Diseño, desarrollo y evaluación clínica de un producto rico en polifenoles

Résumé

SUMMARY Over the past decades, scientific advances in the field of nutrition and health have showed the increased evidence between the consumption of polyphenols and their beneficial effects on health, justifying ancestral knowledge used in traditional medicine, as is the case of green tea polyphenols, being the catechins the main group. Polyphenols are recognized as dietary antioxidants, and have several beneficial effects such as anti-inflammatory, anti-cancer and neuroprotective properties, among others. Although the mechanisms of actions of these compounds and their metabolites are not fully known, the regulation of oxidative stress is one of the biological activities related to several diseases such as cancer, diabetes, degenerative diseases and aging. Nowadays, the development of functional foods is justified by the significant changes in our society, namely, the increase in life expectancy, the higher social stress levels and the growing concern about keeping us healthy over the years, which have had dramatical consequences on individuals 'eating habits in developed countries. In this context, the general objective of this thesis has been to design, develop and evaluate the efficacy of a product rich in polyphenols that reduces oxidative damage in healthy individuals. To achieve this goal, four empirical studies, grouped in three phases, were carried. In the first phase (product design), we did a study (Study 1) to assess the amount of catechins in green tea infusions sold in Spain. Then, we identified and selected commercial green tea extracts (Study 2) to be added in the functional food based on the catechin and caffeine content, as well as sensory impact in the final product. In the next phase, we developed the product taking into account the target nutritional objectives (equivalence of catechins and EGCG in 2 cups of green tea, quercetin content in an apple, and anthocyanins content of one serving of red berries), and the results obtained in prior research. Next, the bioactive compounds of the developed product were characterized, and stability and acceptability were evaluated during shelf life (Study 3). Finally, in the third phase, a randomized double-blind clinical trial with 40 healthy subjects was performed, in which the participants were allocated to consume a daily dose of the product rich in polyphenols or a placebo for 10 weeks (Study 4). We evaluated the efficacy in blood measuring biomarkers of oxidative stress, and in the skin by the exposure of UVB radiation and the measurement of photoprotection. The results of these studies showed that the product is safe and significantly reduced the levels of F2-isoprostane and MDA (markers of lipid peroxidation). On the other hand, no significant differences in plasma concentrations of oxidized LDL, CRP and GSSG / GSH ratio were found. Moreover, after the induction of oxidative stress by ultraviolet radiation in the treatment group, a photoprotective effect was observed by the increase of the minimum erythemal dose (MED). In the subjects where we took skin biopsies to assess the damage at cellular level, no significant differences were found for DNA damage (measured as pyrimidine dimers) and genomics protection parameters (p53 expression and number of sunburn cells). However, an immunoprotective trend was observed by preserving the number of Langerhans cells. The product did not show any significant improvements on skin quality parameters (hydration, transepidermal water loss and elasticity).