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Sources of blood glycerol during fasting.

To determine the source(s) of blood and very low density lipoprotein (VLDL)-triglyceride glycerol during fasting, four men ingested (2)H(2)O from 14 to 20 h into a 60-h fast to achieve ~0.5% body water enrichment. At 60 h of fasting, glycerol flux was measured using [2-(14)C]glycerol. Blood was taken for measurement of (2)H enrichment at carbon 6 of glucose and at carbon 3 of free glycerol and VLDL-triglyceride glycerol. (2)H enrichment of the 2 hydrogens bound to carbon 3 of VLDL-triglyceride glycerol was 105 +/- 2% of the (2)H enrichment of the 2 hydrogens bound to carbon 6 of glucose, indicating isotopic equilibrium between hepatic glyceraldehyde 3-P and glycerol 3-P. The (2)H enrichment of the 2 hydrogens bound to carbon 3 of free glycerol was 17 +/- 3% of VLDL-triglyceride glycerol, indicating that a significant percentage of free glycerol in blood originated from the hydrolysis of circulating VLDL-triglyceride or a pool of glycerol with similar (2)H enrichment. Glycerol flux was 6.3 +/- 1.1 micromol. kg(-1). min(-1). Glycerol appearing from nonadipose tissue sources was then approximately 1.1 micromol. kg(-1). min(-1). Seven other subjects were fasted for 12, 42, and 60 h. A small percentage of glycerol in the circulation after 12 h of fasting was enriched with (2)H. The enrichment of the 2 hydrogens bound to carbon 3 of free glycerol in the longer periods of fasting was approximately 16% of the enrichment of the 2 hydrogens bound to carbon 6 of glucose. Therefore, as much as 15-20% of systemic glycerol turnover during fasting is not from lipolysis of adipose tissue triglyceride.

Adult↗

Fasting in alpha1-antitrypsin deficient liver: constitutive [correction of consultative] activation of autophagy.

Alpha1-antitrypsin (alpha1-AT) deficiency causes severe liver injury in a subgroup of patients. Liver injury is thought to be caused by retention of a polymerized mutant alpha1-ATZ molecule in the endoplasmic reticulum (ER) of hepatocytes and is associated with an intense autophagic response. However, there is limited information about what physiologic stressors might influence liver injury. In this study, we examined the effect of fasting in the PiZ mouse model of alpha1-AT deficiency, because fasting is a well-characterized physiological stressor and a known stimulus for autophagy. Results show that there is a marked increase in fat accumulation and in alpha1-AT-containing globules in the liver of the PiZ mouse induced by fasting. Although fasting induced a marked autophagic response in wild-type mice, the autophagic response was already activated in PiZ mice and did not further increase with fasting. PiZ mice also had a significantly decreased tolerance for prolonged fasting compared with wild-type mice (PiZ mice 0% survival of 72-h fast; wild-type 100% survivial). These results demonstrate an altered response to stress in the alpha1-AT-deficient liver, including inability to further increase an activated autophagic response, a developmental state-specific increase in alpha1-AT-containing globules, and increased mortality.

Aging↗

Effect of age on induction of hepatic phosphoenolpyruvate carboxykinase by fasting.

This study examines the effect of age on the induction of the rate-limiting enzyme in gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), in response to fasting and refeeding in male Fischer 344 rats aged 3-18 mo. The rats were fasted for 30 h to increase the activity of PEPCK and subsequently were refed for 24 h to lower activity toward basal levels. PEPCK activity increased 2.2-fold in the 3-mo-old rats and 2.3-fold in the 18-mo-old rats during the 30-h fast. Therefore PEPCK induction during the 30-h fast was not altered with age. Similarly, refeeding resulted in a significant decrease in PEPCK activity at all ages. After the 24-h refeeding period, the rats were fasted a second time, and the time course of induction from the basal refed level was measured. In the young rats (6 mo), the activity of PEPCK increased rapidly from 18.12 +/- 1.61 to 42.66 +/- 5.94 U/g protein (P < 0.01) within 8 h of fasting. However, in the 18-mo-old rats, the initiation of the induction of PEPCK activity was delayed, and, after 12 h, PEPCK activity had increased from 17.34 +/- 1.34 to only 32.50 +/- 3.21 U/g protein (P < 0.01). Furthermore, the rate of induction appears to be decreased in the older animals. The activity after 24 h of fasting was equivalent in all four age groups (ranging from 44.72 +/- 5.38 at 3 mo to 40.18 +/- 5.42 U/g protein at 18 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effect of fasting on hepatic ligandin, Z protein, and organic anion transfer from plasma in rats.

The effect of fasting on the rate of disappearance from plasma of bromsulphthalein (BSP) and dibromsulphthalein (DBSP), the hepatic content of BSP, and the concentration of ligandin and Z protein, two hepatic organic anion-binding proteins, was studied in the rat. Fasting for 48 h decreased the plasma disappearance of BSP and DBSP and the hepatic content of BSP as well as the amount of ligandin and Z protein. Phenobarbital given prior to fasting partially prevented these changes. A method of quantitation of Z by radioimmunoassay is described. Discrepancies in Z quantiation by dye binding and immunological methods in fasted but not control rats suggest the presence of competitors for organic anion binding to Z in fasting as well as after phenobarbital administration. Results of studies of ligandin turnover during fasting suggest decreased synthesis and increased degradation of the protein. Similar events may be of pathogenetic importance in nonhemolytic unconjugated hyperbilirubinemia observed during fasting in man, horses, and other animals.

Animals↗

Metabolism and thermoregulation during fasting in king penguins, Aptenodytes patagonicus, in air and water.

We measured oxygen consumption rate (Vo(2)) and body temperatures in 10 king penguins in air and water. Vo(2) was measured during rest and at submaximal and maximal exercise before (fed) and after (fasted) an average fasting duration of 14.4 +/- 2.3 days (mean +/- 1 SD, range 10-19 days) in air and water. Concurrently, we measured subcutaneous temperature and temperature of the upper (heart and liver), middle (stomach) and lower (intestine) abdomen. The mean body mass (M(b)) was 13.8 +/- 1.2 kg in fed and 11.0 +/- 0.6 kg in fasted birds. After fasting, resting Vo(2) was 93% higher in water than in air (air: 86.9 +/- 8.8 ml/min; water: 167.3 +/- 36.7 ml/min, P < 0.01), while there was no difference in resting Vo(2) between air and water in fed animals (air: 117.1 +/- 20.0 ml O(2)/min; water: 114.8 +/- 32.7 ml O(2)/min, P > 0.6). In air, Vo(2) decreased with M(b), while it increased with M(b) in water. Body temperature did not change with fasting in air, whereas in water, there were complex changes in the peripheral body temperatures. These latter changes may, therefore, be indicative of a loss in body insulation and of variations in peripheral perfusion. Four animals were given a single meal after fasting and the temperature changes were partly reversed 24 h after refeeding in all body regions except the subcutaneous, indicating a rapid reversal to a prefasting state where body heat loss is minimal. The data emphasize the importance in considering nutritional status when studying king penguins and that the fasting-related physiological changes diverge in air and water.

Air↗

Sleep changes in long-term fasting geese in relation to lipid and protein metabolism.

The proportion and the distribution over 24 h of the different arousal stages characterized in geese--wakefulness (W), drowsiness (D), and slow-wave (SWS) and paradoxical sleep (PS)--were studied in caged birds when fed and then fasted during about 40 days. In both the fed and fasted state, each arousal stage was distributed through numerous episodes of a short duration. The geese slept a little more during the night than during the day, a difference that was moderately emphasized during the fast. Fasting induced only a slight decrease in W. There were important changes in SWS and D in relation to the periods of fasting that were previously found to correspond to changes in lipid and protein utilization. When proteins were spared and lipids accounted for most of the energy expenditure, the fasted geese went more and more rapidly from W to SWS (proportion of D decreased from 33 to 13%/day) and slept for progressively longer periods (SWS increased from 23 to 49%/day). By contrast, when protein utilization rose, the general trend in sleep was a decrease in SWS and an increase in D. During the fast, changes in PS were in the same proportion as those in SWS. These reactions are examined for their implications in energy-saving and sleep mechanisms.

Animals↗

Ketone body metabolism in a ground squirrel during hibernation and fasting.

Hibernating Belding's ground squirrels (Spermophilus beldingi) are ketotic relative to fed nonhibernators. Muscles from torpid individuals, when incubated in media containing physiological concentrations of glucose and ketone, show reduced uptake of glucose in the presence of ketone. The magnitude of the reduction is dependent on ketone concentration and reaches 60% in heart and 100% in pectoralis at 1.4 mM ketone. Fasted squirrels are also ketotic. However, ketone does not reduce glucose uptake in muscles from fed or fasted animals. Glucose utilization by muscles decreases during a long-term fast, but the reduction is independent of ketone. Thus both a long-term fast and hibernation lead to changes in muscle tissues that decrease their reliance on glucose as an energy source. Ketosis leads to glucose sparing during hibernation, whereas muscle glucose utilization is decreased independently of ketone during a fast. The glucose sparing achieved in both hibernation and fasting leads to conservation of body protein, the major source of gluconeogenic precursors in fasting mammals.

Animals↗

Effect of fasting interval on CCK-8 suppression of food intake in the baboon.

Baboons were infused intravenously for 5 min with the octapeptide of cholecystokinin (CCK-8) after either a 16.5- or 3.5-h fast. After a 3.5-h fast, food intake was significantly suppressed over the ensuing 30 min by 2 micrograms/kg of CCK-8 (-156 +/- 34 kcal compared with control days, P less than 0.02) and by 4 micrograms/kg of CCK-8 (-257 +/- 31 kcal, P less than 0.01). In contrast, CCK-8 had no reliable effect on food intake after the same baboons had been fasted for 16.5 h (2 micrograms/kg: -93 +/- 40 kcal, P greater than 0.05; 4 micrograms/kg: -30 +/- 82 kcal, P greater than 0.05). There was no reliable effect of 1 microgram/kg of CCK-8 on food intake at either deprivation interval. CCK-8 infusions resulted in a small increase of fasting plasma immunoreactive insulin (IRI); this effect was not related to either dose or deprivation length. Postprandial IRI and glucose concentrations were significantly suppressed by CCK-8 independently of its effect on food intake. Thus, after a 16.5-h fast, 4 micrograms/kg of CCK-8 decreased postprandial IRI from 145 +/- 65 to 29 +/- 4 microU/ml (P less than 0.01) and glucose from 101 +/- 5 to 80 +/- 3 mg/dl (P less than 0.02), despite no concomitant effect on food intake. Similar suppression of plasma IRI and glucose were observed after infusions of 1 and 2 micrograms/kg in 16.5-h-fasted animals. All doses of CCK-8 (1, 2, and 4 micrograms/kg) suppressed postprandial IRI and glucose after a 3.5-h fast.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nonshivering thermogenesis and the thermogenic capacity of brown fat in fasted and/or refed mice.

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.

Adipose Tissue, Brown↗

Effect of fasting on tubular phosphorus reabsorption.

In the thyroparathyroidectomized (TPTX) rat, fasting increased urinary phosphorus excretion by decreasing the tubular reabsorption of P1 (TRP) and resulted in hypophosphatemia. The administration of either sucrose or NaHCO3 prevented the metabolic acidosis associated with fasting and decreased the phosphaturia, indicating that the phosphaturia in fasting is in part due to metabolic acidosis. In rats on partial reduction of P1 intake selectively, the phosphaturic response to parathyroid hormone (PTH) was completely suppressed. On the other hand, the fasting rat partially retained the phosphaturic response to PTH, although dietary P1 intake was totally absent. These findings suggest that the renal P1 wasting in fasting may take place by dual mechanisms: a) the PTH-independent decrease in TRP, and b) an inability to totally suppress the response to PTH. Cyclic AMP generation in response to PTH, determined both in vivo and in vitro, was not measurably altered in fasting. However, the phosphaturic response to cyclic AMP was decreased in fasting, suggesting that the mechanism of partial resistance to PTH is probably not at but after cyclic AMP generation.

Adenylyl Cyclases↗

Impact of hydrogen ion on fasting ketogenesis: feedback regulation of acid production.

To determine whether acid-base balance regulates hydrogen ion production, seven obese volunteers were given NaHCO3 and NH4Cl (2 mmol.kg-1.day-1) during two separate 7-day fasts. On days 5-7 plasma bicarbonate was lower in the NH4Cl fasts (14.0 +/- 1.4 mM) than in the NaHCO3 fasts (18.3 +/- 1.1 mM), while urine pH and net acid excretion did not differ. Acid production (acid excretion minus intake) was greater by 204 mmol/day in the NaHCO3 fasts (274 +/- 16 mmol/day) than in the NH4Cl fasts (70 +/- 19 mmol/day). Ketoacid excretion, which reflected net ketoacid production, paralleled acid production, decreasing from 213 +/- 24 mmol/day in the NaHCO3 fasts to 67 +/- 18 mmol/day in the NH4Cl fasts. Thus, during starvation, alterations in hydrogen ion intake and the associated changes in acid-base balance modify the net production of endogenous acid by influencing the synthesis or utilization of ketoacids. Although the specific site of this metabolic regulation is undefined, these results indicate that systemic acid-base status can exert feedback control over hydrogen ion production.

Acid-Base Equilibrium↗

Effects of a 36-hour fast on human endurance and substrate utilization.

To determine if prolonged fasting affects substrate utilization and endurance time, seven trained men exercised to exhaustion on a cycle ergometer at 50% maximum oxygen consumption (VO2max) in an overnight-fasted [postabsorptive (PA)] state and after a 36-h fast (F). Fasting produced significant elevations in the resting concentrations of blood free fatty acids (FFA; 1.16 +/- 0.05 vs. 0.56 +/- 0.06 mM, F vs. PA, respectively, a 107% increase), beta-hydroxybutyrate (beta-OH, 2.06 +/- 0.66 vs. 0.15 +/- 0.06 mM, a 1,270% increase), and glycerol (0.12 +/- 0.03 vs. 0.04 +/- 0.01 mM, a 200% increase), with a significant decline in glucose (79.79 +/- 2.12 vs. 98.88 +/- 3.11 mg/dl, a 19% decrease). Exercise in the F trial increased FFA, decreased glucose, and significantly elevated beta-OH and glycerol over the PA trial. There was no difference in blood glucose concentration between trials at exhaustion. However, F produced a significant decrement in exercise endurance time compared with the PA trial (88.9 +/- 18.3 vs. 144.4 +/- 22.6 min, F vs. PA, a 38% decrease). Based on the respiratory exchange ratio, fasting led to a greater utilization of lipids during rest and exercise. It was concluded that 1) a 36-h fast significantly altered substrate utilization at rest and throughout exercise to exhaustion, 2) glucose levels do not appear to be the single determinant of time to exhaustion in submaximal exercise, and 3) despite the apparent sparing of carbohydrate utilization with the 36-h fast, endurance performance was significantly decreased.

Blood Glucose↗

Exercise endurance and fuel utilization: a reevaluation of the effects of fasting.

The effect of fasting on energy utilization during running or swimming was studied in adult male Wistar rats. Compared with fed rats, fasted animals displayed a decreased contribution of carbohydrates in energy supply, with decreased liver and muscle glycogen contents and decreased rate of glycogen breakdown. This was compensated by an enhanced rate of beta-oxidation. In addition, fasting induced an exaggerated sympathoadrenal response during exercise, reflected by a greater epinephrine plasma level and a higher norepinephrine turnover rate in both liver and soleus. Nevertheless, endurance capacity was similar in fasted and fed animals. These results contrast with the impairment of endurance observed in fasting humans but also with the improvement of endurance in rats previously reported by Dohm et al. (J. Appl. Physiol. 55: 830-833, 1983). These data suggest that the metabolic responses to exercise subsequent to food deprivation depend not only on the considered species but also, in the same species (rat), on the age of the animals and the duration of the fast. These factors probably determine the hormonal secretion and substrate utilization during prolonged exercise in fasting conditions.

Animals↗

[Progression of intestinal secretory immunoglobulin A and the condition of the patients during naturopathic therapy and fasting therapy].

BACKGROUND: In clinical observations it was noticed that patients who have been treated with naturopathic methods - especially with the treatment of heal fasting - experience a stabilization of their immune system. The immune system stands in close relation to the intestinal flora and influences the condition of the patient. QUESTION: For this reason the influence of a 3-week in-hospital naturopathic therapy - among others a heal-fasting therapy -, a corresponding follow-up on the intestine-associated immune system as well as the condition of the patients have been examined. PATIENTS AND METHODS: Classical naturopathic treatments based on standardized therapy concepts were applied. The patients (n = 55) showed different kinds of basic diseases, whereof in 56% of the cases the patients suffered of diseases of the skeleton, the muscles, and the connective tissue. The patients got a 3-week standardized high-quality nutrition or they took part in a juice-modified fasting therapy. The state of the local endogenous defense system within the intestine was measured by the concentration of the secretory immunoglobulin A (sIgA) in the feces of the patients. A positive criterion was a sIgA concentration in the stool of under 0.5 mg/g. Additionally the judgement of the patients concerning their own condition ('quality of life') was determined by the condition scale. RESULTS: It was shown that the content of the sIgA within the stool was increased during the course of the in-hospital stay, in the complete population of patients as well as in the different subgroups 'with heal-fasting' and 'without heal-fasting'. Even in the follow-up analysis it could be observed that 3 months after the treatment the content of secretory IgA in the stool of all groups was between 0.78 and 0.89 mg/g. This value was significantly higher than the starting values. The most intensive effects concerning the change of sIgA were measured within the group of the patients who performed heal fasting (epsilon > 1.0). Aside from the increase of the secretory IgA, a mediocre improvement of the condition of the patients within the pre-post comparison could be noticed, but no correlation between the secretory IgA values and the values concerning the condition was found. CONCLUSION: A 3-week in-hospital therapy with classical naturopathic treatments (but especially the application of the heal-fasting therapy) leads to a significant improvement of the immune condition of the intestine and consequently of the whole organism. The improving effect lasts beyond the stay in hospital.

Fasting↗

Nonselective Beta-adrenergic blockade augments fasting hyperkalemia in hemodialysis patients.

BACKGROUND/AIM: Fasting hyperkalemia in patients with end-stage renal failure is a well-documented phenomenon. Both a decreased secretion of insulin and decreased beta-adrenergic receptor sensitivity may take part in this effect. METHODS: Twelve anuric, long-term (6.4 +/- 2.7 years; mean +/- SD) hemodialysis patients underwent three periods of 18-hour fasting (from 6 p.m. to 12 a.m.). At the beginning of each fasting period a single dose of the nonselective beta-blocker, nadolol (80 mg), or the beta(1)-selective blocker, betaxolol (20 mg), or placebo were given in a random order and in blinded fashion. The wash-out period was 7 days. RESULTS: The mean decrease in blood pressure was similar after nadolol and betaxolol (18 +/- 10 vs. 19 +/- 11 mm Hg) as was a decrease in heart rate (20 +/- 3 and 19 +/- 6, respectively). Serum potassium was not different before each of the fasting periods. The increase in serum potassium during fasting was highly significant in each case. The mean increase in serum potassium was 1.2 +/- 0.4 mmol/l after nadolol, 0.9 +/- 0.6 after betaxolol and 0.6 +/- 0.6 after placebo. This effect was significantly larger after nadolol than after placebo (p = 0.01), but this relation was not significant with respect to betaxolol (p = 0.30). Serum insulin as well as glucose decreased significantly and to a similar extent during each fasting period. Plasma aldosterone was unchanged. CONCLUSION: Nonselective beta-adrenergic blockade increases the hyperkalemic effect of fasting in hemodialysis patients.

Adrenergic beta-Antagonists↗

Effects of intermittent fasting on serum lipid levels, coagulation status and plasma homocysteine levels.

BACKGROUND: During Ramadan, Muslims fast during the daylight hours for a month. The duration of restricted food and beverage intake is approximately 12 h/day which makes Ramadan a unique model of intermittent fasting. Many physiological and psychological changes are observed during Ramadan that are probably due to the changes in eating and sleeping patterns. METHODS: Serum total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), prothrombin time, activated partial thromboplastin time (aPTT), plasma fibrinogen, D-dimer and homocysteine levels were measured in 24 healthy fasting volunteers (12 females, 12 males) aged 21-35 years. Venous blood samples were taken 1 week before Ramadan, on the 21st day of Ramadan and 20 days after Ramadan. RESULTS: No significant changes were observed on serum total cholesterol, triglycerides and LDL levels. HDL levels were significantly elevated during Ramadan (p < 0.001) and 20 days after Ramadan (p < 0.05). Prothrombin time, aPTT, fibrinogen and D-dimer levels were in the physiologic limits in all samples but D-dimer levels were significantly low at the end of Ramadan in comparison to pre- and post-fasting levels (p < 0.001). Homocysteine levels, being still in reference ranges, were low during Ramadan (p < 0.05) and reached the pre-fasting levels after Ramadan. CONCLUSION: Our results demonstrate that intermittent fasting led to some beneficial changes in serum HDL and plasma homocysteine levels, and the coagulation status. These changes may be due to omitting at least one meal when the body was particularly metabolically active and possibly had a low blood viscosity level at the same time. We conclude that intermittent fasting may have beneficial effects on hemostatic risk markers for cardiovascular diseases.

Adult↗

C-reactive protein is independently associated with fasting insulin in nondiabetic women.

OBJECTIVE: Insulin resistance is associated with chronic subclinical inflammation, and both conditions are linked with increased risk for type 2 diabetes mellitus and atherothrombotic cardiovascular disease. METHODS AND RESULTS: In a cross-sectional study conducted among participants in the Women's Health Study, an ongoing US primary prevention trial of cardiovascular disease and cancer, we evaluated the correlates of elevated fasting insulin, a marker of insulin resistance, among 349 healthy, nondiabetic women who remained free from clinically diagnosed type 2 diabetes mellitus during a 4-year period from biomarker assessment. Fasting insulin was strongly associated with body mass index (BMI) (r=0.53, P<0.001), C-reactive protein (CRP) (r=0.38, P<0.001), and interleukin-6 (r=0.33, P<0.001). Physical activity level, alcohol consumption, and use of hormone replacement therapy were also related to fasting insulin. However, in multivariable linear regression analysis, BMI and CRP were the only independent correlates of log-normalized fasting insulin. Overall, the final model explained 32% of the variance in log insulin level. In multivariable logistic regression, the fully adjusted odds ratio (OR) for elevated fasting insulin (>or=51.6 pmol/L) increased with tertile of BMI, CRP, and IL-6, such that the ORs in the highest versus lowest tertile of each parameter were 9.0 (95% confidence interval [CI], 4.4 to 18.7), 4.4 (95% CI, 1.9 to 10.1), and 2.0 (95% CI, 0.9 to 4.2), respectively. Furthermore, increasing levels of CRP were associated with a stepwise gradient in odds for elevated fasting insulin among both lean and overweight women. CONCLUSIONS: CRP is independently associated with fasting hyperinsulinemia in nondiabetic women. These data provide additional support for previously reported associations between subclinical inflammation and the risk of type 2 diabetes and cardiovascular disease.

Adipose Tissue↗

A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men.

Despite many previous studies, controversy remains concerning the effects of dietary cholesterol on plasma cholesterol concentrations. In addition, the focus of previous studies has been fasting lipid and lipoprotein concentrations; there are no published studies with postprandial measurements. We studied the effects of four levels of dietary cholesterol intake on fasting lipid, lipoprotein, and apoprotein levels, as well as postprandial lipid levels, in a group of young, healthy men who were otherwise eating a low-fat, American Heart Association step 1 diet. Twenty young, healthy men completed a randomized, four-way crossover design study to test the effects of an American Heart Association step 1 diet containing 0, 1, 2, or 4 eggs per day. Dietary cholesterol ranged from 128 to 858 mg cholesterol per day. Each diet was eaten for 8 weeks, with a break between diets. Three fasting blood samples were obtained at the end of each diet period. In addition, blood samples were obtained just before and 2, 4, and 6 hours after ingestion of a standard lunch containing the various amounts of egg cholesterol. We also obtained blood 4 and 8 hours after the subjects ingested a standard, high-fat formula. Fasting plasma total cholesterol concentrations increased by 1.47 mg/dL (0.038 mmol/L) for every 100 mg dietary cholesterol added to the diet (P < .001). Low-density lipoprotein (LDL) cholesterol increased in parallel. Responsiveness varied but appeared to be normally distributed. Fasting plasma apoprotein B concentrations increased approximately 10% between the 0- and 4-egg diets and were correlated with changes in total and LDL cholesterol concentrations. Although there was a trend toward a greater response in men with an apoprotein E4 allele, this was not statistically significant. Fasting plasma cholesteryl ester transfer protein levels were higher only on the 4-egg diet, and changes in cholesteryl ester transfer protein levels between the 0- and 4-egg diets correlated with changes in total and LDL cholesterol. There were no differences in the postlunch or post-fat-formula responses of plasma lipids across the diets. Incubation of the 4-hour postlunch serum with J774 macrophages did not affect cell cholesteryl ester content at any level of dietary cholesterol. Cellular free cholesterol levels were slightly higher on each of the egg-containing diets versus the 0-egg diet. In summary, increases in dietary cholesterol resulted in linear increases in fasting total and LDL cholesterol in young, healthy men.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗