Effect of replacement of fat by nonabsorbable fat (sucrose polyester) in meals or snacks as a function of dietary restraint.

The effect of replacement of fat by nonabsorbable fat on energy intake and on feelings of hunger and satiety was assessed, in normal-weight dietary-restrained (n = 11), dietary-unrestrained (n = 13) and in postobese dietary-restrained women (n = 12), using 2 experimental designs. First, during breakfast and lunch on 2 sequential weekdays, 23 g of dietary fat was replaced by 23 g of a nonabsorbable fat. Second, dietary fat was replaced by a nonabsorbable fat in snacks consumed ad lib during a different week. Fat replacement in meals or in snacks did not result in changes in hunger and satiety ratings throughout the day. Replacement in meals yielded an energy intake reduction of 0.5 MJ/day (not significant) in dietary-unrestrained and in postobese dietary-restrained subjects; this reduction included 44% energy intake compensation. In normal-weight dietary-restrained subjects, energy intake reduction of 0.7 (p < 0.05) MJ/day was observed; this reduction included 22% energy intake compensation. Moreover, fat replacement in meals showed a shift in macronutrient composition from 35-40% energy from fat to 31-32% energy from fat. Replacement in snacks yielded an energy intake reduction of 0.4-0.5 MJ/day (not significant) in normal-weight dietary-restrained subjects and a reduction of 0.6-0.7 (p < 0.05) MJ/day in dietary-unrestrained and in postobese dietary-restrained subjects. In this situation, energy intake from snacks consisted of 48-78% energy from reduced-fat reduced-energy snacks, which implied a replacement of 10-15 g fat by 10-15 g SPE (sucrose polyester) and a shift in macronutrient composition from 35-40 percentage energy from fat to 33-36 percentage energy from fat. These results suggest short-term beneficial effects of fat replacement on energy and fat intake.

A dual-respiration chamber system with automated calibration.

This study characterizes respiration chambers with fully automated calibration. The system consists of two 14-m3 pull-type chambers. Care was taken to provide a friendly environment for the subjects, with the possibility of social contact during the experiment. Gas analysis was automated to correct for analyzer drift and barometric pressure variations and to provide ease of use. Methods used for checking the system's performance are described. The gas-analysis repeatability was within 0.002%. Results of alcohol combustion (50-350 ml/min CO2) show an accuracy of 0.5 +/- 2.0 (SD) % for O2 consumption and -0.3 +/- 1.6% for CO2 production for 2- to 24-h experiments. It is concluded that response time is not the main factor with respect to the smallest practical measurement interval (duration); volume, mixing, gas-analysis accuracy, and levels of O2 consumption and CO2 production are at least equally important. The smallest practical interval was 15-25 min, as also found with most chamber systems described in the literature. We chose to standardize 0.5 h as the minimum measurement interval.

Induction of oxidative DNA damage and early lesions in rat gastro-intestinal epithelium in relation to prostaglandin H synthase-mediated metabolism of butylated hydroxyanisole.

The effect of metabolic activation of the food additive 3-tert-butyl-4-hydroxyanisole (BHA) by prostaglandin H synthase on the gastro-intestinal cell proliferation was determined by studies of the nature and the time dependency of early lesions in the forestomach, glandular stomach and colon/rectum of rats given BHA with and without co-administration of acetylsalicyclic acid (ASA: an inhibitor of prostaglandin H synthase), in combination with the formation of oxidative DNA damage in the epithelial cells of glandular stomach and colon/rectum as well as in the liver. BHA appeared to be a strong inducer of oxidative DNA damage in the epithelial cells of the glandular stomach, increasing the level of 7-hydro-8-oxo-2'deoxyguanosine (8-oxodG) with increasing duration of BHA administration. Similar observations were made in colorectal DNA although levels of oxidative DNA damage tend to be smaller. In liver DNA, BHA appeared to be capable of increasing background 8-oxodG levels only after 14 days of treatment. This relatively slow response may be related to very low prostaglandin H synthase activity of liver cells. The severity of hyperplasia and inflammation in both forestomach and glandular stomach appeared to increase gradually with continued BHA administration. The hyperplasia induced by BHA was paralleled by inflammatory changes. In colorectal tissue, however, no tissue abnormalities were observed. This indicates that oxidative DNA damage induced by BHA is not a consequence of early lesions in gastro-intestinal epithelium, but might be the initial step in the stimulation of gastro-intestinal cell proliferation which, as shown previously, also occurs in colon epithelium. Co-administration of the prostaglandin H synthase inhibitor ASA resulted in a significant decrease of both epithelial oxidative DNA damage and the incidence of lesions, which indicates that this enzyme system is involved in the enhancement of cellular proliferation induced by BHA. Co-oxidation by prostaglandin H synthase of the BHA-metabolite tert-butylhydroquinone into tert-butylquinone, yielding active oxygen species, might therefore be responsible for the carcinogenic effects of this food antioxidant.

Role of oxidative DNA damage in the mechanism of fecapentaene-12 genotoxicity.

Fecapentaene-12 (FP-12), a fecal unsaturated, ether-linked lipid excreted by most human individuals in Western populations, has been found to be a potent genotoxin in mammalian cells. Its mechanism of genotoxicity may be mediated by oxygen radical-induced DNA damage or by direct DNA alkylation, of which the relative importance remains to be determined. In the present study, induction of oxidative genetic damage by FP-12 has been investigated, in combination with the biological inactivation of single-stranded bacteriophage phi X-174 DNA. It was shown that formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG), a marker for oxidative DNA damage, is induced dose dependently by FP-12 in 2'-deoxyguanosine (dG). It was demonstrated by application of radical scavengers that production of both the superoxide anion and singlet oxygen may be involved in the induction of 8-oxodG. The effect of OH radical scavenging appeared to be less pronounced. Enzymatic peroxidation of FP-12, which has been demonstrated to stimulate oxygen radical formation, was found to increase the hydroxylation ratio in dG, an effect which was less pronounced in single-stranded DNA and even absent in double-stranded DNA. No induction of 8-oxodG was observed after exposure of human skin fibroblasts to 60 microM FP-12 for 3 h in vitro. It was concluded that the induction of 8-oxodG by FP-12 is determined by the accessibility of the guanine molecule rather than the rate of oxygen radical formation. Although free radical formation is known to be stimulated by enzymatic peroxidation of FP-12, the inactivation of phi X-174 DNA spontaneously induced by FP-12 was found to be reduced by application of peroxidases. This furthermore demonstrates that the increased formation of reactive oxygen species by enzymatic peroxidation of FP-12 does not directly relate to increased induction of genotoxic effects. The fact that addition of radical scavengers shows limited effects on the inactivation of phi X-174 DNA suggests that the contribution of oxidative DNA damage to the genotoxic potential of FP-12 is only of minor importance.

Food intake in the daily environment after energy-reduced lunch, related to habitual meal frequency.

Twenty women were offered two energy-reduced lunches in 48 h and five similar normal-energy lunches within a week, with snacks and evening meals provided and their own standard breakfasts. The subjects were categorized as "nibblers" or "gorgers" (10 per group), by the criterion of habitual eating of "snacks" between mealtimes. Compensatory energy intake occurred in the nibblers within 5 h of the "light" lunch. In the gorgers compensation of energy intake was not reached within 48 h. We conclude that differences in short-term compensation of intake can arise from habitual snacking or its absence.

Substrate utilization in man: effects of dietary fat and carbohydrate.

In man there is evidence that the ability to adjust fat oxidation to fat intake is less effective than the ability to adjust carbohydrate and protein oxidation to carbohydrate and protein intake. The short-term (3-day) effects of a low-fat (LF), mixed (M), and high-fat (HF) diet on human substrate balances were studied using a respiration chamber. Subjects were 14 young female students classified by means of their scores on psychometric questionnaires as "restrained" or "unrestrained" eaters. Subjects were in energy balance, ie, the mean difference between energy intake (EI) and energy expenditure (EE) was 86 +/- 85 kJ/d. The fat content of the food significantly influence the 24-hour respiratory quotient (RQ) and nonprotein respiratory quotient (NPRQ). For both the LF and M diets, the 24-hour RQ was significantly lower than the food quotient (FQ), whereas the RQ on the HF diet was not different from the FQ. Oxidation of fat and carbohydrate significantly increased with, respectively, an increasing fat and carbohydrate content of the diet for both restrained- and unrestrained-eating subjects. Restrained-eating subjects showed a decreased fat oxidation compared with unrestrained eaters in response to a HF diet, resulting in a positive fat balance for restrained-eating subjects. On a LF diet, fat balance was negative for both groups of subjects, indicating net endogenous fat oxidation. In conclusion, restrained-eating subjects have more difficulty in the handling of a HF diet, possibly explaining their higher susceptibility to becoming obese.

The role of prostaglandin H synthase-mediated metabolism in the induction of oxidative DNA damage by BHA metabolites.

The carcinogenicity of the phenolic food antioxidant butylated hydroxyanisole may be related to its oxidative biotransformation in vivo. In order to determine the ability of BHA, 2-tert-butyl(1,4)hydroquinone (TBHQ) and 2-tert-butyl(1,4)paraquinone (TBQ) to induce oxidative DNA damage, biological inactivation of single-stranded bacteriophage phi X-174 DNA, as well as induction of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in dG by these compounds was studied in vitro, in the presence and absence of peroxidases. Both test systems showed that BHA and TBQ (probably due to lack of reductase activity in vitro) were not capable of inducting oxidative DNA damage. TBHQ, however, appeared to be a strong inactivator of phage DNA as well as a potent inducer of 8-oxodG formation. Addition of radical scavengers showed that this damage was due to formation of superoxide anion, hydrogen peroxide and hydroxyl radicals. Addition of iron chelators and metal ions showed that the one-electron oxidations of TBHQ via the semiquinone radical into TBQ are toxic via the formation of oxygen radicals and are not directly due to the hydroquinone itself or the formation of semiquinone radicals. Although peroxidation of TBHQ by prostaglandin H synthase (PHS) is indicated to result in a superoxide anion burst, this is not accompanied by an increase in oxidative DNA damage in vitro. This might be due to the use of hydrogen peroxide as a substrate by PHS itself, consequently resulting in less formation of hydroxyl radicals. Oxidation of TBHQ by lipoxygenases showed that no semiquinone radicals or oxygen radicals were formed, probably due to a two-electron oxidation of TBHQ directly into TBQ. The present results indicate that metabolic activation of BHA yielding reactive oxygen species may induce a carcinogenic potential, since the BHA metabolite TBHQ, appeared to be a strong inducer of oxidative DNA damage.

In vitro study on the effects of fecal composition on fecapentaene kinetics in the large bowel.

Dietary factors have been shown to affect excretion of fecapentaenes, potent mutagens present in human feces. Apart from effects of the diet on the bacterial synthesis of fecapentaenes in the bowel, fecapentaene excretion is likely to be indirectly influenced by the composition of the bowel contents, in particular fecapentaene-binding or -solubilizing factors. In the present study, interactions between dietary fiber and fecapentaene-12 (FP-12), as well as the effects of bile acids and calcium on the solubility of FP-12 in aqueous solutions, have been investigated in vitro. The results demonstrated that FP-12 may strongly adsorb to fiber, as indicated by reduced concentrations in the aqueous PBS phase when increasing amounts of fiber are added. This fecapentaene-binding capacity of fiber may explain the positive correlations that have previously been found between excreted fecapentaene concentrations and fiber consumption in human population studies. Further, it was found that at concentrations physiologically occurring in feces, both cholic and deoxycholic acid as well as mixtures of bile acids may increase the aqueous solubility of FP-12. This solubilizing effect of bile acids can be reduced by adding calcium at physiological concentrations of 2.5 mg/ml. It is hypothesized that high dietary fiber intake may increase fecapentaene excretion as a result of this fecapentaene fiber adsorption, which in turn may result in diminished exposure of the human bowel epithelium to these putative initiators of colorectal cancer. In contrast, high concentrations of fecal bile acids may act as fecapentaene-solubilizing factors which increase fecapentaene bioavailability, thereby possibly resulting in increased risk for colorectal cancer.

Comparison of dietary intake data with guidelines: some potential pitfalls (Dutch nutrition surveillance System).

In evaluating dietary data with reference to guidelines for a healthy diet, some potential pitfalls (i.e., method of food consumption assessment and calculation to include or exclude energy derived from alcohol) were investigated. The percentage of energy intake (en%) derived from total fat, saturated fatty acids (SFA), mono- and disaccharides (MD) and intake of cholesterol and dietary fiber per megajoule were calculated using 2-day records obtained in the Dutch National Food Consumption Survey of 1987-1988. Subjects (aged 4-85, n = 5595) were classified into age-sex groups. Mean values and intake distributions were calculated with and without adjustment for within-person variation. Except for the intake of cholesterol and MD, mean intake levels were not in accord with guidelines. About 20% of the women and 23% of the men met the goal for fat intake, 20% of the men and 27% of the women for dietary fiber, and about 60 and 70% for MD and cholesterol. Only 3% of subjects had SFA intake < or = 10 en%, whereas < 1% had a diet in accord with all criteria studied. After adjustment for within-person variation, percentages meeting the guidelines were generally lower for fat, SFA and dietary fiber and slightly higher for cholesterol and MD. Among elderly, unadjusted results were more in agreement with the prevalence estimates based on habitual dietary intake data than with adjusted ones. Fat intake (en%) was inversely related with intake of added MD and alcohol. Our data indicate that guidelines should state explicitly whether energy-related recommendations include energy derived from alcohol, and that the prevalence of a high-fat intake is more affected by the calculation method than by food consumption assessment.

Oxygen radical formation during prostaglandin H synthase-mediated biotransformation of butylated hydroxyanisole.

The dominant metabolic pathway of the presumably carcinogenic food antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) includes O-demethylation to 2-tert-butyl(1,4)hydroquinone (TBHQ) and subsequent peroxidation to 2-tert-butyl(1,4)paraquinone (TBQ). In order to determine the ability of TBHQ to induce the formation of oxygen radicals, electron spin resonance measurements were performed in presence and absence of peroxidases. ESR analyses showed that prostaglandin H synthase resulted in a substantially accelerated metabolism of TBHQ into TBQ, which is accompanied by formation of superoxide anion, hydroxyl radical and hydrogen peroxide. Spectrophotometric measurements revealed that prostaglandin H synthase and lipoxygenase are both capable of converting TBHQ into TBQ. In order to determine the effect of prostaglandin H synthase on BHA (dose-level: 1.5% BHA of the diet) metabolism in vivo, we coadministered two inhibitors of prostaglandin H synthase acetylsalicylic acid and indomethacin, with BHA to rats. Coadministration of acetylsalicylic acid (0.2%) in the drinking water resulted in a significant increase of urinary TBHQ excretion. Both acetylsalicylic acid and indomethacin (dose-level: 0.002% in the drinking water) induced a significant decrease in TBQ excretion into urine. Co-oxidation by prostaglandin H synthase of the BHA-metabolite TBHQ into TBQ, yielding reactive oxygen species might therefore be responsible for the carcinogenic and toxic responses elicited by this antioxidant.

Effects of electrolytes in carbohydrate beverages on gastric emptying and secretion.

Two experiments were done at rest to examine gastric residue and secretion volume and electrolyte composition after ingestion of beverages of varying composition. In the first experiment the effects of two different sport drinks, one isotonic (7% carbohydrate, primarily sucrose) (I) and one hypertonic (18% carbohydrate, primarily maltodextrin) (H), and a control beverage (0.08 g.l-1 aspartame in water) (C) on titratable acid, pH, osmolality, gastric emptying and secretion volume, and Na+, K+, and Cl- content were measured. In a second experiment five solutions were tested all containing 150 g.l-1 maltodextrin, with 28 meq.l-1 Na+ (low Na), 140 meq.l-1 Na+(high Na), 28 meq.l-1 K+(K), or 140 meq.l-1 Na+ and 28 meq.l-1 K+(high NaK). Beverages H and C, and distilled water (W) were also tested. Samples were taken via a nasogastric tube. A dye dilution technique for serial sampling was employed to determine beverage and secretion volumes. After receiving a bolus of 8 ml.kg-1 body weight, samples of gastric residue were taken at 0, 10, 20, 30, 40, 60, and 80 min. Gastric secretion of Na+, K+, and Cl- was fairly constant despite large differences in beverage composition. Changes in gastric residue pH, titratable acid, osmolality, and electrolyte composition reflected the increasing proportion of the residue that was from gastric secretions. The effects of varying concentrations of Na+ and K+ (in a 150 g.l-1 maltodextrin solution) on gastric emptying were not significant. The high carbohydrate concentration and/or the large volume ingested may have overridden any effect of sodium or potassium. No differences were observed between W and C. Secretion was decreased in these two solutions versus all the others. Although nonsignificant, there was a trend for greater secretion in H versus the other carbohydrate containing solutions in experiment 2. This may be a result of the higher pH maintained after ingestion of this beverage.

Chromatographic methods for the determination of toxicants in faeces.

Modern chromatographic techniques and their application in the determination of toxic compounds in faeces are reviewed. Faecal analysis may be of importance in toxicokinetic studies of xenobiotics in order to determine factors such as metabolism, body burden and major routes of elimination. Compounds of interest include various food constituents, drugs and occupational or environmental factors. Further, various mutagenic or carcinogenic compounds which are excreted by faeces have been indicated to represent risk factors for colorectal cancer. In this context, the chromatographic determination of the endogenously generated fecapentaenes and bile acids, both postulated etiological factors in colorectal carcinogenesis, is reviewed. For fecapentaene determination, several high-performance liquid chromatographic (HPLC) methods are available; however, the applicability of some of these methods is limited owing to insufficient separation of various isomeric forms or discrimination between fecapentaenes and their precursors. For the determination of bile acids in faeces, many chromatographic procedures have been reported, and the characteristics of the most relevant methods are compared and discussed. It is concluded that separation by gas chromatography (GC) in combination with mass spectrometry provides the highest selectivity and sensitivity. A relatively rapid alternative analysis for the determination of total and aqueous faecal bile acids is proposed. Further, methods for the determination of polycyclic aromatic hydrocarbons (PAHs) are reviewed. Although the use of radiolabelled PAHs in animal studies has many advantages, it cannot be applied for human biological monitoring and HPLC and GC provide sensitive alternatives. An HPLC method for the determination of non-metabolized PAHs in faeces is described.

Clustering of dietary variables and other lifestyle factors (Dutch Nutritional Surveillance System).

STUDY OBJECTIVE: The aim was to investigate whether dietary factors cluster in a favourable or unfavourable way and to characterise the groups identified by lifestyle and sociodemographic variables. DESIGN AND SETTING: This cross sectional study was based on data of the 1987-1988 Dutch national food consumption survey (DNFCS), obtained from a panel by a stratified probability sample of the non-institutionalised Dutch population. PARTICIPANTS: 3781 adults (1802 males and 1979 females) of the DNFCS, aged 19 to 85 years, were studied. MEASUREMENTS AND MAIN RESULTS: To estimate dietary intake two day food records were used. Lifestyle factors were collected by structured questionnaire and sociodemographic variables were available from panel information. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. Subsequently, these groups were characterised by sociodemographic and lifestyle factors as well as by the consumption of food groups. Eight clusters were found. In comparison with the guidelines, the dietary quality in four clusters was poor. The cluster with the poorest dietary intake (high intake of fat, cholesterol, and alcohol; low intake of dietary fibre) showed on average a high consumption of animal products (except milk), fats and oils, snacks, and alcoholic beverages, and a low consumption of fruit, potatoes, vegetables, and sugar rich products. Smoking, body mass index, dietary regimen on own initiative, hours of sleep, gender, age, socioeconomic status, and day of the week were found to discriminate among the clusters. CONCLUSIONS: Cluster analysis resulted in substantial differences in mean nutrient intake and seems useful for dietary risk group identification. Undesirable lifestyle habits were interrelated in some clusters, but an exclusive lifestyle for health risk has not been found.

Long-term effect of physical activity on energy balance and body composition.

We studied the effect of an increase in physical activity on energy balance and body composition without interfering with energy intake (EI). Sixteen women and sixteen men, aged 28-41 years, body mass index 19.4-26.4 kg/m2, not participating in any sport before the start of the experiment, prepared to run a half-marathon competition after 44 weeks. Measurements of body composition, EI and energy expenditure (EE) were performed before (0 weeks), and 8, 20, and 40 weeks after the start of training. Body composition was measured with hydrodensitometry and isotope dilution, and EI with a 7 d dietary record. EE was measured overnight in a respiration chamber (sleeping metabolic rate (SMR)) and in a number of subjects over 2-week intervals with doubly-labelled water (average daily metabolic rate (ADMR)). ADMR showed an average increase of 30% in both sexes from the start of training onwards while SMR tended to decrease. EI showed a tendency to drop from week 20 to week 40 in the men and a tendency to increase from week 20 to week 40 in the women. Body mass (BM) did not change in both sexes until the observation at 40 weeks when the median value of the change in men was -1.0 kg (P < 0.01; Wilcoxon signed-rank) while the corresponding change of -0.9 kg in the women was not statistically significant. Body composition changes were most pronounced in men as well. Based on changes in BM, body volume and total body water, men lost 3.8 kg fat mass (FM) (P < 0.001; Wilcoxon signed-rank) and gained 1.6 kg protein mass (P < 0.01; Wilcoxon signed-rank) while the corresponding changes in women were 2.0 kg (P < 0.05; Wilcoxon signed-rank) and 1.2 kg (P < 0.05; Wilcoxon signed-rank). In men the loss of FM was positively correlated with the initial percentage body fat (Pearson r 0.92, P < 0.001). In conclusion, body fat can be reduced by physical activity although women tend to compensate for the increased EE with an increased EI, resulting in a smaller effect on BM and FM compared with men.

Electron spin resonance spectroscopy of oxygen radicals generated by synthetic fecapentaene-12 and reduction of fecapentaene mutagenicity to Salmonella typhimurium by hydroxyl radical scavenging.

Fecapentaenes form a class of potent fecal mutagens and have been suggested to play an initiating role in colon carcinogenesis. Although several indications have been found that fecapentaenes may induce oxidative DNA damage as well as DNA alkylation, the mechanism of genotoxicity remains unknown. In this study, electron spin resonance spectroscopy with several spin traps has been used in order to determine whether reactive oxygen species can be formed by fecapentaene-12 (FP-12). No specific conditions could be defined that resulted in the direct formation of oxygen radicals from FP-12. However, peroxidation of FP-12 by various peroxidative enzymes has been shown to result in the formation of superoxide adducts of the spin traps alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Addition of superoxide dismutase resulted in a decreased spectrum intensity, whereas the hydroxyl radical scavenger t-butyl alcohol (tBA) appeared of no influence on the signal, both confirming the formation of superoxide. The formation of hydroxyl radical spin adducts has been demonstrated after peroxidation of FP-12 in incubations with the spin-trapping agent 2,2,6,6-tetramethyl-piperidine (TMP). Further, the effects of scavenging hydroxyl radicals with respect to the genotoxic potential of FP-12 in the Salmonella mutagenicity assay has been investigated. It was clearly shown that radical scavenging reduced the number of revertants in Salmonella strains TA100, TA102 and TA104. This mutagenicity-reducing effect was more convincing using both spin traps DMPO and TMP as compared to the effect of hydroxyl radical scavengers tBA and DMSO. Based on these findings, a reaction scheme is proposed that suggests the formation of superoxide after peroxidation of FP-12, which is subsequently converted to hydroxyl radicals by the iron-catalysed Haber-Weiss reaction.

Accuracy of estimates of forthcoming ingestion as a function of menu familiarity and dietary restraint.

Estimates of forthcoming intake were compared with amount eaten in women who were normal-weight restrained eaters, unrestrained eaters or overweight restrained eaters, for three four-course lunches of which the first consisted mainly of an Italian menu, the second and third mainly a Japanese menu. The differences between estimated and eaten amounts for the first and third lunch correlated negatively with degree of restraint. This indicates that those who score high on dietary restraint have learnt better ways of estimating their intake. No relation was found between the difference in estimated and eaten amount and degree of restraint during the second lunch. This indicates that the unfamiliarity of a meal makes it more difficult to predict how much of it would be satiating.

Effects of butylated hydroxyanisole on arachidonic acid and linoleic acid metabolism in relation to gastrointestinal cell proliferation in the rat.

In order to determine the effect of oral administration of 2(3)-tert-butyl-4-hydroxyanisole (BHA; dose-level: 1.5% BHA of the diet) on arachidonic acid (AA) and linoleic acid (LA) metabolism in correlation with changes in gastrointestinal cell kinetics, we coadministered two inhibitors of prostaglandin H synthase, acetylsalicylic acid (ASA) and indomethacin (IM), to rats. Coadministration of ASA (0.2%) and IM (0.002%) in the drinking water, resulted in a significant reduction of the BHA-induced enhancement of cell proliferation in forestomach and glandular stomach. ASA completely counteracted the effect of BHA on labeling indices in colon/rectum whereas IM exhibited no effect in this organ. Both inhibitors had no direct effect on cell kinetics in the control groups. ASA, and to a lesser degree IM, inhibited prostaglandin E2 release in all tissues examined. Whereas ASA did inhibit lipoxygenase-mediated metabolism of AA in forestomach tissue, ASA did not affect the release of AA- and LA-derived hydroxy fatty acids in glandular stomach and colon/rectum. IM did not affect lipoxygenase production. BHA, however, appeared to be a strong inhibitor of both routes of AA metabolism. While ASA nor IM affected LA metabolism, BHA inhibited both prostaglandin H synthase-mediated and lipoxygenase-mediated metabolism of AA and LA. A causal role of AA or LA metabolites in the process of cell proliferation enhancement induced by BHA, can therefore be excluded. Prostaglandin H synthase may, however, be involved in BHA activation by converting the hydroquinone metabolite of BHA to the corresponding quinone by redox cycling, which is probably accompanied by reactive intermediate production.

Diet-induced thermogenesis and cumulative food intake curves as a function of familiarity with food and dietary restraint in humans.

Cumulative food intake curves and diet-induced thermogenesis were recorded in women during four-course solid-food lunches, consisting of familiar and unfamiliar food, offered in ad lib or restricted portions, in order to assess a possible relation between eating behaviour on the one hand and a reflection of internal processes and subject characteristics on the other. The subjects were characterized as normal weight restrained, normal weight unrestrained, and overweight restrained. A negative relation was found between degree of restraint and deceleration of the cumulative food intake curve during the ad lib courses of any menu, and between degree of restraint and diet-induced thermogenesis (p less than 0.001). Consequently, a positive relation was found between deceleration of the cumulative food intake curves during the ad lib courses of any menu and diet-induced thermogenesis (p less than 0.001). Diet-induced thermogenesis during the first serving of a meal consisting of unfamiliar food was significantly higher in all groups than during the other two times, when meals consisting of more familiar food were served (+0.98%; 0.71%, p less than 0.05).