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Bioactive component:The four steps of Bioavailability

August 7, 2018

 

 

 

Bioavailability is a complex process involving different stages as defined by the 4 steps “LADME”: Liberation, Absorption, Distribution, Metabolism, and Elimination. Regarding the efficacy of oral drugs as for bioactive food components, the bioavailability is the first step to interest before studying the efficacy. In nutrition, we distinguish two concepts: the bioaccessibility and the bioavailability. Bioaccessibility has been defined as the fraction of a compound which is released from the food matrix in the gastrointestinal lumen and thereby made available for intestinal absorption. Bioavailability is the rate and extent to which the bioactive component is absorbed and becomes available at the site of action.

 

Bioaccessibility can be influenced by the digestion processes: “mastication in the mouth initiates the process and several digestive fluids containing different enzymes continue to break down the food matrix in the stomach and throughout the remainder of the gastrointestinal lumen” [1]. It is also influenced by physicochemical properties of the food (pH, temperature and texture of the matrix, interaction between ingredients, etc.).

 

In fact, the bioavailability in nutrition is twice challenging because the component has to be released from the food matrix (becoming bioaccessible) and then, absorbed in the gastrointestinal tract to be released, transformed and use by the body. No matters the sources (plant or animal), bioactive food components need to be bioavailable in order to exert any beneficial effects and the knowledge of the circulating metabolites leads to understanding the mechanisms of action in relation to the benefit.

 

Inter-individual variability

Some randomized clinical trials are conducted but the results remain contradictory and shreds of evidence are not easy to demonstrate. Could this be explained by the inter-individual variability in bioavailability? Maybe. It is in this context that the COST ACTION FA 1403 – POSITIVe examines the main factors likely to affect the individual responses to consumption of plant food bioactives [2]. (Epi)-genetics profiles, metabolism, age, sex or gut microbiome composition were identified as influenced factors. In their recent publication, Manach et al. explain that “some plant bioactives can be absorbed in their native form from the stomach or gut, but most of the glycosylated, polymeric, or esterified native plant compounds have to be hydrolyzed before absorption, a step partly carried out by the gut microbiota. The well-known example is the conversion of soy isoflavones into equol by the gut microbiota, leading to distinguish equol producers and non-producers with more beneficial health effects related to soy consumption for equol producers. Others examples can be cited, -caffeine and genetic polymorphisms, glucuronidation of resveratrol with enzyme expression profiles regulated by sex hormones, or -differences in cardiovascular parameter response between male and female for flavan-3-ol enriched dark chocolate. All these examples are further detailed in their review.

 

Responders vs non-responders?

The fact that significant results can be observed only on subgroups and not in the whole population “be suggesting that the consumption of particular foods or bioactive constituents may benefit some individuals more than others” [2]. Then, well-defined populations become essential to design correctly clinical trials and understand the mechanisms of actions of products.

 

This concepts also leads to personalize the supplementation in order to ensure the beneficial effects of the product to the subject, which is part of the trend of personalized nutrition, growing these last years. Identifying bioavailability of bioactive food components is essential to investigate health effect as toxicity. Understanding which individual factors can influence it remains challenging since many factors as to be taken into account as product-related factors (food matrix effect) and subject-related factors (gut microbiota).

 

Author : Hélène Chevallier - Clinical methodologist at Biofortis Mérieux NutriSciences. 

 

 

References :

1-Rein, Maarit J., Mathieu Renouf, Cristina Cruz‐Hernandez, Lucas Actis‐Goretta, Sagar K. Thakkar, and Marcia da Silva Pinto. 2013. ‘Bioavailability of Bioactive Food Compounds: A Challenging Journey to Bioefficacy’. British Journal of Clinical Pharmacology 75 (3): 588–602. https://doi.org/10.1111/j.1365-2125.2012.04425.x.

2-Manach, Claudine, Dragan Milenkovic, Tom Van de Wiele, Ana Rodriguez‐Mateos, Baukje de Roos, Maria Teresa Garcia‐Conesa, Rikard Landberg, et al. 2017. ‘Addressing the Inter-Individual Variation in Response to Consumption of Plant Food Bioactives: Towards a Better Understanding of Their Role in Healthy Aging and Cardiometabolic Risk Reduction’. Molecular Nutrition & Food Research 61 (6): 1600557. https://doi.org/10.1002/mnfr.201600557.

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