Aedin Cassidy’s research while affiliated with Queen's University Belfast and other places

Higher habitual intakes of dietary flavonoids have been linked with a lower risk of all-cause mortality and major chronic disease. Yet, the contribution of diversity of flavonoid intake to health outcomes remains to be investigated. Here, using a cohort of 124,805 UK Biobank participants, we show that participants who consumed the widest diversity of dietary flavonoids, flavonoid-rich foods and/or specific flavonoid subclasses had a 6–20% significantly lower risk of all-cause mortality and incidence of cardiovascular disease, type 2 diabetes, cancer, respiratory disease and neurodegenerative disease. Furthermore, we report that both quantity and diversity of flavonoids are independent predictors of mortality and several chronic diseases, suggesting that consuming a higher quantity and wider diversity is better for longer-term health than either component alone. These findings suggest that consuming several different daily servings of flavonoid-rich foods or beverages, such as tea, berries, apples, oranges or grapes, may lower risk of all-cause mortality and chronic disease.

Background Significant advancements in treatment and care, as well as early detection, have contributed to an increase in cancer survival rates. Recently, the EAT-Lancet Commission on Food, Planet, Health proposed the “planetary health diet” but to date, no study has investigated the potential associations between adherence to the EAT-Lancet reference diet and mortality in cancer survivors. To determine whether higher adherence to the EAT-Lancet reference diet is associated with lower risk for all-cause, cancer, and cardiovascular mortality in cancer survivors. Methods Data from the prospective UK Biobank study were used. Information from UK Biobank’s Touchscreen questionnaire was used to develop a score reflecting adherence to the EAT-Lancet reference diet. Cox proportional hazards regression was used to assess the association of the EAT-Lancet reference diet score with all-cause, cancer, and cardiovascular mortality in cancer survivors. Results Within 25,348 cancer survivors, better adherence to the EAT-Lancet reference diet was inversely related to all-cause mortality (hazard ratio (HR): 0.97, 95% confidence interval (CI): 0.95–0.99), 1 unit increase) and cancer mortality (HR: 0.98, 95% CI: 0.96–1.00), while mostly null associations were observed for major cardiovascular mortality (HR: 0.99, 95% CI: 0.95–1.03). Conclusions Our findings suggest the adoption of the EAT-Lancet reference diet is associated with lower all-cause and cancer-specific mortality among cancer survivors.

Background Plant-based diets are gaining popularity due to their well-documented cardiometabolic benefits and environmental sustainability. However, these diets are often lower in specific micronutrients such as iodine, raising concerns about their potential impact on thyroid health. Therefore, we examined the associations between plant-based diets and the risk of hypothyroidism. Methods We analysed data from the UK (United Kingdom) Biobank cohort. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident hypothyroidism across vegans, vegetarians, pescatarians, poultry-eaters, low meat-eaters, and high meat-eaters aged 40–69 years. Ancillary to this, we carried out logistic regression analyses to evaluate associations between the diet groups and prevalent hypothyroidism according to International Classification of Diseases (ICD) codes at baseline. Results We included 466,362 individuals from the UK Biobank, of which 220,514 followed a high meat, 221,554 a low meat, 5242 a poultry-based, 10,598 a pescatarian, 8057 a vegetarian, and 397 a vegan diet. During a median SD (Standard Deviation) follow-up of 12.7 (± 3.2) years, 10,831 participants developed hypothyroidism. In multivariable Cox regression models without adjustment for body mass index (BMI), none of the diets were significantly associated with the risk of hypothyroidism. However, there was a tendency for a higher risk of hypothyroidism among vegetarians compared to people following a high meat diet (HR = 1.13, 95% CI 0.98–1.30). After controlling for BMI, a potential collider, the association for vegetarians (HR = 1.23, 95% CI 1.07–1.42) became stronger and statistically significant. Furthermore, we observed a positive association between low meat-eaters (OR = 1.05, 95% CI 1.03–1.08), poultry-eaters (OR = 1.15, 95% CI 1.04–1.28), pescatarians (OR = 1.10, 95% CI 1.01–1.19) and vegetarian (OR = 1.26, 95% CI 1.15–1.38) with hypothyroidism prevalence. Conclusions In the present study, we found a moderately higher risk of hypothyroidism among vegetarians, after controlling for BMI, a potential collider. This slightly higher risk of hypothyroidism among vegetarians requires further investigation, taking iodine status and thyroid hormone levels into account.

There is an increasing body of evidence indicating that phenolic compounds derived from microbiota-mediated breakdown of dietary (poly)phenolics in the colon are at least partially responsible for the beneficial effects of a plant-based diet. Investigating the role of these catabolites and defining their particular biological effects is challenging due to the complex microbial pathways and the diversity of structures that are produced. When reviewing the data this is further exacerbated by the inconsistency and lack of standardization in naming the microbial phenolics. Here we update the nomenclature of colonic catabolites of dietary (poly)phenols, extending the proposals of Kay et al. (Am. J. Clin. Nutr., 2020, 112, 1051-1068, DOI: 10.1093/ajcn/nqaa204), by providing additional structures, and addressing the difficulties that can arise when investigating regioisomers and stereoisomers, where subtle differences in structure can have a substantial impact on bioactivity. The information provided will help to better harmonize the literature, facilitate data retrieval and provide a reference for researchers in several fields, especially nutrition and biochemistry.

Background Our knowledge of the importance of flavonoid-rich foods in preventing unhealthy aging across its different domains is limited. Objectives This study aimed to examine prospective associations between flavonoid-rich food and flavonoid intakes and indicators of unhealthy aging, namely frailty, impaired physical function, and poor mental health. Methods We followed up 62,743 females and 23,687 males, all aged ≥60 y, from the Nurses’ Health Study (1990–2014) and Health Professionals Follow-up Study (2006–2018), respectively. Both time-updated and change in intakes of a flavodiet score (an aggregate of intakes of major flavonoid-rich foods and beverages) and individual flavonoid-rich foods and beverages and time-updated intakes of total flavonoids and flavonoid subclasses were calculated from food frequency questionnaires collected at baseline and every subsequent 4 y. Associations with incident frailty, impaired physical function, and poor mental health, assessed from self-reported questionnaire responses, were examined with multivariable-adjusted Cox proportional hazards models. Results In the Nurses’ Health Study, participants with the highest flavodiet scores, compared with the lowest, had a 15% lower risk of frailty (HRQ5vsQ1: 0.85; 95%CI: 0.80, 0.90), a 12% lower risk of impaired physical function (HRQ5vsQ1: 0.88; 95% CI: 0.84, 0.91), and a 12% lower risk of poor mental health (HRQ5vsQ1: 0.88; 95% CI: 0.82, 0.94). Increases in flavodiet scores and both higher intakes and increases in intakes of tea, red wine, apples, blueberries, and oranges tended to be associated with lower risks of all outcomes. Higher intakes of total flavonoids and all flavonoid subclasses tended to be associated with a lower risk of each outcome. Although fewer associations were observed among males in the Health Professionals Follow-up Study, those with the highest flavodiet scores had a lower risk of poor mental health. Conclusions High intakes of flavonoid-rich foods may support healthy aging. Further research is needed, including examining sex-specific associations, as incorporating flavonoid-rich foods in the diet may be a simple strategy to support healthy aging.

Mechanistic studies and short-term randomised trials suggest that higher intakes of dietary flavonoids may protect against non-alcoholic fatty liver disease (NAFLD) (1–3) . However, little research has been conducted at a population level, and to date no long term prospective study has assessed the associations between flavonoid intakes and NAFLD risk ⁽⁴⁾ . We aim to perform the first population-based study with long-term follow-up on flavonoid consumption and NAFLD incidence. In a prospective study, we assessed the associations between flavonoid intakes based on ≥2 24hour dietary assessments and NAFLD risk among 121,563 adults aged 40 to 69 years by multivariable regression analyses. Flavonoid intakes were assessed on three levels: a novel flavodiet score (FDS), flavonoid rich foods, and flavonoid subclasses. Cox proportional hazard models were used to assess NAFLD risk, and linear trend tests were used to test for significance. Additional sensitivity analysis was conducted using both a FDS excluding red wine, and non flavonoid containing equivalent foods as negative controls. Over 10 years of follow-up, 1090 cases of NAFLD were observed. When compared to the lowest Quartile, the highest quartile (Q4) of the Flavodiet Score (FDS) was associated with a 20% lower risk of NAFLD (HR (95%CI): 0.80 (0.66−0.96), P trend = 0.02). Additionally, higher apple intake was associated with a 22% lower risk of NAFLD (HR (95%CI): 0.78 (0.66 - 0.92), P trend = <0.01), while higher tea consumption was associated with a 13% lower risk of NAFLD (HR (95%CI): 0.87 (0.73 -1.03), P trend = 0.046). Of the flavonoid subclasses, we observed that higher intakes of proanthocyanidins, theaflavins and thearubigins, flavonols and flavan-3-ols were also associated with lower risk. In a large UK cohort, we demonstrate for the first time that flavonoid-rich diets, containing approximately 6-servings of flavonoid rich food per day, are associated with lower risk of NAFLD. As such, the consumption of flavonoid-rich foods may reduce the risk of NAFLD and its sequalae among middle-aged adults.

Chronic kidney disease (CKD) is highly prevalent among people with diabetes (1,2) . While identifying modifiable risk factors to prevent a decline in kidney function among those living with diabetes is pivotal, there is limited evidence on dietary risk factors for CKD. In this study we examined the associations between healthy and less healthy plant-based diets (PBDs) and the risk of CKD among those with diabetes, and to identify potential underlying mechanisms. We conducted a prospective analysis among 7,747 UK Biobank participants with prevalent diabetes (Type 1 and Type 2). Multivariable Cox proportional hazard regression models were used to examine the associations between healthful and unhealthful plant-based indices (hPDI and uPDI) and the risk of CKD. Fruits, legumes, nuts, tea and coffee, vegetables and whole grains were classified as healthy plant-based foods, whereas fruit juice, potatoes, refined grains, sugary drinks as well as sweets and desserts were classified as unhealthy plant-based foods. Animal-based foods used for the PDIs were grouped into meat, eggs, dairy products, animal fat, seafood or fish, and miscellaneous animal-based foods. Causal mediation analyses were further employed to explore the underlying mechanisms of the observed associations. Among 7,747 study participants with diabetes, 1,030 developed incident CKD over 10.2 years of follow-up. The mean (SD) age was 58.8 (7.2) years, 6,910 (89.2%) were White, and 3,829 (49.4%) had a BMI over ≥30kg/m ² . Higher adherence to a healthy PBD was associated with a 24% lower CKD risk (HR Q4 versus Q1 : 0.76 [95%CI: 0.63−0.92], p trend = 0.002), while higher adherence to an unhealthy PBD was associated with a 35% higher risk (HR Q4 versus Q1 : 1.35 [95%CI: 1.11-1.65], p trend = 0.006). The observed associations were predominantly mediated by markers of body fatness (proportion mediated: 11-25%) and kidney function (23-89%). In this prospective cohort study of UK adults with diabetes, adherence to a healthy PBD was associated with lower CKD risk, whereas adherence to an unhealthy PBD was associated with a higher CKD risk. Associations were primarily mediated by markers of lower body fatness and improved kidney function.

Background: Globally, plant-based diets are gaining in popularity. Whilst their cardiometabolic benefits are well-documented, there is a lack of studies examining the associations between plant-based diets and risk of hypothyroidism. Methods: We analysed data from the UK Biobank cohort. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident hypothyroidism across vegans, vegetarians, pescatarians, poultry eaters, low meat eaters, and high meat eaters aged 40-69 years. Ancillary to this, we carried out logistic regression analyses to evaluate associations between the diet groups and prevalent hypothyroidism (according to International Classification of Diseases (ICD) codes at baseline. Results: We included 494,437 individuals from the UK Biobank, of which 231,906 followed a high-meat, 236,510 a low-meat, 5,662 a poultry-based, 11,286 a pescatarian, 8,654 a vegetarian, and 419 a vegan diet. During a median (SD) follow-up of 12.7 (+/- 3.2) years, 24,240 participants developed hypothyroidism. In multivariable Cox regression models without adjustment for body mass index (BMI), none of the diets were significantly associated with the risk of hypothyroidism. However, there was a tendency for a higher risk of hypothyroidism among vegetarians compared to people following a high-meat diet (HR: 1.08, 95% CI: 0.98 - 1.19). After controlling for BMI the association for vegetarians (HR = 1.18, 95% CI 1.07 - 1.30) became stronger and statistically significant. Furthermore, we observed a positive association between a vegetarian (OR: 1.37, 95% CI: 1.14 - 1.63) and a poultry diet (OR: 1.35, 95% CI: 1.10 - 1.63) with hypothyroidism prevalence. Conclusion: In the present study, we found a moderately higher risk of hypothyroidism among vegetarians, after controlling for BMI, a potential collider. This slightly higher risk of hypothyroidism among vegetarians, requires further investigation, taking iodine status and thyroid hormone levels into account. Keywords Plant-based diets, hypothyroidism, vegan, vegetarian, thyroid, iodine