Lower Plasma Cholesterol Concentrations Research Articles

Distinct mechanisms of plasma LDL lowering by dietary fiber in the guinea pig: specific effects of pectin, guar gum, and psyllium

Pectin (PE), guar gum (GG), and psyllium (PSY) lower plasma low density lipoprotein (LDL) cholesterol concentrations in guinea pigs with different orders of magnitude by inducing defined alterations in hepatic cholesterol homeostasis (Fernandez et al. 1994. Am. J. Clin. Nutr. 59: 869-879; 61: 127-134 and 1995. J. Lipid Res. 36: 1128-1138). To further explore specific mechanisms responsible for the differences in plasma and hepatic cholesterol lowering, the effects of these fibers were evaluated on cholesterol absorption, hepatic cholesterol 7 alpha-hydroxylase activity, the rate-limiting enzyme of bile acid synthesis, and in vivo LDL transport to target specific primary and secondary mechanisms accounting for the observed responses. Fibers were fed with physiological (0.04%), low cholesterol (LC), or pharmacological high cholesterol (HC) (0.25%) levels to assess whether cholesterol intake influences plasma LDL lowering mechanisms. Intake of PE, GG, or PSY with LC or HC diets lowered plasma and hepatic cholesterol concentrations (P < 0.001). PE and PSY up-regulated 7 alpha-hydroxylase activity 3-fold with LC and PE by 5-fold with HC diets. In contrast, GG intake had no effect on 7 alpha-hydroxylase activity. Cholesterol absorption was reduced 30% by PE intake while no differences were found between control and PSY groups. GG reduced cholesterol absorption only with HC diets. Intake of PE, GG, or PSY with HC diets resulted in faster plasma LDL fractional catabolic rates (FCR) (P < 0.01) with no effect on LDL apoB flux rates (FR) or pool size, suggesting that fiber reduced LDL cholesterol concentration without decreasing the number of LDL particles. In addition to reducing LDL apoB FR, PE and PSY increased LDL FCR with HC diets while GG effects were limited to lowering LDL apoB FR. These results indicate that the distinctive reductions in hepatic cholesterol induced by PE, GG, and PSY associated with plasma cholesterol lowering result from different mechanisms specific to each fiber and that the levels of dietary cholesterol contribute to the different metabolic responses.

Effect of unprocessed and baked inulin on lipid metabolism in normo- and hypercholesterolemic rats

Male Wistar rats were fed a bread diet containing either corn starch or 6% raw or 6% baked inulin. Furthermore, the diets were either cholesterol-free or contained 1% cholesterol and 0.1% cholic acid. Adding unprocessed or baked inulin to the cholesterol-free diets resulted in significantly lower plasma cholesterol concentrations as well as in decreased liver cholesterol concentrations, while higher daily fecal excretions of bile acids were found. The normocholesterolemic rats showed a tendency to elevated fecal excretion of neutral steroids when inulin was fed, in spite of some decrease in the coprostanol excretion. In these groups there was a significantly inverse linear relationship between liver cholesterol concentrations and daily fecal bile acid output. The results suggest that the cholesterol lowering effect of inulin in normocholesterolemic rats may be due to higher fecal steroid excretion. Moreover, these rats tended to show higher HDL LDL cholesterol ratios when they received one of the inulin containing diets. In the hypercholesterolemic groups no significant effect from inulin intake on the plasma and liver cholesterol concentrations was found. In these rats, fecal cholesterol excretion was significantly increased by 40% when baked or unprocessed inulin was added to the diet, but fecal coprostanol excretion was significantly decreased by 95%. As a consequence, consumption of inulin did not change total neutral steroid excretion in the hypercholesterolemic groups. Moreover, fecal bile acid output was not significantly affected by dietary treatment. The fact that inulin intake did not change total steroid output might explain why plasma cholesterol was not reduced in the hypercholesterolemic rats receiving inulin, in contrast to the results obtained with the normocholesterolemic rats. Also no effect from inulin consumption was found on the HDL LDL cholesterol ratio in the hypercholesterolemic animals. Including inulin in bread did not alter its effect on lipid metabolism, neither in normo- nor in hypercholesterolemic rats.

Management of Primary Hyperlipidemia

Epidemiologic, clinical, genetic, experimental, and pathological studies have clearly established the primary role of lipoproteins in atherogenesis.1,2 Lowering plasma cholesterol concentrations reduces the availability of atherogenic lipoproteins and also, presumably, the accumulation of cholesterol in the intima of arteries. Measures to lower plasma cholesterol have become fundamental to the practice of preventive cardiology, and their use in both patients who already have coronary disease and healthy people has materially contributed to the 50 percent reduction in mortality from coronary heart disease in the United States in the past two decades.3,4 Lowering the plasma cholesterol concentration by a variety . . .

Lower patients' cholesterol now

The first principle of the lipid hypothesis is that raised plasma cholesterol concentrations are associated with a high incidence of atherosclerosis and an increased risk of coronary heart disease. That assertion no longer stirs argument in medical circles. But the second principle—that both this risk and total mortality can be reduced by lowering plasma cholesterol concentrations—remains controversial. Polarisation of views has led over the past 20 years to the emergence of enthusiasts for whom cholesterol lowering and the prevention of coronary heart disease are almost synonymous and sceptics who attribute to lipid reduction more harm than good. This lack of consensus has been widely publicised by the media, and many people believe that the case for treating raised cholesterol concentrations is flawed and can be disregarded. The publication in 1994 of the results of several new trials has shown that this attitude is no longer tenable for one clearly defined category of patients—those who have already developed coronary heart disease. Clinical decisions are rarely black or white. More often than not they are made with incomplete knowledge. This is certainly true in the prevention of cardiovascular disease. No one would challenge a policy aimed at reducing cigarette smoking, even in the absence of formal evidence from trials of a positive effect on the incidence of coronary …

The impact of breakfast especially ready-to-eat cereals on nutrient intake and health of children

Ready-to-eat (RTE) foods including cereals and more prevalent and likely to be consumed today by youth regardless of age. Convenience and companionship have been shown to reduce meal skipping and enhance the consumption of cereal products, which are an economically competitive source of nutrients. Research has shown that age of the child and meal composition determine the amount of daily protein and energy supplied by breakfast. Since the Iowa breakfast studies of the 1960s, researchers have continued to investigate how this meal aids students besides “breaking the fast.” A few well-designed and controlled studies have shown that this complex issue is difficult to discern due to the interactions presented by school breakfast programs and family economics. However, it is clear that children without breakfast must depend on lactate and free fatty acids for energy to a greater extent than those consuming a morning meal. Breakfast skipping has clearly been shown to be a detrimental health practice for all ages of youth resulting in decreased daily intakes of metabolic regulators essential for growth and health. This is particularly true for young low income children who never do “catch up” on their nutrients missed at breakfast as shown by 50% of the 1–3 year old low income children not consuming 70% of the RDA for vitamins A,E,C and iron and zinc. RTE cereals are the best source of daily iron and B vitamins regardless of the family's economic status. Additionally, children consuming a fiber containing RTE cereal have lower plasma cholesterol concentrations than those eating another type of breakfast. The impact of such a consumption pattern on long term health is extremely important as we strive to reduce this measurable health index. Many health professionals have forgotten that schools have the opportunity to provide a majority of a child's meals. Breakfast programs need to be enhanced in many schools so that a RTE cereal, fruit and milk breakfast can aid the child who comes to school without an important tool for academic success, “brain food.”

Hypocholesterolemia and Affective Disorders

The authors' specific aim was to assess hypocholesterolemia in 203 patients hospitalized because of affective disorders (depression, bipolar disorder, and schizoaffective disorder) compared with 1,595 self-referred subjects in an urban supermarket screening and with 11,864 subjects in the National Health and Nutrition Examination Survey II, a national probability sample. Low plasma cholesterol concentrations (< 160 mg/dL) were much more common in patients with affective disorders (20%) than in urban supermarket screenees (4%, P < or = 0.001) or in the National Health and Nutrition Examination Survey II subjects (10%, P < or = 0.001). When paired with supermarket screenees by age and sex, patients with affective disorders had much lower plasma total cholesterol (P < or = 0.0002), low-density lipoprotein cholesterol (P < or = 0.001), and high-density lipoprotein cholesterol (P < or = 0.0001), and higher triglyceride concentrations (P < or = 0.03). Neither the severity of the affective disorders nor severity-age interactions were associated with plasma cholesterol concentrations (P > 0.1); age and plasma cholesterol were positively associated (P = 0.01). None of the psychoactive drugs had a significant independent association with the patients' low-density lipoprotein cholesterol. Plasma cholesterol in patients hospitalized with affective disorders is shifted markedly downward toward hypocholesterolemic concentrations (< 160 mg/dL). There is no evidence that low plasma cholesterol could cause or worsen affective disorders.

Plasma lipoproteins and apolipoproteins B and E in rats fed a high-fiber fructose-based diet

This study was conducted as an attempt to provide additional informations on the effects of high-fiber diets on plasma lipoprotein metabolism. For this purpose, male Wistar rats were fed control or sugar-beet fiber diets for 3 weeks. High-fiber-diet-fed rats presented lower plasma triglyceride and cholesterol concentrations than fiber-free-diet-fed animals. The lipid-lowering effect of dietary fiber is associated with a decrease of triglycerides in all lipoprotein fractions and with a decrease of cholesterol in very low density lipoproteins and high density lipoproteins. Very low density lipoproteins isolated from fiber-fed animals contained significantly fewer triglycerides and more proteins compared with fiber-free-diet-fed rats. Mean size of very low density lipoprotein particles was smaller in fiber-fed rats compared with control rats. Plasma apolipoprotein B concentration did not differ significantly between both groups studied, but fiber feeding decreased plasma apolipoprotein E concentration. Similar levels of apolipoprotein B and of apolipoprotein E mRNAs were found in the livers in these two groups. In short, this work provides an unequivocal demonstration of lipid-lowering effect of a sugar-beet diet, which is associated with marked modifications in lipoprotein distribution and characteristics.

Psyllium augments the cholesterol-lowering action of cholestyramine in hamsters by enhancing sterol loss from the liver

Background/Aims: Psyllium hydrophilic mucilloid is a nonabsorbable soluble fiber that lowers plasma cholesterol levels in several species, including humans. However, its mechanism of action has not been fully elucidated. Therefore, using a hamster model, experiments were performed to determine whether psyllium given alone or in combination with a submaximal dose of cholestyramine blocks intestinal cholesterol absorption. Methods: The efficiency of cholesterol absorption and concentrations of plasma and hepatic total cholesterol were measured in male hamsters fed a cholesterol-enriched chow diet (0.1%) that contained either avicel (cellulose) (7.5%), surfomer (3%), cholestyramine (1% or 3%), or psyllium (7.5%) as single agents or a fixed level of cholestyramine (1%) combined with variable levels of psyllium (2%, 4%, 6%, or 8%). Results: Psyllium, cholestyramine, and surfomer, when given alone, markedly lowered plasma and hepatic cholesterol concentrations. Surfomer, and cholestyramine at the higher dose (3%), blocked cholesterol absorption by 54% and 75%, respectively, whereas psyllium had no effect. Combining psyllium with a submaximal dose of cholestyramine augmented the cholesterol-lowering action of the resin without effecting any marked change in the level of cholesterol absorption, except at the highest dose used. Conclusions: Psyllium, given either as a single agent or as an adjunct to treatment with cholestyramine, exerts a significant hypocholesterolemic effect by enhancing net negative sterol balance across the liver.

Red Palm Oil to Combat Vitamin A Deficiency in Developing Countries

Red palm oil (RPO), besides providing calorie density to the diet, is also the richest natural source of β-carotene, a precursor of vitamin A and an antioxidant that destroys singlet oxygen and free radicals. Chemical analysis of the fatty acid composition of RPO indicates that it has 50% saturated, 40% mono-unsaturated, and 10% polyunsaturated fatty acids. RPO contains 550 mg/g of total carotenoids, of which 375 mg/g represent β-carotene. It also contains 1,000 mg/g of tocopherols and tocotrienols.Nutritional values in rats fed 10% RPO in a 10% casein diet were comparable to those fed 10% ground nut oil (GNO) or 10% RBDPO (refined, bleached, deodorized palm oil). Rats fed RPO or RBDPO had significantly lower plasma cholesterol concentrations than those fed GNO. Significant inhibition of micro-somal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was observed in the RPO and RBDPO groups, indicating reduced synthesis of endogenous cholesterol. Toxicological studies also indicate that RPO is safe for human consumption. Indian school children fed supplementary snacks prepared with RPO for 60 days had significant increases in serum retinol levels as well as an increased liver retinol store, suggesting the ready bioavailability of β-carotene.

Food carbohydrates and plasma lipids””an update

An increase in dietary energy from carbohydrates is usually associated with a moderate increase in fasting plasma triglycerides--but not cholesterol--in the first weeks after the change. In the long-term the triglyceride returns to or to near the original concentration. Ordinary intakes of sucrose or fructose do not have any special elevating effect on plasma triglycerides in most normal and diabetic people, provided energy balance is not changed. Although biochemical theory predicts that fructose is more lipogenic than glucose, nearly all the animal reports of elevated plasma lipids with sucrose- or fructose-rich diets were obtained with diets unnaturally high in these sugars, and in rats and not other species. In humans, increased (fasting) triglycerides are observed with very high intakes, > 35% of energy from sucrose or > 20% of energy from fructose, and even then triglyceride elevation is unlikely unless the subjects are male and dietary fat is saturated. In people with hypertriglyceridemia (type IV), reduction of percent dietary carbohydrate is not recommended; this implies a higher percent of energy from fat, which leads to higher daylong triglycerides. However, in a minority of these patients, reduction of refined sucrose (or fructose) may be followed by lower triglycerides. Epidemiologically, high carbohydrate intakes are associated with low plasma cholesterol and variable plasma triglyceride concentrations.

Prune Fiber or Pectin Compared with Cellulose Lowers Plasma and Liver Lipids in Rats with Diet-Induced Hyperlipidemia

Previous research indicated that prunes in the diet of men with hypercholesterolemia lowered plasma and LDL cholesterol concentrations. To further study lipid metabolism in response to ingesting prunes, we conducted an animal study to test the hypotheses that fiber extracted from prunes, compared with purified cellulose, lowers plasma and liver cholesterol in rats with diet-induced hyperlipidemia and that the response is dose dependent. Rats were randomly assigned to one of five experimental diet groups. Four of the diets contained cholesterol and cholic acid to induce hyperlipidemia. The fiber source in the hyperlipidemic diets was 6% cellulose, 3% prune fiber, 6% prune fiber or 3% pectin. The fifth group, the nonhyperlipidemic control, was fed a diet containing 6% cellulose without cholesterol or cholic acid. Rats consumed one of the five diets ad libitum for 28 d, then were killed after 16 h without food. Plasma, LDL and liver cholesterol concentrations were higher in the hyperlipidemic control than the nonhyperlipidemic control and lower in the groups fed diets containing pectin or prune fiber than in the hyperlipidemic control group. No differences in plasma or liver cholesterol concentrations were detected between groups fed either dose level of prune fiber or between groups fed 6% prune fiber and pectin. These results indicate that fiber extracted from prunes lowers plasma and liver cholesterol in hyperlipidemic rats, although a dose-dependent response was not detected.

Fat Containing Stearic Acid Increases Fecal Neutral Steroid Excretion and Catabolism of Low Density Lipoproteins Without Affecting Plasma Cholesterol Concentration in Hamsters Fed a Cholesterol-Containing Diet

To examine the effect of different saturated fatty acids on the dietary cholesterol-induced elevation of serum cholesterol concentration and suppression of LDL catabolism, for 4 wk hamsters were fed purified diets containing 8% purified fats in which saturated fatty acids, lauric, myristic, palmitic and stearic acids were the sole variable. The dietary fat was composed of 50% saturated fatty acid, 30% oleic acid and 20% linoleic acid (polyunsaturated:saturated = 0.4). In hamsters fed the cholesterol-containing diet, fat containing stearic acid, compared with the fats containing other saturated fatty acids resulted in greater fractional catabolic rate of [125I]-labeled homologous LDL, greater fecal excretion of neutral steroids and lower liver cholesterol concentration, although the elevation of serum cholesterol concentration due to consuming a cholesterol-containing diet was not ameliorated. Stearic acid fat resulted in greater excretion of fecal fatty acids and lower apparent absorption of the dietary fats in hamsters fed diets with and without cholesterol. In hamsters fed the cholesterol-free diets, type of dietary fat did not affect the fractional catabolic rate of LDL, although stearic acid fat resulted in greater fecal neutral steroid excretion and lower serum and liver cholesterol concentrations. These observations suggested that purified fat containing stearic acid results in lower plasma cholesterol concentration in hamsters via stimulation of neutral steroid excretion, but addition of cholesterol to the diets obscures this effect.

Relationships between Viscosity of Hydroxypropyl Methylcellulose and Plasma Cholesterol in Hamsters

Dietary high viscosity hydroxypropyl methylcellulose (HPMC) lowered plasma and liver cholesterol concentrations in cholesterol-fed hamsters. To determine the level of viscosity needed to effect a significant reduction in total plasma cholesterol, hamsters were fed for 3 wk diets containing 0.12% cholesterol and either 4% cellulose or one of four preparations of HPMC that varied in viscosity between 14 and 1698 centipoise (cP), as estimated in vitro. Blood was collected for plasma cholesterol determination, and intestinal contents were obtained by finger-stripping of the excised small intestine. Contents were centrifuged and the supernatant (ex vivo) viscosity determined. In vitro and ex vivo viscosities were correlated (R2 = 0.96). Plasma cholesterol concentrations declined as in vitro or ex vivo viscosity increased. Maximal plasma cholesterol reduction occurred at an ex vivo viscosity of approximately 150 cP. There was a linear relationship between plasma cholesterol and the logarithm of ex vivo viscosity (R2 = 0.98). Our results suggest that materials that increase the viscosity of intestinal contents can be effective in reducing plasma cholesterol and that only moderate increases in viscosity are necessary to achieve this effect.

Regulatory effects of individual n-6 and n-3 polyunsaturated fatty acids on LDL transport in the rat

Dietary triglycerides containing predominantly poly-unsaturated fatty acids (PUFAs) are known to reduce plasma total and low density lipoprotein (LDL) cholesterol concentrations relative to triglycerides containing predominantly saturated fatty acids. However, there is little information regarding the independent effects of individual n-6 and n-3 PUFAs on LDL metabolism. The present studies were therefore undertaken to examine the effects of individual n-6 (linoleic acid) and n-3 (alpha-linolenic, eicosapentaenoic, and docosahexaenoic acid) PUFAs on plasma lipid levels and on the major transport processes that determine plasma LDL concentrations. Rats were fed a semisynthetic cholesterol-free diet supplemented with 4% (by wt) linoleic, alpha-linolenic, eicosapentaenoic, or docosahexaenoic acid for 2 weeks. Dietary eicosapentaenoic and docosahexaenoic acids lowered plasma triglyceride concentrations by 62% and 52%, respectively, and lowered plasma cholesterol concentrations by 54% and 43%, respectively. In contrast, dietary linoleic and alpha-linolenic acids had relatively little effect on plasma triglyceride or cholesterol concentrations. Dietary eicosapentaenoic and docosahexaenoic acids increased hepatic LDL receptor activity by 72% and 58%, respectively, and reduced the rate of LDL cholesterol entry into plasma by 36% and 30%, respectively. As a consequence plasma LDL cholesterol concentrations fell by 60% in animals fed eicosapentaenoic acid and 54% in animals fed docosahexaenoic acid. In contrast, these parameters of LDL metabolism were not significantly altered by dietary linoleic or alpha-linolenic acids. Thus, eicosapentaenoic acid and docosahexaenoic acid (the two major n-3 PUFAs present in fish oil) were equally effective in reducing the rate of LDL formation and stimulating hepatic LDL receptor activity, and were much more active in this regard than their parent compound (alpha-linoleic acid) or linoleic acid.

Ileorectostomy or Cecectomy but Not Colectomy Abolishes the Plasma Cholesterol-Lowering Effect of Dietary Beet Fiber in Rats

Adult male rats were fed a cholesterol-free diet with no added fiber (fiber-free) or with 10% cellulose or beet fiber. After 7 d of feeding, plasma total cholesterol concentrations were significantly lower in rats fed beet fiber than in those fed fiber-free or cellulose diets. This difference was due mainly to lower HDL cholesterol concentrations and remained significant for 28 d. The hypocholesterolemic effect of beet fiber relative to fiber-free disappeared when the cecum and colon were concurrently resected (ileorectostomy). Plasma cholesterol concentrations were the same in colectomized rats as in sham-operated rats fed the same diet and significantly lower in animals fed the beet fiber diet than in those fed the fiber-free diet. In cecectomized rats fed beet fiber, plasma cholesterol concentrations were intermediate between sham-operated rats fed the beet fiber diet and cecectomized or sham-operated rats fed the fiber-free diet. Fecal bile acid excretion was higher in rats fed the beet fiber diet than in those fed the fiber-free diet but did not correlate with plasma total cholesterol concentration. In rats with intact ceca, cecal total and individual short-chain fatty acids correlated negatively with plasma total cholesterol concentration. Dietary beet fiber lowers plasma cholesterol concentrations in rats, and the lower digestive tract, especially the cecum, seems to be necessary for this effect.

Childhood consumption of dietary polyunsaturated fat lowers risk for coronary artery atherosclerosis in African green monkeys.

This study was designed to test the hypothesis that consumption of diets enriched in polyunsaturated fatty acids beginning at birth and continuing into young adulthood would lower the risk for atherosclerotic coronary heart disease early in life through their effects on plasma lipid and apolipoprotein concentrations while supporting good health and normal development. Accordingly, African green monkeys (n = 140) were raised on atherogenic diets (0.8 mg cholesterol per kcal) enriched with either saturated or n-6 polyunsaturated fatty acids. Breast milk from mothers fed the polyunsaturated fat diet became enriched in polyunsaturated fatty acids relative to the saturated group; thus, the period of nursing also reflected the dietary fatty acid shift. Age, gender, and dietary fat type independently affected plasma lipid and apolipoprotein concentrations. Age effects were similar for all lipid and lipoprotein variables; the concentrations were low immediately after birth, increased dramatically during the first 4-6 months of life, and then attained levels similar to those of adult animals by 2 years of age. Significant differences by gender were found such that females maintained lower total plasma cholesterol concentrations and higher high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations. Dietary fat effects were age dependent. Before weaning at 5 months of age, total plasma cholesterol and apoB concentrations were lower in animals consuming polyunsaturated fat, and this pattern was maintained into young adulthood. Lower concentrations of plasma triglycerides, HDL cholesterol, and apoA-I for polyunsaturated fat-fed animals were found only in the postweaning period (6-60 months of age). Since this pattern of response to dietary polyunsaturated fat in the juvenile animals was similar to that for adult animals fed these same diets in which there was less atherosclerosis and because subsequent studies have documented less coronary artery atherosclerosis in the polyunsaturated fat-fed juveniles, we conclude that early dietary intervention was beneficial in this group for lowering the risk of coronary artery atherosclerosis. The results in this primate model support the concept that intervention to modify coronary heart disease risk that is initiated early in childhood will have beneficial effects.

Influence of dietary fish proteins on plasma and liver cholesterol concentrations in rats

The effects of amount and type of dietary fish proteins on plasma and liver cholesterol concentrations were evaluated in female rats. The isonitrogenous diets used contained 10 g cholesterol/kg and were carefully balanced for residual fat, cholesterol, Ca, Mg and P in the protein preparations. Cod meal, soya-bean protein or casein was incorporated into the diets as the only source of dietary protein at three levels: either 24, 48 or 72 g N/kg diet. Extra protein was added to the diet at the expense of the glucose component. In a second experiment soya-bean protein, casein, cod meal, whiting meal or plaice meal was added to the diet at a level of 24 g N/kg. When compared with casein, cod meal and soya-bean protein decreased plasma and liver cholesterol concentrations. A further cholesterol-lowering effect was achieved by increasing the proportion of either soya-bean protein or cod meal in the diet. Substitution of casein for glucose did not influence plasma and liver cholesterol concentrations. Plaice meal in the diet produced lower group mean plasma cholesterol concentrations than did whiting meal. In rats fed on the diet containing plaice meal, liver cholesterol concentrations were significantly lower than those in their counterparts fed on either cod meal or whiting meal. The present study demonstrates that different fish proteins in the diet have different effects on cholesterol metabolism and that the cholesterol-influencing properties of cod meal can be enhanced by the incorporation of higher proportions of this protein in the diet.

Dietary Non-Starch Polysaccharides Interact with Cholesterol and Fish Oil in their Effects on Plasma Lipids and Hepatic Lipoprotein Receptor Activity in Rats

Male rats were fed the non-starch polysaccharides pectin, methylcellulose or guar gum with corn oil or with 60% of the corn oil replaced by fish oil. They were also fed these diets with or without cholesterol (+ cholic acid). Plasma total cholesterol concentration was higher overall in rats fed cholesterol and lower in those fed fish oil or fish oil + cholesterol. Plasma triacylglycerols were lower in rats fed fish oil with or without cholesterol. Hepatic LDL receptor activity was higher overall in rats fed fish oil or fish oil + cholesterol than in those fed cholesterol. Liver HDL receptor was lower overall in rats fed fish oil or cholesterol. Type of non-starch polysaccharide influenced these dietary effects so that in cholesterol-fed rats plasma cholesterol was highest in those fed methylcellulose, intermediate in those fed guar gum and in those fed pectin was unchanged from concentrations in rats fed pectin without cholesterol. Fish oil feeding lowered plasma cholesterol concentration in rats fed pectin or methylcellulose but not in those fed guar gum. Plasma triacylglycerols were lower in rats fed fish oil and all three non-starch polysaccharides, but concentrations were similar in rats fed pectin + fish oil + cholesterol and in those fed pectin. In rats fed methylcellulose + cholesterol and any non-starch polysaccharide + fish oils, HDL receptor activity was uniformly lower than in rats fed pectin, methylcellulose or guar gum. Low density lipoprotein receptor activity was higher in rats fed pectin + fish oil or pectin + fish oil + cholesterol than in rats fed pectin.

Plasma cholesterol and depressive symptoms in older men

In several clinical trials of interventions designed to lower plasma cholesterol, reductions in coronary heart disease mortality have been offset by an unexplained rise in suicides and other violent deaths. We have tried to find out whether depressive illness is related to low plasma cholesterol concentrations in men of 50 years and older. In 1985-87, Beck depression inventories were obtained from 1020 white men, aged 50-89 years, in the Rancho Bernardo, California, cohort. Disease history and behaviours were assessed by standard questionnaires. Plasma cholesterol and weight were measured at this time, as they had been in 1972-74. Among men aged 70 years and older, categorically defined depression was three times more common in the group with low plasma cholesterol (<4·14 mmol/L) than in those with higher concentrations (5/31 [16%] vs 22/363 [6%]; p=0·033). Depressive symptom scores correlated significantly and inversely with plasma cholesterol concentrations, even after adjustment for age, health status, number of chronic illnesses, number of medications, and exercise, as well as measured weight loss and change in plasma cholesterol in the previous 13 years. Our finding that low plasma cholesterol is associated with depressive symptoms in elderly men is compatible with observations that a very low total cholesterol may be related to suicide and violent death. Since cholesterol lowering in the general population is widely recommended, this observation warrants further investigation.

Glucose, Insulin, and Lipid Metabolism in Doxazosin-Treated Patients With Hypertension

The metabolic changes associated with doxazosin treatment of hypertension were evaluated in ten patients with mild hypertension (mean +/- SEM = 150 +/- 3/100 +/- 1 mm Hg) and a plasma triglyceride (TG) concentration > 1.50 mmol/L. The blood pressure was lower after 4 to 6 months of doxazosin treatment (mean +/- SEM = 134 +/- 4/87 +/- 1 mm Hg), which was also associated with a significantly lower plasma insulin response to a 75 g oral glucose load, and lower plasma TG and cholesterol concentrations. In addition, insulin-mediated glucose uptake was significantly greater after doxazosin treatment. These data suggest that doxazosin treatment of patients with mild hypertension is associated with changes in insulin and lipid metabolism that should decrease the risk of coronary heart disease.