Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we discuss the importance of phenolic compounds’ bioavailability to accomplish their physiological functions, and highlight main factors affecting such parameter throughout metabolism of phenolics, from absorption to excretion. Besides, we give an updated overview of the health benefits of phenolic compounds, which are mainly linked to both their direct (e.g., free-radical scavenging ability) and indirect (e.g., by stimulating activity of antioxidant enzymes) antioxidant properties. Such antioxidant actions reportedly help them to prevent chronic and oxidative stress-related disorders such as cancer, cardiovascular and neurodegenerative diseases, among others. Last, we comment on development of cutting-edge delivery systems intended to improve bioavailability and enhance stability of phenolic compounds in the human body.

Background Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes.Methods We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations.ResultsWe observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54–0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43–0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63–1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40–0.94; P = 0.024 versus CC) in the multivariable-adjusted model.ConclusionsIn agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0327-8) contains supplementary material, which is available to authorized users.