Changes In Plasma Cholesterol Research Articles

Regulation of hepatic cholesterol metabolism in the rat in vivo: effect of a synthetic fat-free diet on sterol synthesis and low-density lipoprotein transport.

A synthetic fat-free diet, previously shown to decrease hepatic cholesterol synthesis, was utilized to manipulate cholesterol balance in vivo in female Sprague-Dawley rats. A significant 65% decrease of hepatic cholesterol synthesis compared to controls was shown after 1 week of treatment, which remained constant during the following 3 weeks. The inhibitory effect of the diet was completely abolished by cholestyramine supplementation. At week 3 of the experimental diet, bile acid synthesis was reduced by 63%, this reduction being correlated with decreased recycling frequency of the bile acid pool. Hepatic clearance of low-density lipoprotein (LDL) was slightly decreased, with no changes in plasma cholesterol, hepatic LDL-cholesterol uptake and whole body LDL-cholesterol production. When cholesterol and saturated fatty acids were supplemented to the diets in the attempt to disclose alteration in LDL transport, LDL clearance was unaffected; plasma LDL-cholesterol and hepatic LDL-cholesterol uptake were increased, as a consequence of increased LDL-cholesterol production. On the other hand, hepatic cholesterol synthesis was further suppressed; bile acid synthesis was increased by cholesterol supplementation in the fat-free group, even if to subnormal levels. These findings suggest that: (1) bile acid synthesis is decreased by feeding a synthetic fat-free diet, probably due to slower recirculation of bile acids along the entero-hepatic axis in conditions of reduced functional need; (2) consequently, a significant reduction of hepatic cholesterol synthesis is observed with no changes in LDL-cholesterol uptake; (3) further supplementation of dietary cholesterol and saturated fats is compensated for by changes in the rates of cholesterol and bile acid synthesis, but not of LDL transport. The data confirm the existence of independent regulation for hepatic sterol synthesis and LDL transport in this species.

Effects of hydrogen peroxide on arterial contraction: Involvement of nitric oxide and increase in intracellular Ca 2+ of vascular smooth muscle

After menopause, most healthy women show an impairment of peripheral vasodilation and an increase of plasma cholesterol levels. Statins have been shown to improve endothelial function in hypercholesterolemic men and women. The present study tests whether atorvastatin (10 mg) influences endothelium-dependent vasodilation in postmenopausal normocholesterolemic women. Twenty-eight healthy, postmenopausal women (mean age 51 ± 2 years) with serum total cholesterol and low-density lipoprotein cholesterol within the desirable range entered a double-blind, single-crossover study. Postmenopausal women were randomized to receive either atorvastatin (10 mg/day) or placebo for 10 days and then crossed to the complementary treatment. Endothelium-dependent and -independent responses were assessed by means of strain-gauge plethysmography before and after intra-arterial infusion of acethylcholine (ACh) and sodium nitroprusside, in comparison to physiologic saline. The nitric oxide pathway was evaluated by repeating the infusion of ACh during admininstration of l-arginine and (G)-monomethyl-l-arginine (l-NMMA). Serum lipoproteins were not significantly modified by the active treatment. The vasodilation induced by ACh was significantly higher in the atorvastatin-treated women compared with the placebo-treated group (24 ± 3 vs 13 ± 2 ml/100 ml tissue/min, p <0.01). In contrast, responses to the endothelium-independent vasodilator sodium nitroprusside were not significantly modified by atorvastatin. The ACh-stimulated vasodilation induced by atorvastatin was additionally potentiated by l-arginine (800 ± 105% vs 370 ± 60%, p <0.05) and blunted by l-NMMA. No correlation was found between changes in plasma cholesterol and improvement in forearm blood flow. Our data show that the beneficial effect of atorvastatin on endothelium-dependent vasodilation is independent from changes in the lipid profile.

Effects of stimulated growth hormone secretion on age-related changes in plasma cholesterol and hepatic low density lipoprotein messenger RNA concentrations

Growth hormone (GH) secretion declines during aging. Since GH alters plasma cholesterol (PC) concentrations, it was of interest to determine how GH secretagogues affect age-related hypercholesterolemia. Fischer 344 rats (3 and 14 months old) were co-administered (s.c.) GH releasing hormone (3 μg/kg; GHRH) and GH releasing hexapeptide (100 μg/kg; GHRP) for 120 consecutive days. Aging was associated with a progressive increase in PC, which was reduced in rats administered GHRH and GHRP compared to those administered vehicle, i.e. changes in PC during the study were 26.5 ± 1.2 mg/dl vs. 40.1 ± 0.9 mg/dl ( P < 0.05) in the younger rats and 17.6 ± 2.3 mg/dl vs. 31.6 ± 5.3 mg/dl ( P < 0.05) in the older rats, respectively. The lower concentrations of PC in GH secretagogue-treated older rats were associated with higher mean concentrations of hepatic LDL receptor mRNA (1.27 ± 0.4 vs. 0.4 ± 0.1; P < 0.05) but not cholesterol 7-α hydroxylase mRNA. Although GH secretagogue treatment was also associated with lower plasma cholesterol in the younger rats, it was not accompanied by quantitative changes in mean group concentrations of hepatic LDL receptor mRNA. Instead, daily administration of GHRH and GHRP in the younger rats correlated with a significant reciprocal relationship ( P < 0.05) between PC and hepatic LDL receptor mRNA for individual group members. The results of this study suggest that reduced GH secretion during aging contributes, at least in part, to a progressive increase in plasma cholesterol that can be partially prevented with GH secretagogues. Furthermore, the effects on PC may result from GH-mediated, qualitative and quantitative changes in hepatic LDL receptor mRNA that increase receptor-mediated cholesterol clearance.

Laser aggregometer studies, ATP release and thromboxane B 2 release and cAMP concentration of the platelets in nephrotic syndrome

Platelet function was studied in 56 children with nephrotic syndrome, 33 were on oral prednisolone (P) treatment (group 1), while 23 were in early (< 6 months) remission (group 2): 12 on P (group 2a) and 11 not on P (group 2b), and there were 18 controls (group 3). The following tests were used: platelet aggregation with collagen in a laser rheoaggregometer; adenosine triphosphate (ATP) release: during aggregation with luciferin-luciferase in a lumiaggregometer; thromboxane B 2 (TXB 2) release: by radio-immunoassay; platelet cAMP concentration: by binding assay. The changes in plasma cholesterol (C) and triglycerides (TG) were compared with the platelet aggregation results. Patients in group 1 and 2 exhibited significantly higher aggregability, TXB 2 release and ATP release in response to collagen than those in group 3 (p < 0.01), but there was no difference between groups 1 and 2 or groups 2a and 2b. Some differences were observed between the histological groups. Patients with IgA and SLE nephropathy displayed higher aggregability than those with minimal change nephrotic syndrome in remission (p < 0.05). The highest level was in membranous nephropathy. The platelet cyclic adenosine monophosphate (cAMP) concentration was significantly lower in groups 1 and 2 than in group 3 (p < 0.001). No differences were observed between groups 1 and 2 or between groups 2a and 2b. Plasma C and TG levels did not show any correlation with the platelet aggregation. The increased platelet aggregation, TXB 2 release and ATP release and decreased cAMP concentration in the platelets may play a role in the pathogenesis of nephrotic syndrome which remains altered in early remission. Oral P and plasma lipids did not change the platelet function significantly.

Longitudinal changes in plasma cholesterol and triglyceride levels in Japanese male workers, 1977-1992.

Longitudinal changes in plasma cholesterol and triglyceride levels in Japanese male workers, 1977-1992.

Polymeric grape seed tannins prevent plasma cholesterol changes in high-cholesterol-fed rats

The objective of this study was to determine the effect of grape seed tannins in either monomeric or polymeric form on plasma cholesterol in rats. These tannins were supplemented at a level of 2% of the diet of high-cholesterol-fed Sprague Dawley rats for 9 weeks; the diets were compared with a diet without tannins (control diet) and with a standard diet. Rats fed diets containing 1% cholesterol showed an increase in total and low-density lipoprotein plasma cholesterol and a decrease in plasma high-density lipoprotein. These changes were prevented by the addition of 2% polymeric grape tannins but not by monomeric tannins. Similarly, liver weight, liver lipids and total liver cholesterol were increased by dietary cholesterol and these increases were largely inhibited by the tannin polymers but not the monomers. The polymers significantly increased the faecal excretion of lipids and cholesterol. In conclusion, we have shown that polymeric grape seed tannins exert a hypocholesterolaemic effect in high-cholesterol-fed rats.

Mevalonate availability and cardiovascular functions.

Data delineating the relationship between disorders of cholesterol metabolism and elevated blood pressure (BP) do not exist. We postulated that mevalonate, the metabolic precursor of endogenous cholesterol and the direct product of 3-hydroxy-3-methylglutaryl-CoA reductase, was a contributing factor for the maintenance of vascular tone and systemic BP. We conducted in vivo, ex vivo, and in vitro experiments in normotensive and hypertensive rats, where exogenous mevalonate and lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, were used, respectively, to increase or limit mevalonate availability. Mevalonate decreased BP in the whole animal without significant change in plasma cholesterol. Incubation of aortas with mevalonate attenuated their reactivity to norepinephrine and increased their response to endothelium-dependent and -independent relaxing factors. Lovastatin, in contrast, had the opposite effect in vivo and in vitro: it increased BP, enhanced vascular response to norepinephrine, and impaired endothelium-dependent and -independent relaxations. Neither agent modified cholesterol vascular content. Alteration of vascular reactivity was also observed in resistance vessels from animals pretreated with lovastatin. Our findings suggest that mevalonate availability is an unrecognized metabolic contributor to vascular tone and BP. They imply that (i) metabolites of the mevalonate pathway other than cholesterol could potentially control vascular functions and cardiovascular hemodynamics, (ii) elevated arterial pressure could be in part the consequence of primary disorders of this pathway, and (iii) pharmacological inhibition of mevalonate production as a means to lower plasma cholesterol may have an adverse impact on other cardiovascular risk factors, such as BP.

‘Healthy living’ and sulphonylurea theraphy have different effects on glucose tolerance and risk factors for vascular disease in subject with impaired glucose tolerance

This study was undertaken to determine whether impaired glucose tolerance and associated risk factors for cardiovascular disease can be improved with 'healthy living' by diet and exercise or with sulphonylurea therapy. Patients were recruited by screening subjects with either a family history of type II diabetes, previous gestational diabetes, or a previously raised plasma glucose (5.6-6.6 mmol/l). Impaired glucose tolerance was defined as hyperglycaemia on two separate tests, an achieved glucose level after a glucose infusion test above the 90th percentile of an age-matched normal population (> 9.3 mmol/l) or a fasting plasma glucose above the 95th percentile (> 5.6 mmol/l). Thirty-seven subjects with impaired glucose tolerance were entered into a randomized, prospective study for 6 months with allocations to healthy living or double blind to sulphonylurea (gliclazide 40 mg twice daily) or placebo tablets. The study took place in an out-patient setting, with three times weekly exercise sessions at a Sports Centre. After 6 months the placebo group showed no change in plasma glucose, cholesterol and blood pressure. The subjects receiving gliclazide showed improved glucose levels (mean fasting plasma glucose levels fell from 5.8 to 5.1 mmol/l, p < 0.05) but no significant change in plasma cholesterol or blood pressure. The healthy living group, after exclusion of four non-compliant subjects, showed no change in glucose levels, but a decreased systolic blood pressure (fall in mean from 124 to 116 mmHg, p < 0.05) and plasma cholesterol levels (fall in mean from 5.2 to 4.5 mmol/l, p < 0.01). with an increase in HDL:LDL ratio (rise in mean from 0.39 to 0.46, p < 0.05). Subjects with impaired glucose tolerance may benefit in different ways from gliclazide and healthy living. The metabolic responses to each therapy may help to decrease the risk of developing diabetes and cardiovascular disease.

Mechanisms of high-density lipoprotein reduction after probucol treatment: Changes in plasma cholesterol esterification/transfer and lipase-activities

Probucol treatment results in a significant reduction of plasma high-density lipoprotein (HDL) levels. Since the remodeling of HDL within the plasma compartment is a crucial determinant of HDL levels, the activities of several factors participating in the process, ie, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and lipoprotein and hepatic lipases (LPL, HL), were evaluated in 15 hypercholesterolemic patients treated with probucol (1 g/d) for 8 weeks. Drug treatment was associated with significant reductions of HDL cholesterol ([HDL-C] −32%), HDL 2-C (−65%), HDL 3-C (−22%), apolipoprotein (apo) A-I (−27%), and apo A-II (−11%) levels and with the accumulation of small HDL in plasma. CETP activity increased by 48%, with minor changes in LCAT (−7%), LPL (+4%), and HL (−7%) activities. By linear regression analysis, CETP activity correlated inversely with HDL-C, HDL 2-C, and apo A-I levels ( r = −.63, −.52, and −.73, respectively) and with HDL particle size. In multivariate analysis, CETP activity was the strongest predictor of HDL-C levels, apo A-I levels, and HDL particle size. The hypothetical mechanism of probucol is a stimulation of CETP activity, resulting in the formation of triglyceride (TG)-enriched HDL. These are acted on by HL, leading to the accumulation of small HDL in plasma.

Body Fat and Fat Distribution by Anthropometry and the Response to High-Fat Cholesterol-Containing Diet in Monkeys

Considerable variability exists among individuals in the response of plasma cholesterol to changes in dietary fat and cholesterol, and obesity is one variable reported to affect this response. This study was performed to determine the relationship between body fat and changes in plasma cholesterol in cynomolgus monkeys fed a high-fat cholesterol-containing diet for 12 months. The animals gained significant body weight (body mass index increased from 30.5 ± 0.5 to 35.7 ± 2.8 kg/m 2) and skinfold parameters of body fat increased as well. Total cholesterol increased from 109 ± 4 to 390 ± 25 mg/dl ( P < 0.001), and there were also significant increases in LDL- and HDL-cholesterol and triglyceride. While there was very little relationship between body fat and plasma lipids before the diet, after 12 months, there were significant negative correlations between total and LDL-cholesterol and anthropometric measures of body fat ( r ranged from -0.37 to -0.55, P < 0.01). The correlations were not affected when the effects of baseline body mass index and serum cholesterol and total food intake were controlled by partial correlation analysis. In this sample of animals, the acquisition of greater body fat appeared to protect against rises in cholesterol in response to consumption of a high-fat cholesterol-containing diet.

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.

Psyllium husk I: effect on plasma lipoproteins, cholesterol metabolism, and atherosclerosis in African green monkeys

Psyllium's effects on plasma and lipoprotein cholesterol concentrations, cholesterol metabolism, and diet-induced atherosclerosis were studied in adult male African green monkeys (Cercopithecus aethiops). Animals were fed for 3.5 y one of three experimental diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). The LCC and HCP groups had significantly (P less than 0.05) lower plasma cholesterol concentrations (39% lower) at 1 mo than did the HCC group. These responses persisted throughout the study. Plasma cholesterol changes were due to a reduction in intermediate-density and low-density lipoproteins; very-low and high-density-lipoprotein concentrations were similar among groups. Aortic atherosclerosis, evaluated as percent sudanophilia at 3.5 y, was lowest in the LCC group, intermediate in the HCP group, and highest in the HCC group. Cholesterol absorption, neutral steroid and fat excretion, HMGCoA reductase activity (in intestine and liver), and body weight were unrelated to psyllium's hypocholesterolemic effects.

Fibrates influence the expression of genes involved in lipoprotein metabolism in a tissue-selective manner in the rat.

The influence of different fibrates on apolipoprotein metabolism was investigated. Administration of fenofibrate provoked a dose-dependent decrease in plasma cholesterol concentration that was already evident after 1 day. Intestinal apolipoprotein (apo) A-I and apo A-IV mRNA levels remained fairly constant. In contrast, liver apo A-I, apo A-II, and apo A-IV mRNA levels decreased in a dose-dependent fashion, which was associated with a lower transcription rate of the apo A-I but not the apo A-II gene. The decline in hepatic apo A-I, apo A-II, and apo A-IV mRNA had already started after 1 day and was associated with a drop in plasma apo A-I and apo A-IV concentrations. Plasma apo E had already decreased after 1 day of fenofibrate, whereas apo B initially remained constant and increased only after 14 days of fenofibrate at the highest dose. Hepatic and intestinal apo B mRNA contents and liver, heart, kidney, and testis apo E mRNA contents were only marginally affected after treatment with fenofibrate. Liver low density lipoprotein receptor mRNA levels rose slightly after a 3-day administration of the highest dose of fenofibrate. Both clofibrate and gemfibrozil had effects comparable to those of fenofibrate on liver and intestinal apolipoprotein mRNA levels except for liver apo A-II mRNA, which decreased only marginally. Compared with fenofibrate, clofibrate caused similar changes in plasma cholesterol, apo A-I, apo A-IV, and apo E concentrations, whereas gemfibrozil increased plasma cholesterol and apo E without changing apo A-I and apo A-IV concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Dependence on dietary cholesterol for n-3 polyunsaturated fatty acid-induced changes in plasma cholesterol in the Syrian hamster.

Male Syrian hamsters consumed diets containing incremental increases in dietary n-3 fatty acids from fish oil with either low (0.015% w/w) or moderate (0.1% w/w) dietary cholesterol content. Animals consuming diets containing moderate cholesterol, but not animals consuming diets containing low cholesterol, had increased plasma very low (VLDL)- and low density lipoprotein (LDL)-cholesterol levels with increasing fish oil consumption. The plasma concentration of high density lipoprotein (HDL)-cholesterol decreased by 43 and 32% with the consumption of the highest fish oil diets in the low and moderate dietary cholesterol groups, respectively. Hepatic LDL-receptor binding activity did not change with the consumption of low cholesterol diets, but gradually decreased with fish oil consumption in animals consuming the moderate cholesterol diets. Hepatic LDL-receptor binding and plasma LDL-cholesterol levels of the different dietary fish oil groups were highly correlated (r = -0.91). Fish oil consumption also caused an increase in hepatic free cholesterol but a decreased cholesteryl ester content. Therefore, in the Syrian hamster, the consumption of n-3 fatty acids increases LDL-cholesterol levels which can be partially explained by decreased hepatic LDL-receptor binding and this response to dietary n-3 fatty acids is dependent on the dietary cholesterol content. However, the effects of dietary n-3 fatty acids on HDL-cholesterol are independent of dietary cholesterol content.

The Diet Habit Survey: A new method of dietary assessment that relates to plasma cholesterol changes

The Diet Habit Survey was designed to identify eating habits and measure dietary changes made over time by 442 adults in the Family Heart Study, a coronary heart disease prevention project. Reliability was determined by test-retest analysis. Validity was assessed by comparison with 24-hour dietary recalls and by comparing changes in diet with changes in plasma cholesterol levels. At baseline, 89% of the subjects were classified as eating the current American diet (37% fat), 10% reported eating Diet 1 (30% fat), and 1% reported eating Diet 2 (25% fat). After 5 years of dietary intervention, the population's eating habits had shifted; 48% reported eating the current American diet, 37% reported Diet 1, 14% reported Diet 2, and 1% reported Diet 3 (20% fat). Significant plasma cholesterol lowering was associated with changes in Diet Habit Survey scores reflecting lower cholesterol and saturated fat and higher complex carbohydrate intakes. This questionnaire is an inexpensive, reliable, and valid instrument for rapid assessment of eating habits and diet composition and, thus, is an important new tool for dietetics researchers and practitioners.

Palm oil in lipid metabolism

Historically, research relating to effects of edible oils has involved diets in which the oils under study were the only ones fed and in which one oil was always totally substituted for another. While the results thus obtained are valid considering the type of experiment they do not reflect effects of fats or oils as they are normally used. Using those modalities, various authors arrived at formulae for predicting plasma cholesterol changes based on alterations in dietary fat and cholesterol. These formulae proved to have utility although one study concluded that palmitic acid was the most hypercholestorelemic fatty acid and another concluded that it was myristic. In both sets of studies stearic acid did not fit the formulation. It is of interest that recent work has suggested that oleic acid, which had been thought of as neutral, possesses hypocholesterolemic properties. Studies carried out on the basis of total substitution and often using formula diets have shown, generally, that substitution of any formula for ordinary diet may be hypocholestorelemic and that the effects on plasma cholesterol in man are predictable based on fatty acid spectrum. It is noteworthy that in comparing coconut, beef tallow and safflower oil in real diets one study concluded that beef tallow (whose fatty acid pattern resembles that of palm oil) could not be regarded as a saturated fat. Recent data from experiments in which palm oil has been fed as part of a diet have suggested that it may not exhibit hypercholeserolemic properties in man. Some investigators have devised a variety of oil mixes to provide fats of a range of different fatty acids which fats were fed to three different strains of monkeys and showed that fats rich in lauric or myristic acid were significantly more cholesterolemic than those containing high levels of palmitic acid. For example, the fat mix containing 23% palmitic acid and 1% lauric plus myristic acid gave total serum cholesterol levels 15% lower than the one containing 25% palmitic acid and 19% lauric plus myristic acid. The LDL/HDL cholesterol ratio of monkeys fed the first mix was 15% lower than that of monkeys fed the second. It is hoped that these experiments will set a new standard for dietary studies in which fats will be fed at levels consistent with their usual intake.

Body, Abdominal Fat, and Testes Weights, and Line by Sex Interactions in Japanese Quail Divergently Selected for Plasma Cholesterol Response to Adrenocorticotropin ,

Line by sex interactions of BW, abdominal fat, testes weight, and plasma cholesterol were investigated in two Japanese quail lines. High (H-PCHOL) and low (L-PCHOL) quail lines had been developed by 18 generations of divergent selection for plasma cholesterol response to adrenocorticotropin (ACTH). Quail were from Generation 28 breeders maintained under a normal environment with no exposure to exogenous ACTH after Generation 18. Quail from growth-selected lines were also used to examine relationships between BW and plasma cholesterol.Body weights of H-PCHOL quail were significantly (P≤.05) heavier than BW of L-PCHOL quail at 2 and 4 wk of age. However, at 8, 16, and 28 wk BW were similar. Quail from long-term, growth-selected lines were observed to have plasma cholesterol levels similar to those of control lines. Therefore, early BW changes in H-PCHOL and L-PCHOL lines may not be related to plasma cholesterol changes. At 2 and 4 wk, male and female plasma cholesterol values were similar in the H-PCHOL and L-PCHOL lines, however, at 8 and 16 wk males had higher values than females in the H-PCHOL line, and females had higher values than males in the L-PCHOL line. Because interactions were present only after sexual maturity was reached, sex hormones may be involved in the expression of these interactions. Quail in the L-PCHOL line were observed to have significantly (P≤.05) more abdominal fat and significantly (P≤.05) smaller testes than quail in the H-PCHOL line.

Effects ofω3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men

Forty healthy men were fed diets providing 40% of energy from fat and a minimum of 25 mg vitamin E for 28 wk. During the first 10 wk diets were supplemented with placebo, 15 g mixed fat/d. During the second 10 wk placebo was replaced by 15 g fish-oil concentrate/d. During the last 8 wk 200 mg vitamin E/d was added to fish oil. Compared with placebo, fish-oil feeding significantly increased plasma glucose and decreased triacylglycerol, insulin, glucagon, growth hormone, and somatomedin C. The changes in plasma cholesterol, cortisol, and dehydroepiandrosterone sulphate (DHEA-S) were not significant. Fish oil plus vitamin E further decreased insulin, growth hormone, and DHEA-S and reversed the effect of fish-oil on somatomedin C. The changes in glucose, glucagon, growth hormone, and cortisol were not significant. Thus, changes in plasma glucose and lipids caused by dietary fish oil alone and with fish oil plus vitamin E appear to be due to alterations in hormones involved in carbohydrate and lipid metabolism.

Comments on Some Changes in Plasma Cholesterol and Vitamin E when Different Fats are Fed

Dear Dr. Visek: It has been suggested that a record be made of some data obtained during the latter days of the study of vitamin E sponsored by the Food and Nutrition Board of the National Research Council (1). The data ob tained (now in SI units) on cholesterol in the plasma were not a part of the main protocol, and, although they have been used in oral presentations, they have not previously appeared in print. The subjects, all males, were fed a controlled diet daily of natural foods formulated to contain 9614 kj (2300 kcal) in a closed metabolic unit (Table 1). The fat in the diet contained 60 g of commercial corn oil, which was replaced with 60 g of beef fat (stearin) after 7 mo. Nothing new is claimed but the data, although sparse, do reinforce the following conceptions: 1) Older men tend to have higher levels of plasma cholesterol. 2) A few days of a change in diet from more unsaturated fats to less unsaturated fat can have a marked effect on the level of cholesterol in the blood. 3) Five of the eight subjects had higher levels of plasma tocopherols after being fed the diet con taining beef fat despite the much higher level of tocopherols in com oil. The significance of this did not become apparent until after our research on the relationship of the level of vitamin E to lipids in the blood (2).

Plasma Cholesterol and Lipoprotein Levels during Fetal Development and Infancy

Intrauterine changes in plasma cholesterol and lipoprotein concentrations have been linked to the development of the adrenal gland (utilization of cholesterol) and liver (production of cholesterol by new synthesis). At term birth, racial and gender differences have been observed with white compared to black, and female compared to male, infants having higher cholesterol concentrations. Within hours of the beginning of oral feeding, total and LDL cholesterol rise significantly. Little further increase occurs after 7 days, and the concentration seen after this time is highly dependent upon the cholesterol and polyunsaturated fat content of the diet. By 12 months of age, investigators cease to find any effect of the milk source fed earlier in infancy on cholesterol and lipoproteins. This is not evidence that diet no longer influences cholesterol and lipoprotein concentrations, but only that individual lipid intakes are varied and difficult to quantitate. Cross-cultural comparisons of infants at this age in fact provide strong suggestive evidence that a large environmental component determines the circulating cholesterol and lipoprotein concentrations seen at one year and beyond.