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Biomedical subjects

H Verhagen

Publications and source records attributed to H Verhagen.

At least 19 recordsLinked to original sources
PubMed2005

Kinetics of biomarkers: biological and technical validity of isoprostanes in plasma.

Isoprostanes, non-enzymatic peroxidation products of arachidonic acid, are attractive biomarkers of oxidative stress in research in biology, medicine and nutrition. For the appropriate use of biomarkers it is required that these are both biologically and technically valid. Whereas the biological validity of isoprostanes is well-established, it is technically quite complicated to measure isoprostanes and its metabolites in body fluids, and its rapid disappearance from plasma may hamper practical application. This paper shortly introduces isoprostanes as a biomarker for studies with humans, describes a novel fast and sensitive method for measuring isoprostanes in plasma by high-performance liquid chromatography and tandem mass spectrometry, and provides several examples of the use of the method in studies in humans. By taking care of the biological and technical validity of this biomarker it is possible to establish the antioxidant effects of some food ingredients in studies with human volunteers.

Biomarkers↗
PubMed2004

Risk-benefit analysis of micronutrients.

Traditionally, different approaches have been used to determine the recommended dietary allowances for micronutrients, above which there is a low risk of deficiency, and safe upper levels, below which there is a negligible risk of toxicity. The advice given to risk managers has been in the form of point estimates, such as the recommended dietary allowance (RDA) and the tolerable upper level (UL). In future, the gap between the two intake-response curves may become narrower, as more sensitive indicators of deficiency and toxicity are used, and as health benefits above the recommended daily allowance are taken into account. This paper reviews the traditional approaches and proposes a novel approach to compare beneficial and adverse effects across intake levels. This model can provide advice for risk managers in a form that will allow the risk of deficiency or the risk of not experiencing the benefit to be weighed against the risk of toxicity. The model extends the approach used to estimate recommended dietary allowances to make it applicable to both beneficial and adverse effects and to extend the intake-incidence data to provide a range of estimates that can be considered by the risk manager. The data-requirements of the model are the incidence of a response at one or more levels of intake, and a suitable coefficient of variation to represent the person-to-person variations within the human population. A coefficient of variation of 10% or 15% has been used for established recommended dietary allowances and a value of 15% is proposed as default for considerations of benefit. A coefficient of variation of 45% is proposed as default for considerations of toxicity, based on analyses of human variability in the fate and effects of therapeutic drugs. Using this approach risk managers, working closely with risk assessors, will be able to define ranges of intake based on a balance between the risks of deficiency (or lack of benefit) and toxicity.

Animals↗
PubMed2003

The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo.

There is increasing evidence that chemicals/test substances cannot only have adverse effects, but that there are many substances that can (also) have a beneficial effect on health. As this journal regularly publishes papers in this area and has every intention in continuing to do so in the near future, it has become essential that studies reported in this journal reflect an adequate level of scientific scrutiny. Therefore a set of essential characteristics of studies has been defined. These basic requirements are default properties rather than non-negotiables: deviations are possible and useful, provided they can be justified on scientific grounds. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo concern the following areas: (1) Hypothesis-driven study design; (2) The nature of the test substance; (3) Valid and invalid test systems; (4) The selection of dose levels and gender; (5) Reversal of the effects induced by oxidants, carcinogens and mutagens; (6) Route of administration; (7) Number and validity of test variables; (8) Repeatability and reproducibility; (9) Statistics; and (10) Quality Assurance.

Animals↗
PubMed2001

Antimutagenic activity of green tea and black tea extracts studied in a dynamic in vitro gastrointestinal model.

An in vitro gastrointestinal model, which simulates the conditions in the human digestive tract, was used to determine potential antimutagenic activity of extracts of black tea and green tea. In this paper, results are presented on the availability for absorption of potential antimutagenic compounds present in tea and on the influence of the food matrix on this activity. Between 60 and 180min after the tea was introduced into the model, antimutagenic activity was recovered from the jejunal compartment by means of dialysis: the dialysate appeared to inhibit the mutagenicity of the food mutagen MeIQx in the direct plate assay with Salmonella typhimurium (Ames test). The maximum inhibition was measured at 2h after the start of the experiment and was comparable for black tea and green tea extract. To determine the influence of food matrices on the antimutagenic activity of tea, the model was loaded with black tea together with milk or a homogenized standard breakfast. The maximum inhibition observed with black tea was reduced by 22, 42 and 78% in the presence of whole milk, semi-skimmed milk, and skimmed milk, respectively. Whole milk and skimmed milk abolished the antimutagenic activity of green tea by more than 90%; for semi-skimmed milk the inhibition was more than 60%. When a homogenized breakfast was added into the model together with the black tea extract, the antimutagenic activity was completely eliminated. When tea and MeIQx were added together into the digestion model, MeIQx mutagenicity was efficiently inhibited, with green tea showing a slightly stronger antimutagenic activity than black tea. In this case, the addition of milk had only a small inhibiting effect on the antimutagenicity. Antioxidant capacity and the concentration of catechins were also measured in the jejunal dialysates. The reduction in antimutagenic activity corresponded with reduction in antioxidant capacity and with a decrease of concentration of three catechins, viz. catechin, epigallocatechin gallate and epigallocatechin. The in vitro gastrointestinal model appears to be a useful tool to study the antimutagenicity of food components.

Animals↗
PubMed2001

A critical assessment of some biomarker approaches linked with dietary intake.

In this review many examples are given of the complexities involved in using some biomarkers in relation to assessing the effects of dietary exposure, when there is frequently a need to determine changes following long-term low level exposure to dietary components. These range from understanding why the biomarker might be valuable and how best it can be measured, to the pitfalls which can occur in the interpretation of data. Analytical technique is considered in relation to folate and selenium, and flavonoid and carotenoid species are used to illustrate how the metabolism of a compound may alter the validity or adequacy of a marker. Vitamin A is discussed in relation to the difficulties which can arise when there are several biomarkers that may be available to assess exposure to one nutrient. Vitamin B12 is discussed in relation to the dietary choices made by individuals. Possible interactions and the role of measuring total antioxidant capacity is considered in some detail. In contrast to most nutrients, there is a marked lack of biomarkers of either exposure or effect for most non-nutrients. The role of biological effect monitoring is considered for dietary contaminants, fumonisins and polyhalogenated aromatic hydrocarbons. Aflatoxins are discussed to exemplify food contaminants for which the biomarker approach has been extensively studied. Finally some compounds which are deliberately added to foods and some which appear as processing contaminants are each considered briefly in relation to the requirement for a biomarker of exposure to be developed.

Aflatoxins↗
PubMed2001

Biomarkers in disease and health.

Biomarkers have considerable potential in aiding the understanding of the relationship between diet and disease or health. However, to assess the role, relevance and importance of biomarkers on a case by case basis it is essential to understand and prioritise the principal diet and health issues. In the majority of cases, dietary compounds are only weakly biologically active in the short term, have multiple targets and can be both beneficial and deleterious. This poses particular problems in determining the net effect of types of foods on health. In principle, a biomarker should be able to contribute to this debate by allowing the measurement of exposure and by acting as an indicator either of a deleterious or of an enhanced health effect prior to the final outcome. In this review, the examples chosen - cancer (stomach, colon/rectal, breast); coronary heart disease and osteoporosis - reflect three major diet-related disease issues. In each case the onset of the disease has a genetic determinant which may be exacerbated or delayed by diet. Perhaps the most important factor is that in each case the disease, once manifest, is difficult to influence in a positive way by diet alone. This then suggests that the emphasis for biomarker studies should focus on predictive biomarkers which can be used to help in the development of dietary strategies which will minimise the risk and be of greater benefit.

Biomarkers↗
PubMed2001

Biomonitoring the intake of garlic via urinary excretion of allyl mercapturic acid.

Allium vegetables (onions, leeks, chives) and in particular garlic have been claimed to have health-promoting potential. This study was conducted to get insight into the perspectives for monitoring the intake of garlic by a biomarker approach. Chemically, the biomarker results from exposure to gamma-glutamyl-S-allyl-l-cysteine, which is first hydrolysed by gamma-glutamine-transpeptidase resulting in the formation of S-allyl-l-cysteine. The latter compound is subsequently N-acetylated by N-acetyltransferase into S-allyl-mercapturic acid (ALMA) and excreted into urine. The mercapturic acid was measured in urine using gaschromatography with mass spectrometry. Thus the intake of garlic was determined to check the compliance of garlic intake in a placebo-controlled intervention study. Results indicate that S-allyl-mercapturic acid could be detected in 15 out of 16 urine samples of garlic supplement takers, indicating good compliance. In addition, the intake of garlic was also monitored in a cross-section study of vegans versus controls in Finland, in which no differences in garlic consumption nor in ALMA output were recorded between vegans and controls. These data indicate good possibilities for further studies in the field of biomarkers to investigate the putative chemopreventive effects of garlic and garlic-containing products.

Acetylcysteine↗
PubMed2000

Mediterranean diet of Crete: foods and nutrient content.

OBJECTIVES: To describe the traditional diet of Crete and evaluate the nutrient composition of 3 types of diet common in Crete by means of chemical analyses of composite food samples. To compare results with dietary analyses from a nutrient database developed at the University of Crete, Greece. DESIGN: Three composite diet samples were obtained based on 7-day weighed food records representing the traditional Cretan Mediterranean diet (diet A), typical diet of present-day Greek adolescents (diet B), and fasting diet of the Eastern Orthodox church (diet C). Analyses were performed chemically and using a nutrient database. RESULTS: Chemical analyses provided a definitive measure, for the first time, of the nutrient composition of the complete Greek diet as it was in the early 1960s. In comparing chemical analyses with nutrient database analyses, differences greater than 15% of the analyzed value were found in all 3 diets for cholesterol and some vitamins. The differences between analyzed and calculated values in total fat and saturated fat content were less than 15% in all diets. APPLICATIONS/CONCLUSIONS: The present study provides 2 practical examples of the Mediterranean diet, which although widely publicized has rarely been analyzed chemically. Diet A has been shown to be related to the lowest rates for coronary heart disease and cancer mortality compared with the diets of the other populations of the Seven Countries study. As such, it could be recommended for health promotion and prevention of disease. Diet C contains even lower amounts of saturated fatty acids and would be excellent for patients with hypercholesterolemia. The high antioxidants in diet C probably maintain very low levels of low-density lipoprotein cholesterol. Dietary analyses of the Greek diet could be based on an operational database such as ours if further chemical analyses are performed on specific foods. These would result in improved precision of the database and possible extension into national food composition tables and a national dietary database.

Adolescent↗
PubMed2000

Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands Cohort Study.

Both carcinogenic and anticarcinogenic properties have been reported for the synthetic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The association between dietary intake of BHA and BHT and stomach cancer risk was investigated in the Netherlands Cohort Study (NLCS) that started in 1986 among 120,852 men and women aged 55 to 69 years. A semi-quantitative food frequency questionnaire was used to assess food consumption. Information on BHA or BHT content of cooking fats, oils, mayonnaise and other creamy salad dressings and dried soups was obtained by chemical analysis, a Dutch database of food additives (ALBA) and the Dutch Compendium of Foods and Diet Products. After 6.3 years of follow-up, complete data on BHA and BHT intake of 192 incident stomach cancer cases and 2035 subcohort members were available for case-cohort analysis. Mean intake of BHA or BHT among subcohort members was 105 and 351 microg/day, respectively. For consumption of mayonnaise and other creamy salad dressings with BHA or BHT no association with stomach cancer risk was observed. A statistically non-significant decrease in stomach cancer risk was observed with increasing BHA and BHT intake [rate ratio (RR) highest/lowest intake of BHA = 0.57 (95% confidence interval (CI): 0.25-1.30] and BHT = 0.74 (95% CI: 0.38-1.43). In this study, no significant association with stomach cancer risk was found for usual intake of low levels of BHA and BHT.

Aged↗
PubMed2000

Application of a dynamic in vitro gastrointestinal tract model to study the availability of food mutagens, using heterocyclic aromatic amines as model compounds.

The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlled in vitro system that mimics the human physiological conditions in the stomach and small intestine. In the current TIM physiological parameters such as pH, temperature, peristaltic movements, secretion of digestion enzymes, bile and pancreatic juices, and absorption of digested products-by removal through dialysis-was simulated. Heterocyclic aromatic amines (HAA; viz. IQ, MeIQ, MeIQx and PhIP) were used as model compounds for food mutagens, and the passage through TIM was investigated for each of these compounds separately. Subsequently, the influence of a matrix and different rates of passage on the availability for absorption and distribution were studied in experiments with prepared meat, supplemented with MeIQx. Samples taken at various time points from the jejunal and ileal dialysates and from the lumen at the end of the small intestine (ileal delivery) were tested for the presence of mutagenic activity in the Ames test with Salmonella typhimurium strain TA98 as indicator, in the presence of mammalian metabolic activation (rat S9 mix). The results show that, comparable with the human in vivo situation, all four HAA are quickly removed (approx. 50% in 2 hr; approx. 95% in 6 hr) and mainly recovered from the lumen into the jejunal and ileal dialysates (94% of recovery). Only 5+/-1.5% is recovered in the chyme at the end of the small intestine. When MeIQx was added to meat, its availability for absorption was slower, although the influence of the gastrointestinal passage time on the availability of MeIQx was more pronounced than this matrix effect. More MeIQx was found in the jejunal dialysate (23%; P<0.01) and less in the ileal delivery (8%; P<0.01) when simulating the gastrointestinal passage of solid meals was compared to simulating that of liquid meals. The present experiments demonstrate that TIM can be applied to study in vitro the availability of heterocyclic aromatic amines in the gastrointestinal tract. More generally, these studies indicate that TIM shows promise as a useful tool for various research purposes dealing with the availability for absorption of mutagenic as well as antimutagenic components in food.

Biological Availability↗
PubMed2000

Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate.

BACKGROUND: Protein induces an increase in insulin concentrations when ingested in combination with carbohydrate. Increases in plasma insulin concentrations have been observed after the infusion of free amino acids. However, the insulinotropic properties of different amino acids or protein (hydrolysates) when co-ingested with carbohydrate have not been investigated. OBJECTIVE: The aim of this study was to define an amino acid and protein (hydrolysate) mixture with a maximal insulinotropic effect when co-ingested with carbohydrate. DESIGN: Eight healthy, nonobese male subjects visited our laboratory, after an overnight fast, on 10 occasions on which different beverage compositions were tested for 2 h. During those trials the subjects ingested 0.8 g*kg(-)(1)*h(-)(1) carbohydrate and 0.4 g*kg(-)(1)*h(-)(1) of an amino acid and protein (hydrolysate) mixture. RESULTS: A strong initial increase in plasma glucose and insulin concentrations was observed in all trials, after which large differences in insulin response between drinks became apparent. After we expressed the insulin response as area under the curve during the second hour, ingestion of the drinks containing free leucine, phenylalanine, and arginine and the drinks with free leucine, phenylalanine, and wheat protein hydrolysate were followed by the largest insulin response (101% and 103% greater, respectively, than with the carbohydrate-only drink; P < 0.05). CONCLUSIONS: Insulin responses are positively correlated with plasma leucine, phenylalanine, and tyrosine concentrations. A mixture of wheat protein hydrolysate, free leucine, phenylalanine, and carbohydrate can be applied as a nutritional supplement to strongly elevate insulin concentrations.

Adult↗
PubMed2000

Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans.

BACKGROUND: (-)-Hydroxycitrate (HCA), a competitive inhibitor of ATP-citrate lyase, should reduce the extramitochondrial acetyl-CoA pool. It has been hypothesized that HCA ingestion can reduce malonyl-CoA concentrations and consequently increase fatty acid oxidation in vivo. OBJECTIVE: This study investigated the acute effects of HCA supplementation on substrate utilization at rest and during exercise in endurance-trained humans. DESIGN: Ten cyclists [x+/- SD) age: 24 +/- 2 y, weight: 73 +/- 2 kg, maximal oxygen uptake: 4.95 +/- 0.11 L/min, maximal work output (W:max): 408 +/- 8 W] were studied at rest and during 2 h of exercise at 50% W:max on 2 occasions. Both 45 and 15 min before exercise and 30 and 60 min after the start of exercise, 3.1 mL/kg body wt of an HCA solution (19 g/L) or placebo was ingested. Total fat and carbohydrate oxidation rates were assessed. Blood samples were collected at 15-min intervals at rest and every 30 min during exercise. RESULTS: Plasma HCA concentrations increased after HCA ingestion up to 0.39 +/- 0.02 mmol/L (82.0 +/- 4.8 mg/L). However, no significant differences in total fat and carbohydrate oxidation rates were observed between trials. Accordingly, plasma glucose, glycerol, and fatty acid concentrations did not differ between trials. Plasma lactate concentrations were significantly lower in the HCA than in the placebo trial after 30 min of exercise but at the end of the exercise period they did not differ between trials. CONCLUSION: HCA, even when provided in large quantities, does not increase total fat oxidation in vivo in endurance-trained humans.

Adult↗
PubMed2000

Ingestion of protein hydrolysate and amino acid-carbohydrate mixtures increases postexercise plasma insulin responses in men.

To optimize the postexercise insulin response and to increase plasma amino acid availability, we studied postexercise insulin levels after the ingestion of carbohydrate and wheat protein hydrolysate with and without free leucine and phenylalanine. After an overnight fast, eight male cyclists visited our laboratory on five occasions, during which a control drink and two different beverage compositions in two different doses were tested. After they performed a glycogen-depletion protocol, subjects received a beverage (3.5 mL. kg(-1)) every 30 min to ensure an intake of 1.2 g. kg(-1). h(-1) carbohydrate and 0, 0.2 or 0.4 g. kg(-1). h(-1) protein hydrolysate (and amino acid) mixture. After the insulin response was expressed as the area under the curve, only the ingestion of the beverages containing wheat protein hydrolysate, leucine and phenylalanine resulted in a marked increase in insulin response (+52 and + 107% for the 0.2 and 0.4 g. kg(-1). h(-1) mixtures, respectively; P: < 0. 05) compared with the carbohydrate-only trial). A dose-related effect existed because doubling the dose (0.2-0.4 g. kg(-1). h(-1)) led to an additional rise in insulin response (P: < 0.05). Plasma leucine, phenylalanine and tyrosine concentrations showed strong correlations with the insulin response (P: < 0.0001). This study provides a practical tool to markedly elevate insulin levels and plasma amino acid availability through dietary manipulation, which may be of great value in clinical nutrition, (recovery) sports drinks and metabolic research.

Adult↗
PubMed2000

Fruits and vegetables increase plasma carotenoids and vitamins and decrease homocysteine in humans.

Observational epidemiologic studies have shown that a high consumption of fruits and vegetables is associated with a decreased risk of chronic diseases. Little is known about the bioavailability of constituents from vegetables and fruits and the effect of these constituents on markers for disease risk. Currently, the recommendation is to increase intake of a mix of fruits and vegetables ("five a day"). We investigated the effect of this recommendation on plasma carotenoids, vitamins and homocysteine concentrations in a 4-wk dietary controlled, parallel intervention study. Male and female volunteers (n = 47) were allocated randomly to either a daily 500-g fruit and vegetable ("high") diet or a 100-g fruit and vegetable ("low") diet. Analyzed total carotenoid, vitamin C and folate concentrations of the daily high diet were 13.3 mg, 173 mg and 228.1 microg, respectively. The daily low diet contained 2.9 mg carotenoids, 65 mg vitamin C and 131.1 microg folate. Differences in final plasma levels between the high and low group were as follows: lutein, 46% [95% confidence interval (CI) 28-64]; beta-cryptoxanthin, 128% (98-159); lycopene, 22% (8-37); alpha-carotene, 121% (94-149); beta-carotene, 45% (28-62); and vitamin C, 64% (51-77) (P < 0.05). The high group had an 11% (-18 to -4) lower final plasma homocysteine and a 15% (0.8-30) higher plasma folate concentration compared with the low group (P < 0.05). This is the first trial to show that a mix of fruits and vegetables, with a moderate folate content, decreases plasma homocysteine concentrations in humans.

Adult↗
PubMed1999

In vitro and in vivo inhibition of human flavin-containing monooxygenase form 3 (FMO3) in the presence of dietary indoles.

The effect of consumption of glucosinolate-containing Brussels sprouts on flavin-containing monooxygenase functional activity in humans was investigated in 10 healthy, male, non-smoking volunteers. After a 3-week run-in period, 5 volunteers continued on a glucosinolate-free diet for 3 weeks (control group), and 5 others consumed 300 g of cooked Brussels sprouts per day (sprouts group). Human flavin-containing monooxygenase activity was measured by determining the levels of urinary trimethylamine and trimethylamine N-oxide. In the control group similar trimethylamine to trimethylamine N-oxide ratios were observed, while in the sprouts group the trimethylamine to trimethylamine N-oxide ratios were increased 2.6- to 3.2-fold, and thus flavin-containing monooxygenase functional activity was decreased significantly. To investigate the molecular basis for the in vivo inhibition of functional human flavin-containing monooxygenase activity, in vitro studies were carried out examining the effect of acid condensation products of indole-3-carbinol, anticipated to be formed after transit of Brussels sprouts through the gastrointestinal system, on the prominent cDNA-expressed human flavin-containing monooxygenase form 3 enzymes. Two indole-containing materials were observed to be potent inhibitors of human flavin-containing monooxygenases, having Ki values in the low micromolar range. The results suggested that acid condensation products expected to be formed upon transit of Brussels sprouts materials through the gastrointestinal system were potent competitive inhibitors of human flavin-containing monooxygenase form 3 enzymes. The findings indicate that daily intake of Brussels sprouts may lead to a decrease in human flavin-containing monooxygenase activity, and this may have consequences for metabolism of other xenobiotics or dietary constituents.

Adult↗
PubMed1999

The role of biotransformation in dietary (anti)carcinogenesis.

The fact that dietary compounds influence the susceptibility of human beings to cancer, is widely accepted. One of the possible mechanisms that is responsible for these (anti)carcinogenic effects is that dietary constituents may modulate biotransformation enzymes, thereby affecting the (anti)carcinogenic potential of other compounds. This ambiguous theme is the basis for the present paper. The possible effects of enzymatic bioactivation and detoxification of dietary constituents are discussed using two representative examples of phase I and phase II biotransformation enzymes i.e., cytochrome P450 and glutathione S-transferase. Furthermore, the impact of genetic polymorphisms of these two enzyme systems is considered. Although it is very difficult on the basis of the enzyme inducing or inhibiting properties of dietary compounds, especially to characterize them as anticarcinogenic, for certain constituents it is acknowledged that they have anticarcinogenic properties. As such, this provides for an important mechanistic substantiation of the established cancer chemopreventive effect of a diet rich in fruits and vegetables.

Biotransformation↗