Amount Of Dietary Cholesterol Research Articles

DIETARY CHOLESTEROL LOWERS RISK OF TYPE 2 DIABETES IN THE FRAMINGHAM OFFSPRING STUDY

Beginning in the 1960s, limiting dietary cholesterol (DC) was widely considered a strategy for protecting against cardiovascular disease (CVD) risk. Recently, the 2013 American College of Cardiology/American Heart Association Lifestyle Guidelines for the Reduction of Cardiovascular Disease concluded that the evidence was insufficient to support continued restriction of DC intake for prevention of CVD; the Dietary Guidelines Advisory Committee no longer considers DC to be a “nutrient of concern”. However, questions remain about whether DC is a risk factor for type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the effects of DC alone and in combination with selected markers of a healthy diet (e.g. fruits & vegetables, whole grains, fiber) on fasting glucose (FG) and risk of developing T2DM. Men and women without T2DM who were 35–64 years of age at the time of dietary assessment in the Framingham Offspring Study were included these analyses and followed for 20 years. Three‐day food records were collected at exams 3 and 5. Individuals were classified according to sex‐specific DC intake (low, moderate, and high intakes for men: <200, 200–<400, and ≥400 mg/day; for women: <150, 150–<350, and ≥350 mg/day). Longitudinal mixed models were used to estimate the adjusted mean fasting glucose (FG) at five follow‐up exams, 4 years apart. Cox proportional hazard's models were used to estimate the risk of developing T2DM; final models were adjusted for age, education, physical activity, cigarette smoking, alcohol intake, and baseline body mass index (BMI). At baseline, men consuming ≥400 mg of DC had lower mean FG than those consuming <200 mg (FG: 93.8 vs 96.6, p‐trend: 0.0006); results were similar in women. There was no evidence that higher DC intake had an adverse effect on FG throughout all years of follow‐up. Among both men and women, longitudinal mixed models showed that those consuming the highest (vs. lowest) amounts of DC had the lowest FG levels at baseline (p<0.0001) and lowest throughout the 20 years of follow‐up (p=0.0008). In addition, those subjects with high intakes of DC had a 22% lower risk of developing T2DM (HR: 0.78; 95% CI: 0.52–1.15) over time. To evaluate the combined effects of DC and other healthy diet patterns, we cross‐classified subjects according to their intake of both DC and the particular food serving as a marker of a healthy diet. The foods most strongly associated with a lower risk of T2DM and that modified the effects of DC were whole grains and fiber. Adults consuming ≥300 mg/day of DC and ≥0.5 servings/day of whole grains had a 38% lower risk of developing T2DM (95% CI: 0.41–0.93), while those consuming ≥300 mg/day of DC who had low whole intakes had only a 21% lower risk and those with lower DC intakes but higher intakes of whole grains had a 13% lower risk. These results suggest a positive synergistic effect between DC and whole grain consumption. Dietary fiber also modified the effects of DC on T2DM risk. Subjects consuming ≥300 mg/day of DC and ≥15 grams of dietary fiber had a 43% lower risk of T2DM (95% CI: 0.40–0.83) than those consuming less DC and less fiber. These results suggest that higher intakes of DC do not adversely affect fasting glucose levels or risk of T2DM and may even be beneficial when consumed in combination with a healthy diet.Support or Funding InformationNational Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. HHSN268201500001I) and a small grant from the American Egg Board ‐ Egg Nutrition Center.

P32 EVALUATION OF SYSTEMIC INFLAMMATION IN FAMILIAL HYPERCHOLESTEROLEMIA BY BIOMARKER PROFILING ON BIOCHIP ARRAYS: IMPACT OF LDL-APHERESIS

The extent and kinetics of postprandial changes are highly variable and are modulated by numerous factors including diet, lifestyle conditions, genetic background and pathological conditions. This review focuses on dietary factors affecting postprandial chylomicron and lipoprotein metabolism in humans. The first key step in the process is fat digestion within the stomach and small intestine which can be modulated by fat and dietary fiber amounts and types.The second key step is intestinal absorption per se. The uptake and secretion of absorbed nutrients in chylomicrons is affected by numerous factors, including nutrients themselves. The amount of dietary triglycerides as well as the nature of fatty acids ingested from habitual diet or present in a test meal modulates the extent of chylomicron and plasma triglyceride levels postprandially. The amount of dietary cholesterol also modulates the extent of postprandial chylomicron and plasma triglycerides. Other nutrients can alter the postprandial occurrence of chylomicrons such as proteins, alcohol, carbohydrates or fibers. Addition of glucose and more markedly fructose, to a fat test meal increases the accumulation of chylomicrons, as does a high-glycemic index meal. In contrast, some sources of dietary fibers such as oat bran noticeably decrease the occurrence of chylomicron postprandially. Overall, changing the habitual dietary pattern, for instance from a Western-type diet to Mediterranean-type one, can in turn alter the postprandial response of the subjects. The last step in postprandial lipid metabolism is clearance from plasma through combined lipolysis processes and tissue uptake of chylomicron remnants. Both the processes can also be modulated by the nutrients.Because most day-time is usually spent in a postprandial state, the link between dietary patterns and cardiovascular health or risk is clearly mediated by the secretion and clearance rates of chylomicrons in the circulation.

Macronutrient intake and modulation on chylomicron production and clearance

The extent and kinetics of postprandial changes are highly variable and are modulated by numerous factors including diet, lifestyle conditions, genetic background and pathological conditions. This review focuses on dietary factors affecting postprandial chylomicron and lipoprotein metabolism in humans. The first key step in the process is fat digestion within the stomach and small intestine which can be modulated by fat and dietary fiber amounts and types. The second key step is intestinal absorption per se. The uptake and secretion of absorbed nutrients in chylomicrons is affected by numerous factors, including nutrients themselves. The amount of dietary triglycerides as well as the nature of fatty acids ingested from habitual diet or present in a test meal modulates the extent of chylomicron and plasma triglyceride levels postprandially. The amount of dietary cholesterol also modulates the extent of postprandial chylomicron and plasma triglycerides. Other nutrients can alter the postprandial occurrence of chylomicrons such as proteins, alcohol, carbohydrates or fibers. Addition of glucose and more markedly fructose, to a fat test meal increases the accumulation of chylomicrons, as does a high-glycemic index meal. In contrast, some sources of dietary fibers such as oat bran noticeably decrease the occurrence of chylomicron postprandially. Overall, changing the habitual dietary pattern, for instance from a Western-type diet to Mediterranean-type one, can in turn alter the postprandial response of the subjects. The last step in postprandial lipid metabolism is clearance from plasma through combined lipolysis processes and tissue uptake of chylomicron remnants. Both the processes can also be modulated by the nutrients. Because most day-time is usually spent in a postprandial state, the link between dietary patterns and cardiovascular health or risk is clearly mediated by the secretion and clearance rates of chylomicrons in the circulation.

Carbohydrate restriction and dietary cholesterol distinctly affect plasma lipids and lipoprotein subfractions in adult guinea pigs

To evaluate the effects of carbohydrate restriction (CR) and dietary cholesterol on lipoprotein metabolism, adult male guinea pigs (10 guinea pigs/diet) were fed either low (0.04 g/100 g) or high (0.25 g/100 g) amounts of dietary cholesterol, in combination with either low (10% total energy) or high (54.2% total energy) dietary carbohydrate (control groups) for a total of four groups: high carbohydrate–low cholesterol (control-L), high carbohydrate–high cholesterol (control-H), low carbohydrate–low cholesterol (CR-L) and low carbohydrate–high cholesterol (CR-H). Plasma triglyceride concentrations were lower ( P<.01%), while high-density lipoprotein cholesterol concentrations were higher ( P<.05) in the CR groups compared to the control groups. In contrast, high dietary cholesterol (CR-H and control-H) resulted in higher concentrations of total and low-density lipoprotein (LDL) cholesterol compared to those guinea pigs fed the low-cholesterol diets ( P<.01). Dietary cholesterol significantly increased the total number of LDL particles ( P<.001) and the number of small LDL ( P<.001), as determined by nuclear magnetic resonance. In contrast, carbohydrate restriction (CR-L and CR-H) resulted in lower concentrations of medium very-low-density lipoprotein and small LDL particles compared to the high-carbohydrate groups. Plasma lecithin:cholesterol acyltransferase (LCAT) activity was decreased and cholesterol ester transfer protein activity was increased by dietary cholesterol, whereas carbohydrate restriction increased LCAT activity ( P<.05). These findings are similar to those observed in humans, thus validating the use of adult guinea pigs to study lipid responses to carbohydrate restriction. The results also indicate that the atherogenicity of lipoproteins induced by high dietary cholesterol is attenuated by carbohydrate restriction in guinea pigs.

The Amount of Dietary Cholesterol Changes the Mode of Effects of (n-3) Polyunsaturated Fatty Acid on Lipoprotein Cholesterol in Hamsters

This study was designed to investigate the effects of the interaction between dietary (n-3) polyunsaturated fatty acids (PUFA) and different dietary cholesterol content on plasma and liver cholesterol in hamsters. Male Syrian hamsters consumed diets containing an incremental increase in dietary cholesterol content (0, 0.025, 0.05, 0.1 and 0.2%, w/w) with either (n-3) PUFA (21 g/100 g fatty acids) or (n-6) PUFA (37.4 g/100 g fatty acids) fat for 6 weeks. In hamsters fed the nonatherogenic diet (0 or 0.025% dietary cholesterol), very low density lipoprotein (VLDL)-cholesterol levels in the (n-3) PUFA group were not significantly different from those in the (n-6) PUFA group, and low density lipoprotein (LDL)-cholesterol levels in the (n-3) PUFA group were significantly lower than those in the (n-6) PUFA group. In contrast, in hamsters fed the atherogenic diet (0.1 or 0.2% dietary cholesterol), VLDL- and LDL-cholesterol levels in the (n-3) PUFA group were significantly higher than those in the (n-6) PUFA group, in a dose-dependent manner. When the hamsters were fed with 0, 0.025, 0.05, 0.1 or 0.2% (w/w) dietary cholesterol, high density lipoprotein (HDL) cholesterol concentration was significantly lower in the (n-3) PUFA group than those in the (n-6) PUFA group. Hepatic cholesteryl esters were significantly lower, while hepatic microsomal acyl-coenzyme A:cholesterol acyltransferase activity and VLDL-cholesteryl esters were significantly higher in hamsters fed (n-3) PUFA with the atherogenic diet (0.1 or 0.2% dietary cholesterol) than in those fed (n-6) PUFA with the atherogenic diet. Our results demonstrate that the amount of dietary cholesterol is an important factor in determining the mode and extent of effects of dietary (n-3) PUFA, especially on VLDL- and LDL-cholesterol levels. When dietary cholesterol intake was above 0.1% (w/w), the plasma cholesterol-lowering effect of (n-3) PUFA disappeared, and instead, it showed a cholesterol-increasing effect. However, the effects of dietary (n-3) PUFA on HDL-cholesterol are independent of dietary cholesterol content.

Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis

Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. Studies were identified by MEDLINE and Biological Abstracts searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.

Effects of different dietary cholesterol concentrations on lipoprotein plasma concentrations and on cholesterol efflux from Fu5AH cells

BackgroundThe fatty acid composition of the diet can modulate the effect of dietary cholesterol on plasma lipoproteins.However, HDL composition and its capacity to promote cholesterol efflux can be influenced by the diet. ObjectiveModifications in plasma lipids and in the capacity of serum to stimulate the cholesterol efflux induced by a low-fat diet [National Cholesterol Education Program (NCEP) Step I diet], by a monounsaturated fatty acid (MUFA)–rich diet, and by addition of cholesterol to both diets was studied. DesignFifteen young, healthy men followed 2 NCEP Step I diets ((<30% of fat as energy, with (< 10% saturated fat and 14% MUFAs) for 24 d, providing 0.027 or 0.068 mg cholesterol kJ-1d-1, and 2 oleic acid–enriched diets (38% of energy as fat,with 24% MUFAs) providing the same amount of dietary cholesterol as the NCEP Step I diets. ResultsTotal cholesterol, LDL cholesterol, apolipoprotein (apo)B, and apo A-I concentrations decreased after the NCEP Step I and MUFA diets compared with the usual diet. HDL cholesterol also decreased after the NCEP Step I diet. Total:HDL cholesterol, apo B, and apo B:apo A-I were lower after the MUFA diets than after the NCEP Step I diets. There were no significant differences between the lipid profiles obtained after the NCEP Step I and MUFA diets were enriched with cholesterol. The capacity of serum to promote cholesterol efflux was significantly higher after the cholesterol-enriched NCEP Step I diet than after the NCEP Step I diet. ConclusionsThe MUFA diet induced a better lipid profile than the NCEP Step I diet; however, the increase in the cholesterol content of both diets produced similar plasma lipid changes. The cholesterol in the NCEP Step I diet increased the cholesterol efflux induced by total serum. Am J Clin Nutr 1998;68:1028–33.

Effect of oestrogen replacement therapy on development of experimental arteriosclerosis: A study in transplanted and balloon-injured rabbit aortas

The mechanism underlying possible protection of oestrogen replacement therapy against cardiovascular disease appears to go beyond beneficial changes in plasma lipoproteins. A direct action of oestrogen on the metabolism of lipoproteins after entering the arterial wall may occur. The present study evaluated whether oestrogen replacement therapy affects the development of experimental arteriosclerosis in immunologically injured (experiment A + B) and balloon-injured (experiment B) aortas in ovariectomized rabbits maintained at a human level of plasma cholesterol; both models involve severe damage to the endothelium with resulting rapid accumulation of lipoproteins in the arterial intima and therefore appear suitable for studying factors directly affecting subendothelial lipoprotein metabolism. In experiment A, dietary cholesterol required to maintain a human level of plasma cholesterol was significantly higher for the oestrogen group than for the placebo group. Similarly, cholesterol accumulation in the aortic grafts was borderline higher for the oestrogen than the placebo group, whilst intimal hyperplasia was without difference between the groups. Due to a modified schedule of cholesterol feeding in experiment B, oestrogen and placebo groups received the same amount of dietary cholesterol, and cholesterol accumulation and intimal hyperplasia were similar in immunologically injured and balloon-injured parts of the aorta in both groups. These results suggest that in the female rabbit maintained at a human level of plasma cholesterol, oestrogen replacement therapy has no direct action on the development of experimental arteriosclerosis when induced by immunological or mechanical injury to the endothelium.

Diurnal variations in the plasma concentrations of mevalonic acid in patients with abetalipoproteinaemia

Previous studies have demonstrated that changes in the rates of cholesterol biosynthesis can be evaluated by the determination of plasma concentrations of sterol intermediates, including mevalonic acid and lathosterol and that, in normal human subjects, a diurnal rhythm exists in which the highest concentrations of sterol intermediates are observed at night. The factors responsible for this diurnal rhythm in cholesterol synthesis are, however, unknown. To test the hypothesis that the nocturnal increase in cholesterol biosynthesis is attributable to a reduced rate of hepatic uptake of chylomicron remnants at night as compared to higher rates of uptake during the daytime in response to alimentary lipaemia, we have examined the diurnal rhythm of mevalonic acid in six normal volunteers and three patients with phenotypic abetalipoproteinaemia. The latter patients do not absorb appreciable amounts of dietary cholesterol and are unable to synthesize chylomicron particles. Plasma concentrations of mevalonic acid exhibited a diurnal rhythm in the normal subjects, and the highest plasma concentrations were observed between 24.00 hours/04.00 hours. A similar rhythm was observed in the plasma of patients with abetalipoproteinaemia. These results suggest that the nocturnal increase in cholesterol biosynthesis which occurs in humans is not attributable to reduced hepatic uptake of chylomicron remnants at night; further studies are needed to better define those factors which influence the periodicity of cholesterol biosynthesis in humans.

Effect of dietary fish oil on serum lipids and lipoproteins of rats fed diets differing in cholesterol and fat.

The investigation was attempted to clarify the effects of fish oil on the concentration of lipids in serum and lipoproteins in rats fed diets differing in cholesterol and fat. Male Sprague-Dawley rats were maintained on low-fat/high-fat diets without and with 1.5% cholesterol (base diets) for 28 days. Half of each group was then switched to a fish oil diet for 20 days with 5.6% fish oil for exchange of coconut oil and beef tallow. Total cholesterol in rat serum was increased following feeding high amounts of dietary cholesterol. This increase was due to raised VLDL and LDL cholesterol. Rats fed the high-cholesterol/high-fat diet had lower HDL cholesterol concentration than groups fed the other base diets. Dietary fish oil lowered serum and lipoprotein cholesterol, even in the presence of dietary cholesterol. In rats fed the high-fat/cholesterol-free diet triglyceride levels in total serum and VLDL were higher than in rats fed the other base diets. The hypertriglyceridemia in rats was diminished fed dietary cholesterol. Serum triglyceride concentration was markedly lowered by fish oil, whereas, this effect reached significance only using cholesterol-free diets. This was mainly associated with a reduction in VLDL triglycerides. Fish oil lowered HDL triglycerides only in rats fed the low-fat diet without cholesterol. Lipid components in the base diets did not influence serum and LDL phospholipids. Rats fed the high-fat/cholesterol-free diet had a higher VLDL phospholipid level than the other base groups. Irrespective of the base diet, phospholipid levels in serum and lipoproteins were markedly reduced by dietary fish oil. In conclusion, this study suggests that other dietary lipids should be considered when examining the hypolipemic effect of fish oil.

EDTA reduces liver cholesterol content in cholesterol-fed rabbits

A study conducted in 1953 by one of the authors (H.S.M. Uhl) reported that orally administered ethylenediamine tetraacetic acid (EDTA) both prevented the accumulation of cholesterol in the liver of cholesterol-fed rabbits and caused the removal of accumulated cholesterol from the liver. These observations were made in rabbits fed high concentrations of cholesterol and have never been confirmed in the literature. The purpose of the present study was to determine if this original observation could be confirmed using lower amounts of dietary cholesterol and more modern and comprehensive methods for analysis of tissue lipids and plasma lipoproteins. New Zealand White rabbits were fed diets containing 0.1% cholesterol with or without EDTA (3 g/day). After 16 weeks, significantly lower concentrations of hepatic cholesterol were found in rabbits fed EDTA (6.95 mg/g wet weight) compared with controls fed the same cholesterol-containing diet without EDTA (16.6 mg/g wet weight). Plasma cholesterol levels in both groups of animals were not significantly different from one another; therefore, the effect of EDTA in reducing liver cholesterol accumulation was independent of changes in plasma cholesterol concentrations. Although the mechanism of this EDTA effect is unknown, it may provide a tool to gain further insight into mechanisms of regulation of hepatic lipoprotein and cholesterol metabolism.

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.

Differential effects of dietary fat on the tissue-specific expression of the apolipoprotein A-I gene: relationship to plasma concentration of high density lipoproteins.

Isocaloric substitution of polyunsaturated fat for saturated fat reduces concentrations of total plasma cholesterol and high density lipoproteins (HDL) in nonhuman primates. The biochemical mechanisms through which polyunsaturated fat lowers plasma HDL concentrations are not well understood but must involve changes in HDL production or HDL clearance from plasma, or both. To determine whether dietary polyunsaturated fat (P/S = 2.2) alters apolipoprotein (apo) A-I production, African green monkeys (Cercopithecus aethiops) were fed diets containing polyunsaturated fat or saturated fat (P/S = 0.3) each in combination with high (0.8 mg/kcal) and low (0.03 mg/kcal) amounts of dietary cholesterol. Animals fed polyunsaturated fat at either cholesterol level had lower plasma concentrations of total cholesterol and HDL cholesterol. Plasma apoA-I concentration was reduced by 16% by polyunsaturated fat in the high cholesterol group. The rate of hepatic apoA-I secretion, as estimated by the accumulation of perfusate apoA-I during recirculating liver perfusion, was reduced by 19% in animals consuming the high cholesterol, polyunsaturated fat diet. Hepatic apoA-I mRNA concentrations, as measured by DNA-excess solution hybridization, also were reduced by 22% in the high cholesterol, polyunsaturated fat-fed animals. In contrast, intestinal apoA-I mRNA concentrations were not altered by the type of dietary fat. Plasma apoA-II and hepatic apoA-II mRNA concentrations also were not altered by the type of dietary fat. These data indicate that dietary polyunsaturated fat can selectively alter the expression of the apoA-I gene in a tissue-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of β-sitosterol alone or in combination with chenic acid on cholesterol saturation of bile and cholesterol absorption in gallstone patients

Studies aimed at testing whether β-sitosterol, a plant sterol known to block cholesterol absorption, would induce bile cholesterol desaturation or enhance the desaturating effect of chenic acid were carried out in 7 gallstone patients. Cholesterol absorption was also measured. β-Sitosterol (250 mg/ kg-day) or chenic acid (10 mg/kg-day) was fed alone or in combination for 6-wk randomized periods. At the end of each period, fasting-state duodenal bile was obtained for lipid analysis and biliary bile acid composition; cholesterol absorption was measured by an isotope ratio technique. β-Sitosterol caused no significant bile desaturation, despite its markedly decreasing cholesterol absorption. Chenic acid lowered bile saturation, but bile remained supersaturated at this low dosage; addition of β-sitosterol induced no additional desaturation. Cholesterol absorption, averaging 48%, remained unchanged (43%) during chenic administration. The results suggest that β-sitosterol has little influence on bile saturation and therefore is of little therapeutic value for the treatment of cholesterol gallstones, either alone or in combination with chenic. The results also indicate that the desaturating effect of chenic, at least at this dosage, is not mediated by changes in cholesterol absorption, and they confirm previous studies showing no association between changes in bile cholesterol and serum cholesterol levels. The results also imply that variations in the amount of dietary cholesterol are unlikely to be an important determinant of bile saturation in gallstone patients.

Plasma and dietary cholesterol in infancy: Effects of early low or moderate dietary cholesterol intake on subsequent response to increased dietary cholesterol

Variations in dietary cholesterol and polyunsaturated or saturated fatty acids were studied in the first yr of life in 21 normal and 18 hypercholesterolemic neonates to determine if the amount of dietary cholesterol in early infancy affects subsequent adaptation to increased dietary cholesterol in later infancy and childhood. At age 12 mo, plasma cholesterol levels in normal ( 129 mg 100 ml ) and hypercholesterolemic infants ( 200 mg 100 ml ) did not appear to be influenced by antecedent low or moderate cholesterol intake in early infancy.

A relatively non-toxic thrombogenic diet for rats

Summary Rats were fed either a basal high-fat diet containing, among other ingredients, 5 % cholesterol and 0.3 % propylthiouracil or one of four modifications of the diet containing lesser amounts of these two ingredients. It was found that the amounts of dietary cholesterol and propylthiouracil could be reduced to at least 1 % and 0.02 %, respectively, without decreasing the incidence of cardiac thrombi and infarcts, but the high mortality seen during the first month when animals were given the basal diet, was abolished.

Chapter VIII: Faribault Materials and Methods

The National Diet-Heart Study included a feasibility trial in an institution for the mentally retarded, the Faribault State School and Hospital, Faribault, Minnesota. In order to recruit 225 men from a total institutional population of 3,179, the age range had to be expanded to 40-59, and the medical criteria for eligibility relaxed. In both the First and Extended Studies, four groups were followed, B, C, and D (as in the open centers), plus a group E. (40% of calories from fat, low in saturated fat and cholesterol, very high in polyunsaturated fat). In the Extended Study, less expensive lean meats were procured locally, and fed to half the men, while the other half continued to eat D-H meats. A considerable investment had to be made to assure successful feeding of the four diets to the subjects. The Second Study at Faribault evaluated the effects on serum cholesterol of simultaneously varying amount of dietary cholesterol, and amount and type of dietary fat (for design and results, cf. Chapter XVII).

Dietary fat and cholesterol and serum cholesterol in the gerbil

Groups of gerbils were fed purified diets containing either 10 or 20% of safflower, olive, or coconut oil. Each diet was fed without cholesterol and with 0.1 and 0.2% of added cholesterol. The animals were bled after 2, 4, and 8 wk for the determination of the level of serum cholesterol. The major factors affecting the level of serum cholesterol were the kind of dietary oil, the amount of dietary cholesterol, and the length of time the diet was fed. The level of safflower oil had a statistically significant effect but the level of olive or coconut oil had no significant effect. Various other statistically significant interactions were observed which make simple interpretations of the data difficult. The levels of serum cholesterol achieved in the gerbils fed the different oils with no or very low levels of dietary cholesterol were similar to those seen in men fed the same oils. Although the gerbil is apparently resistant to the development of atherosclerosis, it may be a useful model for studying the effect of dietary fats upon cholesterol metabolism.

Dietary control of serum cholesterol levels in rats fed high-fat, cholate-containing diets.

In a series of experiments, rats were fed semisynthetic atherogenic diets containing variable amounts of cholesterol (from 0 to 5%) with 40% of either cocoa butter, dairy butter, corn oil, or linseed oil as the source of fat, and 2% sodium cholate. It was found that serum cholesterol levels increased as the amount of dietary cholesterol increased to the 1% level, but raising the dietary cholesterol above this level did not provoke a proportional change in serum cholesterol during the first 3 months of the experiment.

Interrelations Between the Kind and Amount of Dietary Fat and Dietary Cholesterol in Experimental Hypercholesterolemia

An extremely large number of variables are reported to influence hypercholesterolemia and atherosclerosis in experimental studies, and there is need for experimental designs adequate to evaluate the relative importance of these variables and their interrelation to each other. A study is reported in which five different oils, each at three levels, and two different levels of dietary cholesterol were investigated. Only two animals per groups were used. All of the major variables (time, kinds of oil, level of oil, and amount of dietary cholesterol) have significant effects upon the hypercholesterolemia and many of the numerous interactions are also significant. It would appear, therefore, that the action of any of these variables can only be stated at the present time in terms relative to the others. The same situation is probably true with other variables not specifically included in this study. Such interrelations may well account for the apparently contradictory results in the literature as to the effects of various fats upon hypercholesterolemia in human subjects. Regression equations relating the amount of fatty acid (saturated, monounsaturated, and polyunsaturated) in the diet to the serum cholesterol level were calculated. With these three variables in the equation, the coefficient for the monounsaturated acid is positive. The coefficients for the saturated and polyunsaturated acids are negative. The equation suggests that the monounsaturated acid raises the serum cholesterol level while the saturated and polyunsaturated acids reduce it, the saturated acids being about one-fourth as active as the polyunsaturated acid. However, other equations can be derived which give as good a “fit” as this equation, and the magnitude and even the sign of the coefficients vary depending upon the variables included in the equation. Caution should be used in assigning too much significance to the calculated coefficients.