NAT-TEST: Safety and working mechanisms of natural compounds

Objectives: develop animal-test-free methods to assess safety and efficacy of natural health products, derived from food or natural resources.

Keywords: Natural compounds, in vitro strategy, inflammation, obesity

Key collaborations: Danone - Nutricia Research BV, Utrecht University (Institute for Risk Assessment Sciences), Wageningen University & Research Centre (Human Nutrition and Food and Biobased Products), TNO, Bio Detection Systems BV, Fytagoras BV, Phytogenix BV, Biqualys BV

Funding: Regieorgaan SIA (SIA-RAAK), Danone

Project group: Dr. Robert Jan Veldman (WP1); Dr. Jean-Paul ten Klooster (WP2); Dr. Cristina Chamorro-Perez (WP3); Dr. Laura M’Rabet; Dr. Cyrille Krul; Dr. Marc Teunis; Tineke Malherbe-Dupont; Dr. Raymond Pieters (PL)

External partnersWUR (Human Nutrition), IRAS (UU), Fytagoras, PhytoGenix and Danone

Authors: Dr. Raymond Pieters, Dr. Robert Jan Veldman, Dr. Jean Paul ten Klooster, Dr. Cristina Chamorro-Peres, Dr. Marc Teunis

This project was awarded with the SIA RAAK Award on November 21, 2013

Watch the movie on this project which was produced by Regieorgaan SIA, April 2014

Project summary

The idea that ‘you are what you eat’ has inspired an increasing interest for new plant- and nutrition-derived natural health products, often forgotten in Western society. These natural compounds could contribute to maintaining and improving health but could also serve as a basis for new medicines and dietary supplements.

However, assessing the safety and efficacy of these products and their chemical content remains a challenge. This has resulted in European legislation to ensure scientific validation of health claims (The EFSA Journal 2008, 644, 1-44). In these validation processes, knowledge regarding the working mechanism of a product in relation to the safety and efficacy is of crucial importance. In addition, there is an urgent need to reduce and replace animal testing. The current project aims to meet both demands. In collaboration with several project partners (i.e. WUR (Human Nutrition), IRAS (UU), Fytagoras, PhytoGenix and Danone) we aim to develop animal test-free methods to assess safety (toxicity) and efficacy of natural health products, derived from food or other natural resources.

We focus on developing new techniques for efficient extraction of food or natural products (mostly plants). Furthermore we focus on developing innovative cell cultures (stem cells of intestinal origin, 3D cultures, co-cultures) that allow for a more cost-effective method and efficient translation to whole organisms (i.e. man, but also husbandry animals). New innovative techniques that have been developed (or are under development) have already led to 4 additional projects (RAAK-MKB Green health, ILSI-HESI (organoids), Naturalis (Hogeschool Leiden), DOPharma (MKB). One of our great achievements has been the development of the new RAAK-DIAGRAMS project.

We are highly involved in educational programmes and offer many student projects, especially in the fields of Life Sciences and Chemistry.

The project activities are translated into 3 workpackages:

WP1 - Development of an in vitro test battery for testing of natural anti-oxidants Contents analysis and health-promoting biological activities of natural products.

WP2 - Methods to assess inflammatory and other immune reactions, in relation to gut health.

WP3 - Innovative methods to determine the chemical composition of plant-derived compounds in relation to biological effect parameters (biomarkers).

A schematic overview of the test battery. The strategy is based on the concept that safety vs efficacy is largely determined by the dose (or concentration in vitro) and time of exposure. The ultimate focus of the strategy is on gut health in relation to inflammatory effects, e.g. metabolic syndrome and food allergy. A tiered approach is used: the first tier includes assays to assess whether a product or its content can be metabolically converted, and whether it has anti- or pro-oxidant, sensitizing, reprotoxic and/or mutagenic potential. This should be established before further research is conducted, because if a products proves to be mutagenic, for example, no further research will be performed. The second tier focuses on organ-specific assays (intestinal and adipocyte models) and the translation to health-related effects in target species. Ideally this information may help to make strategic decisions on further development and to decide on first studies in man or other target animals.