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University of Cambridge

1. Overview

The University of Cambridge is one of the world’s leading universities for research. Mars, Incorporated has partnered with them on a number of flavanol studies since 2014. Cambridge is one of the collaborators on the EPIC study of Norfolk, a large multi-centre cohort study looking at the connection between diet, lifestyle and disease. The partnership between Mars and Cambridge has made it possible to use this data to investigate flavanol content in the diet, flavanol metabolism and cardiovascular disease risk.

2. Partnership outcomes

Below are some recent outcomes from research conducted by Mars and the University of Cambridge.

Dietary intake of flavanols in the EU

Several studies have shown that flavanol intake can improve blood vessel function, blood pressure and cholesterol. A team of researchers from Mars, the University of Reading, the University of Cambridge and Heinrich Heine University Düsseldorf conducted a study that was published in the British Journal of Nutrition in 2014 whose aim was to understand how much of these beneficial compounds people in the European Union were consuming on a daily basis. Using the EFSA Comprehensive European Food Consumption Database and a recently developed flavanol food composition database, we managed to establish average intake amounts across fourteen EU countries. Overall, mean habitual intake of flavanols was 369 mg/d. However, intake varied considerably. In Ireland, the mean habitual intake was 793 mg/d while, in Czechia, it was only 181 mg/d. We found that tea was the largest source of dietary flavanols in the EU, accounting for 62% of flavanol intake. Pome fruits (e.g., apples and pears), berries, cocoa products and stone fruits were also notable sources of dietary flavanols. The intake of flavanol monomers and theaflavins was particularly high in the British Isles and Central Europe, where consuming tea is common. Intake of proanthocyanidins, on the other hand, was highest in Spain, Italy and France due to a large amount of fruit in the diet.

At 368 mg/d, the mean habitual intake of dietary flavanols is well below the amount used in various dietary intervention studies that have shown improved blood vessel function and cardiovascular risk after flavanol consumption. It is therefore possible that residents in EU countries are not consuming adequate amounts of flavanols to exploit the full cardioprotective benefit of these compounds. Thanks to this study, scientists are in a better position to investigate the impact of different flavanol intake amounts on public health.

Image: Heat maps showing mean habitual intake of total flavanols, flavanol monomers, proanthocyanidins and theaflavins in 14 countries across the EU. The consumption of total flavanols, flavanol monomers and theaflavins is higher in the British Isles and central Europe, where the consumption of tea is common. In southern Europe, the intake of proanthocyanidins is higher due to the consumption of fruit, in particular pome fruit.

Read more about this study: Vogiatzoglou, A., et al., Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols, proanthocyanidins and theaflavins in the European Union. Br J Nutr, 2014

Prospective cohort study indicates flavanol intake not sufficient to reduce CVD risk

A team from Mars, Incorporated, the University of Reading, the University of Cambridge and Heinrich Heine University Düsseldorf conducted an investigation into the association between flavanol consumption and cardiovascular disease risk, which was published in the journal Free Radical Biology and Medicine in 2015. The research team had access to detailed dietary information from almost 25,000 participants from the EPIC-Norfolk cohort who had completed a 7-day food diary. The study found no association between flavanol intake and blood pressure and cardiovascular disease risk. This result is corroborated by earlier epidemiological studies, however it contradicts the findings of dietary intervention studies, which have shown previously that individuals consuming a diet high in flavanols see improvements in vascular function measures (which are markers of cardiovascular disease risk) when compared to placebo controls. The reason for this discrepancy could lie in the types of flavanols being consumed by the EPIC-Norfolk cohort. Using food composition tables, we estimated that only 10% of the EPIC-Norfolk population were consuming more than 50 mg/d of (−)-epicatechin, which is the threshold beyond which improvements in blood pressure have been observed in the past. The flavanol (−)-epicatechin is also the only member of the flavanol group to have been directly and causally linked to improvements in blood vessel function.

Read more about this study: Vogiatzoglou, A., et al., Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk). Free Radic Biol Med, 2015

Gamma-valerolactone a reliable biomarker of flavanol intake

Another recent outcome from the relationship came from a study conducted by a team from Mars, the University of California, Davis, the University of Reading and the University of Cambridge in the UK. We managed to identify a nutritional biomarker that can be used to assess intake of flavan-3-ols, a type of commonly consumed flavanol found in food. A nutritional biomarker is, roughly speaking, a sort of test that scientists or medical professionals can perform to get an idea of what is going on inside the body. The biomarker discovered in this project is a compound present in the urine called gamma-valerolactone (gVL). Gamma-valerolactone only appears in the urine after people have consumed food or drink containing certain flavan-3-ols, including (−)-epicatechin. Using a urine test, scientists will now be able to assess whether people are consuming a diet high or low in these flavanols. They can use that information in scientific studies to determine whether the amount of flavanols in the diet affects study endpoints, such as the risk of developing cardiovascular disease. Previously, scientists would have to ask study participants to complete a food diary to determine the amount of flavanols in their diet, which can be unreliable.

Importantly, using urinary gamma-valerolactone concentration as a nutritional biomarker meets the criteria laid down by the International Agency for Research on Cancer (IARC) and the Institute of Medicine (IOM) for nutritional biomarkers. As part of the study, we found that the biomarker is specific for flavan-3-ols present in tea, fruits, wine and cocoa-derived products. There is no formation of gVL with other flavonoids or polyphenols. There is also a consistent relationship between the amount of flavan-3-ols consumed in the diet and the amount of gVL in the urine.

Image: Gamma-valerolactone is only formed when people consume certain flavan-3-ols, such as epicatechin gallate (ECG) and the epicatechin monomer (−)-epicatechin. Other polyphenolic compounds such as thearubigins do not result in gVL formation. This makes urinary gVL concentration a biomarker specific to the consumption of certain flavanol compounds.

Read more about this study: Ottaviani, J.I., et al., Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies. Sci Reports 2018