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PubMed2004

Circulating melanin-concentrating hormone, agouti-related protein, and alpha-melanocyte-stimulating hormone levels in relation to body composition: alterations in response to food deprivation and recombinant human leptin administration.

We evaluated whether circulating levels of melanin-concentrating hormone (MCH), agouti-related protein (AGRP), and alpha-MSH could serve as useful markers of energy homeostasis in humans. We first assessed correlations of serum MCH, AGRP, and alpha-MSH with anthropometric, dietary, and hormonal variables in a cross-sectional study of 108 healthy humans. We then performed interventional studies to evaluate the effects of fasting and/or leptin administration. In eight healthy, normal weight men, we measured serum MCH, AGRP, and alpha-MSH levels at baseline, after 2 d of fasting alone (a low leptin state), and after 2 d of fasting with replacement dose recombinant methionyl human leptin (r-metHuLeptin) administration to normalize circulating leptin levels. In a separate group of five lean and five obese men, we measured MCH levels in response to increasing circulating leptin levels to the pharmacological range by administration of one r-metHuLeptin dose in the fed state. In the cross-sectional study, serum MCH levels were independently and positively associated with body mass index and fat mass and were higher in women than in men. Furthermore, in our interventional studies, fasting for 2 d significantly decreased leptin levels and increased serum MCH levels. Administration of replacement dose r-metHuLeptin during fasting prevented the fasting-induced increase in MCH levels, but administration of a pharmacological r-metHuLeptin dose in the fed state did not further alter MCH levels. Serum AGRP levels tended to change in directions similar to MCH, but this change was less pronounced and needs to be investigated in larger studies. In contrast, serum alpha-MSH levels did not correlate with body composition parameters, were not associated with caloric or macronutrient intake, and were not significantly affected by fasting or r-metHuLeptin administration. These findings suggest that serum MCH and possibly AGRP levels could serve as useful peripheral markers of changes in energy homeostasis and thus merit additional investigation.

Adolescent↗

PubMed1975

Serum gastrin response to food stimulation in male azotemic patients.

In 37 patients with hypertension and/or renal disease, blood from a peripheral and a renal vein was drawn during renal vein catheterization. The serum gastrin concentrations were determined and found by paired comparison to be statistically significantly (p less than 0.05) higher in the peripheral than in the renal vein. A test meal was given to 9 male controls and 7 male azotemic patients, and the serum gastrin concentration response determined. The mean fasting serum gastrin values were 173 +/- 22 pg/ml in the group of patients versus 42 +/- 5.5 pg/ml in the controls. The serum gastrin response was significantly higher and of longer duration in the azotemic patients than in the controls. The pentagastrin-stimulated gastric acid secretion was, however, equal in the two groups.

Digestion↗

PubMed2002

Structural flexibility of the small intestine and liver of garter snakes in response to feeding and fasting.

Garter snakes Thamnophis sirtalis parietalis feed frequently but also tolerate extended periods of fasting when food is unavailable. We studied the dynamics, reversibility and repeatability of size changes of the small intestine and liver using ultrasonography. We employed light and transmission electron microscopy and flow cytometry to study the tissue mechanism that drives this flexibility. We compared garter snakes that fed every other day, snakes that fed once a week and fasting snakes. In all feeding trials, the size of the small intestine and the liver increased rapidly after feeding. Constantly feeding snakes maintained an elevated level of organ size, while snakes that were fed only once a week showed a marked up- and downregulation of organ size. Histology revealed the mucosal epithelium to be a transitional epithelium that can change cell configuration considerably to accommodate organ size changes. Upregulation of small intestine and liver size was always associated with the incorporation of lipid droplets into enterocytes and hepatocytes. Cell proliferation was not involved in upregulation of organ size. In contrast, cell proliferation increased during downregulation of organ size, indicating that cells worn out during digestion were replaced. The dynamics of flexibility and the functional features of the tissue were the same as described for the Burmese python Python molurus bivittatus. We suggest that garter snakes employ the same energetically cheap mechanism of organ size regulation as pythons, which allows for rapid, repeated and reversible size changes with no cell proliferation involved. Comparative evidence suggests that the transitional mucosal epithelium is an ancestral character of snakes and that feeding ecology is not directly related to the cytological features of the mucosal epithelium.

Animals↗

PubMed1975

Serum gastrin response to food stimulation and gastric acid secretion in male patients with ileal resection.

Gastric acid secretion before and after stimulation with pentagastrin and serum gastrin response to a test meal were recorded in 9 male controls and in 7 male patients from whom more than 50 cm of the terminal ileum had been resected because of Crohn's disease. The mean gastric acid secretion before and after stimulation was not found to be significantly different in the two groups. The mean fasting serum gastrin concentration and the serum gastrin response in absolute values were not different in the two groups. The MAO-BAO/'integrated gastrin response' was higher (p less than 0.05), and the gastrin response in relation to fasting level was lower in the patients than in the controls (p less than 0.05). The results indicate that an increased parietal cell sensitivity to gastrin is present after ileal resection. The negative acid feed back mechanism, however, seems to be at work. Under physiological conditions, therefore, the increased sensitivity may not result in acid hypersecretion.

Crohn Disease↗

PubMed1986

Role of cholecystokinin and opioid peptides in control of food intake.

Of the many factors that influence food intake, there is strong evidence that opioid and CCK peptides, which stimulate feeding and elicit satiety, respectively, are important components that may act in concert to regulate energy balance. Cholecystokinin peptides have been isolated in both the brain and gastrointestinal tract, and changes in concentration in the brain and in plasma have been shown to vary with feeding. Peripherally injected CCK has been shown to elicit satiety in many species, including humans, an effect that may be mediated in the CNS via the vagus. In several species, most notably the sheep, direct injection into the CSF potently decreases food intake. Questions remaining regarding the role of CCK peptides in eliciting satiety include the sites and mechanisms of action. It is unknown whether CCK acts directly on receptors, indirectly on some other parameter, or as a neurotransmitter. Although opioid peptides have also been localized in portions of both the periphery and brain, a specific physiological role for their presence has not yet been determined. Opioid peptides from three families--endorphins, enkephalins, and dynorphins--have been shown to stimulate feeding in various species. They have been active at several opioid receptor types in the CNS, but there is limited evidence to suggest they affect food intake when administered peripherally. In contrast, peripheral injection of opiate antagonists has effectively decreased food intake, an observation that led to the original hypothesis that opioids were involved in the hunger component in the control of food intake and that excess concentrations might be involved in the development of obesity. An increasing body of evidence supports the concept that opioid and CCK peptides may interact to control food intake, but the evidence is more suggestive than conclusive.

Amino Acid Sequence↗

PubMed1990

Absorption of doxycycline from a controlled release pellet formulation: the influence of food on bioavailability.

A three-way crossover study was performed to compare the bioavailability of a new pelletised doxycycline product administered either with food or without food and a reference product taken without food. Four different methods were used to calculate pharmacokinetic parameters from the data. The sums of squares, Akaike's Information Criterion (AIC), and the ranges for the parameters obtained were used for comparison. Good fits to the data were obtained when all four methods were used, each with a lag time. The two compartment open model was the most efficient method for describing the data. The one compartment open model was the least efficient, particularly with respect to predicting the peak concentration of doxycycline in plasma. All the models gave similar rank order results with respect to bioavailability differences between the three treatments. Analysis of the data by different methods suggests that pelletised doxycycline is bioequivalent to the reference product when taken in the absence of food. A standardized feeding regimen affected the rate, but not extent of absorption of doxycycline from the pelletised formulation.

Absorption↗

PubMed2003

Associations between diet and the metabolic syndrome vary with the validity of dietary intake data.

BACKGROUND: Underreporting is a common problem in dietary surveys. Few studies have shown the implication of this when investigating diet-disease relations. OBJECTIVE: We investigated how underreporting affects the associations between dietary factors and the metabolic syndrome. DESIGN: Dietary intake measured with a 7-d food record, fasting insulin concentrations, and other variables of the metabolic syndrome were assessed in a cross-sectional study of 301 healthy men aged 63 y. Biological markers for intakes of protein, sodium, and potassium were measured in 24-h urine samples. Underreporters (URs, n = 88) were identified by Goldberg's equation, which compares energy intake with energy expenditure, both expressed as multiples of the basal metabolic rate. Physical activity level was estimated, and individual cutoffs were calculated. RESULTS: The URs had higher nutrient and food densities in their diet than did the non-URs, which suggested that they followed a healthier diet. The URs had a higher prevalence of the metabolic syndrome than did the non-URs (18% and 9%, respectively; P = 0.029). The biological markers confirmed a low validity of the dietary data in the URs. The correlations between fasting insulin concentrations, a central component of the metabolic syndrome, and the intakes of polyunsaturated fats, n-6 fats, and fat from milk products were stronger in the URs than in the non-URs, which indicates that inaccurate data can introduce spurious associations. CONCLUSION: The association between diet and fasting insulin differed between URs and non-URs in this study of 301 healthy men aged 63 y. If URs are not identified and excluded or treated separately in studies in nutritional epidemiology, spurious diet-disease relations may be reported.

Cross-Sectional Studies↗

PubMed1978

Measurement of bile acids in fasting gastric aspirates: an objective test for bile reflux after gastric surgery.

We measured the concentration of bile acids in gastric aspirates from patients who had had operations for peptic ulcer. Some patients were asymptomatic and some had postoperative symptoms of the type that have been attributed to duodenogastric reflux. Samples were obtained via a nasogastric tube when the patients were fasting, after food, after pentagastrin, and overnight. We related the concentration and amount of bile acid and the volume aspirated to the presence or absence of symptoms and compared the results with radiological and endoscopic assessments of duodenogastric reflux. The most useful index to discriminate between symptomatic and asymptomatic patients was the amount of bile reflux in half an hour's aspiration from the fasting stomach; this we have termed 'fasting bile reflux' (FBR) and expressed as mumol bile acids refluxing/hour. A figure greater than 120 mumol/h was present in 17 of 22 symptomatic patients and in all who complained of bile regurgitation or bile vomiting. The FBR was less than 120 mumol/h in all of 20 asymptomatic patients, although some of them had reflux detected radiologically and endoscopically.

Adult↗

PubMed1987

gamma-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora.

In recent hypotheses concerning the pathogenesis of hepatic encephalopathy, gamma-aminobutyric acid (GABA) is claimed to be produced by the colonic flora, although enzymes necessary to generate GABA have been reported to be present in intestinal mucosa. In this study, using normal and germ-free Wistar rats, we determined GABA levels and amino-grams of arterial blood and of venous effluent from small and large bowel. The data indicate that large and small intestinal mucosa significantly contribute to GABA production. In the fasted state GABA concentrations are greater in the venous effluent of the small bowel than in the venous effluent of the large bowel. Feeding increases the arterioportal differences, and uptake in the small bowel is still significantly higher than in the large bowel. This process is not, or can only be to a minor degree, bacterially mediated, because GABA production in the gut both in the fed and fasted state is of similar magnitude in germ-free and normal animals. gamma-Aminobutyric acid release correlates significantly with glutamine uptake in the small bowel of fasted rats. Only a small fraction of the glutamine taken up is needed to account for GABA release, so that conclusions concerning which amino acids may serve as precursors of GABA cannot be drawn. Further studies are needed to delineate the metabolic pathways leading to GABA synthesis.

Aminobutyrates↗

PubMedDate not supplied

Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers.

STUDY OBJECTIVES: To evaluate the effect of food on the bioavailability of itraconazole (ITR) hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solution under multiple-dose to steady-state conditions, and to determine the pharmacokinetics of ITR solution at steady state. DESIGN: Open-label, randomized, multiple-dose, crossover study SETTING: University-affiliated health center. PATIENTS: Thirty healthy men randomized to one of two treatment sequences (fasted-fed, fed-fasted). INTERVENTIONS: Subjects were either fasted or fed a standard breakfast before receiving ITR oral solution 200 mg once/day for 15 days. Crossover phases were separated by a 4-week washout period. MEASUREMENTS AND MAIN RESULTS: On day 1, blood samples were collected before the dose (time zero) and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. Trough samples were obtained before the dose on days 4, 7, 12, 13, and 14. On day 15, samples were obtained at the same times as day 1, and at 36, 48, 72, 96, 168, 240, and 360 hours. Samples were analyzed by high-performance liquid chromatography for ITR and its major metabolite hydroxyitraconazole (OH-ITR). Urine was collected on days 1 and 15 before and 0-8 and 8-24 hours after the dose; HP-beta-CD was measured by size-exclusion chromatography. Mean bioavailabilities of ITR and OH-ITR were 43% and 38% higher, respectively, when ITR solution was taken as a single dose under fasted conditions. With multiple dosing, steady state was achieved by day 14. At steady state, mean bioavailabilities were 29% and 17% higher, respectively, in the fasted state; terminal half-life was similar under fasted and fed conditions (mean 39.8 and 37.5 hrs for ITR, respectively; 27.3 and 26.2 hrs for OH-ITR, respectively). HP-beta-CD was eliminated almost exclusively in urine. CONCLUSION: The bioavailability of ITR and OH-ITR is enhanced when ITR oral solution is given in the fasted state; this was true for both single and multiple dosing to steady state.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1996

[From empirical 'dietetics' to rational dietetics].

From the outset, the terms 'dietetics' and 'diet' applied in their general acceptance to all the measures, whether or not alimentary, that can provide optimal living conditions for both the healthy and the diseased. In that meaning they are synonymous with hygiene or way of life. In their more restricted acceptance, which will be used henceforth, the terms apply to the choice of food and beverages which promotes or restores health of normal and sick people. In its most restricted meaning, the term 'diet' is confined to the nutrition of the sick, consisting either in a more or less drastic limitation of food intake, or in the prescription of specific foods. Due to the absence of scientific knowledge concerning the processes of life in general, and in particular concerning the physiology of the digestive system and the metabolism, the 'dietetic' rules and principles were governed until the middle of the nineteenth century by empiricism with a strong background of intuition, tradition, magic and religion. In his continuous struggle for life, man has been confronted with the dramatic consequences of the ingestion of toxic and spoiled food. Nausea, vomiting, diarrhea, cramps and eventually death have soon been linked with the ingestion of particular food, although the symptoms were attributed to supernatural forces. Intuitively and later by laws and prohibition, the use of certain foods was to be avoided or was forbidden. Moreover, with the development of cultures and civilizations food and food intake have acquired -besides their vital necessity-social and often magic-religious values which sometimes resulted in food taboos. In most civilizations these taboos have particulars in common: they are mainly directed against food of animal origin, more against meat than fish and particularly against red meat, which is being considered as symbol of strength and power and as endowed with exciting and stimulatory properties. The meat taboos are selective for some animals or parts of an animal, but what is allowed in some cultures is forbidden in others. More or less severe and long lasting abstinence from food or fasting was also self-inflicted or imposed to individuals or whole populations by religion, sometimes seemingly on hygienic grounds but in most cases without any logic reason. Since the earliest time, diets take-together with other dietetic measures-a prevailing place in the treatment of the sick and sickness. Most alimentary prescriptions are based on a more or less drastic restriction of food and - particularly in the seventeenth century with the iatrochemical school - also of fluids. The restrictions were not only quantitative, but also qualitative with restriction of meat consumption-particularly of red meat-and the prescription of more or less diluted decoctions of barley (infusions) or broth. The numerous works on 'dietetics' published-thanks to the development of printing-from the seventeenth on through the nineteenth century concern mainly the description of foodstuffs and beverages available at the time, and of the ways of preparing them. They also provide indications concerning the way these foodstuffs can improve health and/or list which of them can be prescribed or must be avoided in the treatment of the sick and of specific diseases. Some of these 'dietetical' prescriptions and maxims seem perfectly valid from a scientific and therapeutical point of view, - at least according to our actual knowledge - however, many are totally ineffective or are ridiculous and even dangerous. Except for the "dietetical" measures imposed by public hygiene or by religion to everyone, most of the dieteticotherapeutical prescriptions (food restrictions, clysters, purgation, bleeding) involved only the small fraction of the population that could afford medical assistance. The common people - the majority - could afford neither medical help, nor food abuse - except for an occasional feast - and had only access to a limited quantity and choi

Diet↗

PubMed1990

Influence of food on the pharmacokinetics of perindopril and the time course of angiotensin-converting enzyme inhibition in serum.

Food has been shown to reduce the bioavailability of the angiotensin-converting enzyme inhibitor captopril, but not the bioavailability of inhibitors administered as ester prodrugs. Perindopril is the ester pro-drug of the angiotensin-converting enzyme inhibitor perindoprilat. The influence of food on the pharmacokinetics of perindopril (4 mg administered orally) and the time course of angiotensin-converting enzyme inhibition in serum was studied in a randomized crossover short-term study of 12 healthy subjects. Food significantly decreased the relative availability of perindoprilat by 35% +/- 42%, the fractional urinary excretion of perindoprilat from 19% +/- 7% to 13% +/- 4% (p less than 0.05), and the partial metabolic clearance of perindopril to perindoprilat from 102 +/- 57 ml.min-1 to 72 +/- 32 ml.min-1 (p less than 0.05). These changes were associated with a significant decrease in the area under the percent angiotensin-converting enzyme inhibition-versus-time curve by 15% (p less than 0.05). Food did not alter the total amount of drug recovered in urine as perindopril and its metabolites, and it did not alter perindoprilat renal clearance. We concluded that food alters the conversion of perindopril to its active metabolite perindoprilat after single-dose administration of perindopril.

Administration, Oral↗

PubMed1994

Pharmacokinetic interaction between praziquantel and albendazole in Sudanese men.

It has been suggested that praziquantel (40 mg/kg) and albendazole (400 mg) administered together may have a synergistic effect on intestinal parasites. In the present study, the pharmacokinetics of these agents, alone and in combination, were investigated in the presence and absence of food in two groups of Sudanese males. The results indicated that praziquantel pharmacokinetics were not effected by co-administration of albendazole although, in the presence of food, the area under the curve (AUC(0-infinity)) of praziquantel increased 2.6 fold. The AUC(0-infinity) of albendazole sulphoxide (the active metabolite of albendazole) increased 4.5-fold when administered with praziquantel, eight-fold when given with food and 12-fold when given with praziquantel and food. The balance between the therapeutic efficacy of this combination of drugs and its safety profile needs to be studied, especially with regard to albendazole.

Adult↗

PubMed1993

Effect of time of food administration on the bioavailability of didanosine from a chewable tablet formulation.

The effect of the time of food administration on the bioavailability of didanosine, administered as a 300-mg dose of a chewable tablet formulation, was evaluated in 10 men seropositive for the human immunodeficiency virus (HIV), but free of any symptoms of acquired immune deficiency syndrome (AIDS). Using an open, randomized, balanced, incomplete block crossover study design, each patient received the dose of didanosine under four of the five following conditions: (1) after an overnight fast, (2) 30 minutes before a meal, (3) 1 hour before a meal, (4) 1 hour after a meal, or (5) 2 hours after a meal. The meal consisted of a standard high-fat, high-calorie breakfast, consumed over a 15-minute period. Serial blood samples and the total urinary output were collected over a 12-hour interval after each dose for analysis using validated high-pressure liquid chromatography (HPLC)/ultraviolet (UV) methods. Concentration data were used to calculate pharmacokinetic parameters using noncompartmental methods. There were no significant differences among the fasting, 30-minute before, and 1-hour before the meal treatments with respect to maximum peak plasma concentration (Cmax), area under the curve (AUC(0-infinity)), or urinary recovery (%UR). Values for Cmax, AUC(0-infinity), and %UR observed for the 1 and 2 hours after the meal treatments were significantly less than those obtained under either fasting conditions or before the meal. There were no significant differences among any of the treatments with respect to time to reach peak concentration (tmax), half-life (t1/2), or renal clearance (CLR).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1987

Absorption of di- and trivalent iron. Experimental evidence.

The present experiments were carried out on normal and iron deficient rats which were fed low iron diet and bled several times; the haemoglobin content of blood of normal rats was in the range of 12-14 g/dl, that of iron deficient rats between 6 and 8 g/dl. Iron was administered by a gastric tube and the retention of the radioactively labelled 59Fe-iron compounds was measured on the 6th day after the administration. There is no difference of the absorption of divalent and trivalent iron provided iron is administered in ionized form. This is possible when the iron solution administered is of pH less than 2.5. Since the pH values of gastric juice is in the same order of magnitude, this procedure is hardly to be called unphysiological. The decisive role of pH for the bioavailability of iron ions can be derived from an experiment with cobaltous ions that, in the range of physiological pH values, cannot be hydrolysed. Therefore, no difference of the retention of cobaltous ions was measured regardless whether the solution administered into a tied-off jejunal loop was of pH 2 or 5.5. The administration of either divalent or trivalent iron ions together with food to normal rats is followed by a slight decrease of the amount of iron retained. However, this difference of retention disappears when the ionized iron is administered to fed iron deficient rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The gastrointestinal absorption of the actinide elements.

The greatest uncertainty in dose estimates for the ingestion of long-lived, alpha-emitting isotopes of the actinide elements is in the values used for their fractional absorption from the gastrointestinal tract (f1 values). Recent years have seen a large increase in the available data on actinide absorption. Human data are reviewed here, together with animal data, to illustrate the effect on absorption of chemical form, incorporation into food materials, fasting and other dietary factors, and age at ingestion. The f1 values recommended by the International Commission on Radiological Protection, by an Expert Group of the Nuclear Energy Agency and by the National Radiological Protection Board are discussed.

Actinoid Series Elements↗

PubMed2003

Characteristics of the gastric pH profiles of unfed and fed cynomolgus monkeys as pharmaceutical product development subjects.

Gastric pH is an important factor which significantly affects the dissolution of drugs, and therefore their bioavailability. In this study, the gastric pHs were measured directly with a miniature pH electrode inserted through the nostril into the body of the stomach of cynomolgus monkeys. Results from three separate sets of measurements using the same male monkeys indicated that the median gastric pH profiles of unfed monkeys were low, fluctuating between pH 1 and pH 3. However, the median gastric pHs in fed monkeys given about 108 g of a biscuit-type solid food, which are commonly provided, shifted toward a more neutral range between pH 5 and pH 7, and remained in this range for about 9 h. This result contrasted with reported results for humans after eating a standard meal, which showed a neutral range between pH 5 and pH 7 for a brief period. Consequently, these results indicate that although the gastric pH of unfed cynomolgus monkeys is similar to that of fasting humans, there is a great difference in the gastric pH profiles between humans and monkeys after eating, which suggests that further studies are needed to establish optimal feeding conditions for bioavailability studies in monkeys.

Animals↗

PubMed1980

Can food influence the absorption of methotrexate in children with acute lymphoblastic leukaemia?

Serum levels of methotrexate (MTX) were measured in 10 children with acute lymphoblastic leukaemia over a 4 hour period after oral administration. The drug was given to each child on three occasions: first, with no food, then with a milky meal, and finally with a citrus meal. Peak serum MTX levels were significantly reduced by the milky meal and both meals delayed drug absorption in most children. The area under the absorption curve was also significantly reduced by the milky meal. Thus, for maximum serum levels, MTX should not be given with food, and if patients are to be grouped on the basis of their MTX absorption profile this should be determined under standard conditions in relation to meals.

Administration, Oral↗