The effect of beta-carotene on sputum cytology in smokers: a preliminary study.

The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.

The safety assessment of novel foods. Guidelines prepared by ILSI Europe Novel Food Task Force.

The diversity of novel foods and novel ingredients covered by the scope of the EU regulation is such that a check list approach to safety evaluation is inappropriate. Rather, a case-by-case approach is required taking into account the composition of the novel food, its intake, its role in the diet and the intended target group. The SAFEST approach provides a means of targeting the safety evaluation on those aspects, nutritional or toxicological, of a novel food which are of particular concern. Using this approach, novel foods are assigned to one of three classes on the basis of certain background information. For those novel foods which can be shown to be in SAFEST class 1, namely those which are substantially equivalent to a traditional counterpart, no further information is required to demonstrate their safety. For those novel foods in SAFEST class 2, i.e. those sufficiently similar to a traditional counterpart or differing from it only in particular, well defined, characteristics, the evaluation will focus on those differences. Only in the case of novel foods which are not in class 1 or class 2 is extensive testing of the whole food likely to be required. Even in these cases, the testing should follow a scientifically-based hierarchical approach involving: literature reviews; chemical analysis; appropriate in vitro and in vivo tests; and, if necessary, confirmation of safety and nutritional value in humans. Examination of the causes of any adverse effects reported by consumers after the novel food or ingredient has been approved and is introduced into the market may provide additional reassurance of safety.

Prevalence of food allergy and intolerance in the adult Dutch population.

The prevalence of food allergy and intolerance (FA/FI) was studied in a random sample (n = 1483) of the Dutch adult population. First, the self-reported FA/FI reactions were investigated by questionnaire. Subsequently, in a clinical follow-up study, it was determined in how many cases this self-reported FA/FI could be objectively confirmed by double-blind placebo-controlled food challenge. More than 10% of the population (12.4%) reported FA/FI to specific food(s). Of the 144 subjects potentially available for the clinical follow-up study, 73 completed the whole protocol. In 12 subjects FA/FI could be confirmed by double-blind placebo-controlled food challenge. This indicates a minimum prevalence of FA/FI in the population of 0.8% (12 of 1483). Assuming that FA/FI is equal among participants, nonparticipants, and dropouts, the prevalence of FA/FI in the Dutch adult population is estimated to be 2.4%. The food (ingredients) involved included pork, white wine, and menthol. Two persons reacted to additives. In three persons glucose intolerance was observed. However, these specific intolerances probably do not reflect the distribution in the general population because the study population formed an extremely heterogeneous group, both with regard to the offending foods and the symptoms. The majority of the subjects had no serious complaints that required medical advice. We conclude that there is a gap between self-reported FA/FI and FA/FI that can be objectively confirmed by double-blind placebo-controlled food challenge.

Body composition, health status and urinary magnesium excretion among elderly people (Dutch Nutrition Surveillance System).

Magnesium (Mg) requirements depend on body weight. Recommended dietary allowances (RDA) are mostly given in absolute amounts and are mostly similar for adults, despite differences in body composition in the adult age range. We therefore studied the interrelations of 24 h urinary Mg excretion with body build and body composition indicators, as well as with factors potentially affecting the metabolism of Mg, among 520 elderly men and women seen in a nationwide survey. Mg intake data were also obtained in the Dutch Food Composition Survey amount 5898 subjects. The results showed lower mean Mg intake among elderly people (especially men) and positive associations of body weight and body height with urinary Mg excretion, but not when expressed per mmol of creatinine excreted. Mg excretion per mmol of creatinine was not associated with body weight, body height, body mass index or body fatness (women), suggesting that the amount of fat mass did not affect Mg excretion. Mg excretion was positively correlated with Mg intake, creatinine clearance, excretion of sodium, potassium and calcium, and coffee consumption, indicating interactions at the kidney level that may increase Mg losses. Elderly people using diuretics and/or anticholinergics and male diabetics had a higher mean Mg excretion per mmol of creatinine. The results show that, besides the Mg intake, several factors affect the urinary Mg excretion among elderly people. These factors were body build and body composition, dietary intake, drug use, kidney function, and diabetes. A quantification of the effects cannot be made yet, and controlled studies on those factors potentially affecting the requirement of Mg are needed.

Alcohol consumption in relation to food intake and smoking habits in the Dutch National Food Consumption Survey.

The interrelationships between alcohol consumption, energy and food intake and smoking habits were studied in 1145 men and 1171 women, aged 22-49 years, in the Dutch National Food Consumption Survey, in which a 48-h dietary record method was used. The aim of the study was to investigate the effects of alcohol consumption on dietary habits and smoking. A strong relationship between alcohol consumption and energy intake was found. The energy derived from alcohol was not compensated for by lower intake of other nutrients. There was no increase in Quetelet's index with increasing alcohol consumption, except for non-smoking men who were heavy drinking on midweek days. Possible explanations for this apparent lack of an overall effect of alcohol calories are discussed. Alcohol consumption was much higher on weekend days than on midweek days. No differences in nutrient intake were found between non-drinkers, moderate drinkers and heavy drinkers on midweek days. On weekend days, however, there was a slightly higher total fat and saturated fat intake in moderately drinking men. For women cholesterol intake was found to be higher in moderate and heavy drinkers. Finally, a strong positive relationship between alcohol consumption and smoking was observed. It is concluded that the observations with respect to energy and nutrient intake and smoking habits are not indicative of a healthier lifestyle in moderate alcohol users between 22 and 49 years of age. Consequently, the more favourable prognosis of moderate drinkers cannot be ascribed to a more healthy lifestyle.

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.

Effect of beta-carotene on immunological indexes in healthy male smokers.

To evaluate the immunomodulatory effects of beta-carotene we performed a randomized, double-blind trial in healthy male cigarette smokers. Lymphocyte subsets in peripheral blood were assessed by using double labeling with monoclonal antibodies before and after 14 wk beta-carotene (20 mg/d; n = 21) or placebo (n = 24) supplements. In addition we measured the ex vivo phytohemagglutinin and concanavalin A induced lymphocyte proliferation in a separate group (23 placebo, 24 beta-carotene). The beta-carotene and placebo groups were comparable on all initial characteristics. During the intervention plasma concentrations of beta-carotene increased 13-fold in the treatment group whereas retinol concentrations remained constant. Beta-carotene had no effect on lymphocyte subpopulations in peripheral blood. After treatment the beta-carotene group showed 12% higher PHA-induced lymphocyte proliferations than the placebo group (P = 0.02). For ConA induced proliferations no significant difference was observed. These results suggest that supplementary beta-carotene can moderately enhance certain aspects of immune response in healthy male cigarette smokers.

Effects of the colour additive caramel colour III on the immune system: a study with human volunteers.

Administration of the colour additive Caramel Colour III to rats has been associated with decreased numbers of lymphocytes and several other changes in the immune system, as well as in immune function parameters, specifically in animals fed a diet with a relatively low vitamin B6 content. The effects are caused by the imidazole derivative 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). Caramel Colour III is commonly used in food products such as bakery products, soya-bean sauces, brown sauces, gravies, soup aromas, brown (dehydrated) soups, brown malt caramel blend for various applications, vinegars and beers, and effects in humans on dietary intake cannot be excluded. Elderly male volunteers with a marginal deficit in vitamin B6 were considered a relevant and potentially sensitive group to study possible effects of Caramel Colour III on blood lymphocyte numbers (total and within subsets) or on proliferative responses of lymphocytes to mitogenic stimulation. In addition, several other haematological parameters, as well as serum immunoglobulin levels and immunoglobulin production in vitro by pokeweed mitogen-stimulated mononuclear blood cells were studied. The results of this double-blind intervention study demonstrated that in a selected test group of apparently healthy elderly male volunteers with a biochemically marginally deficient vitamin B6 status, Caramel Colour III containing 23 (commercial sample) or 143 (research sample) ppm THI and administered at the level of the current acceptable daily intake of 200 mg/kg body weight/day for 7 days did not affect any of the factors investigated.

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.

Supplementation with selenium-rich bread does not influence platelet aggregation in healthy volunteers.

In order to establish the effect of an increased dietary selenium supply on platelet glutathione peroxidase (EC 1.11.1.9.; GSH-Px) and platelet aggregation, six healthy subjects were supplemented with 200 micrograms Se as Se-rich bread for 6 weeks. Another six subjects received low-Se bread and served as controls. Platelet GSH-Px activity increased significantly in the supplementation group, whereas no effect could be observed on platelet aggregation. The results of this study do not support the hypothesis that an increased dietary Se intake has a favourable influence on platelet aggregation.

Effects of Caramel Colour III on the number of blood lymphocytes: a human study on Caramel Colour III immunotoxicity and a comparison of the results with data from rat studies.

Administration of the colour additive Ammonia Caramel Colour (Caramel Colour III) to rats has been associated with decreased lymphocyte counts, specifically in rats fed a diet low in vitamin B6. This effect is rapidly reversible and is caused by an imidazole derivative (THI) in Caramel Colour III. In the present paper, the conduct of a human study with Caramel Colour III is outlined and the results of blood lymphocyte counts are presented. No decrease in the number of blood lymphocytes occurred in marginally vitamin B6-deficient humans who consumed Caramel Colour III at the acceptable daily intake level (200 mg/kg body weight/day) for 7 days. These data are discussed in relation to the effects of Caramel Colour III and THI on blood lymphocyte numbers in rats.

Hematocrit and cardiovascular risk factors among elderly men and women (Dutch Nutrition Surveillance System).

Changes in whole blood viscosity associated with hematocrit could be one of the pathways along which the cardiovascular disease (CVD) risk factors affect these diseases. Therefore, we studied in a nationwide survey comprising 514 apparently healthy Dutch elderly men and women aged 65-79 the possibility of any association between hematocrit and CVD risk factors (tobacco smoking, serum cholesterol, body mass index and blood pressure). Among men, diastolic blood pressure and total serum cholesterol were positively associated with hematocrit in both bivariate and multivariate regression analysis, whereas positive associations of hematocrit with body mass index and smoking were only significant (p < 0.05) in bivariate analysis. Among women, hematocrit was positively associated with body mass index and smoking. Except for smoking, which was associated with the mean corpuscular volume of the erythrocytes, hematocrit was positively correlated with hemoglobin and the number of erythrocytes. It is concluded that hemorrheological aspects should be considered when studying CVD among elderly people.

Serum IgG and IgA anti-gliadin antibodies as markers of mucosal damage in children with suspected celiac disease upon gluten challenge.

Serum anti-gliadin antibodies (AGAs) of the IgG and IgA isotypes were determined in 17 children (mean age of 5.6 years) by means of an enzyme-linked immunosorbent assay (ELISA). All children were suspected of celiac disease. They had been on dietary treatment for at least 10 months before they were challenged with gluten. Based on jejunal biopsy findings, 10 of the 17 children had to be considered positive. The sensitivity of the measurement of AGA at 6 weeks after gluten challenge was found to be 90% for IgG, 100% for IgA, and 100% for IgG/IgA combined. The specificity for IgG, IgA, and the IgG/IgA combination was 100, 71, and 100%, respectively. Twelve weeks after gluten challenge, the sensitivity as well as the specificity of AGA determination for IgG, IgA, and IgG/IgA were 100%. It is concluded that testing both IgG AGA and IgA AGA in children suspected of celiac disease is valuable in monitoring the course of the diagnostic provocation protocol and that jejunal biopsies can be abolished. This inexpensive tool can be useful in reducing the number of intestinal biopsies.

Application of a three-compartment model to a study of the effects of sex, alcohol dose and concentration, exercise and food consumption on the pharmacokinetics of ethanol in healthy volunteers.

A recently developed three-compartment model for the absorption and elimination of ingested alcohol was applied to re-analyse a study on the effects of various factors known to influence the blood-alcohol curve. The absorption and elimination of alcohol after drinking diluted alcohol were studied in healthy volunteers under strictly standardized conditions. The factors studied were sex, dose, concentration, physical exercise, meal consumption before drinking, energy content and composition of the meal, and time of drinking in relation to meal consumption. Gastric emptying and absorption from the small intestine were assumed to be first-order, and a possible delay (or acceleration) of gastric emptying was accounted for by a feedback-control parameter. The elimination process was assumed to follow Michaelis-Menten kinetics. Clear effects were observed of sex and dose, and aspects of meal consumption on absorption and elimination of alcohol. The ingestion of a meal prior to the intake of alcohol reduced both the gastric emptying rate and absorption efficiency of alcohol, increased the gastric emptying delay and reduced the rate of elimination. The absorption efficiency was even lower when the alcohol was consumed during the meal instead of after the meal. Using alcohol during the meal accelerated gastric emptying and reduced absorption efficiency as well as rate of elimination. High-fat meals resulted in the highest gastric emptying rate and rate of absorption from the small intestine, whereas high-protein and high-sucrose meals resulted in the lowest gastric emptying rate. Simultaneous consumption of a high-sucrose meal and alcohol increased gastric emptying delay.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of various levels of selenium in wheat and meat on blood Se status indices and on Se balance in Dutch men.

After a 5-week period of low selenium intake, twenty-four Dutch men received 55, 135 or 215 micrograms Se/d as Se-rich meat or bread for a 9-week period. Four unsupplemented subjects served as controls. Plasma Se increased more rapidly than erythrocyte Se levels; the increases were significantly dependent (P less than 0.001) on Se intake level. Glutathione peroxidase (EC 1.11.1.9; GSH-Px) activity in platelets increased rapidly after supplementation and plateaued after 4-9 weeks. At 10 weeks after supplementation ended, plasma Se levels and platelet GSH-Px were still higher than the baseline values whereas erythrocyte Se levels continued to increase. Except for the higher erythrocyte Se levels after supplementation with high-Se meat, there were no differences in bioavailability of Se between meat and wheat products. Daily urinary and faecal Se excretions as well as Se retention increased with an increased Se intake irrespective of the form of the supplement. Regression of Se excretion v. intake indicated that 33 micrograms Se/d is necessary to compensate for urinary and faecal losses.

Effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator and plasminogen activator inhibitor.

Short-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20-30 and 45-55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.

Effect of dietary fiber on the vitamin B6 status among vegetarian and nonvegetarian elderly (Dutch nutrition surveillance system).

To obtain more insight into the effect of dietary fiber on vitamin B6 status among elderly people, we studied dietary interrelationships as well as associations between dietary intake and plasma pyridoxal-5'-phosphate (PLP) and cofactor stimulation of aspartate aminotransferase in erythrocytes (EAST-AC) among 441 nonvegetarian (aged 65-79) and 32 vegetarian elderly (aged 65-94). EAST-AC was found to be inversely related with intake of vitamin B6 and dietary fiber in bivariate regression analyses. After adjustment for age, intake of energy, protein, and fiber, the intake of vitamin B6 was still inversely related with EAST-AC. The association between EAST-AC and dietary fiber disappeared in the multivariate analysis, whereas total protein intake proved to be positively related with EAST-AC in the multivariate analysis only. The differences between bi- and multivariate analyses are most likely due to the observed interrelationships between intake of vitamin B6, fiber, and protein. It is concluded that dietary fiber does not have a significant impact on the vitamin B6 status among Dutch elderly people, since only protein (positively) and vitamin B6 (inversely) intake appeared to be related with EAST-AC in the multivariate analysis.

Dietary fat and the risk of breast cancer.

Age-adjusted dietary fat intake of 133 incident Dutch breast cancer cases was significantly (p less than 0.01) higher than in 289 apparently healthy controls (mean and standard deviation: 102 +/- 36 g and 92 +/- 30 g, respectively). The age-adjusted relative odds of breast cancer showed a positive trend (p less than 0.05) with increasing fat intake. The multivariate adjusted relative odds was 3.5 (95% Cl = 1.6-7.6) for subjects in the highest quintile of fat intake (above 113 g) compared to those in the lowest quintile (below 65 g); this corresponds to a 30% increased risk per 10% of energy derived from fat. The association could not be attributed to energy intake, nor to the degree of saturation of the fat nor to any specific dietary source of fat.

Effects of a moderate dose of alcohol on blood lipids and lipoproteins postprandially and in the fasting state.

Effects of a moderate dose of alcohol on blood lipids and lipoproteins were studied in volunteers of two age groups (20-30 and 45-55 years), each consisting of eight healthy men. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. In the postprandial phase, one hour after intake, alcohol increased high-density lipoprotein cholesterol (HDL-C) by 11.5%, triglycerides (TG) by 15.3% and apolipoprotein A2 (Apo-A2) by 7.3% (P = 0.002, P = 0.044 and P = 0.024, respectively). The increase in HDL-C appeared to be mainly attributed to the HDL2-C subfraction which increased by 15.3% (P = 0.066). Furthermore, the increases in HDL-C, HDL2-C and TG were more pronounced in the middle-aged men then in the young men. After fasting overnight the effects of alcohol had disappeared.