Discovery of urinary biomarkers of seaweed intake using untargeted lc–ms metabolomics in a three-way cross-over human study

Seaweeds are a marine source rich in potentially bioactive components, and therefore have attracted attention since the middle of the twentieth century. Accurate and objective assessment of the intake of seaweeds to study their health effects is hampered by a lack of validated intake biomarkers. In this three-armed, randomized, cross-over study, an untargeted metabolomics approach was applied for discovering novel intake biomarkers. Twenty healthy participants (9 men and 11 women) were provided each of three test meals in a randomized order: 5 g of Laminaria digitate (LD), 5 g of Undaria pinnatifida (UP), or a control meal with energy-adjusted pea protein. Four urine samples and a 24 h pooled urine were collected along with blood samples at seven time-points. All samples were profiled by LC-ESI-QTOF-MS and the data were analyzed by univariate analysis and excretion kinetics to select putative intake biomarkers. In total, four intake biomarkers were selected from urine samples. They were identified as hydroxyl-dihydrocoumarin at Level III, loliolid glucuronide at level I, and isololiolid glucuronide at level II, while the last one remains unknown. Further identification and validation of these biomarkers by a cross-sectional study is essential to assess their specificity and robustness

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins

Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet

Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease and cancer. The objective of the present study was to investigate the effect of green tea extract (GTE) used as a food antioxidant on markers of oxidative status after dietary depletion of flavonoids and catechins. The study was designed as a 2×3 weeks blinded human cross-over intervention study (eight smokers, eight non-smokers) with GTE corresponding to a daily intake of 18·6 mg catechins/d. The GTE was incorporated into meat patties and consumed with a strictly controlled diet otherwise low in flavonoids. GTE intervention increased plasma antioxidant capacity from 1·35 to 1·56 (P<0·02) in postprandially collected plasma, most prominently in smokers. The intervention did not significantly affect markers in fasting blood samples, including plasma or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the erythrocyte superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase. Neither were fasting plasma triacylglycerol, cholesterol, α-tocopherol, retinol, β-carotene, or ascorbic acid affected by intervention. Urinary 8-oxo-deoxyguanosine excretion was also unaffected. Catechins from the extract were excreted into urine with a half-life of less than 2 h in accordance with the short-term effects on plasma antioxidant capacity. Since no long-term effects of GTE were observed, the study essentially served as a fruit and vegetables depletion study. The overall effect of the 10-week period without dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood proteins, and plasma lipids, concomitantly with marked changes in antioxidative defenc

Combining traditional dietary assessment methods with novel metabolomics techniques: present efforts by the Food Biomarker Alliance

FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health. Keywords: Dietary assessment; Food intake biomarkers; Food metabolome; Metabolomics

Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation

Background-In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Methods and Results-Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. Conclusions-Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD even