Publications by authors named "Joshua R Lewis"

142 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 Oct 30;36(10):1005-1014. 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
October 2021

Association between vitamin D status and long-term falls-related hospitalization risk in older women.

J Am Geriatr Soc 2021 Sep 10. Epub 2021 Sep 10.

Medical School, University of Western Australia, Perth, Western Australia, Australia.

Background: The dose-response relationship of vitamin D status and the risk of serious falls requiring hospitalization in older women is unclear. We examined the association between plasma 25-hydroxyvitamin D (25OHD) with falls-related hospitalizations over 14.5 years in a large cohort of older women.

Methods: In 1348 community-dwelling Australian women aged ≥70 years, plasma 25OHD concentrations were assessed at baseline (1998) using LC-MS/MS. Fall-related hospitalizations were obtained from linked data systems. Baseline grip strength and timed-up-and-go (TUG) were assessed as measures of muscle strength and physical function, respectively.

Results: Mean plasma 25OHD was 66.9 ± 28.2 nmol/L. The number of women in the low (LOW; <50 nmol/L), medium (MED; 50 to <75 nmol/L), and higher 25OHD (HIGH; ≥75 nmol/L) categories were 384 (28.5%), 491 (36.4%), and 473 (35.1%), respectively. In the multivariable-adjusted analysis, compared to LOW, women in HIGH had significantly lower hazards for a falls-related hospitalization (HR 0.76 95%CI 0.61-0.95). Restricted cubic spline regression models highlight increasing gradient of risk for a falls-related hospitalization with decreasing 25OHD levels. Generalized additive modeling highlighted higher 25OHD to be associated with better TUG performance. Including TUG into the multivariable-adjusted models did not alter the relationship between 25OHD and injurious falls (HIGH vs. LOW HR 0.76 95%CI 0.60-0.95).

Conclusions: In community-dwelling older Australian women, maintaining plasma 25OHD at 75 nmol/L or above may confer benefits to muscle function and long-term prevention of injurious falls requiring hospitalization. This relationship appears to be independent of better physical function observed in women with higher 25OHD levels.
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http://dx.doi.org/10.1111/jgs.17442DOI Listing
September 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

Abdominal aortic calcification is associated with a higher risk of injurious fall-related hospitalizations in older Australian women.

Atherosclerosis 2021 07 12;328:153-159. Epub 2021 May 12.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, 6027, Australia; Medical School, The University of Western Australia, Perth, WA, 6000, Australia; Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, 2145, Australia.

Backgrounds And Aims: Abdominal aortic calcification (AAC) is associated with weaker grip strength, an established risk factor for fall-related hospitalizations. However, its association with long-term fall-related hospitalisations remains unknown. This study investigated the association between AAC and long-term fall-related hospitalizations in community-dwelling older women.

Methods: Fall-related hospitalizations were obtained from linked data over 14.5-years in a prospective cohort of 1053 older women (mean age 75.0 ± 2.6 years). At baseline (1998/99), AAC was assessed from lateral spine images obtained using dual-energy X-ray absorptiometry, and scored using a semi-quantitative method (AAC24, range 0-24). The presence of any AAC was defined by AAC24 ≥ 1.

Results: Over 14.5-years, 413 (39.2%) women experienced a fall-related hospitalization. In the multivariable-adjusted model, each unit increase in baseline AAC24 was associated with a 3% increase in relative hazards for a fall-related hospitalization (HR 1.03 95%CI, 1.01 to 1.07). Compared to women with no AAC, women with any AAC had a 40% (HR 1.40 95%CI, 1.11 to 1.76) and 39% (HR 1.39 95%CI, 1.10 to 1.76) greater risk for fall-related hospitalizations in the minimal and multivariable-adjusted models, respectively. This relationship was not attenuated by including measures of muscle function such as grip strength and timed-up-and-go.

Conclusions: The presence of AAC is associated with long-term fall-related hospitalizations risk, independent of muscle function, in community-dwelling older women. Concurrent assessment of AAC may be a simple and cost-effective way to identify older women at higher risk of falling as part of routine osteoporosis screening.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.003DOI 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

Association between Fruit and Vegetable Intakes and Mental Health in the Australian Diabetes Obesity and Lifestyle Cohort.

Nutrients 2021 Apr 24;13(5). Epub 2021 Apr 24.

Institute for Nutrition Research, Edith Cowan University, Perth 6027, Australia.

Increasing prevalence of mental health disorders within the Australian population is a serious public health issue. Adequate intake of fruits and vegetables (FV), dietary fibre (DF) and resistant starch (RS) is associated with better mental and physical health. Few longitudinal studies exist exploring the temporal relationship. Using a validated food frequency questionnaire, we examined baseline FV intakes of 5845 Australian adults from the AusDiab study and estimated food group-derived DF and RS using data from the literature. Perceived mental health was assessed at baseline and 5 year follow up using SF-36 mental component summary scores (MCS). We conducted baseline cross-sectional analysis and prospective analysis of baseline dietary intake with perceived mental health at 5 years. Higher baseline FV and FV-derived DF and RS intakes were associated with better 5 year MCS ( < 0.001). A higher FV intake (754 g/d vs. 251 g/d, Q4 vs. Q1) at baseline had 41% lower odds (OR = 0.59: 95% CI 0.46-0.75) of MCS below population average (<47) at 5 year follow up. Findings were similar for FV-derived DF and RS. An inverse association was observed with discretionary food-derived DF and RS. This demonstrates the association between higher intakes of FV and FV-derived DF and RS with better 5 year mental health outcomes. Further RCTs are necessary to understand mechanisms that underlie this association including elucidation of causal effects.
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http://dx.doi.org/10.3390/nu13051447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146262PMC
April 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

The effect of Vitamin-K and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial.

J Nucl Cardiol 2021 Apr 6. Epub 2021 Apr 6.

School of Medicine, Faculty of Health and Biomedical Science, University of Western Australia, Royal Perth Hospital Campus, M570, Po Box X2213, Perth, Western Australia, Australia.

Background: There is currently no treatment for attenuating progression of arterial calcification. F-sodium fluoride positron emission tomography (F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K or colchicine affected arterial calcification activity.

Methods: 154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on F-NaF PET.

Results: 149 subjects completed follow-up (vitamin-K: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K.

Conclusions: In patients with type 2 diabetes, neither vitamin-K nor colchicine significantly decreases coronary calcification activity, as estimated by F-NaF PET, over a period of 3 months.

Clinical Trial Registration: ACTRN12616000024448.
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http://dx.doi.org/10.1007/s12350-021-02589-8DOI Listing
April 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

Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures.

J Bone Miner Res 2021 05 17;36(5):892-900. Epub 2021 Mar 17.

University of Minnesota, Minneapolis, MN, USA.

Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24-point AAC score were ascertained on baseline lateral spine radiographs. Self-reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC-24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13-1.69) among men with AAC-24 score ≥2 alone, 1.71 (95% CI 1.37-2.14) for men with PVFx alone, and 2.35 (95% CI 1.75-3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi-square = 17.3, p < .001) or including only PVFx (chi-square = 8.5, p = .036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131243PMC
May 2021

Higher Undercarboxylated to Total Osteocalcin Ratio Is Associated With Reduced Physical Function and Increased 15-Year Falls-Related Hospitalizations: The Perth Longitudinal Study of Aging Women.

J Bone Miner Res 2021 03 3;36(3):523-530. Epub 2020 Dec 3.

Medical School, University Western Australia, Perth, Australia.

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed-up-and-go (TUG) and grip strength were assessed at baseline and at 5 years. Falls-related hospitalizations (14.5-year follow-up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p < .01). Grip strength and 5-year change of TUG and grip were not different (p > .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles (p < .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5-year change in performance, increased walking aid use, and fear of falling (all p < .05). Higher ucOC was related to lower grip strength at baseline (p < .05) but not 5-year change in strength. Those with the highest ucOC/tOC had greater falls-related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09-1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long-term decline and increased risk of falls-related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR)..
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http://dx.doi.org/10.1002/jbmr.4208DOI Listing
March 2021

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.

Nat Commun 2021 01 28;12(1):654. Epub 2021 Jan 28.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10), arthritis (GDF5 p = 4 × 10), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
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http://dx.doi.org/10.1038/s41467-021-20918-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844411PMC
January 2021

Evaluating and Strengthening the Evidence for Nutritional Bone Research: Ready to Break New Ground?

J Bone Miner Res 2021 02 27;36(2):219-226. Epub 2021 Jan 27.

Department of Medicine, Stanford Prevention Research Center, Stanford University, Stanford, CA, USA.

A healthy diet is essential to attain genetically determined peak bone mass and maintain optimal skeletal health across the adult lifespan. Despite the importance of nutrition for bone health, many of the nutritional requirements of the skeleton across the lifespan remain underexplored, poorly understood, or controversial. With increasingly aging populations, combined with rapidly changing diets and lifestyles globally, one anticipates large increases in the prevalence of osteoporosis and incidence of osteoporotic fractures. Robust, transparent, and reproducible nutrition research is a cornerstone for developing reliable public health recommendations to prevent osteoporosis and osteoporotic fractures. However, nutrition research is often criticized or ignored by healthcare professionals due to the overemphasis of weak science, conflicting, confusing or implausible findings, industry interests, common misconceptions, and strong opinions. Conversely, spurious research findings are often overemphasized or misconstrued by the media or prominent figures especially via social media, potentially leading to confusion and a lack of trust by the general public. Recently, reforms of the broader discipline of nutrition science have been suggested and promoted, leading to new tools and recommendations to attempt to address these issues. In this perspective, we provide a brief overview of what has been achieved in the field on nutrition and bone health, focusing on osteoporosis and osteoporotic fractures. We discuss what we view as some of the challenges, including inherent difficulties in assessing diet and its change, disentangling complex interactions between dietary components and between diet and other factors, selection of bone-related outcomes for nutrition studies, obtaining evidence with more unbiased designs, and perhaps most importantly, ensuring the trust of the public and healthcare professionals. This perspective also provides specific recommendations and highlights new developments and future opportunities for scientists studying nutrition and bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4236DOI Listing
February 2021

Prognostic Value of Abdominal Aortic Calcification: A Systematic Review and Meta-Analysis of Observational Studies.

J Am Heart Assoc 2021 01 13;10(2):e017205. Epub 2021 Jan 13.

Centre for Kidney Research School of Public Health Faculty of Medicine and Health Children's Hospital at WestmeadThe University of Sydney New South Wales Australia.

Background The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all-cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random-effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older-elderly (median, 68 years; range, 60-80 years) populations (26%) had sufficient data to meta-analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40-2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44-2.39), and all-cause mortality (RR, 1.98; 95% CI, 1.55-2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21-5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32-5.84), and all-cause mortality (RR, 2.40; 95% CI, 1.95-2.97). Conclusions Higher-risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients' cardiovascular risk better.
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http://dx.doi.org/10.1161/JAHA.120.017205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955302PMC
January 2021

F-Sodium Fluoride Positron Emission Tomography Activity Predicts the Development of New Coronary Artery Calcifications.

Arterioscler Thromb Vasc Biol 2021 01 3;41(1):534-541. Epub 2020 Dec 3.

School of Medicine (J.W.B., R.J.F., S.C.L., A.R., J.R.L., G.F.W., C.J.S.), University of Western Australia, Perth.

Objective: The coronary calcium score (CCS) predicts cardiovascular disease risk in individuals with diabetes, and rate of progression of CCS is an additional and incremental marker of risk. F-sodium fluoride positron emission tomography (F-NaF PET) detects early and active calcifications within the vasculature. We aimed to ascertain the relationship between F-NaF PET activity and CCS progression in patients with diabetes. Approach and Results: We identified individuals between 50 and 80 years with diabetes and no history of clinical coronary artery disease. Those with a CCS ≥10 were invited to undergo F-NaF PET scanning and then repeat CCS >2 years later. F-NaF PET and CCS analysis were performed on a per-coronary and a per-patient level. We compared the proportion of CCS progressors in F-NaF PET-positive versus F-NaF PET-negative coronary arteries. Forty-one participants with 163 coronary arteries underwent follow-up CCS 2.8±0.5 years later. F-NaF PET-positive coronary arteries (n=52) were more likely to be CCS progressors, compared with negative coronary arteries (n=111; 86.5% versus 52.3%, <0.001). Adjusting for baseline CCS, F-NaF PET-positive disease was an independent predictor of subsequent CCS progression (odds ratio, 2.92 [95% CI, 1.32-6.45], =0.008). All subjects (100%, 15/15) with ≥2 F-NaF-positive coronary arteries progressed in CCS.

Conclusions: In subjects with diabetes, F-NaF PET positivity at baseline, independently predicted the progression of calcifications within the coronary arteries 2.8 years later. These findings suggest F-NaF PET may be a promising technique for earlier identification of patients at higher risk of cardiovascular events.
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http://dx.doi.org/10.1161/ATVBAHA.120.315364DOI Listing
January 2021

Fruit and Vegetable Knowledge and Intake within an Australian Population: The AusDiab Study.

Nutrients 2020 Nov 25;12(12). Epub 2020 Nov 25.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, WA 6000, Australia.

Understanding the relationship between fruit and vegetable knowledge (FVK) and fruit and vegetable intake (FVI) is an important consideration for improved public health and successful targeting of health promotion messaging. The aim of this study was to investigate the association between FVK and FVI in Australian adults and to identify subgroups most at risk of poor knowledge. Using data from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), we investigated associations between FVK and FVI, as well as demographic and lifestyle factors. Baseline FVK was measured using two self-reported questions. FVI was assessed using a validated, self-reported, food frequency questionnaire in 1999/00 (baseline), 2004/05, and 2011/12. Amongst the 8966 participants assessed at baseline, 24.1% had adequate, 73.0% had insufficient, and 2.9% had poor FVK. Using linear regression, those with insufficient or poor FVK reported significantly lower FVI (grams/day) compared to those with adequate FVK: baseline (coefficient (95%CI)): -67.1 (-80.0, -54.3) and -124.0 (-142.9, -105.1), respectively, whilst, at 12 years, the differences were -42.5 (-54.6, -30.5) and -94.6 (-133.8, -55.5) grams/day, respectively (all < 0.001). Poor FVK was more likely to be reported in males, older individuals (>65 years), socio-economically disadvantaged, smokers, and those with insufficient physical activity/sedentary behavior. We demonstrate that having adequate knowledge of FVI, defined as knowing to consume fruit and vegetables several times a day for a well-balanced diet, is strongly associated with FVI, with several demographic and lifestyle factors predicting FVK. Health promotion messages aimed at increasing FVK should target these subgroups for maximal effect.
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http://dx.doi.org/10.3390/nu12123628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759833PMC
November 2020

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

Association between Circulating Osteocalcin and Cardiometabolic Risk Factors following a 4-Week Leafy Green Vitamin K-Rich Diet.

Ann Nutr Metab 2020 24;76(5):361-367. Epub 2020 Nov 24.

Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia,

Background: Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether individuals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors.

Materials And Methods: Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study. The primary analysis involved using data obtained from participants following a high vitamin K1 diet (HK; 4-week intervention of increased leafy green vegetable intake). High and low responders were defined based on the median percent reduction (30%) in ucOC following the HK diet. Blood pressure (resting and 24 h), arterial stiffness, plasma glucose, lipid concentrations, and serum OC forms were assessed.

Results: Following the HK diet, ucOC and ucOC/tOC were suppressed more (p < 0.01) in high responders (41 and 29%) versus low responders (12 and 10%). The reduction in ucOC and ucOC/tOC was not associated with changes in blood pressure, arterial stiffness, plasma glucose, or lipid concentrations in the high responders (p > 0.05).

Discussion/conclusion: Suppression of ucOC via consumption of leafy green vegetables has no negative effects on cardiometabolic health, perhaps, in part, because of cross-talk mechanisms.
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http://dx.doi.org/10.1159/000511660DOI Listing
September 2021

The effects of acute exercise on bone turnover markers in middle-aged and older adults: A systematic review.

Bone 2021 02 21;143:115766. Epub 2020 Nov 21.

Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC, Australia; Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St Albans, VIC, Australia. Electronic address:

Background: Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs.

Objectives: This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex.

Methods: We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359.

Results: Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women.

Conclusion: Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.
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http://dx.doi.org/10.1016/j.bone.2020.115766DOI Listing
February 2021

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

Osteocalcin and measures of adiposity: a systematic review and meta-analysis of observational studies.

Arch Osteoporos 2020 09 18;15(1):145. Epub 2020 Sep 18.

Department of Physiology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Osteocalcin, the osteoblast-derived protein, has been shown to be modulated in patients with problematic glucose metabolism. Our systematic review and meta-analysis found that in humans, higher blood osteocalcin level is associated with lower body indices of fat.

Purpose/introduction: Osteocalcin (OC) was found to be inversely correlated with measures of glucose and energy metabolism, with some groups suggesting the undercarboxylated form (ucOC) to be metabolically active, although the link is not clear, especially in humans. Given obesity is a major risk factor for metabolic disorders, we aimed to assess the correlation between OC and two measures of body weight: body mass index (BMI) and percentage body fat (%BF).

Methods: MEDLINE and EMBASE were searched to identify observational studies in adult populations that reported the crude correlation coefficients (r) between OC and BMI and %BF. Pool r were obtained using random-effects models.

Results: Fifty-one publications were included in this analysis. Both total OC (TOC) (pooled r = - 0.151, 95% CI - 0.17, - 0.130; I = 52%) and ucOC (pooled r = - 0.060, 95% CI - 0.103, - 0.016; I = 54%) were inversely correlated with BMI. The pooled r between TOC and BMI in Caucasian-and-other-regions (r = - 0.187) were stronger than those in Asian populations (r = - 0.126; intra-group p = 0.002; R = 0.21). The mean/median BMI of the reported cohort was the major contributor to between-study heterogeneity in correlation between TOC/ucOC and BMI (R = 0.28 and 0.77, respectively). Both TOC and ucOC were also inversely correlated with %BF (TOC: pooled r = - 0.185, 95% CI - 0.257 to - 0.112; ucOC: pooled r = - 0.181, 95% CI - 0.258 to - 0.101).

Conclusion: Higher OC and ucOC were correlated with lower BMI and %BF. The inverse correlations between TOC/ucOC and BMI appear to be affected by ethnicity and obesity status.
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http://dx.doi.org/10.1007/s11657-020-00812-6DOI Listing
September 2020
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