Lars O. Dragsted

The food metabolome: a window over dietary exposure

The food metabolome is defined as the part of the human metabolome directly derived from the digestion and biotransformation of foods and their constituents. With >25,000 compounds known in various foods, the food metabolome is extremely complex, with a composition varying widely according to the diet. By its very nature it represents a considerable and still largely unexploited source of novel dietary biomarkers that could be used to measure dietary exposures with a high level of detail and precision. Most dietary biomarkers currently have been identified on the basis of our knowledge of food compositions by using hypothesis-driven approaches. However, the rapid development of metabolomics resulting from the development of highly sensitive modern analytic instruments, the availability of metabolite databases, and progress in (bio)informatics has made agnostic approaches more attractive as shown by the recent identification of novel biomarkers of intakes for fruit, vegetables, beverages, meats, or complex diets. Moreover, examples also show how the scrutiny of the food metabolome can lead to the discovery of bioactive molecules and dietary factors associated with diseases. However, researchers still face hurdles, which slow progress and need to be resolved to bring this emerging field of research to maturity. These limits were discussed during the First International Workshop on the Food Metabolome held in Glasgow. Key recommendations made during the workshop included more coordination of efforts; development of new databases, software tools, and chemical libraries for the food metabolome; and shared repositories of metabolomic data. Once achieved, major progress can be expected toward a better understanding of the complex interactions between diet and human health.

Effect of parsley ( Petroselinum crispum ) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects

Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly controlled diet low in flavones and other naturally occurring antioxidants during the 2 weeks of intervention. This basic diet was supplemented with parsley providing 3.73-4.49 mg apigenin/MJ in one of the intervention weeks. Urinary excretion of apigenin was 1.59-409.09 micrograms/MJ per 24 h during intervention with parsley and 0-112.27 micrograms/MJ per 24 h on the basic diet (P < 0.05). The fraction of apigenin intake excreted in the urine was 0.58 (SE 0.16)% during parsley intervention. Erythrocyte glutathione reductase (EC 1.6.4.1; GR) and superoxide dismutase (EC 1.15.1.1; SOD) activities increased during intervention with parsley (P < 0.005) as compared with the levels on the basic diet, whereas erythrocyte catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9) activities did not change. No significant changes were observed in plasma protein 2-adipic semialdehyde residues, a biomarker of plasma protein oxidation. In this short-term investigation, an overall decreasing trend in the activity of antioxidant enzymes was observed during the 2-week study. The decreased activity of SOD was strongly correlated at the individual level with an increased oxidative damage to plasma proteins. However, the intervention with parsley seemed, partly, to overcome this decrease and resulted in increased levels of GR and SOD.

Bioactive compounds: definition and assessment of activity.

Biomarkers and their role in evaluating efficacy and safety were the topic of the 23rd Hohenheim Consensus Meeting at the University of Hohenheim in Stuttgart. Scientists who had published and reviewed scientific and regulatory papers on the topic were invited, among them basic researchers, toxicologists, clinicians, and nutritionists. The participants were presented with 11 questions (in bold font), which were discussed and answered (in italic font) at the workshop, with the aim of summarizing the current state of knowledge on the subject. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome – a randomized study (SYSDIET)

Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome.

Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes in female rat.

1. Gavage administration of the natural flavonoids tangeretin, chrysin, apigenin, naringenin, genistein and quercetin for 2 consecutive weeks to the female rat resulted in differential effects on selected phase 1 and 2 enzymes in liver, colon and heart as well as antioxidant enzymes in red blood cells (RBC). 2. Glutathione transferase (GST) activity assayed by use of the substrate 1-chloro-2,4- dinitrobenzene was significantly induced by apigenin, genistein and tangeretin in the heart but not in colon or liver. 3. In RBC chrysin, quercetin and genistein significantly decreased the activity of glutathione reductase (GR), catalase (CAT) and glutathione peroxidase (GPx), whereas superoxide dismutase (SOD) was only significantly decreased by genistein. 4. The oxidative status of the animal, measured as plasma malondialdehyde, revealed that chrysin, quercetin, genistein, and beta-naphthoflavone (BNF) significantly protected against, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP)-induced oxidative stre...

Two-electron electrochemical oxidation of quercetin and kaempferol changes only the flavonoid C-ring

Bulk electrolysis of the antioxidant flavonoids quercetin and kaempferol in acetonitrile both yield a single oxidation product in two-electron processes. The oxidation products are more polar than their parent compounds, with an increased molecular weight of 16g/mol, and were identified as 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone and 2-(4-hydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone for quercetin and kaempferol, respectively. Two-electron oxidation of the parent flavonoid is suggested to yield a 3,4-flavandione with unchanged substitution pattern in the A- and B-ring, which may rearrange to form the substituted 3(2H)-benzofuranone through the chalcan-trione ring-chain tautomer. The acidity of the 3-OH group is suggested to determine the fate of the flavonoid phenoxyl radical, originally formed by one-electron oxidation, as no well-defined oxidation product of luteolin (lacking the 3-OH group) could be isolated despite rather similar half-peak potentials: Ep/2 = 0.97V, 0.98 V and 1.17 V vs. NHE for quercetin, kaempferol and luteolin, respectively, as measured by cyclic voltammetry in acetonitrile.

Regeneration of phenolic antioxidants from phenoxyl radicals: An ESR and electrochemical study of antioxidant hierarchy

Radicals from the flavonoids quercetin, (+)-catechin, (+/-)-taxifolin and luteolin, and from all-rac-alpha-tocopherol have been generated electrochemically by one-electron oxidation in deaerated dimethylformamide (DMF), and characterised by electron spin resonance spectroscopy (ESR) after spin-trapping by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Simulations of the ESR spectrum based on estimated coupling constants of the spin-trapped quercetin radical, confirmed that this antioxidant radical is oxygen-centered. The complex mixture of radicals, quinoid intermediates and stable two-electron oxidation products, were for each antioxidant allowed to react with each of the four other antioxidants, and the progression of reaction followed by ESR after addition of DMPO, and the product solution further analysed by HPLC. All-rac-alpha-tocopherol was found to be most efficient in regenerating each of the other antioxidants from their oxidation products with a regeneration index (defined as moles regenerated of the oxidised phenolic antioxidant divided with moles of all-rac-alpha-tocopherol consumed) of 0.90+/-0.16 for quercetin, 0.48+/-0.11 for (+)-catechin, 0.48+/-0.06 for (+/-)-taxifolin and 0.50+/-0.10 for luteolin in equimolar 1.00 mM solution. Quercetin was found to have the highest regeneration index among the flavonoids: 0.88+/-0.13 for (+/-)-catechin, 0.41+/-0.03 for (+/-)-taxifolin and 0.41+/-0.02 for luteolin. The antioxidant hierarchy based on the reduction potentials determined by cyclic voltammetry under similar conditions (0.93 V for all-rac-alpha-tocopherol, 1.07 V for quercetin, 1.15 V for luteolin, 1.16V for (+)-catechin and 1.20 V for (+/-)-taxifolin) is compared with the observed over-all regeneration (34% for quercetin, 34% for (+)-catechin, 52% for (+/-)-taxifolin and 43% for luteolin by all-rac-alpha-tocopherol).

Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease

Objective:Some epidemiological studies found a lower risk of cardiovascular disease among wine drinkers than among drinkers of other types of ethanol. This difference might be due to an effect of nonalcohol compounds in wine on important cardiovascular risk factors. The objective of this study was to compare the effect of red wine, nonalcohol compounds of red wine and placebo on established cardiovascular risk factors.Design:A parallel, four-armed intervention study.Subjects:A total of 69 healthy 38–74-y-old men and women.Interventions:Subjects were randomised to either 1: red wine (males: 300 ml/day, 38.3 g alcohol/day, female subjects: 200 ml/day, 25.5 g alcohol/day), 2: water+red grape extract tablets (wine-equivalent dose), 3: water+red grape extract tablets (half dose), or 4: water+placebo tablets for a period of 4 weeks. No other sources of alcohol or anthocyanin were allowed. Plasma high-density lipoprotein (HDL)-cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C), HDL-C/LDL-C-ratio, very-low-density lipoprotein (VLDL)-triacylglycerol, total cholesterol, fibrinogen, factor VII coagulant activity (FVIIc), blood pressure, and body weight were determined before and after intervention.Results:Wine consumption was associated with a significant 11–16% increase in fasting HDL-C and 8–15% decrease in fasting fibrinogen relative to not drinking wine. There were no significant treatment effects on fasting LDL-C, HDL-C/LDL-C-ratio, VLDL-triacylglycerol, total cholesterol, FVIIc, or blood pressure. Drinking wine was associated with relative body weight increments closely corresponding to the energy contributed by the alcohol component.Conclusion:Moderate red wine consumption for 4 weeks is associated with desirable changes in HDL-C and fibrinogen compared with drinking water with or without red grape extract. The impact of wine on the measured cardiovascular risk factors thus seems primarily explained by an alcohol effect. Our finding suggests that the putative difference in cardiac risk associated with wine vs other alcoholic beverages might be rather explained by other life-style confounders than by red wine contents of nonalcohol components.Sponsorship:This study was supported by Chr. Hansen A/S, Denmark.

Guidelines for the New Nordic Diet.

OBJECTIVE Diet has a significant impact on health, and ensuring that the population eats a healthy diet remains a public health challenge. Research is needed in order to improve the palatability of a healthy diet and make it attractive to the consumer. It has also been suggested that dietary recommendations should be tailored to regional conditions. The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) project investigates whether it is possible to develop a healthy New Nordic Diet (NND) that is palatable, environmentally friendly and based on foods originating from the Nordic region. The present paper describes the overall guidelines for the NND, developed and investigated in the multidisciplinary, 5-year OPUS research project. All guidelines are described in relation to the key principles: health, gastronomic potential and Nordic identity, and sustainability. RESULTS The NND is described by the overall guidelines: (i) more calories from plant foods and fewer from meat; (ii) more foods from the sea and lakes; and (iii) more foods from the wild countryside. These overall guidelines result in a set of proposed dietary components which will be presented in a subsequent paper. CONCLUSIONS Both the guidelines and the diet are composed taking the potential health-promoting properties and Nordic identity of the NND into account, as well as concern for environmental issues and gastronomic potential.

Cancer risk and occupational exposure to aflatoxins in Denmark.

A study of cancer risk among male employees at 241 livestock feed processing companies in Denmark was conducted on the basis of a data linkage system for detailed investigation of occupational cancer providing employment histories back until 1964, established at the Danish Cancer Registry. Crops imported for feed production have often been contaminated with highly variable concentrations of aflatoxins; an estimated average concentration of at least 140 micrograms aflatoxin B1 kg-1 prepared mixed cattle feed prevailed in the past, yielding a daily intake for workers via the respiratory route of approximately 170 ng. Risk was established on the basis of cancer cases among male workers, whose employment in one of the companies was the job they had held for the longest time since 1964. Elevated risks for liver cancer and for cancers of the biliary tract were observed, which increased by two- to three-fold significance after a 10-year latency. Exposure to aflatoxins in the imported crops was judged to be the most probable explanation for these findings, although the influence of lifestyle factors, e.g. alcohol consumption on the results cannot be fully disregarded. Increased risks for salivary gland tumours and multiple myeloma were also detected. However, due to multiple comparisons carried out in this study these new associations must await further confirmation. A decreased risk for lung cancer was observed; despite possible negative confounding due to the smoking habits of the employees, the lung does not seem to be a target organ for the carcinogenic effect of inhaled aflatoxins in humans.