reduction in the risk for CAD in individuals with diabetes. The only data indicating that low-fat high-carbohydrate diets lead to beneficial effects on carbohydrate and lipoprotein metabolism are confounded either by the lack of suitable experimental control, by the fact that diets also differed in the type of dietary fat and amount of dietary cholesterol, or were enormously enriched in dietary fiber. When these factors are taken into consideration, there appears to be little evidence in support of the view that substituting carbohydrate for fat in the diets of individuals with diabetes results in any measurable beneficial effect. Indeed, it could be argued that the most characteristic defects in carbohydrate and lipoprotein metabolism are exacerbated in response to low-fat high-carbohydrate diets. Alternatively, the data presented herein strongly suggest that diets containing conventional quantities of fat, in which saturated fat is replaced by unsaturated fat and dietary cholesterol reduced, would result in the desired reductions to total and low-density lipoprotein cholesterol concentrations without the adverse effects of increased postprandial glucose and insulin concentrations, increased fasting and postprandial total and very-low-density lipoprotein triglyceride concentrations, and decreased fasting high-density lipoprotein cholesterol concentrations.

Blood Glucose↗

[Effect of unsaturated dietary fats on growth and lipogenesis in rats].

In the growing rats weighting between 70 and 300 g, when 20% of the total daily energy intake consists either of 'lard (with 36% oleic acid) or sunflowerseed oil (with 61% linoleic acid)', lipogenesis, proteinogenesis, feed efficiency ratio and body compositions are identical. With the nutritional conditions used during these experiments, the occurrence of a high level of polyunsaturated fatty acids level in the diet cannot be considered as an exogenous factor able to modify the parameters studied.

Animals↗

Effect of dietary fat saturation on survival of mice with L1210 leukemia.

We examined L1210 murine leukemia growth rate and survival of host male DBA/2J mice fed a diet rich in either polyunsaturated fat (16% sunflower oil) or saturated fat (16% coconut oil). The survival of mice that received transplants of L1210 leukemia cells was longer among the animals that had ingested a diet rich in the saturated fat as compared to those fed the more unsaturated fat. In duplicate experiments, the mean survivals of mice fed coconut oil were 200.9 +/- 1.6 and 202.5 +/- 3.4 hours compared to 188.7 +/- 5.3 and 187.6 +/- 3.5 hours for those fed sunflower oil. Tumor growth rate or the rate of DNA synthesis by the leukemia cells did not differ between the two experimental groups. Therefore, the alteration in survival was apparently due to an effect of the diets on the responses of the hosts rather than their effect on tumor size or growth rate.

Animals↗

Effect of dietary fat on phospholipid class distribution and fatty acid composition in rat fat cell plasma membrane.

The effect of dietary fats on phospholipid class distribution and fatty acid composition was studied in rat fat cell plasma membrane. Three groups of male Wistar weanling rats were fed for 8 wk three diets differing in the amount and nature of the fats: 1.5% sunflower oil (low fat control; LFC), 10% sunflower oil (high fat, unsaturated; HFU), 1.5% sunflower oil + 8.5% cocoa butter (high fat, saturated; HFS). Plasma membranes were prepared from epididymal adipocytes. The amount and type of dietary fat significantly altered membrane phospholipid distribution. Phospholipid content was lowered with HFU as compared to LFC or HFS diets, but no changes were observed for cholesterol. Phosphatidylinositol (PI) and phosphatidylserine (PS) were less affected by dietary changes than were other phospholipid classes. Major changes were detected for phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents. No large changes in PC and PE fatty acid compositions were observed between the LFC and HFS groups, but the HFU diet induced several changes. Correlations with plasma membrane 5'-nucleotidase activities are discussed.

Adipose Tissue↗