In the present study, the aim was to investigate the correlation between the acute and habitual dietary intake of flavanones, their main food sources and the concentrations of aglycones naringenin and hesperetin in 24 h urine in a European population. A 24-h dietary recall (24-HDR) and a 24-h urine sample were collected the same day from a subsample of 475 people from four different countries of the European Prospective Investigation into Cancer and Nutrition study. Acute and habitual dietary data were captured through a standardised 24-HDR and a country/centre-specific validated dietary questionnaire (DQ). The intake of dietary flavanones was estimated using the Phenol-Explorer database. Urinary flavanones (naringenin and hesperetin) were analysed using tandem MS with a previous enzymatic hydrolysis. Weak partial correlation coefficients were found between urinary flavanone concentrations and both acute and habitual dietary flavanone intakes (Rpartial = 0·14–0·17). Partial correlations were stronger between urinary excretions and acute intakes of citrus fruit and juices (Rpartial ∼ 0·6) than with habitual intakes of citrus fruit and juices (Rpartial ∼ 0·24). In conclusion, according to our results, urinary excretion of flavanones can be considered a good biomarker of acute citrus intake. However, low associations between habitual flavanone intake and urinary excretion suggest a possible inaccurate estimation of their intake or a too sporadic intake. For assessing habitual exposures, multiple urinary collections may be needed. These results show that none of the approaches tested is ideal, and the use of both DQ and biomarkers can be recommended.

Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0·66, 95 % CI 0·46, 0·96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0·58, 95 % CI 0·39, 0·86), 3,4-dihydroxyphenylpropionic acid (OR 0·63, 95 % CI 0·46, 0·87), ferulic acid (OR 0·65, 95 % CI 0·44, 0·96) and caffeic acid (OR 0·69, 95 % CI 0·51, 0·93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0·67, 95 % CI 0·48, 0·93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.

Several descriptive studies on the intake of polyphenols, mostly flavonoids, have been published, especially in Europe and the USA, but insufficient data are still available in Latin-American countries, where different types of foods are consumed and different dietary habits are observed. The goal of this cross-sectional study was to estimate dietary intakes of polyphenols, including grand total, total per classes and subclasses and individual compounds, and to identify their main food sources in Mexican women. The Mexican Teachers’ Cohort includes 115 315 female teachers, 25 years and older, from twelve states of Mexico, including urban and rural areas. Dietary data were collected in the period 2008–2011 using a validated FFQ, and individual polyphenol intake was estimated using food composition data from the Phenol-Explorer database. Median total polyphenol intake was the highest in Baja California (750 mg/d) and the lowest in Yucatan (536 mg/d). The main polyphenols consumed were phenolic acids (56·3–68·5 % total polyphenols), followed by flavonoids (28·8–40·9 %). Intake of other polyphenol subclasses (stilbenes, lignans and others) was insignificant. Coffee and fruits were the most important food sources of phenolic acids and flavonoids, respectively. Intake of a total of 287 different individual polyphenols could be estimated, of which forty-two were consumed in an amount ≥1 mg/d. The most largely consumed polyphenols were several caffeoylquinic acids (ranging from 20 and 460 mg/d), ferulic acid, hesperidin and proanthocyanidins. This study shows a large heterogeneity in intakes of individual polyphenols among Mexican women, but a moderate heterogeneity across Mexican states. Main food sources were also similar in the different states.

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.

In vitro studies have shown several beneficial properties of resveratrol. Epidemiological evidence is still scarce, probably because of the difficulty in estimating resveratrol exposure accurately. The current study aimed to assess the relationships between acute and habitual dietary resveratrol and wine intake and urinary resveratrol excretion in a European population. A stratified random subsample of 475 men and women from four countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study, who had provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day, were included. Acute and habitual dietary data were collected using standardised 24-HDR software and a validated country-specific dietary questionnaire, respectively. Phenol-Explorer was used to estimate the intake of resveratrol and other stilbenes. Urinary resveratrol was analysed using tandem MS. Spearman’s correlation coefficients between estimated dietary intakes of resveratrol and other stilbenes and consumption of wine, their main food source, were very high (r>0·9) when measured using dietary questionnaires and were slightly lower with 24-HDR (r>0·8). Partial Spearman’s correlations between urinary resveratrol excretion and intake of resveratrol, total stilbenes or wine were found to be higher when using the 24-HDR (R2partial approximately 0·6) than when using the dietary questionnaires (R2partial approximately 0·5). Moderate to high correlations between dietary resveratrol, total stilbenes and wine, and urinary resveratrol concentrations were observed. These support the earlier findings that 24-h urinary resveratrol is an effective biomarker of both resveratrol and wine intakes. These correlations also support the validity of the estimation of resveratrol intake using the dietary questionnaire and Phenol-Explorer.

Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Phenolic acid intakes were estimated for 36 037 subjects aged 35–74 years and recruited between 1992 and 2000 in ten European countries using a standardised 24 h recall software (EPIC-Soft), and their food sources were identified. Dietary data were linked to the Phenol-Explorer database, which contains data on forty-five aglycones of phenolic acids in 452 foods. The total phenolic acid intake was highest in Aarhus, Denmark (1265·5 and 980·7 mg/d in men and women, respectively), while the intake was lowest in Greece (213·2 and 158·6 mg/d in men and women, respectively). The hydroxycinnamic acid subclass was the main contributor to the total phenolic acid intake, accounting for 84·6–95·3 % of intake depending on the region. Hydroxybenzoic acids accounted for 4·6–14·4 %, hydroxyphenylacetic acids 0·1–0·8 % and hydroxyphenylpropanoic acids ≤ 0·1 % for all regions. An increasing south–north gradient of consumption was also found. Coffee was the main food source of phenolic acids and accounted for 55·3–80·7 % of the total phenolic acid intake, followed by fruits, vegetables and nuts. A high heterogeneity in phenolic acid intake was observed across the European countries in the EPIC cohort, which will allow further exploration of the associations with the risk of diseases.

A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35 628 subjects, aged 35–74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2 %) and flavan-3-ol monomers (24·9 %) and the principal food sources were tea (25·7 %) and fruits (32·8 %). In the MED region, proanthocyanidins (59·0 %) were by far the most abundant contributor and fruits (55·1 %), wines (16·7 %) and tea (6·8 %) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.

Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35–74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.

Folate plays an important role in the synthesis and methylation of DNA as a cofactor in one-carbon metabolism. Inadequate folate intake has been linked to adverse health events. However, comparable information on dietary folate intake across European countries has never been reported. The objective of the present study was to describe the dietary folate intake and its food sources in ten countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cross-sectional analysis was conducted in 36 034 participants (aged 35–74 years) who completed a single 24 h dietary recall using a computerised interview software program, EPIC-Soft® (International Agency for Research on Cancer, Lyon). Dietary folate intake was estimated using the standardised EPIC Nutrient DataBase, adjusted for age, energy intake, weight and height and weighted by season and day of recall. Adjusted mean dietary folate intake in most centres ranged from 250 to 350 μg/d in men and 200 to 300 μg/d in women. Folate intake tended to be lower among current smokers and heavier alcohol drinkers and to increase with educational level, especially in women. Supplement users (any types) were likely to report higher dietary folate intake in most centres. Vegetables, cereals and fruits, nuts and seeds were the main contributors to folate intake. Nonetheless, the type and pattern of consumption of these main food items varied across the centres. These first comparisons of standardised dietary folate intakes across different European populations show moderate regional differences (except the UK health conscious group), and variation by sex, educational level, smoking and alcohol-drinking status, and supplement use.

The present report summarises a workshop convened by the UK Food Standards Agency (Agency) on 25 March 2010 to discuss the current Agency's funded research on the use of metabolomics technologies in human nutrition research. The objectives of this workshop were to review progress to date, to identify technical challenges and ways of overcoming them, and to discuss future research priorities and the application of metabolomics in public health nutrition research and surveys. Results from studies nearing completion showed that by using carefully designed dietary and sampling regimens, it is possible to identify novel biomarkers of food intake that could not have been predicted from current knowledge of food composition. These findings provide proof-of-principle that the metabolomics approach can be used to develop new putative biomarkers of dietary intake. The next steps will be to validate these putative biomarkers, to develop rapid and inexpensive assays for biomarkers of food intake of high public health relevance, and to test their utility in population cohort studies and dietary surveys.

Anthocyanins are natural pigments abundant in various fruits and berries that are involved in the prevention of various chronic diseases. Their low concentrations in plasma and urine are explained in part by their complex chemistry and the formation of still uncharacterised metabolites. The aim of the present study was to follow the distribution of anthocyanins in the body using 14C-labelled cyanidin 3-O-glucoside (Cy3G) fed by gavage to mice. After the administration of 22·2 kBq 14C-Cy3G (0·93 mg), radioactivity was detected in most organs tested over the following 24 h with a peak observed in inner tissues at 3 h. The major fraction of the radioactivity (44·5 %) was found in the faeces collected 24 h after ingestion. At 3 h after oral administration of 141 kBq 14C-Cy3G (4·76 mg), most of the radioactivity (87·9 % of intake) was recovered in the gastrointestinal (GI) tract, especially in the small intestine (50·7 %) and the caecum (23 %). At this time, 3·3 % of the radioactivity was detected in urine. There was minimal accumulation (0·76 %) of radioactivity in tissues outside the GI tract. Distribution of radioactivity varied among organs, with liver, gallbladder and kidneys showing the highest radioactivity. Taken as a whole, these results show that Cy3G is poorly absorbed in the mouse.

Micronutrients are involved in specific biochemical pathways and have dedicated functions in the body, but they are also interconnected in complex metabolic networks, such as oxidative-reductive and inflammatory pathways and hormonal regulation, in which the overarching function is to optimise health. Post-genomic technologies, in particular metabolomics and proteomics, both of which are appropriate for plasma samples, provide a new opportunity to study the metabolic effects of micronutrients in relation to optimal health. The study of micronutrient-related health status requires a combination of data on markers of dietary exposure, markers of target function and biological response, health status metabolites, and disease parameters. When these nutrient-centred and physiology/health-centred parameters are combined and studied using a systems biology approach with bioinformatics and multivariate statistical tools, it should be possible to generate a micronutrient phenotype database. From this we can explore external factors that define the phenotype, such as lifestage and lifestyle, and the impact of genotype, and the results can also be used to define micronutrient requirements and provide dietary advice. New mechanistic insights have already been developed using biological network models, for example genes and protein-protein interactions in the aetiology of type 2 diabetes mellitus. It is hoped that the challenge of applying this approach to micronutrients will, in time, result in a change from micronutrient oriented to a health oriented views and provide a more holistic understanding of the role played by multiple micronutrients in the maintenance of homeostasis and prevention of chronic disease, for example through their involvement in oxidation and inflammation.

Epidemiological evidence together with preclinical data from animal and in vitro studies strongly support a correlation between soy isoflavone consumption and protection towards breast and prostate cancers. The biological processes modulated by isoflavones, and especially by genistein, have been extensively studied, yet without leading to a clear understanding of the cellular and molecular mechanisms of action involved. This review discusses the existing gaps in our knowledge and evaluates the potential of the new nutrigenomic approaches to improve the study of the molecular effects of isoflavones. Several issues need to be taken into account for the proper interpretation of the results already published for isoflavones. Too often knowledge on isoflavone bioavailability is not taken into account; supra-physiological doses are frequently used. Characterization of the individual variability as defined by the gut microflora composition and gene polymorphisms may also help to explain the discrepancies observed so far in the clinical studies. Finally, the complex inter-relations existing between tissues and cell types as well as cross-talks between metabolic and signalling pathways have been insufficiently considered. By appraising critically the abundant literature with these considerations in mind, the mechanisms of action that are the more likely to play a role in the preventive effects of isoflavones towards breast and prostate cancers are reviewed. Furthermore, the new perspectives opened by the use of genetic, transcriptomic, proteomic and metabolomic approaches are highlighted.

A large variety of phytochemicals are found in vegetables, fruits, spices and staple plant foods(1,2).

Bread is one of the most widely consumed staple foods worldwide. White-wheat bread, largely consumed in France, is made from highly refined flour, which leads to a low nutrient density. Due to a highly porous structure and gelatinised starch, it is easily broken down during digestion, leading to a rapid increase of glucose released into the bloodstream. Low glycaemic responses are considered favourable to health, especially against a background of diabetes. Literature reports show that selection of raw material is an essential factor in decreasing the glycaemic index (GI) of white bread. There are two means of decreasing the rate of starch degradation: either (i) slowing gastric emptying rate and/or glucose diffusion–absorption through the intestinal mucosa, which can be achieved by incorporating soluble fibre or organic acid in bread, or (ii) limiting starch accessibility to α-amylase by using high-amylose cereal varieties and/or incorporating intact cereal grains. Studies on cereal products show that preservation of the food structure during digestion seems to be a more important GI-reducing factor than the degree of starch crystallinity or the presence of soluble fibre. Thus, we should look to produce bread with a more compact food structure or higher density, which is the case in leavened wholewheat bread or bread with intact cereal grains. The baking process should also be improved to achieve this goal, by using, for example, a reduced kneading time or less yeast than usual.

Anthocyanins are natural dietary pigments with a wide array of biological properties that are possibly involved in the prevention of various diseases. These properties depend on their absorption and metabolism in the body. In the present study we first examined the gastric and intestinal absorption of pelargonidin 3-glucoside (Pg 3-glc) using rat in situ models. A high proportion of Pg 3-glc was rapidly absorbed from both the stomach (23 %) and small intestine (24 %). Its metabolism was further studied by feeding rats during 8 d with a diet enriched in freeze-dried strawberries. Only low amounts of total anthocyanins were recovered in 24 h urine (0·163 (sem 0·013) % of ingested anthocyanins; n 8). Strawberry anthocyanins were analysed in urine by HPLC-electrospray ionisation-tandem MS. Similar proportions of intact glycosides (about 53 %) and glucuronidated metabolites (about 47 %) were found. Pg 3-glc was thus glucuronidated to a larger extent than cyanidin 3-glucoside. These results highlight the influence of the aglycone structure on anthocyanin metabolism.

The absorption and metabolism in the small intestine of chlorogenic acid (5-0-caffeoylquinic acid), the main phenolic acid in the human diet, and of caffeic acid were studied in rats in order to determine whether chlorogenic acid is directly absorbed or hydrolysed in the small intestine. Chlorogenic and caffeic acids were perfused into a segment of ileum plus jejunum during 45;min (50;μm, 0·75sp;ml/min) using an in situ intestinal perfusion rat model with cannulation of the biliary duct, and were quantified together with their metabolites in perfusion effluent, bile and plasma. The net absorption (influent flux minus effluent flux of phenolic acids and their metabolites) accounted for 19·5% and 8% of the perfused caffeic and chlorogenic acids, respectively. A minor fraction of the perfused caffeic acid was metabolized in the intestinal wall and secreted back into the gut lumen in the form of ferulic acid (0·5% of the perfused flux). Part of the chlorogenic acid (1·2% of the perfused flux) was recovered in the gut effluent as caffeic acid, showing the presence of trace esterase activity in the gut mucosa. No chlorogenic acid was detected in either plasma or bile, and only low amounts of phenolic acids (less than 0·4%) were secreted in the bile. The present results show that chlorogenic acid is absorbed and hydrolysed in the small intestine. In contrast to numerous flavonoids, absorbed phenolic acids are poorly excreted in the bile or gut lumen. Their bioavailability therefore appears to be governed largely by their uptake into the gut mucosa.

Estimation of dietary intake of polyphenols is difficult, due to limited availability of food composition data and bias inherent to dietary assessment methods. The aim of the present study was to evaluate the associations between the intake of polyphenol-rich foods and the urinary excretion of several phenolic compounds and therefore explore whether these phenolic compounds could be used as a biomarker of intake. Fifty-three participants of the SU.VI.MAX study (a randomised primary-prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases) collected a 24h urine and a spot urine sample and filled a dietary record during a 2d period. Thirteen polyphenols and metabolites, chlorogenic acid, caffeic acid, m-coumaric acid, gallic acid, 4-o-methylgallic acid, quercetin, isorhamnetin, kaempferol, hesperetin, naringenin, phloretin, enterolactone and enterodiol, were measured using HPLC–electrospray ionisation–MS–MS. In spot samples apple consumption was positively correlated to phloretin, grapefruit consumption to naringenin, orange to hesperetin, citrus fruit consumption to both naringenin and hesperetin, with r coefficients ranging from 0·31 to 0·57 (p<0·05). The combination of fruits and/or fruit juices was positively correlated to gallic acid and 4-o-methylgallic acid, isorhamnetin, kaempferol, hesperetin, naringenin and phloretin (r 0·24–0·44, p<0·05). Coffee consumption was positively correlated to caffeic and chlorogenic acids (r 0·29 and 0·63, p<0·05 respectively). Black tea and wine consumption were positively correlated with gallic and 4-o-methylgallic acids (r 0·37–0·54, p<0·001). The present results suggest that several polyphenols measured in a spot urine sample can be used as biomarkers of polyphenol-rich food intake.

Dietary polyphenols are suggested to participate in the prevention of CVD and cancer. It is essential for epidemiological studies to be able to compare intake of the main dietary polyphenols in populations. The present paper describes a fast method suitable for the analysis of polyphenols in urine, selected as potential biomarkers of intake. This method is applied to the estimation of polyphenol recovery after ingestion of six different polyphenol-rich beverages. Fifteen polyphenols including mammalian lignans (enterodiol and enterolactone), several phenolic acids (chlorogenic, caffeic, m-coumaric, gallic, and 4-O-methylgallic acids), phloretin and various flavonoids (catechin, epicatechin, quercetin, isorhamnetin, kaempferol, hesperetin, and naringenin) were simultaneously quantified in human urine by HPLC coupled with electrospray ionisation mass-MS (HPLC-electrospray-tandem mass spectrometry) with a run time of 6 min per sample. The method has been validated with regard to linearity, precision, and accuracy in intra- and inter-day assays. It was applied to urine samples collected from nine volunteers in the 24 h following consumption of either green tea, a grape-skin extract, cocoa beverage, coffee, grapefruit juice or orange juice. Levels of urinary excretion suggest that chlorogenic acid, gallic acid, epicatechin, naringenin or hesperetin could be used as specific biomarkers to evaluate the consumption of coffee, wine, tea or cocoa, and citrus juices respectively.

Flavanols are the most abundant flavonoids in the human diet where they exist as monomers, oligomers and polymers. In the present study, catechin, the procyanidin dimer B3 and a grapeseed extract containing catechin, epicatechin and a mixture of procyanidins were fed to rats in a single meal. After the meals, catechin and epicatechin were present in conjugated forms in both plasma and urine. In contrast, no procyanidins or conjugates were detected in the plasma or urine of any rats. Procyanidins were not cleaved into bioavailable monomers and had no significant effects on the plasma levels or urinary excretion of the monomers when supplied together in the grapeseed extract. We conclude that the nutritional effects of dietary procyanidins are unlikely to be due to procyanidins themselves or monomeric metabolites with the intact flavonoid-ring structure, as they do not exist at detectable concentrations in vivo. Future research should focus on other procyanidin metabolites such as phenolic acids and on the effects of the unabsorbed oligomers and polymers on the human gastrointestinal tract.