Can Polyphenols Inhibit Ferroptosis?

Polyphenols, a diverse group of naturally occurring molecules commonly found in higher plants, have been heavily investigated over the last two decades due to their potent biological activities—among which the most important are their antioxidant, antimicrobial, anticancer, anti-inflammatory and neuroprotective activities. A common route of polyphenol intake in humans is through the diet. Since they are subjected to excessive metabolism in vivo it has been questioned whether their much-proven in vitro bioactivity could be translated to in vivo systems. Ferroptosis is a newly introduced, iron-dependent, regulated mode of oxidative cell death, characterized by increased lipid peroxidation and the accumulation of toxic lipid peroxides, which are considered to be toxic reactive oxygen species. There is a growing body of evidence that ferroptosis is involved in the development of almost all chronic diseases. Thus, ferroptosis is considered a new therapeutic target for offsetting many diseases, and researchers are putting great expectations on this field of research and medicine. The aim of this review is to critically analyse the potential of polyphenols to modulate ferroptosis and whether they can be considered promising compounds for the alleviation of chronic conditions.

1107Dietary polyphenol intake and differentiated thyroid cancer risk: a population-based case-control study in New Caledonia

Background Aetiology of differentiated thyroid cancer is poorly understood. Among the risk factors strongly suspected to be involved in thyroid carcinogenesis are dietary factors. Recent evidence suggests polyphenols (i.e., natural bioactive compounds found in plant species), and their anticancer properties, may deserve closer epidemiological attention. Therefore, we examined the association between polyphenol intake levels and thyroid cancer risk in New Caledonia – a Pacific archipelago with some of the highest recorded thyroid cancer incidence rates in the world. Methods Food frequency questionnaire information from a population-based case-control study was used. Daily lignan and flavonoid intakes, expressed as aglycone equivalents, were estimated using Phenol-Explorer and relevant USDA databases. Unconditional logistic regression analyses were performed on data from 324 histologically confirmed cases of papillary or follicular carcinoma, diagnosed from 1993 to 1999, and 402 controls. Polyphenol intakes were analysed as both continuous and categorical variables (quartiles). Results Estimated median flavonoid and lignan intakes were 351.0 and 2.6 mg, respectively. When adjusting for sex, age, ethnic community, province of residence, BMI, smoking status, alcohol consumption and energy intake, no association with differentiated thyroid cancer risk was observed for flavonoids (OR = 1.06, 95% CI: 0.66, 1.70; comparing extreme quartiles), but a negative association was demonstrated for lignans (ORQ4vs.Q1=0.60, 95% CI: 0.37, 0.96; comparing extreme quartiles). Conclusions Our findings suggest that lignans may exert a protective effect on differentiated thyroid cancer. However, large-scale cohort studies and further analytical data on lignans are required to confirm this association. Key messages Lignans may play a role in thyroid carcinogenesis.

Polyphenol Intake and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Despite some epidemiological evidence on the protective effects of polyphenol intake on epithelial ovarian cancer (EOC) risk from case-control studies, the evidence is scarce from prospective studies and non-existent for several polyphenol classes. Therefore, we aimed to investigate the associations between the intake of total, classes and subclasses of polyphenols and EOC risk in a large prospective study. The study was conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 309,129 adult women recruited mostly from the general population. Polyphenol intake was assessed through validated country-specific dietary questionnaires and the Phenol-Explorer database. During a mean follow-up of 14 years, 1469 first incident EOC cases (including 806 serous, 129 endometrioid, 102 mucinous, and 67 clear cell tumours) were identified. In multivariable-adjusted Cox regression models, the hazard ratio in the highest quartile of total polyphenol intake compared with the lowest quartile (HRQ4vsQ1) was 1.14 (95% CI 0.94–1.39; p-trend = 0.11). Similarly, the intake of most classes and subclasses of polyphenols were not related to either overall EOC risk or any EOC subtype. A borderline statistically significant positive association was observed between phenolic acid intake (HRQ4vsQ1 = 1.20, 95% CI 1.01–1.43; p-trend = 0.02) and EOC risk, especially for the serous subtype and in women with obesity, although these associations did not exceed the Bonferroni correction threshold. The current results do not support any association between polyphenol intake and EOC in our large European prospective study. Results regarding phenolic acid intake need further investigation

Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications

Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.

A useful and simple tool to evaluate and compare the intake of total dietary polyphenols in different populations

Objective: Polyphenols are antioxidant compounds with an impact on different health factors. Thus, it is important to have precise tools to estimate the intake of polyphenols. This study focuses on the development of an intuitive tool to estimating the intake of dietary total polyphenols. Design: The tool was developed in a spreadsheet to improve accessibility and use. It is divided into six different meals for each of the 7 days with a similar format to 24-hour diet recalls. The total polyphenol values of 302 foods were included and the possibility of own values. Setting: Framework of the European project Stance4Health, Granada, Spain. Participants: This tool was tested on 90 participants in different stages of life (girls, women and pregnant women). Ages ranged from 10 to 35. Results: The total polyphenol intake obtained was of 1790 ± 629 mg polyphenols/day. The highest consumption of polyphenols was observed in pregnant women (2064 mg/day). Polyphenols intake during the weekend was lower for the 3 groups compared to the days of the week. The results were comparable with those of other studies. Conclusions: The current tool allows the estimation of the total intake of polyphenols in the diet in a fast and easy way. The tool will be used as a basis for a future mobile application.