The food metabolome: a window over dietary exposure

In the paper

“Information on these biomarkers has been systematically collected in the novel Exposome-Explorer database (V Neveu, DS Wishart, and A Scalbert, unpublished data, 2014); w100 biomarkers could be identified”

What the sources say

• Not checked yetcites V Neveu, DS Wishart, and A Scalbert, unpublished data, 2014

In the paper

“With the exception of 2 studies on dietary fiber and milk protein diet, all discovery studies were conducted on urine samples as opposed to blood samples (Table 3).”

In the paper

“alkylresorcinols for whole-grain cereals (19,20)”

What the sources say

• Not checked yetcites [19] Ross, 2012, Plasma alkylresorcinols as a biomarker of whole-grain food consumption in a large population: results from the WHOLEheart Intervention Study, Am J Clin Nutr source
• Not checked yetcites [20] Andersson, 2011, Plasma alkylresorcinol concentrations correlate with whole grain wheat and rye intake and show moderate reproducibility over a 2-to 3-month period in free-living Swedish adults, J Nutr source

In the paper

“Dietary exposure has traditionally been measured with self-reported methods, namely dietary recalls or food-frequency questionnaires (10).”

What the sources say

• Not checked yetcites [10] Rutishauser, 2005, Dietary intake measurements, Public Health Nutr source

In the paper

“Biomarkers are also useful when little or no data exist on food composition, as is often the case for bioactive molecules such as glucosinolates or food contaminants such as aflatoxins (15,16).”

What the sources say

• Not checked yetcites [15] London, 2000, Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China, Lancet source
• Not checked yetcites [16] Kensler, 2011, Aflatoxin: a 50-year odyssey of mechanistic and translational toxicology, Toxicol Sci source

In the paper

“The application of dietary biomarkers as more objective measures of dietary exposure in nutritional epidemiology has been particularly significant (13).”

What the sources say

• Not checked yetcites [13] Jenab, 2009, Biomarkers in nutritional epidemiology: applications, needs and new horizons, Hum Genet source

In the paper

“polyphenols, carotenoids, and vitamin C for fruit and vegetables (17,18)”

What the sources say

• Not checked yetcites [17] Baldrick, 2011, Biomarkers of fruit and vegetable intake in human intervention studies: a systematic review, Crit Rev Food Sci Nutr source
• Not checked yetcites [18] Mennen, 2006, Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods, Br J Nutr source

In the paper

“These biomarkers may thus be useful only in populations who regularly and frequently consume these dietary sources.”

In the paper

“serotonin metabolism is altered by acute alcohol intake (28)”

What the sources say

• Not checked yetcites [28] Kroke, 2001, Comparison of self-reported alcohol intake with the urinary excretion of 5-hydroxytryptophol: 5-hydroxyindole-3-acetic acid, a biomarker of recent alcohol intake, Br J Nutr source

In the paper

“the activity of selenium-containing enzymes such as erythrocyte glutathione peroxidase depends on selenium intake”

What the sources say

• Not checked yetcites [29] Crews, 2001, A critical assessment of some biomarker approaches linked with dietary intake, Br J Nutr source

In the paper

“amino acids and fatty acids for meat (22,23)”

What the sources say

• Not checked yetcites [22] Allen, 2008, Phytanic acid: measurement of plasma concentrations by gas-liquid chromatography-mass spectrometry analysis and associations with diet and other plasma fatty acids, Br J Nutr source
• Not checked yetcites [23] Myint, 2000, Urinary 1-methylhistidine is a marker of meat consumption in black and in white California Seventh-day Adventists, Am J Epidemiol source

In the paper

“polyphenols for tea and wine (18,25)”

What the sources say

• Not checked yetcites [18] Mennen, 2006, Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods, Br J Nutr source
• Not checked yetcites [25] Hodgson, 2004, Phenolic acid metabolites as biomarkers for tea- and coffee-derived polyphenol exposure in human subjects, Br J Nutr source

In the paper

“In contrast to these global assays, analytic approaches based on the estimation of combinations of dietary constituents may provide more accurate measurements of dietary exposure.”

In the paper

“ceramide synthase is inhibited by exposure to the mycotoxin fumonisins (29).”

What the sources say

• Not checked yetcites [29] Crews, 2001, A critical assessment of some biomarker approaches linked with dietary intake, Br J Nutr source

In the paper

“Vitamin C or the sum of carotenoids or flavonoids have been used as generic biomarkers for fruit and vegetable intake (18,45).”

What the sources say

• Not checked yetcites [18] Mennen, 2006, Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods, Br J Nutr source
• Not checked yetcites [45] Al-Delaimy, 2005, Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC), Eur J Clin Nutr source

In the paper

“Intraindividual variability leads to exposure measurement errors when the objective is to characterize habitual exposure in epidemiologic studies and small numbers of measurements are available across subjects.”

In the paper

“The ratios of 2 alkylresorcinols characteristic of whole-grain wheat or rye were found to be good indicators of the relative consumption of these cereals (20,48).”

What the sources say

• Not checked yetcites [20] Andersson, 2011, Plasma alkylresorcinol concentrations correlate with whole grain wheat and rye intake and show moderate reproducibility over a 2-to 3-month period in free-living Swedish adults, J Nutr source
• Not checked yetcites [48] Ross, 2003, Alkylresorcinols in cereals and cereal products, J Agric Food Chem source

In the paper

“However, a large majority of the metabolites produced by the gut microbiota are derived from the biotransformation of both the endogenous metabolome and the food metabolome and are therefore an integral part of these 2 metabolomes.”

In the paper

“isoflavones for soy (21)”

What the sources say

• Not checked yetcites [21] Verkasalo, 2001, Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition), Br J Nutr source

In the paper

“The gut microbiota is particularly adept at processing polyphenols to phenolic breakdown products.”

In the paper

“However, there are very few such examples in which combinations of biomarkers were used to improve the specificity of dietary exposure measurements.”

In the paper

“The importance of the gut microbiota in contributing metabolites to the human metabolome has also recently emerged (50,66).”

What the sources say

• Not checked yetcites [50] van der Werf, 2007, Microbial metabolomics: toward a platform with full metabolome coverage, Anal Biochem source
• Not checked yetcites [66] Guo, 2013, ECMDB: the E-coli Metabolome Database, Nucleic Acids Res source

In the paper

“Consequently, these exogenously derived metabolites can be quite useful as specific food biomarkers.”

In the paper

“For polyphenols, .230phase I/II metabolites have been identified and associated with the consumption of specific polyphenol-containing foods (70).”

What the sources say

• Not checked yetcites [70] Rothwell, 2012, Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals, Database source

In the paper

“fatty acids for dairy products and fish (22,24)”

What the sources say

• Not checked yetcites [22] Allen, 2008, Phytanic acid: measurement of plasma concentrations by gas-liquid chromatography-mass spectrometry analysis and associations with diet and other plasma fatty acids, Br J Nutr source
• Not checked yetcites [24] Arsenault, 2009, Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia, Am J Epidemiol source

In the paper

“A recent meta-analysis (68) of the metabolic fate of .1000xenobiotics showed that cytochrome P450 catalyzed oxidations (40%) and UDP-glucuronosyltransferase glucuronidations (14%) were the most common followed by reactions involving dehydrogenases (8%), hydrolases (7%), glutathione-S-transferases (6%), and sulfatases (5%).”

What the sources say

• Not checked yetcites [68] Testa, 2012, Foundation review: reactions and enzymes in the metabolism of drugs and other xenobiotics, Drug Discov Today source

In the paper

“Metabolomics constitutes a comprehensive approach to identify new panels of biomarkers that are specific or common to particular foods or food groups, as shown recently for citrus fruit (49).”

What the sources say

• Not checked yetcites [49] Pujos-Guillot, 2013, Mass spectrometry-based metabolomics for the discovery of biomarkers of fruit and vegetable intake: citrus fruit as a case study, J Proteome Res source

In the paper

“As previously described, the identification of candidate dietary biomarkers is complicated by the fact that the majority of food compounds are treated as xenobiotics by the human body in phase I and phase II reactions or undergo fermentation in the colon by the gut microbiota (139).”

What the sources say

• Not checked yetcites [139] Del Rio, 2013, Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases, Antioxid Redox Signal source

In the paper

“All available software tools differ in their peak picking algorithms.”

In the paper

“For this reason, it is often difficult to evaluate the degree of confidence in biomarker identification.”

In the paper

“It is essentially impossible to use standards or isotopically labeled references to quantify the thousands of compounds in the food metabolome.”

In the paper

“However, the combination of available targeted analysis methods is still far from covering the whole chemical space of the food metabolome.”

In the paper

“For instance, depending on the predominant microbiota, polyphenols can be transformed by ring cleavage to a variety of aromatic compounds such as benzoate and various derivatives of hydroxyphenylacetic and hydroxypropionic acids.”

In the paper

“Despite some increase in their availability over the past few years, these highly diverse metabolites are largely absent from most databases.”

In the paper

“However, because of its sensitivity and breadth of coverage, LC-MS has certainly become the method of choice for untargeted analysis of the food metabolome.”

In the paper

“Analyzing the food metabolome is a particularly challenging task for 3 reasons.”

In the paper

“As is the case for the other parts of the metabolome, mass spectrometry (MS) coupled with gas chromatography or liquid chromatography and NMR are currently the most widely used technologies for food metabolome analysis (Table 3).”

What the sources say

• Not checked yetcites Table 3

In the paper

“The lack of a gap-filling algorithm creates major problems for normalization and for statistical analysis.”

In the paper

“These advances may allow researchers to target larger areas of the food metabolome chemical space with the use of standardized quantitative methods.”

In the paper

“Furthermore, chain length and degree of saturation of fatty acids in glycerophosphatidylcholines were associated with intake of specific foods or nutrients such as fish and dietary fiber.”

What the sources say

• Not checked yetcites [109] Altmaier, 2011, Questionnaire-based self-reported nutrition habits associate with serum metabolism as revealed by quantitative targeted metabolomics, Eur J Epidemiol source

In the paper

“There is only a 50-70% overlap between the peaks detected by different packages from the same raw data set, even with similar settings (125).”

What the sources say

• Not checked yetcites [125] Gürdeniz, 2012, The effect of LC-MS data preprocessing methods on the selection of plasma biomarkers in fed vs. fasted rats, Metabolites source

In the paper

“This technique has been successful in detecting compounds such as terpene metabolites, diketopiperazine metabolites, phenylvalerolactones, and benzoxazinoid metabolites, which are interesting candidate biomarkers of food intake that would not be easily detected in biofluids by NMR or GC-MS (49,86,96).”

What the sources say

• Not checked yetcites [49] Pujos-Guillot, 2013, Mass spectrometry-based metabolomics for the discovery of biomarkers of fruit and vegetable intake: citrus fruit as a case study, J Proteome Res source
• Not checked yetcites [86] Bondia-Pons, 2013, UPLC-QTOF/MS metabolic profiling unveils urinary changes in humans after a whole grain rye versus refined wheat bread intervention, Mol Nutr Food Res source
• Not checked yetcites [96] Llorach, 2009, An LC-MS-based metabolomics approach for exploring urinary metabolome modifications after cocoa consumption, J Proteome Res source

In the paper

“No single chromatographic method is able to cover the wide range of polarity existing for the food metabolome compounds.”

In the paper

“Both 24-h dietary recalls and food-frequency questionnaires have been used, and new biomarkers for citrus fruit intake or coffee were successfully identified (49, 88) (Table 3).”

What the sources say

• Not checked yetcites [49] Pujos-Guillot, 2013, Mass spectrometry-based metabolomics for the discovery of biomarkers of fruit and vegetable intake: citrus fruit as a case study, J Proteome Res source
• Not checked yetcites [88] Lang, 2011, Urinary N-methylpyridinium and trigonelline as candidate dietary biomarkers of coffee consumption, Mol Nutr Food Res source

In the paper

“New approaches are being developed with isotope labeling and multiple reaction monitoring-based profiling for families of compounds sharing distinctive chemical functionalities (118).”

What the sources say

• Not checked yetcites [118] Guo, 2012, Liquid chromatography-mass spectrometric multiple reaction monitoring-based strategies for expanding targeted profiling towards quantitative metabolomics, Curr Drug Metab source

In the paper

“However, the chances to identify robust biomarkers will rely both on the sensitivity of the analytic equipment used and on the quality of the dietary data against which metabolic profiles are correlated.”

In the paper

“Also, lipophilic biomarkers, which may be more stable over time (see Pharmacokinetics and reliability of dietary biomarkers section), are more likely to be found in blood.”

In the paper

“Consequently, weaker correlations with intakes of foods or of their constituents were observed for microbial metabolites when compared with untransformed food compounds and host-transformed metabolites (41).”

What the sources say

• Not checked yetcites [41] Pérez-Jiménez, 2010, Urinary metabolites as biomarkers of polyphenol intake in humans—a systematic review, Am J Clin Nutr source

In the paper

“In addition, no standard yet exists to report chemical identification of biomarkers in metabolomic studies (110).”

What the sources say

• Not checked yetcites [110] Sumner, 2007, Proposed minimum reporting standards for chemical analysis, Metabolomics source

In the paper

“However, the vast majority of the food metabolome components are not yet represented in these databases, which makes the elucidation of their structure difficult.”

In the paper

“Rapid advances in technology have led to a new generation of much more efficient time-of-flight and single-stage Orbitrap (Exactive; Thermo Scientific) instruments, offering improved linearity, resolution, and mass accuracy, which will be critically important for the analysis of the food metabolome (115).”

What the sources say

• Not checked yetcites [115] He, 2012, Ultra-sensitive measurements of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid in oral fluid by microflow liquid chromatography-tandem mass spectrometry using a benchtop quadrupole/Orbitrap mass spectrometer, Anal Chem source

In the paper

“No standardized method exists yet, and the need for improved harmonization is certainly desirable for further progress on the food metabolome.”

In the paper

“Sparse PCA overcomes this limitation (128, 129).”

What the sources say

• Not checked yetcites [128] Acar, 2012, Coupled matrix factorization with sparse factors to identify potential biomarkers in metabolomics, Int J Knowledge Discov Bioinformatics source
• Not checked yetcites [129] Gürdeniz, 2013, Patterns of time since last meal revealed by sparse PCA in an observational LC-MS based metabolomics study, Metabolomics source

In the paper

“Regression analyses of the concentrations of 363 metabolites in plasma with a number of dietary variables measured with a food-frequency questionnaire showed the highest correlations with phospholipid concentrations (109).”

What the sources say

• Not checked yetcites [109] Altmaier, 2011, Questionnaire-based self-reported nutrition habits associate with serum metabolism as revealed by quantitative targeted metabolomics, Eur J Epidemiol source

In the paper

“Although these compounds may actually contribute to the health effects of the food, as has been well demonstrated in intervention studies in which a whole food has been compared with one of its bioactive constituents (177)”

What the sources say

• Not checked yetcites [177] Morand, 2011, Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers, Am J Clin Nutr source

In the paper

“hippurate has been associated with microbiota colonization of the gut (170).”

What the sources say

• Not checked yetcites [170] Nicholson, 2005, Gut microorganisms, mammalian metabolism and personalized health care, Nat Rev Microbiol source

In the paper

“In their initial untargeted LC-MS/MS investigation (171), the authors showed that the nutrient choline, along with its major metabolites, betaine and TMAO, were associated with risks of cardiovascular disease, particularly TMAO.”

What the sources say

• Not checked yetcites [171] Wang, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature source

In the paper

“The agnostic nature of the untargeted design allows all potentially useful biomarkers to be identified, including not only dietary biomarkers but also those related to endogenous factors (including the microbiota), pollution, and drugs as well as biomarkers of disease progression.”

In the paper

“MWASs have been proposed as useful tools for discovering low-molecular-weight biomarkers that are predictive of either causal exposures or disease progression (59, 165, 166).”

What the sources say

• Not checked yetcites [59] Holmes, 2008, Human metabolic phenotype diversity and its association with diet and blood pressure, Nature source
• Not checked yetcites [165] Nicholson, 2008, The Metabolome-Wide Association Study: a new look at human disease risk factors, J Proteome Res source
• Not checked yetcites [166] Bictash, 2010, Opening up the “black box”: metabolic phenotyping and metabolome-wide association studies in epidemiology, J Clin Epidemiol source

In the paper

“In either case, potentially useful biomarkers may be identified through rigorous comparisons of quantitative or semiquantitative profiles of biospecimens obtained from subjects with and without a particular disease (59).”

What the sources say

• Not checked yetcites [59] Holmes, 2008, Human metabolic phenotype diversity and its association with diet and blood pressure, Nature source

In the paper

“A good example of this approach is given by Saadatian-Elahi et al (168), who correlated food consumption, as determined by 24-h dietary recall, with plasma concentrations of 22 fatty acids determined by gas chromatography in 3000 subjects from the European Prospective Investigation into Cancer and Nutrition cohort.”

What the sources say

• Not checked yetcites [168] Saadatian-Elahi, 2009, Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition, Am J Clin Nutr source

In the paper

“One exception is Phenol-Explorer, which gives a comprehensive overview of the human and animal metabolites formed from polyphenols (70).”

What the sources say

• Not checked yetcites [70] Rothwell, 2012, Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals, Database source

In the paper

“Metabolites such as S-methyl-L-cysteine sulfoxide or proline betaine as biomarkers of cruciferous vegetables or citrus fruit, respectively, could be identified in NMR studies on the basis of their characteristic chemical shifts (Table 3) (80,84).”

What the sources say

• Not checked yetcites [80] Heinzmann, 2010, Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption, Am J Clin Nutr source
• Not checked yetcites [84] Edmands, 2011, Identification of human urinary biomarkers of cruciferous vegetable consumption by metabonomic profiling, J Proteome Res source

In the paper

“Because diets and lifestyle strongly affect the metabolome, any pending disease may lead to reverse causation in MWASs; study design and interpretation must therefore take into account the common responses to early signs of disease in the population under study and other potential confounders.”

In the paper

“Moreover, recently developed bioinformatics approaches aim to narrow the number of possible candidate structures that match with an unknown query metabolite by taking into account the chemical and biological background of the sample (164).”

What the sources say

• Not checked yetcites [164] Kirchmair, 2013, How do metabolites differ from their parent molecules and how are they excreted?, J Chem Inf Model source

In the paper

“The application of metabolomics to foods has allowed the identification of a large variety of novel food constituents that are either naturally present in the food species or formed during food processing (65,173,174).”

What the sources say

• Not checked yetcites [65] Iijima, 2008, Metabolite annotations based on the integration of mass spectral information, Plant J source
• Not checked yetcites [173] Lee, 2011, Metabolomic approach for determination of key volatile compounds related to beef flavor in glutathione-Maillard reaction products, Anal Chim Acta source
• Not checked yetcites [174] Mena, 2012, Rapid and comprehensive evaluation of (poly)phenolic compounds in pomegranate (Punica granatum L.) juice by UHPLC-MSn, Molecules source

In the paper

“As an example, the recent description of benzoxazinoids in rye facilitated the identification of some of their metabolites (2,4-dihydroxy-1,4-benzoxazin-3-one, 2-aminophenol sulfate, and hydroxylated phenylacetamides) in urinary metabolic profiles observed after rye bread consumption (86,114).”

What the sources say

• Not checked yetcites [86] Bondia-Pons, 2013, UPLC-QTOF/MS metabolic profiling unveils urinary changes in humans after a whole grain rye versus refined wheat bread intervention, Mol Nutr Food Res source
• Not checked yetcites [114] Beckmann, 2013, Hydroxylated phenylacetamides derived from bioactive benzoxazinoids are bioavailable in humans after habitual consumption of whole grain sourdough rye bread, Mol Nutr Food Res source

In the paper

“Three fatty acids-oleic acid, a-linolenic acid, and di-homo-g-linolenic acid-were found to be associated with the risk of gastric cancer (169).”

What the sources say

• Not checked yetcites [169] Chajès, 2011, Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST), Am J Clin Nutr source

In the paper

“The investigators showed that metabolite concentrations differed substantially between Asian and Western populations, suggesting important effects of diet and related risk factors, including the microbiota, on the risk of coronary artery disease and stroke.”

What the sources say

• Not checked yetcites [59] Holmes, 2008, Human metabolic phenotype diversity and its association with diet and blood pressure, Nature source
• Not checked yetcites [166] Bictash, 2010, Opening up the “black box”: metabolic phenotyping and metabolome-wide association studies in epidemiology, J Clin Epidemiol source

In the paper

“This example shows that a better characterization of chemicals contained in a given food should markedly improve our understanding of food-derived exposures and their biological effects.”

In the paper

“Subjects from a cohort of .2000patients with cardiovascular disease, who were in the highest quartile for plasma TMAO concentrations, had a .2-foldrisk of a heart attack or stroke compared with subjects from the lowest quartile (108, 172).”

What the sources say

• Not checked yetcites [108] Koeth, 2013, Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med source
• Not checked yetcites [172] Tang, 2013, Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk, N Engl J Med source

In the paper

“In particular, the use of accurate fragmentation mass data as input can enhance the metabolite identification process by selecting the most likely candidates on the basis of similarities in fragmentation pathways and their readily assigned elemental formula with the unknown query metabolite as exemplified by dietary polyphenols (144).”

What the sources say

• Not checked yetcites [144] van der Hooft, 2011, Polyphenol identification based on systematic and robust high-resolution accurate mass spectrometry fragmentation, Anal Chem source

In the paper

“NMR spectroscopy and MS are the 2 essential tools for elucidation of the structure of unknown metabolites in metabolomic studies (140, 141).”

What the sources say

• Not checked yetcites [140] van der Hooft, 2013, Structural elucidation of low abundant metabolites in complex sample matrices, Metabolomics source
• Not checked yetcites [141] Wishart, 2011, Advances in metabolite identification, Bioanalysis source

In the paper

“These benzoxazinoid metabolites certainly deserve further investigation as potential contributors to the health effects of rye products because of some documented anti-inflammatory, immunoregulatory, and appetite-suppressing properties (176).”

What the sources say

• Not checked yetcites [176] Adhikari, 2012, bioactive benzoxazinoids in rye bread are absorbed and metabolized in pigs, J Agric Food Chem source

In the paper

“Software tools such as MetFrag, MyCompoundID, MetiTree, and Mass Frontier can handle metabolite fragmentation data and permit library searches for potential candidates using in silico fragmentation predictions of metabolites or comparisons to previously fragmented metabolites or standards (146, 153-155).”

What the sources say

• Not checked yetcites [146] Li, 2013, MyCompoundID: using an evidence-based metabolome library for metabolite identification, Anal Chem source
• Not checked yetcites [153] Wolf, 2010, In silico fragmentation for computer assisted identification of metabolite mass spectra, BMC Bioinformatics source
• Not checked yetcites [154] Rojas-Cherto, 2012, Metabolite identification using automated comparison of high resolution MSn spectral trees, Anal Chem source
• Not checked yetcites [155] HighChem. Mass Frontier. Available from: http://www.highchem.com/index.php/massfrontier (cited 3 September 2013).

In the paper

“As described earlier, the major online chemical resources (typified by PubChem, Kyoto Encyclopedia of Genes and Genomes, and ChemSpider) contain limited information on human metabolites derived from food compounds.”

In the paper

“Despite the many initiatives to make spectral data sets available to the scientific community, the publicly accessible existing spectral data are still scattered over numerous Web-based (searchable) databases, printed tables in scientific journals, Excel files in supporting information, and scientific books (140, 149, 150).”

What the sources say

• Not checked yetcites [140] van der Hooft, 2013, Structural elucidation of low abundant metabolites in complex sample matrices, Metabolomics source
• Not checked yetcites [149] Tohge, 2009, Web-based resources for mass-spectrometry-based metabolomics: a user’s guide, Phytochemistry source
• Not checked yetcites [150] Scalbert, 2011, Databases on food phytochemicals and their health promoting effects, J Agric Food Chem source

In the paper

“Strong correlations between regional dietary factors and fatty acid concentrations allowed components of the food metabolome to be used as predictor variables in a prospective investigation of gastric cancer in the European Prospective Investigation into Cancer and Nutrition cohort.”

What the sources say

• Not checked yetcites [168] Saadatian-Elahi, 2009, Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition, Am J Clin Nutr source

In the paper

“The investigators showed that metabolite concentrations differed substantially between Asian and Western populations, suggesting important effects of diet and related risk factors, including the microbiota, on the risk of coronary artery disease and stroke.”

What the sources say

• Not checked yetcites [59] Holmes, 2008, Human metabolic phenotype diversity and its association with diet and blood pressure, Nature source
• Not checked yetcites [166] Bictash, 2010, Opening up the “black box”: metabolic phenotyping and metabolome-wide association studies in epidemiology, J Clin Epidemiol source

In the paper

“In the semitargeted approach, preliminary cross-sectional studies are developed to connect dietary records with the food metabolome and thereby identify dietary biomarkers that are highly correlated with the consumption of particular foods.”

In the paper

“Hazen and coworkers showed that consumption of foods rich in choline or carnitine, such as eggs, milk, liver, meat, or fish, produced high concentrations of TMAO in both humans and animals who possessed the requisite microbiota for metabolizing choline or carnitine to trimethylamine, the immediate precursor of TMAO (108, 171, 172).”

What the sources say

• Not checked yetcites [108] Koeth, 2013, Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med source
• Not checked yetcites [171] Wang, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature source
• Not checked yetcites [172] Tang, 2013, Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk, N Engl J Med source

In the paper

“More markers of food intake have been identified in MS-based metabolomic studies on the basis of their accurate mass and mass fragmentation spectra (142-144).”

What the sources say

• Not checked yetcites [142] Draper, 2009, Metabolite signal identification in accurate mass metabolomics data with MZedDB, an interactive m/z annotation tool utilising predicted ionisation behaviour ’rules’, BMC Bioinformatics source
• Not checked yetcites [143] Draper, 2013, Flow infusion electrospray ionisation mass spectrometry for high throughput, non-targeted metabolite fingerprinting: a review, Metabolomics source
• Not checked yetcites [144] van der Hooft, 2011, Polyphenol identification based on systematic and robust high-resolution accurate mass spectrometry fragmentation, Anal Chem source

In the paper

“Given the thousands of potentially important exposures to consider, MWASs and exposome-wide association studies move away from knowledge-driven designs that focus on a priori hypotheses about particular exposures toward data-driven designs using untargeted or semitargeted sets of analytes (167).”

What the sources say

• Not checked yetcites [167] Rappaport, 2012, Biomarkers intersect with the exposome, Biomarkers source

In the paper

“Major progress in assessing complex dietary exposures at the individual level is expected from these biomarkers.”

In the paper

“new metabolites formed from nutrients and other food constituents are continuously being identified, even for widely studied compounds (101, 179).”

What the sources say

• Not checked yetcites [101] Stanstrup, 2013, Intakes of whey protein hydrolysate and whole whey proteins are discriminated by LC-MS metabolomics, Metabolomics
• Not checked yetcites [179] Johnson, 2012, Novel metabolites and roles for alpha-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics, Am J Clin Nutr source

In the paper

“the approach is already being used in the characterization of multicomponent drugs and herbal medicines (178).”

What the sources say

• Not checked yetcites [178] Lan, 2013, Towards polypharmacokinetics: pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach, Evid Based Complement Alternat Med source

In the paper

“Recent analyses of the food metabolome with modern analytic and bioinformatic tools have shown the considerable extent of information on dietary exposure contained in human biospecimens.”

In the paper

“Databases specific for the food metabolome are still largely missing apart from Phenol-Explorer, a database on all known polyphenol metabolites (70).”

What the sources say

• Not checked yetcites [70] Rothwell, 2012, Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals, Database source

In the paper

“Some proof-of-principle studies have established the feasibility of metabolomic approaches to identify novel dietary biomarkers and suggest that these approaches could greatly expand the field of molecular nutritional epidemiology and contribute to future progress in nutrition research.”

In the paper

“Epicatechin metabolite concentrations in plasma after cocoa intake paralleled the increase of plasma nitroso species concentrations and the vascular response (187).”

What the sources say

• Not checked yetcites [187] Schroeter, 2006, (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans, Proc Natl Acad Sci USA source

In the paper

“Various enzymes involved in the biotransformation of xenobiotics and dietary compounds also show genetic polymorphisms (183, 184).”

What the sources say

• Not checked yetcites [183] Lampe, 2009, Interindividual differences in response to plant-based diets: implications for cancer risk, Am J Clin Nutr source
• Not checked yetcites [184] Reszka, 2006, Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility, Br J Nutr