The market of dietary supplements is exponentially increasing in recent years. To gain an edge over the competition, new dietary supplements efficacy and safety need to be scientifically proven. In agreement with European Food Safety Agency (ESFA) recommendations and the 3R principle, Mérieux NutriSciences applies in vitro workflow to evaluate new dietary supplements efficacy and safety, starting from the impact of the digestive process on the formulation to its efficacy on target tissues or organs. This approach is time and costs effective, and it provides a useful tool to valorise novel dietary supplements.
Dietary supplements, ranging from isolated nutrients to processed products, are defined as foods, or part of foods, providing medical and health benefits such as the prevention and treatment of chronic health issues. Since numerous pathologies are directly or indirectly related to bad diet habits, people tried to improve their quality of life either modifying their diet or integrating it with dietary supplements. As a consequence, the nutraceutical market and related R&D increased. To gain a significant commercial edge over the competition in this crowded market, dietary supplements’ efficacy and safety need to be scientifically proven, with data coming from solid, reliable and recognized methods.
Considering the complexity of biological processes such as digestion, intestinal absorption and active principle/s efficacy at the target tissue/organ/apparatus, in vivo approaches still represent the gold standard. However, these models are characterized by high intrinsic variability, significant investments, no success guarantee without preliminary information. To overcome such limitations, and in compliance with EFSA indications and the 3Rs principle (Replacement, Reduction and Refinement), several in vitro models have been proposed to explore the digestive process impact on dietary supplements, their intestinal absorption, and, ultimately, their efficacy and safety. In vitro models ensure lower variability, higher repeatability and the possibility to investigate the mode of action of a formulation down to a molecular level. Moreover, they allow to run multiple experiments in parallel under controlled conditions, making them suitable for reliable high-throughput screening analysis, saving time and costs.
To support companies in valorizing their products both scientifically and commercially, Mérieux NutriSciences has a set of powerful and reliable in vitro models, such as a coupled in vitro model of digestive process and intestinal absorption, and tissue/organ/apparatus specific efficacy and safety in vitro assays.
Where do dietary supplements go?
Regarding dietary supplements, nowadays the major concerns are related to low bioaccessibility and bioavailability, and poor stability during digestive process. Different pharmaceutical forms (i.e., tablets, capsule, etc.) could also affect the efficacy of dietary supplements, as highlighted by recent studies that show half of the tested dietary supplements in tablet form completely excreted without releasing their active principle/s. To investigate dietary supplements’ stability during the digestive process as well as their ability to release active principle/s for intestinal absorption (i.e., bioaccessibility), an in vitro human digestive model was developed to simulate the main typical features of human digestion physiology (i.e., compartmentalization, digestive fluids composition, transition time, volumetric ratio between digestive fluid, etc.). The digestion model ensures (i) high flexibility since different physiological conditions (i.e., adults versus kids and fed versus starved) could be simulated by carefully tweaking the digestion parameter, and (ii) it allows for a compartment (i.e., mouth, stomach and small intestine)-level analytical detail of the digestive process impact on dietary supplements.
Once the digestive process is completed, active principle/s, released from their matrices are ready to be absorbed at the small intestine level, through microvilli located on the apical side of enterocytes. As for the digestive process, validated in vitro models of the intestinal epithelium have been developed, allowing for the study of active principles intestinal absorption without relying on expensive in vivo models. While Caco-2-based intestinal epithelium model has become the gold standard to investigate the absorption of many substances, the model could be improved by adding mucus-secreting goblet cells and/or transcytosis-specialized microfold (M)-cells with the aim to investigate their contribution to active principles intestinal absorption. Based on specific customers’ requests and delivery technologies, different in vitro models can be proposed. These models are not only fundamental in determining the intestinal absorption of dietary supplements, but also their intestinal safety, in terms of cell viability and barrier integrity.
What do dietary supplements do?
Despite the intestinal absorption of dietary supplements, information on their efficacy should be proven. Based on the target for which dietary supplements were manufactured, specific in vitro models and tests are required. Thanks to Mérieux NutriSciences experience and expertise, a plethora of in vitro models and tests can be applied to explore dietary supplements efficacy. As an example, the prostatic efficacy of a formulation for the prevention and treatment of prostate-related disease can be evaluated with a validated in vitro human model by studying its anti-inflammatory and antioxidant activity as well as the impact on prostate-specific antigen (PSA) release and 5α-reductase activity. Again, the anticholesterolemic activity of dietary supplements can be evaluated on both endogenous cholesterol with an in vitro model of the liver and exogenous cholesterol by using an in vitro intestinal model. With these models, it is possible to assess dietary supplement effects on cholesterolemia (i.e., lowering of total cholesterol and rising of free cholesterol, the excreted form of cholesterol) and choleresis, the conversion of cholesterol to bile acids.
As for the intestinal epithelium models, these in vitro models are also instrumental in demonstrating the target-specific safety of dietary supplements, providing a powerful tool for dietary supplement producers to market products with proven efficacy and safety.
Hereafter, the workflow proposed by Mérieux NutriSciences to support customers/partners in developing new efficient and safe dietary supplements is presented. This approach provides reliable scientific data to be used for acquiring commercial edge over the ever-growing competition, patents, scientific publications, information for marketing. The workflow ranges from the evaluation of dietary supplements intestinal absorption to their efficacy and safety to specific tissue/organ/apparatus by using in vitro tests. This model permits high-throughput screening of new formulations to evaluate their efficacy and safety in agreement with EFSA recommendations. Thanks to the modular construction of this workflow, it is possible to provide tailor-made experimental settings, so ensuring a positive product valorization-to-cost ratio.