Knowledge Based Bio-Economy


Targeted delivery of dietary flavanols for optimal human cell function: Effect on cardiovascular health (Nutrition)

Project acronym: FLAVIOLA

Title of project: Targeted delivery of dietary flavanols for optimal human cell function: Effect on cardiovascular health

Research area: Nutrition

Contract No: 226588

EU contribution: €2 999 195

Start date: September 2009

Duration: 42 months

Status: finalised

Nutrition – or our daily diet– has a major impact on human health and disease. Epidemiological evidence suggests that diets rich in plant-based foods and beverages decrease the risk of cardiovascular morbidity and mortality. Various phytochemical constituents, in particular a class of compounds called flavanols, have been the focus of much attention in recent years. Flavanols are commonly present in most higher plants (those which have the xylem and phloem vascular tissues), and their content is high in certain food plants, such as Vitis Vinifera (grape wine), Camellia Sinensis (tea), and Theobroma Cacao (cocoa), which isespecially noteworthy in the context of human nutrition.

The FLAVIOLA project aimed at:

  • (a) investigating the absorption and metabolism of flavanols in humans;
  • (b) establishing the levels of habitual flavanol intake in the EU;
  • (c) assessing the impact of the dietary intake of flavanols on cardiovascular function;
  • (d) developing a cocoa food product prototype containing flavanol  for use in the context of cardiovascular health.

The actual flavanol content of any food ultimately depends on the plant species from which the compounds originate, the specific climate- and agricultural conditions, as well as the methods employed for harvesting and processing plant material in the context of food manufacture or preparation.

The chemical properties of flavanols mean it is not surprising that many common food preparation processes (fermentation, heating, pH-modifications) tend to dramatically decrease the flavanol content of foods, and lead to the isomerization of a significant quantity of the remaining flavanols.

It is important to establish whether our knowledge of how stereo-chemical properties affect nutrients physiologically is applicable to flavanols (not just the loss of flavanols during food manufacture, but also the transformation of epicatechin into catechin (isomerisation)). If so, this is important in terms of the potential health benefits of flavanol-containing foods.

Current epidemiological studies and dietary intake assessments unfortunately fall short of providing this level of information. Moreover, a large proportion of currently published dietary intervention studies exhibits significant gaps with regard to:

  • the adequate characterisation of the flavanol and nutritional content of the foods tested;
  • the use of appropriate controls (nutrient-, and calorically-matched, flavanol-free test materials);
  • the employment of sufficiently rigorous study designs.

Last, but not least, little is currently known about the potential molecular mechanisms of action (MOAs) that underlie the pharmacodynamics effects observed following flavanol intake. This is largely due to the fact that hardly anypublished papers investigated mammalian flavanol metabolites, i.e. the compounds systemically present in humans following flavanol intake.

These investigations therefore ignore the consequences of absorption, distribution, metabolism, and excretion (ADME) on the biological/pharmacological properties of flavanols, which can be significant. The study of native flavanols in cell culture or other in vitro systems is therefore highly unlikely to be informative with regard to the potential mechanisms of action relevant to MOAs in vivo.

It is in this overall context that FLAVIOLA employed a multidisciplinary, translational research approach, aimed at synergistically integrating data and know-how from: analytical chemistry; the study of ADME and population-based dietary flavanol intake; clinical dietary intervention studies; MOA assessments in vitro; and food product prototype development and testing. The consortium planned to address the gaps and challenges detailed above, employing a state-of-the-art analytical and clinical study infrastructure, and by conducting rigorous and well-designed investigations both in vivo and in vitro.

FLAVIOLA resulted in  a number of key outcomes:

  • development of optimised CF-containing food product prototype;
  • creation of dedicated analytical platforms;
  • understanding of flavanol ADME;
  • assessment of habitual dietary intake of CF and procyanidins in the EU;
    • demonstration of CF-mediated cardiovascular health benefits in clinical dietary intervention studies:
    • longer term effect in healthy individuals
    • assessment of age-dependent CF efficacy
    • evaluation of applicability to general population
  • novel insights into potential mechanisms of action.

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Coordinator: Marc W. Merx,

Organisation: The Heinrich-Heine-Universität Düsseldorf,