Dietary (poly)phenols and cardiometabolic health: from antioxidants to modulators of the gut microbiota.

(Poly)phenols are plant secondary metabolites widely abundant in plant foods and beverages comprising a very large number of compounds with diverse structure and biological activities. Accumulating evidence indicates that these compounds exert beneficial effects against cardiometabolic diseases, and this review will provide a summary of current knowledge in this area. Epidemiological and clinical data collectively suggest that intake of flavonoids reduces the risk of cardiovascular disease (CVD), with the evidence being particularly strong for the flavan-3-ol subclass. However, to provide adequate dietary recommendations, a better understanding of their estimated content in foods and intake among the general public is needed. Regarding mechanisms of action, we now know that it is unlikely that (poly)phenols act as direct antioxidants in vivo, as it was hypothesised for decades with the popularity of in vitro antioxidant capacity assays. One of the reasons is that upon ingestion, (poly)phenols are extensively metabolised into a wide array of circulating metabolites with different bioactivities than their precursors. Well-conducted in vitro and in vivo studies and human nutrigenomic analysis have revealed new molecular targets that may be underlying the health benefits of (poly)phenols, such as the nitric oxide pathway. Recently, a bi-directional relationship was established between (poly)phenols and the gut microbiota, suggesting that individual gut microbial metabolising capacity may be a key factor explaining the variability in the cardiometabolic response to (poly)phenols. Future research is needed to elucidate which are the key factors affecting such capacity, and whether it can be modulated, along with the mechanisms of action.

Biomarkers of Berry Intake: Systematic Review Update.

Berries are rich in (poly)phenols, and these compounds may be beneficial to human health. Estimating berry consumption through self-reported questionnaires has been challenging due to compliance issues and a lack of precision. Estimation via food-derived biomarkers in biofluids was proposed as a complementary alternative. We aimed to review and update the existing evidence on biomarkers of intake for six different types of berries. A systematic literature search was performed to update a previous systematic review on PubMed, Web of Science, and Scopus from January 2020 until December 2022. Out of 42 papers, only 18 studies were eligible. A multimetabolite panel is suggested for blueberry and cranberry intake. Proposed biomarkers for blueberries include hippuric acid and malvidin glycosides. For cranberries, suggested biomarkers are glycosides of peonidin and cyanidin together with sulfate and glucuronide conjugates of phenyl-γ-valerolactone derivatives. No new metabolite candidates have been found for raspberries, strawberries, blackcurrants, and blackberries. Further studies are encouraged to validate these multimetabolite panels for improving the estimation of berry consumption.

Comparison between dietary assessment methods and biomarkers in estimating dietary (poly)phenol intake.

Background: although widely used, there is limited understanding of the suitability of different dietary assessment tools to estimate (poly)phenol intake. This study aims to compare the agreement between a food frequency questionnaire (FFQ) and a 7-day food diary (7DD) in assessing (poly)phenol intake and explore their associations with the urinary and plasma (poly)phenol metabolites. Methods: healthy free-living participants aged 18-80 years (n = 413) completed a 7DD and an FFQ (EPIC-Norfolk) and provided a 24 h urine and a fasting plasma sample. A comprehensive in-house (poly)phenol database was used to estimate (poly)phenol intake. The phenolic metabolite levels were analysed using a validated LC-MS method. The agreement between dietary assessment methods and biomarkers were evaluated by intraclass correlation coefficients (ICC), weighted kappa, quartile classification, Bland-Altman plots and correlations. Results: the total (poly)phenol intake estimated from FFQ was higher than from 7DD (median 1463 and 1042 mg d-1, respectively). The agreement between FFQ and 7DD were moderate (ICC 0.51-0.59) for total (poly)phenols, flavan-3-ols, total phenolic acids, hydroxycinnamic acids and alkylmethoxyphenols, and were poor for all the other classes and subclasses (ICC 0.00-0.48). Positive correlations with total urine phenolic metabolites were found in FFQ estimated anthocyanins, dihydroflavonols, total lignans, tyrosols, alkylmethoxyphenols, total phenolic acids, and total stilbenes and the 7DD estimated theaflavins and thearubigins (all FDR adjusted p values < 0.1). No significant correlations were found between total plasma phenolic metabolites and (poly)phenol intake. Conclusion: agreements between dietary assessment tools were moderate for the major classes of (poly)phenols, while agreements between (poly)phenol intake and biomarkers were poor. Future research using biomarker approaches to increase the accuracy of estimating (poly)phenol exposure in larger populations is needed.

Betalain-rich dragon fruit (pitaya) consumption improves vascular function in men and women: a double-blind, randomized controlled crossover trial.

BACKGROUND: Betalains are natural red color pigments abundant in red-fleshed dragon fruit (Hylocereus polyrhizus). Recent research has shown that dragon fruit consumption may help improve blood glucose and lipid profile. However, investigations of its cardioprotective properties in human trials, especially in nutritionally achievable amounts, remain nonexistent. OBJECTIVES: The aim of this study was to investigate the effects of acute and short-term consumption of dragon fruit on vascular function in a healthy population. METHODS: A randomized, double-blind, placebo-controlled, crossover trial was conducted in 19 young, healthy, nonsmoking men and women assigned to consume 24 g whole dragon fruit powder (33 mg betalains) or a nutrient-matched placebo, daily for 14 d. Flow-mediated dilation (FMD), arterial stiffness, and blood pressure (BP) were measured at 0 h, 1 h, 2 h, 3 h, and 4 h and finally at 14 d after daily consumption. RESULTS: A total of 18 participants completed the trial. Dragon fruit consumption significantly improved acute FMD at 2 h (+0.8 ± 0.3%, P = 0.01), 3 h (+1.0 ± 0.3%, P = 0.001), and 4 h (+1.3 ± 0.4%, P < 0.001) postconsumption compared with placebo. This effect was sustained up until 14 d (+1.3 ± 0.2%, P < 0.001). Pulse-wave velocity was acutely significantly reduced at 3 h (-0.5 ± 0.2 m/s, P = 0.003), whereas augmentation index (AIx) also improved after 14 d (-7.0 ± 3.3%, P = 0.02) when compared with placebo. No differences were found in either peripheral or central BP across all time points. CONCLUSIONS: Acute and short-term consumption of dragon fruit in dietary achievable amounts improved endothelial function and arterial stiffness in healthy individuals. This implies that regular dragon fruit consumption may have a meaningful impact on cardiovascular disease risk likely due to the high betalain content. This trial was registered at ClinicalTrials.gov as NCT03995602.

The effects of betalain-rich cacti (dragon fruit and cactus pear) on endothelial and vascular function: a systematic review of animal and human studies.

Dragon fruit (Hylocereus) and cactus pear (Opuntia) are cacti species that have been widely used globally as a reliable source of food as well as traditional folk remedies. They have become of scientific interest recently due to their high levels of bioactive phytochemical compounds, in particular betalains. Earlier systematic reviews have explored the impact of supplementation of these cactus species on obesity, type-2 diabetes mellitus and cardiovascular risk factors: body weight and composition, serum triglycerides, cholesterol, blood glucose and blood pressure. However, effects on vascular health and endothelial function have yet to be reviewed. In order to address this gap in the literature, a systematic review has been conducted to evaluate the physiological effects of Hylocereus and Opuntia cacti on endothelial and vascular function in in vivo animal models and human studies. An electronic search was performed in the following databases: PubMed (MEDLINE), EMBASE (via Ovid), CINAHL, Scopus, Web of Science®, and The Cochrane Library (CENTRAL). All journals were searched since inceptions up to January 2020 without language restriction. Outcomes of interest were blood pressure, arterial stiffness, vascular reactivity and biochemical markers of endothelial dysfunction. Two investigators independently performed the study selection and data extraction. From 394 references, only 16 studies (9 animal and 7 human) fulfilled the eligibility criteria. Animal studies suggested a potential increase in vasodilation and serum nitric oxide and a reduction in vascular stiffness and blood pressure. The small number of human studies showed a reduction in heart rate as well as an increase in heart rate variability. Although these findings appear to indicate improvement in vascular health, there is a severe lack of robust, randomised human intervention studies to identify underlying mechanisms, optimal dose and long-term effects of cacti consumption.

Microbiota Changes Due to Grape Seed Extract Diet Improved Intestinal Homeostasis and Decreased Fatness in Parental Broiler Hens.

In poultry, the selection of broilers for growth performance has induced a deterioration in the health of the parental hens associated with poor reproductive efficiency. To improve these parameters, we administered to laying parental broiler hens a regular diet supplemented or not (Control) with a moderate (1%) or a high level (2%) of grape seed extract (GSE). The 1% GSE diet was administered from a young age (from 4 to 40 weeks of age) and the high level of 2% GSE was administered only during a 2-week period (from 38 to 40 weeks of age) in the laying period. The analysis of 40-week-old hens showed that 2% GSE displayed a reduction in the fat tissue and an improvement in fertility with heavier and more resistant eggs. Seven monomer phenolic metabolites of GSE were significantly measured in the plasma of the 2% GSE hens. GSE supplementation increased the relative abundance of the following bacteria populations: Bifidobacteriaceae, Lactobacilliaceae and Lachnospiraceae. In conclusion, a supplementation period of only 2 weeks with 2% GSE is sufficient to improve the metabolic and laying parameters of breeder hens through a modification in the microbiota.