Publications by authors named "Nicola P Bondonno"

40 Publications

The effect of vitamin K1 on arterial calcification activity in subjects with diabetes mellitus: a post hoc analysis of a double-blind, randomized, placebo-controlled trial.

Am J Clin Nutr 2021 Oct 12. Epub 2021 Oct 12.

Division of Internal Medicine, Medical School, University of Western Australia, Perth, Western Australia, Australia.

Background: Coronary and aortic artery calcifications are generally slow to develop, and their burden predicts cardiovascular disease events. In patients with diabetes mellitus, arterial calcification is accelerated and calcification activity can be detected using 18F-sodium fluoride positron emission tomography (18F-NaF PET).

Objectives: We aimed to determine whether vitamin K1 supplementation inhibits arterial calcification activity in individuals with diabetes mellitus.

Methods: This was a post hoc analysis of the ViKCoVaC (effect of Vitamin-K1 and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial conducted in Perth, Western Australia. Individuals with diabetes mellitus and established coronary calcification (coronary calcium score > 10), but without clinical coronary artery disease, underwent baseline 18F-NaF PET imaging, followed by oral vitamin K1 supplementation (10 mg/d) or placebo for 3 mo, after which 18F-NaF PET imaging was repeated. We tested whether individuals randomly assigned to vitamin K1 supplementation had reduced development of new 18F-NaF PET positive lesions within the coronary arteries and aorta.

Results: In total, 149 individuals completed baseline and follow-up imaging studies. Vitamin K1 supplementation independently decreased the odds of developing new 18F-NaF PET positive lesions in the coronary arteries (OR: 0.35; 95% CI: 0.16, 0.78; P = 0.010), aorta (OR: 0.27; 95% CI: 0.08, 0.94; P = 0.040), and in both aortic and coronary arteries (OR: 0.28; 95% CI: 0.13, 0.63; P = 0.002).

Conclusions: In individuals with diabetes mellitus, supplementation with 10 mg vitamin K1/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis.This trial was registered at anzctr.org.au as ACTRN12616000024448.
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http://dx.doi.org/10.1093/ajcn/nqab306DOI Listing
October 2021

Association between vitamin K intake and mortality in the Danish Diet, Cancer, and Health cohort.

Eur J Epidemiol 2021 Sep 30. Epub 2021 Sep 30.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.

Reported associations between vitamin K and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52-60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87-192 µg/d) intake of vitamin K was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.
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http://dx.doi.org/10.1007/s10654-021-00806-9DOI Listing
September 2021

Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults.

Br J Nutr 2021 Aug 23:1-11. Epub 2021 Aug 23.

School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, Australia.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (-1·56 mmHg, 95 % CI -2·65, -0·48) and cMAP (-1·62 mmHg, 95 % CI -2·82, -0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (-0·93 %, 95 % CI -1·77, -0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.
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http://dx.doi.org/10.1017/S000711452100324XDOI Listing
August 2021

Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study.

J Am Heart Assoc 2021 08 7;10(16):e020551. Epub 2021 Aug 7.

Institute for Nutrition Research School of Medical and Health Sciences Edith Cowan University Perth Australia.

Background Dietary vitamin K (K and K) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K and vitamin K were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K, the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K or K. The similar inverse associations with both vitamin K and K, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.
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http://dx.doi.org/10.1161/JAHA.120.020551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475061PMC
August 2021

Higher Habitual Flavonoid Intakes Are Associated With A Lower Incidence Of Diabetes.

J Nutr 2021 Jul 27. Epub 2021 Jul 27.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.

Background: Higher flavonoid intakes are hypothesised to confer protection against type 2 diabetes mellitus.

Objective: We aimed to 1) investigate associations between flavonoid intakes and diabetes, 2) examine the mediating impact of body fat, and 3) identify subpopulations that may receive the greatest benefit from higher flavonoid intakes in participants of the Danish Diet, Cancer, and Health Study followed-up for 23 years.

Design: Cross-sectional associations between baseline flavonoid intake, estimated using food frequency questionnaires and the Phenol Explorer database, and body fat estimated by bioelectrical impedance, were assessed using multivariable-adjusted linear regression models. Non-linear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines with multivariable-adjusted Cox proportional hazards models.

Results: Among 54,787 participants (median [IQR] age of 56 [52-60] years; (47.3%) men), 6700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1,202 mg/d) had a 1.52 kg lower body fat (95%CI: -1.74, -1.30) and a 19% lower risk of diabetes [hazard ratio (95%CI): 0.81 (0.75, 0.87)] after multivariable adjustments and compared to participants in the lowest intake quintile (median, 174 mg/d). Body fat mediated 57% (95% CI: 42%, 83%) of the association between flavonoid intake and incident diabetes. Of the flavonoid subclasses, moderate to high intakes of flavonols, flavanol monomers, flavanol oligo + polymers, and anthocyanins were significantly associated with a lower risk of diabetes. While associations were not modified by sex, smoking status, BMI or physical activity (pinteraction > 0.05 for all), findings on an absolute scale suggest that those at a higher risk (those with obesity) may benefit the most from a higher flavonoid intake.

Conclusions: These findings suggest that a diet abundant in flavonoid-rich foods may help to ameliorate diabetes risk, in part through a reduction in body fat.
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http://dx.doi.org/10.1093/jn/nxab269DOI Listing
July 2021

Associations Between Fruit Intake and Risk of Diabetes in the AusDiab Cohort.

J Clin Endocrinol Metab 2021 Sep;106(10):e4097-e4108

School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia 6027, Australia.

Context: Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection.

Objective: The aims of this work were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up.

Methods: Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-hour postload plasma glucose, updated homeostasis model assessment of insulin resistance of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models.

Results: This population of 7675 Australians (45% males) had a mean ± SD age of 54 ± 12 years at baseline. Total fruit intake was inversely associated with serum insulin and HOMA2-%β, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had 36% lower odds of having diabetes at 5 years (odds ratio, 0.64; 95% CI, 0.44-0.92), after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant.

Conclusion: A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.
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http://dx.doi.org/10.1210/clinem/dgab335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475213PMC
September 2021

Flavonoid intake and incident dementia in the Danish Diet, Cancer, and Health cohort.

Alzheimers Dement (N Y) 2021 13;7(1):e12175. Epub 2021 May 13.

School of Medical and Health Sciences Edith Cowan University Perth Australia.

Introduction: Prospective studies investigating flavonoid intake and dementia risk are scarce. The aims of this study were to examine associations between flavonoid intake and the risk of incident dementia and to investigate whether this association differs in the presence of lifestyle risk factors for dementia.

Methods: We examined associations in 55,985 participants of the Danish Diet, Cancer, and Health Study followed for 23 years. The Phenol-Explorer database was used to estimate flavonoid intakes. Information on incident dementia and dementia subtypes was obtained using Danish patient and prescription registries. Hazard ratios (HRs) were calculated using restricted cubic splines in multivariable-adjusted Cox proportional hazards models.

Results: For incident dementia, moderate compared to low intakes of flavonols (HR: 0.90 [0.82, 0.99]), flavanol oligo+polymers (HR: 0.87 [0.79, 0.96]), anthocyanins (HR: 0.84 [0.76, 0.93]), flavanones (HR: 0.89 [0.80, 0.99]), and flavones (HR: 0.85 [0.77, 0.95]) were associated with a lower risk. For vascular dementia, moderate intakes of flavonols (HR: 0.69 [0.53, 0.89]) and flavanol oligo + polymers (HR: 0.65 [0.51, 0.83]) were associated with lower risk. Flavonoid intakes were not significantly associated with Alzheimer's disease or unspecified dementia. The inverse association between total flavonoid intake and incident dementia was stronger in "ever" smokers than in "never" smokers and in those without hypercholesterolemia versus those with hypercholesteremia. Furthermore, the inverse association of vascular dementia with a moderate total flavonoid intake was stronger in "ever" smokers and those who were "normal" to "overweight" versus "never" smokers or those who were "obese," respectively.

Conclusion: A moderate intake of flavonoid-rich foods may help to reduce dementia risk.
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http://dx.doi.org/10.1002/trc2.12175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118115PMC
May 2021

Dietary flavonoids are associated with longitudinal treatment outcomes in neovascular age-related macular degeneration.

Eur J Nutr 2021 May 19. Epub 2021 May 19.

Centre for Vision Research, Department of Ophthalmology and The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.

Purpose: To assess whether dietary intake of flavonoids are associated with longitudinal treatment outcomes of patients with neovascular age-related macular degeneration (nAMD).

Methods: 547 participants with nAMD were recruited at baseline, 494 were followed-up after receiving 12 months of anti-vascular endothelial growth factor (anti-VEGF) therapy. Baseline dietary intake of flavonoids was determined using a validated food frequency questionnaire. At follow-up, presence of intra-retinal and sub-retinal fluid (IRF and SRF), retinal pigment epithelium detachment and measurements of central macular thickness (CMT) were recorded from optical coherence tomography scans. Visual acuity (VA) was documented using LogMAR charts.

Results: Participants in the first tertile of intake of the flavonol quercetin, and the flavan-3-ols epigallocatechin-3-gallate and epigallocatechin had significantly worse vision than participants in the third tertile-multivariable-adjusted least square (LS) mean VA: 14.68 vs. 19.53 (p = 0.04); 14.06 vs. 18.89 (p = 0.04); 13.86 vs. 18.86 (p = 0.03), respectively. Participants in the first compared to the third tertile of flavan-3-ol, epigallocatechin-3-gallate and epigallocatechin intake all had a twofold higher risk of IRF, multivariable-adjusted p trend of: 0.03, 0.01 and 0.02, respectively. The first vs. the third tertile of tea intake had significantly worse vision (LS mean VA: 13.49 vs. 19.04, p = 0.02), increased risk of IRF (OR 2.13, 95% CI 1.18-3.85) and greater mean CMT (279.59 μm vs. 256.52 μm, p = 0.04).

Conclusions: Higher intakes of dietary flavonoids, specifically flavonols and flavan-3-ols, could be associated with better long-term treatment outcomes in nAMD patients receiving anti-VEGF therapy. Confirmation of these associations in interventional studies could result in promising new therapeutic approaches to the treatment of nAMD.
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http://dx.doi.org/10.1007/s00394-021-02582-4DOI Listing
May 2021

Habitual flavonoid intake and ischemic stroke incidence in the Danish Diet, Cancer, and Health Cohort.

Am J Clin Nutr 2021 07;114(1):348-357

School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, Australia.

Background: Flavonoid-rich foods have antiinflammatory, antiatherogenic, and antithrombotic properties that may contribute to a lower risk of ischemic stroke.

Objectives: We aimed to investigate the relationship between habitual flavonoid consumption and incidence of ischemic stroke in participants from the Danish Diet, Cancer and Health Study.

Design: In this prospective cohort study, 55,169 Danish residents without a prior ischemic stroke [median (IQR) age at enrolment of 56 y (52-60)], were followed for 21 y (20-22). We used Phenol-Explorer to estimate flavonoid intake from food frequency questionnaires obtained at study entry. Incident cases of ischemic stroke were identified from Danish nationwide registries and restricted cubic splines in Cox proportional hazards models were used to investigate relationships with flavonoid intake.

Results: During follow-up, 4237 individuals experienced an ischemic stroke. Compared with participants in Q1 and after multivariable adjustment for demographics and lifestyle factors, those in Q5-for intake of total flavonoids, flavonols, and flavanol oligo + polymers-had a 12% [HR (95% CI): 0.88 (0.81, 0.96)], 10% [0.90 (0.82, 0.98)], and 18% [0.82 (0.75, 0.89)] lower risk of ischemic stroke incidence, respectively. Multivariable (demographic and lifestyle) adjusted associations for anthocyanins and flavones with risk of ischemic stroke were not linear, with moderate but not higher intakes associated with lower risk [anthocyanins Q3 vs. Q1 HR (95% CI): 0.85 (0.79, 0.93); flavones: 0.90 (0.84, 0.97)]. Following additional adjustment for dietary confounders, similar point estimates were observed; however, significance was only retained for anthocyanins and flavanol oligo + polymers [anthocyanins Q3 vs. Q1 HR (95% CI): 0.86 (0.79, 0.94); flavanol oligo + polymers Q5 vs. Q1 0.86 (0.78, 0.94)].

Conclusions: These findings suggest that moderate habitual consumption of healthy flavonoid-rich foods is associated with a lower risk of ischemic stroke and further investigation is therefore warranted.
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http://dx.doi.org/10.1093/ajcn/nqab138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246625PMC
July 2021

Fruit and vegetable intake is inversely associated with perceived stress across the adult lifespan.

Clin Nutr 2021 05 15;40(5):2860-2867. Epub 2021 Apr 15.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia; Medical School, The University of Western Australia, Perth, Australia; Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Background & Aims: Poor nutritional habits are linked to higher perceived stress, but the relationship between fruit and vegetable (FV) intake and stress is uncertain. The primary aim of this cross-sectional study was to explore the relationship between FV intake and perceived stress in a population-based cohort of men and women aged ≥25 years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. A secondary aim was to investigate the relationship between serum carotenoids, biomarkers of FV intake, and perceived stress.

Methods: In Australian men and women, dietary intake was assessed using a Food Frequency Questionnaire in 1999-2000 (n = 8689). Perceived stress was assessed using a validated Perceived Stress Questionnaire [PSQ index values ranging from 0 (lowest) to 1 (highest)]. Serum carotenoids were measured in a subset of participants (n = 1187) using high-performance liquid chromatography. Multivariable-adjusted linear and logistic regression were performed to investigate the associations between FV intake and perceived stress.

Results: Mean age of participants was 47.4 (SD 14.1) years (49.8% females). Participants with the highest intakes of FV had 10% lower PSQ index values than those with the lowest intake [Q4: 0.27 ± 0.004 vs. Q1: 0.30 ± 0.004 (mean ± SE), p = 0.004]. Similar associations were found for fruits and vegetables, analysed separately. In subgroup analyses higher FV intake was associated with lower perceived stress in the middle-aged adults [≥45-<65 years (p = 0.004)], but not in the younger (<45 years) and older participants (≥65 years). Higher FV intake was also significantly associated with lower perceived stress in men (p = 0.009) and women (p = 0.012), separately. Serum carotenoid levels were inversely associated with perceived stress before, but not after adjusting for age and other confounding factors.

Conclusion: In Australian adults, higher FV intake was associated with lower perceived stress, particularly in the middle-aged adults. These findings support current recommendations that fruit and vegetables are essential for health and well-being.
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http://dx.doi.org/10.1016/j.clnu.2021.03.043DOI Listing
May 2021

Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study.

Eur J Epidemiol 2021 Aug 21;36(8):813-825. Epub 2021 Apr 21.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Level 3, Royal Perth Hospital Research Foundation, Rear 50 Murray St, Perth, WA, 6000, Australia.

Whether the vascular effects of inorganic nitrate, observed in clinical trials, translate to a reduction in cardiovascular disease (CVD) with habitual dietary nitrate intake in prospective studies warrants investigation. We aimed to determine if vegetable nitrate, the major dietary nitrate source, is associated with lower blood pressure (BP) and lower risk of incident CVD. Among 53,150 participants of the Danish Diet, Cancer, and Health Study, without CVD at baseline, vegetable nitrate intake was assessed using a comprehensive vegetable nitrate database. Hazard ratios (HRs) were calculated using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. During 23 years of follow-up, 14,088 cases of incident CVD were recorded. Participants in the highest vegetable nitrate intake quintile (median, 141 mg/day) had 2.58 mmHg lower baseline systolic BP (95%CI - 3.12, - 2.05) and 1.38 mmHg lower diastolic BP (95%CI - 1.66, - 1.10), compared with participants in the lowest quintile. Vegetable nitrate intake was inversely associated with CVD plateauing at moderate intakes (~ 60 mg/day); this appeared to be mediated by systolic BP (21.9%). Compared to participants in the lowest intake quintile (median, 23 mg/day), a moderate vegetable nitrate intake (median, 59 mg/day) was associated with 15% lower risk of CVD [HR (95% CI) 0.85 (0.82, 0.89)]. Moderate vegetable nitrate intake was associated with 12%, 15%, 17% and 26% lower risk of ischemic heart disease, heart failure, ischemic stroke and peripheral artery disease hospitalizations respectively. Consumption of at least ~ 60 mg/day of vegetable nitrate (~ 1 cup of green leafy vegetables) may mitigate risk of CVD.
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http://dx.doi.org/10.1007/s10654-021-00747-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416839PMC
August 2021

Association of habitual intake of fruits and vegetables with depressive symptoms: the AusDiab study.

Eur J Nutr 2021 Oct 29;60(7):3743-3755. Epub 2021 Mar 29.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.

Purpose: To investigate the relationship of habitual FV intake, different types of FV, and vegetable diversity with depressive symptoms.

Methods: Australian men and women (n = 4105) aged > 25 years from the Australian Diabetes, Obesity and Lifestyle Study were included. Dietary intake was assessed using a Food Frequency Questionnaire at baseline, 5 and 12 years. Depressive symptoms were assessed using the validated 10-item Centre for Epidemiology Studies Short Depression Scale at 12 years. Multiple logistic regression models were used to investigate the association between the exposures of interest and depressive symptoms using odds ratios (OR) and 95% confidence intervals (CI) across quartiles of FV intake and vegetable diversity. Analyses were multivariable-adjusted for confounding factors.

Results: At 12 years, 425 (10.4%) participants had "any depressive symptoms". Habitual FV intake was inversely associated with depressive symptoms at 12 years. After adjustment, participants in quartile 2 of FV intake (Q2; median 317 g/day) had a 20% lower odds of having any depressive symptoms (OR [95% CI] 0.80 [0.69, 0.95]) in comparison to those in the lowest quartile of FV intake (Q1; median 223 g/day). Yellow/orange/red and leafy green vegetables were the key vegetable types driving this association. Higher vegetable diversity (4-6 different vegetables/day) was associated with a 24-42% lower odds of having depressive symptoms when compared to < 3 different vegetables/day. The associations remained similar after further adjusting for diet quality.

Conclusion: A FV-rich diet, consisting of a diverse range of vegetables, particularly yellow/orange/red and leafy green vegetables may help to lower depressive symptoms. Promoting such a diet, particularly in men and women with a low FV intake, may have a significant public health impact.
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http://dx.doi.org/10.1007/s00394-021-02532-0DOI Listing
October 2021

Dietary Nitrate Intake Is Positively Associated with Muscle Function in Men and Women Independent of Physical Activity Levels.

J Nutr 2021 05;151(5):1222-1230

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Background: Nitrate supplements can improve vascular and muscle function. Whether higher habitual dietary nitrate is associated with better muscle function remains underexplored.

Objective: The aim was to examine whether habitual dietary nitrate intake is associated with better muscle function in a prospective cohort of men and women, and whether the relation was dependent on levels of physical activity.

Methods: The sample (n = 3759) was drawn from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) (56% female; mean ± SD baseline age: 48.6 ± 11.1 y). Habitual dietary intake was assessed over 12 y by obtaining an average [of at least 2 time points, e.g., baseline (2000/2001) and 2004/2005 and/or 2011/2012] from a food-frequency questionnaire. Nitrate intake was calculated from a validated nitrate database and other published literature. Muscle function was quantified by knee extension strength (KES) and the 8-ft-timed-up-and-go (8ft-TUG) test performed in 2011/2012. Physical activity was assessed by questionnaire. Generalized linear models and logistic regression were used to analyze the data.

Results: Median (IQR) total nitrate intake was 65 (52-83) mg/d, with ∼81% derived from vegetables. Individuals in the highest tertile of nitrate intake (median intake: 91 mg/d) had 2.6 kg stronger KES (11%) and 0.24 s faster 8ft-TUG (4%) compared with individuals in the lowest tertile of nitrate intake (median intake: 47 mg/d; both P < 0.05). Similarly, individuals in the highest tertile of nitrate intake had lower odds for weak KES (adjusted OR: 0.69; 95% CI: 0.47, 0.73) and slow 8ft-TUG (adjusted OR: 0.63; 95% CI: 0.50, 0.78) compared with those in the lowest tertile. Physical activity did not influence the relationship between nitrate intake and muscle function (KES; P-interaction = 0.86; 8ft-TUG; P-interaction = 0.99).

Conclusions: Higher habitual dietary nitrate intake, predominantly from vegetables, could be an effective way to promote lower-limb muscle strength and physical function in men and women.
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http://dx.doi.org/10.1093/jn/nxaa415DOI Listing
May 2021

Effects of Chewing Gum on Nitric Oxide Metabolism, Markers of Cardiovascular Health and Neurocognitive Performance after a Nitrate-Rich Meal.

J Am Coll Nutr 2021 Feb 18:1-13. Epub 2021 Feb 18.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Objectives: Cardiovascular and neurocognitive responses to chewing gum have been reported, but the mechanisms are not well understood. Chewing gum after a nitrate-rich meal may upregulate the reduction of oral nitrate to nitrite and increase nitric oxide (NO), a molecule important to cardiovascular and neurocognitive health. We aimed to explore effects of chewing gum after a nitrate-rich meal on nitrate metabolism (through the enterosalivary nitrate-nitrite-NO pathway), endothelial function, blood pressure (BP), neurocognitive performance, mood and anxiety.

Methods: Twenty healthy men (n = 6) and women (n = 14) with a mean age of 48 years (range: 23-69) were recruited to a randomized controlled cross-over trial. After consumption of a nitrate-rich meal (180 mg of nitrate), we assessed the acute effects of chewing gum, compared to no gum chewing, on (i) salivary nitrate, nitrite and the nitrate reductase ratio (100 x [nitrite]/([nitrate] + [nitrite]); (ii) plasma nitrite, -nitrosothiols and other nitroso species (RXNO); (iii) endothelial function (measured by flow mediated dilatation); (iv) BP; (v) neurocognitive performance; (vi) mood; and (vii) anxiety.

Results: Consumption of the nitrate-rich meal resulted in a significant increase in markers of nitrate metabolism. A significantly higher peak flow mediated dilatation was observed with chewing compared to no chewing (baseline adjusted mean difference: 1.10%, 95% CI: 0.06, 2.14; p = 0.038) after the nitrate-rich meal. A significant small increase in systolic BP, diastolic BP and heart rate were observed with chewing compared to no chewing after the nitrate-rich meal. The study did not observe increased oral reduction of nitrate to nitrite and NO, or improvements in neurocognitive performance, mood or anxiety with chewing compared to no chewing.

Conclusion: Chewing gum after a nitrate-rich meal resulted in an acute improvement in endothelial function and a small increase in BP but did not result in acute effects on neurocognitive function, mood or anxiety.
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http://dx.doi.org/10.1080/07315724.2020.1869119DOI Listing
February 2021

Higher habitual flavonoid intakes are associated with a lower risk of peripheral artery disease hospitalizations.

Am J Clin Nutr 2020 Nov 24. Epub 2020 Nov 24.

Department of Cardiology, Herlev & Gentofte University Hospital, Copenhagen, Denmark.

Background: The role of nutrition in the primary prevention of peripheral artery disease (PAD), the third leading cause of atherosclerotic cardiovascular disease, is undetermined. Flavonoids may attenuate atherosclerosis and therefore persons who consume flavonoid-rich foods may have a lower risk of developing PAD.

Objectives: We aimed to examine the association between flavonoid intake and PAD hospitalizations and investigate if the association differs according to established risk factors for PAD.

Methods: Baseline data from 55,647 participants of the Danish Diet, Cancer, and Health Study without PAD, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from FFQs using the Phenol-Explorer database. Associations were examined using multivariable-adjusted restricted cubic splines based on Cox proportional hazards models.

Results: After a median [IQR] follow-up time of 21 [20-22] y, 2131 participants had been hospitalized for any PAD. The association between total flavonoid intake and total PAD hospitalizations was nonlinear, reaching a plateau at ∼750-1000 mg/d. Compared with the median flavonoid intake in quintile 1 (174 mg/d), an intake of 1000 mg/d was associated with a 32% lower risk of any PAD hospitalization (HR: 0.68; 95% CI: 0.60, 0.77), a 26% lower risk of atherosclerosis (HR: 0.74; 95% CI: 0.62, 0.88), a 28% lower risk of an aneurysm (HR: 0.72; 95% CI: 0.59, 0.88), and a 47% lower risk of a hospitalization for other peripheral vascular disease (HR: 0.53; 95% CI: 0.42, 0.67). A higher total flavonoid intake was also significantly associated with a lower incidence of revascularization or endovascular surgery and lower extremity amputation. The association between total flavonoid intake and PAD hospitalizations differed according to baseline smoking status, alcohol intake, BMI, and diabetes status.

Conclusions: Ensuring the adequate consumption of flavonoid-rich foods, particularly in subpopulations prone to the development of atherosclerosis, may be a key strategy to lower the risk of PAD.
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http://dx.doi.org/10.1093/ajcn/nqaa300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779235PMC
November 2020

Implementation, mechanisms of impact and key contextual factors involved in outcomes of the Modification of Diet, Exercise and Lifestyle (MODEL) randomised controlled trial in Australian adults: protocol for a mixed-method process evaluation.

BMJ Open 2020 11 11;10(11):e036395. Epub 2020 Nov 11.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Introduction: The Modification of Diet, Exercise and Lifestyle (MODEL) study aims to examine the impact of providing visualisation and pictorial representation of advanced structural vascular disease (abdominal aortic calcification), on 'healthful' improvements to diet and lifestyle. This paper reports the protocol for the process evaluation for the MODEL study.

Methods And Analysis: The overall aim of the process evaluation is to understand the processes that took place during participation in the MODEL study trial and which elements were effective or ineffective for influencing 'healthful' behavioural change, and possible ways of improvement to inform wider implementation strategies. A mixed-method approach will be employed with the use of structured questionnaires and semistructured in-depth interviews. All 200 participants enrolled in the trial will undertake the quantitative component of the study and maximum variation sampling will be used to select a subsample for the qualitative component. The sample size for the qualitative component will be determined based on analytical saturation. Interviews will be digitally recorded and transcribed verbatim. Qualitative data will be analysed thematically and reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines.

Ethics And Dissemination: The MODEL study process evaluation has received approval from Edith Cowan University Human Research Ethics Committee (Project Number: 20513 HODGSON). Written informed consent will be obtained from all participants before they are included in the study. The study results will be shared with the individuals and institutions associated with this study as well as academic audiences through peer-reviewed publication and probable presentation at conferences.

Trial Registration Number: ACTRN12618001087246.
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http://dx.doi.org/10.1136/bmjopen-2019-036395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661373PMC
November 2020

Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol.

BMJ Open 2020 11 11;10(11):e036366. Epub 2020 Nov 11.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Introduction: Most cardiovascular disease (CVD)-related events could be prevented or substantially delayed with improved diet and lifestyle. Providing information on structural vascular disease may improve CVD risk factor management, but its impact on lifestyle change remains unclear. This study aims to determine whether providing visualisation and pictorial representation of structural vascular disease (abdominal aortic calcification (AAC)) can result in healthful diet and lifestyle change.

Methods And Analysis: This study, including men and women aged 60-80 years, is a 12-week, two-arm, multisite randomised controlled trial. At baseline, all participants will have AAC assessed from a lateral spine image captured using a bone densitometer. Participants will then be randomised to receive their AAC results at baseline (intervention group) or a usual care control group that will receive their results at 12 weeks. All participants will receive information about routinely assessed CVD risk factors and standardised (video) diet and lifestyle advice with three simple goals: (1) increase fruit and vegetable (FV) intake by at least one serve per day, (2) improve other aspects of the diet and (3) reduce sitting time and increase physical activity. Clinical assessments will be performed at baseline and 12 weeks.

Outcomes: The primary outcome is a change in serum carotenoid concentrations as an objective measure of FV intake. The study design, procedures and treatment of data will adhere to Standard Protocol Items for Randomized Trials guidelines.

Ethics And Dissemination: Ethics approval for this study has been granted by the Edith Cowan University and the Deakin University Human Research Ethics Committees (Project Numbers: 20513 HODGSON and 2019-220, respectively). Results of this study will be published in peer-reviewed academic journals and presented in scientific meetings and conferences. Information regarding consent, confidentiality, access to data, ancillary and post-trial care and dissemination policy has been disclosed in the participant information form.

Trial Registration Number: Australian New Zealand Clinical Trial Registry (ACTRN12618001087246).
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http://dx.doi.org/10.1136/bmjopen-2019-036366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661361PMC
November 2020

Associations between Intake of Dietary Flavonoids and 10-Year Incidence of Age-Related Hearing Loss.

Nutrients 2020 Oct 28;12(11). Epub 2020 Oct 28.

Department of Ophthalmology and Westmead Institute for Medical Research, Centre for Vision Research, University of Sydney, Camperdown, NSW 2006, Australia.

Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing status. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz > 25 dB hearing level (HL). Dietary data were collected through a semi-quantitative food frequency questionnaire. The flavonoid content of foods was estimated using US databases. During the 10-year follow-up, 260 (31.6%) new cases of hearing loss (incident) were observed. After multivariable adjustment, participants in the fourth versus first quartile (reference group) of intake of dietary isoflavone had 36% lower risk of incident hearing loss after 10 years: odds ratios (OR) 0.64 (95% confidence intervals, CI, 0.42-0.99); = 0.03. Nonsignificant associations were observed between the other five flavonoid subclasses and 10-year incidence of hearing loss. Our findings do not support the hypothesis that the intake of dietary flavonoids protect against long-term risk of hearing loss. The association with isoflavone intake needs to be confirmed by other population-based studies.
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http://dx.doi.org/10.3390/nu12113297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693883PMC
October 2020

Phenolic composition of 91 Australian apple varieties: towards understanding their health attributes.

Food Funct 2020 Aug;11(8):7115-7125

School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Dr, Joondalup, WA 6027, Australia. and Royal Perth Hospital Research Foundation, School of Medicine, University of Western Australia, Rear 50 Murray St, Perth, WA 6000, Australia.

Introduction: Apples, an important contributor to total dietary phenolic intake, are associated with cardiovascular health benefits. Determining the phenolic composition of apples, their individual variation across varieties, and the phenolic compounds present in plasma after apple consumption is integral to understanding the effects of apple phenolics on cardiovascular health.

Methods: Using liquid chromatography we quantified five important polyphenols and one phenolic acid with potential health benefits: quercetin glycosides, (-)-epicatechin, procyanidin B2, phloridzin, anthocyanins, and chlorogenic acid, in the skin and flesh of 19 apple varieties and 72 breeding selections from the Australian National Apple Breeding program. Furthermore, we measured the phenolic compounds in the plasma of 30 individuals post-consumption of an identified phenolic-rich apple, Cripp's Pink.

Results: Considerable variation in concentration of phenolic compounds was found between genotypes: quercetin (mean ± SD: 16.1 ± 5.9, range: 5.8-30.1 mg per 100 g); (-)-epicatechin (mean ± SD: 8.6 ± 5.8, range: 0.2-19.8 mg per 100 g); procyanidin B2 (mean ± SD: 11.5 ± 6.6, range: 0.5-26.5 mg per 100 g); phloridzin (mean ± SD: 1.1 ± 0.6, range: 0.3-4.3 mg per 100 g); anthocyanins (mean ± SD: 1.8 ± 4.4, range: 0-40.8 mg per 100 g); and chlorogenic acid (mean ± SD: 11.3 ± 9.9, range: 0.4-56.0 mg per 100 g). All phenolic compounds except chlorogenic acid were more concentrated in the skin compared with flesh. We observed a significant increase, with wide variation, in 14 phenolic compounds in plasma post-consumption of a phenolic-rich apple.

Conclusion: This information makes an important contribution to understanding the potential health benefits of apples.
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http://dx.doi.org/10.1039/d0fo01130dDOI Listing
August 2020

An overview and update on the epidemiology of flavonoid intake and cardiovascular disease risk.

Food Funct 2020 Aug;11(8):6777-6806

School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital Research Foundation, Perth, Australia. and School of Medical and Health Sciences, Edith Cowan University, Perth, Australia and Institute for Global Food Security, Queen's University, Belfast, Northern Ireland.

There is an accumulating body of literature reporting on dietary flavonoid intake and the risk of cardiovascular disease (CVD) in prospective cohort studies. This makes apparent the need for an overview and update on the current state of the science. To date, at least 27 prospective cohorts (in 44 publications) have evaluated the association between estimated habitual flavonoid intake and CVD risk. At this time, the totality of evidence suggests long-term consumption of flavonoid-rich foods may be associated with a lower risk of fatal and non-fatal ischemic heart disease (IHD), cerebrovascular disease, and total CVD; disease outcomes which are principally, though not exclusively, composed of cases of atherosclerotic CVD (ASCVD). To date, few studies have investigated outcome specific ASCVD, such as peripheral artery disease (PAD) or ischemic stroke. Of the flavonoid subclasses investigated, evidence more often implicates diets rich in anthocyanins, flavan-3-ols, and flavonols in lowering the risk of CVD. Although inferences are restricted by confounding and other inherent limitations of observational studies, causality appears possible based on biological plausibility, temporality, and the relative consistency of the reported associations. However, whether the associations observed represent a benefit of the isolated bioactives per se, or are a signal of the bioactives acting in concert with the co-occurring nutrient matrix within flavonoid-bearing foods, are issues of consideration. Thus, the simple interpretation, and the one most relevant for dietary advice, is that consumption of flavonoid-rich foods or diets higher in flavonoids, appear nutritionally beneficial in the prevention of CVD.
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http://dx.doi.org/10.1039/d0fo01118eDOI Listing
August 2020

Cruciferous vegetable intake is inversely associated with extensive abdominal aortic calcification in elderly women: a cross-sectional study.

Br J Nutr 2021 02 17;125(3):337-345. Epub 2020 Jul 17.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA6027, Australia.

We have previously shown that higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a FFQ, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual-energy X-ray absorptiometry lateral spine images and was categorised as 'not extensive' (0-5) or 'extensive' (≥6). Mean age was 74·9 (sd 2·6) years, median cruciferous vegetable intake was 28·2 (interquartile range 15·0-44·7) g/d and 128/684 (18·7 %) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables (>44·6 g/d) were associated with a 46 % lower odds of having extensive AAC in comparison with those with lower intakes (<15·0 g/d) after adjustment for lifestyle, dietary and CVD risk factors (ORQ4 v. Q1 0·54, 95 % CI 0·30, 0·97, P = 0·036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P > 0·05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification.
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http://dx.doi.org/10.1017/S0007114520002706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844610PMC
February 2021

The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals.

Bone Rep 2020 Jun 26;12:100274. Epub 2020 Apr 26.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.

Background: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism.

Objective: To examine the effects of consumption of two to three extra serves of green leafy vegetables daily on bone metabolism.

Methods: Thirty individuals (mean age 61.8 ± 9.9 years, 67% male) completed three experimental phases in a randomised controlled crossover design, each lasting four weeks, with a washout period of four weeks between phases (clinical trial registration: ACTRN12615000194561). The three experimental phases were: (i) increased dietary vitamin K1 by consuming green leafy vegetables (H-K; ~200 g/d containing 164.3 [99.5-384.7] μg/d of vitamin K1); (ii) low vitamin K1 by consuming vitamin K1-poor vegetables (L-K; ~200 g/d containing 9.4 [7.7-11.6] μg/d of vitamin K1); and (iii) control (CON) where participants consumed an energy-matched non-vegetable control. OC forms, total OC (tOC), carboxylated OC (cOC) and undercarboxylated OC (ucOC), were measured in serum pre- and post-intervention for each experimental phase using a sandwich-electrochemiluminescence immunoassay.

Results: Pre-intervention tOC, ucOC and ucOC:tOC levels were similar between phases ( > .05). Following H-K, but not L-K, tOC, ucOC and ucOC:tOC levels were significantly lower compared to pre-intervention levels ( ≤ .001) and compared to CON (~14%, 31% and 19%, respectively, all  < .05), while cOC remained unchanged.

Conclusions: In middle-aged healthy men and women, an easily achieved increase in dietary intake of vitamin K1-rich green leafy vegetables substantially reduces serum tOC and ucOC suggesting increased entry of OC into bone matrix, where it may improve the material property of bone. In conjunction with previous epidemiological and randomised controlled trial data, these findings suggest that interventions to increase vegetable intake over extended periods should include bone end points including fracture risk.
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http://dx.doi.org/10.1016/j.bonr.2020.100274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235933PMC
June 2020

A randomised controlled crossover trial investigating the short-term effects of different types of vegetables on vascular and metabolic function in middle-aged and older adults with mildly elevated blood pressure: the VEgetableS for vaScular hEaLth (VESSEL) study protocol.

Nutr J 2020 05 12;19(1):41. Epub 2020 May 12.

School of Medical and Health Sciences, Edith Cowan University, Royal Perth Hospital Research Foundation, Rear 50, Murray Street, Joondalup, Perth, WA, 6000, Australia.

Background: A diet rich in fruits and vegetables is recommended for cardiovascular health. However, the majority of Australians do not consume the recommended number of vegetable servings each day. Furthermore, intakes of vegetables considered to have the greatest cardiovascular benefit are often very low. Results from prospective observational studies indicate that a higher consumption of cruciferous vegetables (e.g. broccoli, cabbage, cauliflower) is associated with lower cardiovascular disease risk. This may be due to the presence of specific nutrients and bioactive compounds found almost exclusively, or at relatively high levels, in cruciferous vegetables. Therefore, the aim of this randomised controlled crossover trial is to determine whether regular consumption of cruciferous vegetables results in short-term improvement in measures related to cardiovascular disease risk, including ambulatory blood pressure, arterial stiffness, glycaemic control, and circulating biomarkers of oxidative stress and inflammation.

Methods: Twenty-five participants (50-75 years) with mildly elevated blood pressure (systolic blood pressure 120-160 mmHg) will complete two 2-week intervention periods in random order, separated by a 2-week washout period. During the intervention period, participants will consume 4 servings (~ 300 g) of cruciferous vegetables per day as a soup (~ 500-600 mL/day). The 'control' soup will consist of other commonly consumed vegetables (potato, sweet potato, carrot, pumpkin). Both soups will be approximately matched for energy, protein, fat, and carbohydrate content. All measurements will be performed at the beginning and end of each intervention period.

Discussion: The findings of this study will provide evidence regarding the potential cardiometabolic health benefits of cruciferous vegetables, which may contribute to the revision of dietary and clinical guidelines.

Trial Registration: The trial was registered with the Australian New Zealand Clinical Trial Registry on 19th September 2019 (ACTRN12619001294145).
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http://dx.doi.org/10.1186/s12937-020-00559-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218618PMC
May 2020

Flavonoid intake and its association with atrial fibrillation.

Clin Nutr 2020 12 23;39(12):3821-3828. Epub 2020 Apr 23.

Department of Cardiology, Herlev & Gentofte University Hospital, Copenhagen, Denmark.

Background & Aims: Primary prevention of atrial fibrillation (AF) through behavioural and dietary modification is a critically important and unmet need. Flavonoids are bioactive dietary compounds with promising cardiovascular health benefits. Our aim was to investigate the association between flavonoid intake and clinically apparent AF.

Methods: Baseline data from 55 613 participants of the Danish Diet, Cancer and Health Study, without AF, recruited between 1993 and 1997, were cross-linked with Danish nationwide registries. Total flavonoid and flavonoid subclass intakes were calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and incident AF (first-time hospitalization or outpatient visit) were examined using restricted cubic splines based on Cox proportional hazards models.

Results: During a median [IQR] follow-up of 21 [18-22] years, 7291 participants were diagnosed with AF. Total flavonoid intake was not statistically significantly associated with risk of incident AF in the whole cohort. However, compared to the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.06)], and a lower risk of AF in high alcohol consumers [>20 g/d: 0.84 (0.75, 0.95)] but not in low-to-moderate alcohol consumers [<20 g/d: 0.97 (0.89, 1.07)].

Conclusion: Intake of flavonoids was not significantly associated with a lower risk of incident AF. However, higher intakes of flavonoids may be beneficial for those at a higher risk of developing AF.
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http://dx.doi.org/10.1016/j.clnu.2020.04.025DOI Listing
December 2020

Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease.

Br J Nutr 2020 01 24;123(2):182-189. Epub 2019 Dec 24.

School of Biomedical Science, University of Western Australia, Royal Perth Hospital, Perth, 6000 Western Australia, Australia.

A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P < 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption.
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http://dx.doi.org/10.1017/S0007114519002137DOI Listing
January 2020

Dietary inflammatory index and the aging kidney in older women: a 10-year prospective cohort study.

Eur J Nutr 2020 Oct 11;59(7):3201-3211. Epub 2019 Dec 11.

Medical School, University of Western Australia, Level 3 Medical Research Foundation Building, Rear 50 Murray Street, Perth, WA, 6000, Australia.

Purpose: Chronic inflammation plays a role in the pathogenesis of age-related renal disease and the diet can moderate systemic inflammation. The primary objective of this study was to examine the associations between a dietary inflammatory index (DII) score and renal function, the trajectory of renal function decline, and renal disease-related hospitalizations and/or mortality over 10 years.

Methods: The study was conducted in 1422 Western Australian women without prevalent chronic kidney disease and aged ≥ 70 years. Baseline dietary data, obtained from a validated food frequency questionnaire, were used to calculate a DII score for each individual.

Results: In this cohort, the mean [range] DII score was 0.19 [- 6.14 to 6.39]. A higher DII score was associated with poorer renal function at baseline and a greater renal function decline over 10 years; after multivariable adjustments, a one-unit higher DII score was associated with a 0.55 mL/min/1.73 m lower eGFR at baseline (p = 0.01) and a 0.06 mL/min/1.73 m greater annual decline in eGFR over 10 years (p = 0.05). Restricted cubic splines provide evidence of a non-linear association between baseline DII score and risk of a renal disease-related event. Compared to participants in the lowest quintile, those in the highest quintile of DII score were at a higher risk of experiencing a renal disease-related event (adjusted HR 2.06, 95% CI 0.97, 4.37).

Conclusion: Recommending an increased consumption of foods with a higher anti-inflammatory potential could form part of a multifaceted approach to reduce the risk of renal disease through diet and lifestyle changes.
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http://dx.doi.org/10.1007/s00394-019-02160-9DOI Listing
October 2020

Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: a prospective cohort study.

Lancet Planet Health 2019 11;3(11):e450-e459

School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia; School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, WA, Australia.

Background: Flavonoids, compounds found in plant-based foods and beverages, might ameliorate vascular damage and atherosclerosis. Therefore, our aim was to assess the association between flavonoid intake and hospital admissions due to atherosclerotic cardiovascular disease.

Methods: In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study were cross-linked with Danish nationwide registries. Eligible participants were aged 50-65 years, had no previous history of atherosclerotic cardiovascular disease, and had completed a food-frequency questionnaire at baseline. We examined associations between flavonoid intake (calculated from food-frequency questionnaires with use of the Phenol-Explorer database) and hospital admissions for atherosclerotic cardiovascular disease, ischaemic heart disease, ischaemic stroke, or peripheral arterial disease. We obtained hazard ratios (HRs) using restricted cubic splines based on Cox proportional hazards models.

Findings: Of the participants recruited to the Danish Diet, Cancer, and Health study between 1993 and 1997, our study population was comprised of 53 552 participants, with a median follow-up of 21 years (IQR 15-22). During follow-up, 8773 participants were admitted to hospital for atherosclerotic cardiovascular disease. We observed non-linear associations between flavonoid intake and hospital admissions, plateauing at total flavonoid intakes of approximately 1000 mg per day. Compared with an intake of 175 mg per day, an intake of 1000 mg per day was associated with a 14% lower risk of atherosclerotic cardiovascular disease (HR 0·86, 95% CI 0·81-0·91). For disease subtypes, we observed a 9% lower risk of ischaemic heart disease (0·91, 0·85-0·98), a non-significant 9% lower risk of ischaemic stroke (0·91, 0·82-1·01), and a 32% lower risk of peripheral artery disease (0·68, 0·60-0·78). The overall associations were stronger in smokers than in non-smokers, as well as stronger in consumers of high (>20 g per day) quantities of alcohol than in those consuming low-to-moderate (≤20 g per day) quantities.

Interpretation: Our results suggest that ensuring an adequate consumption of flavonoid-rich foods, particularly in subpopulations at risk of atherosclerosis such as smokers and consumers of high quantities of alcohol might mitigate some of the risk of atherosclerotic cardiovascular disease. More studies are needed to support and validate these data.

Funding: Danish Cancer Society.
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http://dx.doi.org/10.1016/S2542-5196(19)30212-8DOI Listing
November 2019

Associations between dietary flavonoids and retinal microvasculature in older adults.

Eur J Nutr 2020 Oct 25;59(7):3093-3101. Epub 2019 Nov 25.

Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Westmead, NSW, 2145, Australia.

Purpose: In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre.

Methods: Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake was assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Flavonoid content of foods in the FFQ was estimated using the US Department of Agriculture Flavonoid, Isoflavone and Proanthocyanidin databases. Fundus photographs were taken and retinal vascular calibre was measured using validated computer-assisted techniques. The associations of intake of dietary flavonoids with retinal vessel calibre were examined in linear regression models and general linear model.

Results: The highest quartile of intake was compared with the lowest quartile using multivariable-adjustment models. Participants with the highest proanthocyanidin intake had narrower retinal venules (223.9 ± 0.62 versus 226.5 ± 0.63, respectively; P = 0.01); and the highest isoflavone intake was associated with wider retinal arterioles (188.1 ± 0.55 versus 186.3 ± 0.56, respectively; P = 0.01). The highest apple/pear consumption (a dietary source of catechin) was associated with narrower retinal venules (223.8 ± 0.57 versus 226.1 ± 0.52; P = 0.01) and wider retinal arterioles (187.9 ± 0.51 versus 186.2 ± 0.51; P = 0.02). Further, participants who were in the highest versus lowest quartile of chocolate consumption had ~ 2.1 μm narrower retinal venules (multivariable-adjusted P = 0.03).

Conclusions: This study shows that higher intakes of specific flavonoid subclasses are associated with a favourable retinal microvascular profile. Greater consumption of flavonoid-rich apples/pears and chocolate was also associated with beneficial variations in retinal vascular calibre.
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http://dx.doi.org/10.1007/s00394-019-02148-5DOI Listing
October 2020

Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort.

Nat Commun 2019 08 13;10(1):3651. Epub 2019 Aug 13.

School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.

Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (>20 g/d) vs. low-moderate (<20 g/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers.
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http://dx.doi.org/10.1038/s41467-019-11622-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692395PMC
August 2019

Association of flavonoids and flavonoid-rich foods with all-cause mortality: The Blue Mountains Eye Study.

Clin Nutr 2020 01 17;39(1):141-150. Epub 2019 Jan 17.

School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, Western Australia, Australia; School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.

Background: Higher intakes of flavonoids provide health benefits, however, the importance of each flavonoid class and which population groups may receive the greatest protection from higher flavonoid intake warrants further investigation.

Objective: To explore the associations of flavonoid and flavonoid-rich wholefood intakes with all-cause mortality and the moderating effects of early mortality risk factors.

Design: The study included 2349 participants of The Blue Mountains Eye Study, with a mean ± SD age at baseline of 64.7 ± 9.2 years. Flavonoid intake was calculated from baseline food frequency questionnaires using US Department of Agriculture food composition databases. Associations were examined using adjusted Cox proportional hazards models.

Results: After 14 years of follow-up, 677 participants died. There was a flavonoid threshold effect with the greatest risk reduction seen between low and moderate intakes of total flavonoids, flavonoid classes and flavonoid-rich foods. Amongst the whole cohort, participants in the highest tertile of anthocyanidin intake had a significantly lower risk of all-cause mortality [multivariable adjusted HR (95%CI): 0.76 (0.61, 0.94)] when compared to those in the lowest tertile. Amongst participants with at least one early mortality risk factor (smoking, high alcohol consumption, no regular exercise or obesity), risk of all-cause mortality was lower in those in the highest intake tertile for total flavonoids [adjusted HR: 0.77 (0.59, 1.00)], flavan-3-ols [0.75 (0.58, 0.98)], anthocyanidins [0.70 (0.54, 0.92)], and proanthocyanidins [0.69 (0.52, 0.92)], compared to those in the lowest tertile. No similar associations were observed among those without any risk factors. Similarly, consumption of apples, tea and the individual flavonoid compounds, quercetin and epicatechin, were associated with a lower risk of all-cause mortality among participants with at least one risk factor, but not amongst other participants.

Conclusion: Moderate to high intakes of flavonoids and certain flavonoid subclasses may provide health benefits, particularly for individuals with at least one early mortality risk factor.
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http://dx.doi.org/10.1016/j.clnu.2019.01.004DOI Listing
January 2020
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