Emeritus Professor Peter Howe

Resveratrol, a vasoactive phytoestrogen, has beneficial effects on cerebrovascular func-tion. Previous research has shown that hormonal migraineurs have poorer cerebrovascular function than non-migraineur women. We aimed to investigate if resveratrol supplementation for three months could reduce the hormonal migraine burden index (HMBI: the number of days with menstrual migraine per month), reduce migraine-related disability and improve migraine-related quality of life. A randomised, double-blind, placebo-controlled, crossover, intervention trial was con-ducted in 62 hormonal migraineurs (mean age: 37.5 ± 0.8 years). Participants consumed 75 mg of resveratrol or matching placebo capsules twice daily for three months before crossing over to the other treatment arm. Participants completed a daily diary and the Headache Impact Test-6¿, Migraine Disability Assessment and Migraine-Specific Quality of Life questionnaires at months 0, 3 and 6. The HMBI was the primary outcome and was calculated using data extracted from the par-ticipant¿s diary. No differences in the HMBI (p = 0.895), the Headache Impact Test-6¿, the Migraine Disability Assessment and Migraine-Specific Quality of Life were found between the resveratrol and placebo treatments. Resveratrol supplementation for three months did not affect the HMBI, the migraine-related disability or quality of life measures in our cohort of hormonal migraineurs.

Ageing and menopause contribute to endothelial dysfunction, causing impaired cerebral perfusion, which is in turn associated with accelerated cognitive decline. In a 14-week pilot study, we showed that supplementation with low-dose resveratrol, a phytoestrogen that can enhance endothelial function, improved cerebrovascular and cognitive functions in postmenopausal women. We sought to confirm these benefits in a larger, longer-term trial. A 24-month randomized, placebo-controlled crossover trial was undertaken in 125 postmenopausal women, aged 45¿85 years, who took 75 mg trans-resveratrol or placebo twice-daily for 12 months and then crossover to the alternative treatment for another 12 months. We evaluated within individual differences between each treatment period in measures of cognition (primary outcome), cerebrovascular function in the middle cerebral artery (cerebral blood flow velocity: CBFV, cerebrovascular responsiveness: CVR) and cardio-metabolic markers as secondary outcomes. Subgroup analyses examined effects of resveratrol by life stages. Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance (Cohen's d = 0.170, P = 0.005). Women =65 years of age showed a relative improvement in verbal memory with resveratrol compared to those younger than 65 years. Furthermore, resveratrol improved secondary outcomes including resting mean CBFV (d = 0.275, P = 0.001), CVR to hypercapnia (d = 0.307, P = 0.027), CVR to cognitive stimuli (d = 0.259, P = 0.032), fasting insulin (d = 0.174, P = 0.025) and insulin resistance index (d = 0.102, P = 0.034). Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women. This may translate into a slowing of the accelerated cognitive decline due to ageing and menopause, especially in late-life women. Further studies are warranted to observe whether these cognitive benefits of resveratrol can reduce the risk of dementia.

Previous studies have investigated whether migraine is a circulatory disorder, as migraineurs are at heightened risk of cerebrovascular disease. However, in most cases, systemic vascular function was evaluated, which may not reflect abnormalities in the cerebral circulation. Therefore, we aimed to determine whether cerebrovascular function differs between migraineurs and controls. A systematic literature search was conducted across three electronic databases to search for studies that compared cerebrovascular function in migraineurs to controls. Where applicable, meta-analyses were used to determine standardised mean differences (SMD) between migraineurs and controls. Seventy articles were identified, 40 of which contained quantitative data. Meta-analyses showed pulsatility index (PI) was higher (SMD = 0.23; 95%CI = 0.05 to 0.42, P = 0.01) and cerebrovascular responsiveness (CVR) to hypercapnia was lower (SMD=-0.34; 95%CI=-0.67 to -0.01, P = 0.04) in the posterior circulation of migraineurs, particularly those without aura. The meta-analyses also indicated that migraineurs have higher resting mean blood flow velocity in both anterior (SMD = 0.14; 95%CI = 0.05 to 0.23, P = 0.003) and posterior circulations (SMD = 0.20; 95%CI = 0.05 to 0.34, P = 0.007). Compared to healthy controls, migraineurs have altered cerebrovascular function, evidenced by elevated PI (representing arterial stiffness) and impaired CVR to hypercapnia (representing cerebral vasodilator function). Future studies should investigate whether improvement of cerebrovascular function is able to alleviate migraine.

Background and aims: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. Methods and results: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50¿80 years, body mass index: 25¿40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. Conclusion: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. Clinical trial registration: ACTRN12616000732482p.

Curcumin has previously been shown to enhance mood in non-depressed older adults. However, observedbenefits were limitedtoshort-termsupplementation(4 weeks). In a 16 week randomized, double-blind, placebo-controlled, 2 × 2 factorial design trial, we supplemented overweight or obese non-depressed adults (50¿80 years) with curcumin (160 mg/day), fish oil (2000 mg docosahexaenoic acid +400 mg eicosapentaenoic acid/day), or a combination of both. Secondary outcomes included mental wellbeing measures (mood states and subjective memory complaints (SMCs)) and quality of life (QoL). Furthermore, plasma apolipoprotein E4 (APOE4) was measured to determine whether APOE4 status influences responses to fish oil. Curcumin improved vigour (p = 0.044) compared to placebo and reduced SMCs compared to no curcumin treatment (p = 0.038). Fish oil did not affect any mood states, SMCs or QoL; however, responses to fish oil were affected by APOE4 status. In APOE4 non-carriers, fish oil increased vigour (p = 0.030) and reduced total mood disturbances (p = 0.048) compared to placebo. Improvements in mental wellbeing were correlated with increased QoL. Combining curcumin with fish oil did not result in additive effects. This exploratory analysis indicates that regular supplementation with either curcumin or fish oil (limited to APOE4 non-carriers) has the potential to improve some aspects of mental wellbeing in association with better QoL.

This article is protected by copyright. All rights reserved. Resveratrol, a naturally-occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. In vitro and in vivo studies in rodent models also indicate a bone-protective role for resveratrol, particularly in ovariectomised rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesising a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Ageing in Women (RESHAW) trial was a 24-month randomised, double-blind, placebo-controlled, two-period crossover intervention conducted to evaluate the effects of resveratrol (75mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers and well-being in postmenopausal women. Following 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016±0.003 g/cm2 ) and neck of femur (+0.005±0.002 g/cm2 ), which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared to placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T-score (+0.070±0.018) and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score with resveratrol correlated with improvement in perfusion. Our sub-analysis also revealed that the bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. This article is protected by copyright. All rights reserved.

The impaired ability of the autonomic nervous system to respond to hypoglycemia is termed ¿hypoglycemia-associ-ated autonomic failure¿ (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycemia counterregulation under controlled conditions, hypoglycemia prevention remains the current mainstay therapy for HAAF. Epinephrine-synthesizing neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic neurons that regulate peripheral epinephrine release. Here we determined whether or not C1 and C3 neuronal activation is impaired in HAAF and whether or not 1 wk of hypoglycemia prevention or treatment with naloxone could restore C1 and C3 neuronal activation and improve HAAF. Twenty male Sprague-Dawley rats (250 ¿300 g) were used. Plasma epinephrine levels were significantly increased after a single episode of hypoglycemia (n = 4; 5,438 ± 783 pg/ml vs. control 193 ± 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia (n = 4; 2,179 ± 220 pg/ml vs. 5,438 ± 783 pg/ml, P < 0.05). Activation of medullary C1 (n = 4; 50 ± 5% vs. control 3 ± 1%, P < 0.05) and C3 (n = 4; 45 ± 5% vs. control 4 ± 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 (n = 4; 12 ± 3%, P < 0.05) and C3 (n = 4; 19 ± 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia.

Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy-derived flavonoid, against BM sinusoidal damage caused by treatment with methotrexate (MTX). The groups of young adult rats were gavaged daily with genistein (20 mg/kg) or placebo. After 1 week, rats also received daily injections of MTX (0.75 mg/kg) or saline for 5 days and were killed after a further 4 days. Histological analyses showed that BM sinusoids were markedly dilated (p < 0.001) in the MTX-alone group but were unaffected or less dilated in the genistein+MTX group. In control rats, genistein significantly enhanced expression of vascular endothelial growth factor (VEGF; p < 0.01), particularly in osteoblasts, and angiogenesis marker CD31 (p < 0.001) in bone. In MTX-treated rats, genistein suppressed MTX-induced apoptosis of BM SECs (p < 0.001 vs MTX alone group) and tended to increase expression of CD31 and VEGF (p < 0.05). Our in vitro studies showed that genistein in certain concentrations protected cultured SECs from MTX cytotoxic effects. Genistein enhanced tube formation of cultured SECs, which is associated with its ability to induce expression of endothelial nitric oxide synthase and production of nitric oxide. These data suggest that genistein can protect BM sinusoids during MTX therapy, which is associated, at least partially, with its indirect effect of promoting VEGF expression in osteoblasts and its direct effect of enhancing nitric oxide production in SECs.

Objectives: Improvements in the management of complex congenital heart disease, including those with single ventricle physiology, have resulted in increased survival. As this population ages, the recognition of cognitive impairment is increasingly important. At present, little is known about the potential mechanisms of cognitive dysfunction. In this cross-sectional study, we aimed to characterize the nature of abnormalities in cerebral blood flow and the relationship to cognitive deficits in adults with single ventricular physiology. Patients: Ten adults with single ventricular physiology (age 18-40¿years) and 12 age- and gender-matched controls underwent transcranial Doppler ultrasound and accompanying cognitive assessment. Outcome Measures: Patients underwent neuropsychological testing that assessed differing cognitive domains, with subjective cognitive decline determined from a 24-question survey. Transcranial Doppler ultrasound was used to assess baseline cerebral blood flow as well as change in cerebral blood flow velocities from baseline and during cognitive testing. Age, ethnicity, individual, and parental education levels were considered in the multivariate analyses. Results: On assessment of cognitive function, the patient group performed more poorly across each of the measured domains. The control group had a significantly greater increase in cerebral blood flow in response to cognitive stimuli compared to the patient cohort; these differences in response to cognitive stimuli were seen to a similar extent across each of the measured cognitive domains. Conclusion: Adults with Fontan physiology are underperforming in assessments of executive function with associated abnormalities in cerebral perfusion potentially contributing to cognitive deficits.

Food cravings are common in type 2 diabetes (T2D). Higher-protein diets are effective in improving satiety but their effect on cravings is unclear. It was hypothesized that a high protein (HP) diet would provide greater reductions in cravings than an isocaloric higher-carbohydrate diet (HC). In a randomized controlled trial, 61 adults (54% males) with T2D (means ± SD: BMI 34.3 ± 5.1 kg/m 2 ; aged 55 ± 8 years) consumed either a HP diet (mean across study: 29% protein, 34% carbohydrate, 31% fat) or an isocaloric HC diet (21%:48%:24%) for 12-weeks each of weight loss (WL) and weight maintenance (WM). The Food Craving Inventory (FCI), measuring types of foods craved and the General Food Craving Questionnaires measuring traits (G-FCQ-T) and states (G-FCQ-S) were assessed at Weeks 0, 12 and 24. Weight changes were similar between groups (means ± SEM: WL: -7.8 ± 0.6 kg, WM: -0.6 ± 0.4 kg). No group effects or group x time interactions were found for any outcome (P =.07). Independent of group, all food cravings (except carbohydrates) and G-FCQ-T subscales decreased over the 24-week study (P =.04) with sweets and fast food cravings, loss of control and emotional cravings reducing following WL (P =.03). Obsessive preoccupation with food decreased following both phases (WL: P =.03; WM: P =.001). Weight was associated with several FCI subscales (r = 0.24, P =.04). In conclusion, both the HP and HC diets provided significant reductions in food cravings after similar weight losses which were maintained when weight was stabilized.

Snacking is associated with intakes of non¿core foods which may predispose to obesity. Peanuts have potential satiety benefits and may assist with weight management; we hypothesized that peanut consumption would reduce intake of non¿core snack foods due to compensation. We investigated the effects of adding peanuts to a habitual diet on snacking habits and energy intake. Sixty-one healthy participants (65¿±¿7¿years, body mass index 31¿±¿4¿kg/m2) consumed their habitual diet with or without peanuts (56¿g/d for 32 women, 84¿g/d for 29 men) for 12¿weeks each in a randomized crossover design. Food diaries were analyzed at baseline and after each 12-week period for meal and snack content and timing. Total energy intake was higher (17% for men [P¿<¿.001], 9% for women [P¿<¿.001]) during the peanut phase. Body weight was 0.5¿±¿0.2¿kg (P¿=¿.010) greater during the peanut phase. Snacking occasions increased during the peanut phase (53% for men [P¿=¿.001], 14% for women [P¿=¿.01]). Servings of other snack foods did not change during the peanut phase (P¿=¿.6) compared with control. However, sex-specific analysis revealed that men and women consumed less savory (P¿<¿.001) and sweet (P¿=¿.01) non¿core snacks, respectively, during the peanut phase. Despite increased energy intake and snacking frequency, peanuts may improve the diet through sex-specific reductions of non¿core foods; for optimal energy balance, peanuts should be substituted rather than added to the diet.

Background Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve obstruction. Late sequelae are recognised, including stroke, hypertension, and intracerebral aneurysm formation, with the underlying mechanisms being unclear. We hypothesised that patients with a history of aortic coarctation may have abnormalities of cerebral blood flow compared with controls. Methods Patients with a history of aortic coarctation underwent assessment of cerebral vascular function. Vascular responsiveness of intracranial vessels to hypercapnia and degree of cerebral artery stiffness using Doppler-derived pulsatility indices were used. Response to photic stimuli was used to assess neurovascular coupling, which reflects endothelial function in response to neuronal activation. Patient results were compared with age- and sex-matched controls. Results A total of 13 adult patients (males=10; 77%) along with 13 controls underwent evaluation. The mean age was 36.1±3.7 years in the patient group. Patients with a background of aortic coarctation were noted to have increased pulse pressure on blood pressure assessment at baseline with increased intracranial artery stiffness compared with controls. Patients with a history of aortic coarctation had less reactive cerebral vasculature to hypercapnic stimuli and impaired neurovascular coupling compared with controls. Results Adult patients with aortic coarctation had increased intracranial artery stiffness compared with controls, in addition to cerebral vasculature showing less responsiveness to hypercapnic and photic stimuli. Further studies are required to assess the aetiology and consequences of these documented abnormalities in cerebral blood flow in terms of stroke risk, cerebral aneurysm formation, and cognitive dysfunction.

Recent evidence indicates that resveratrol, a phytoestrogen, can improve cognitive function in postmenopausal women by enhancing cerebral vasodilator responsiveness. We examine the effects of phytoestrogen supplementation on cognition and compare resveratrol with other phytoestrogens. Databases were searched for reports of randomized controlled trials (RCTs) containing terms describing phytoestrogens together with terms relating to cognition. Effect sizes were determined for changes in cognition. We identified 23 RCTs, 15 with isoflavone and eight with resveratrol or grape formulations. Six soy isoflavone studies showed positive cognitive effects of medium size. Greater benefits were seen in women who were <10 years postmenopausal and supplemented for <6 months. Small-to-medium effect¿size cognitive benefits of resveratrol were seen in four studies of older adults of mixed gender and in postmenopausal women who took 150¿200 mg resveratrol daily for at least 14 weeks. No benefits were seen in three studies using red clover or grape formulations. Supplementation with either soy isoflavone or resveratrol improved executive function and memory domains of cognitively normal older adults in half of the included studies, mostly with medium effect sizes. The cognitive benefit of resveratrol was related to improved cerebral perfusion.

Objective: Pain is a common complaint among postmenopausal women. It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease, namely age-related osteoarthritis. We evaluated whether supplementation with resveratrol, a phytoestrogen, could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women. Methods: A 14-week randomized, double-blind, placebo-controlled intervention with trans-resveratrol (75mg, twice daily) was conducted in 80 healthy postmenopausal women. Aspects of well-being, including pain, menopausal symptoms, sleep quality, depressive symptoms, mood states, and quality of life were assessed by Short form-36 at baseline and at the end of treatment. Rating scales were averaged to provide a composite score representing overall well-being. Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function. Results: Compared with placebo treatment, there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation. Both benefits, including measures of quality of life, correlated with improvements in cerebrovascular function. Conclusions: Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis. Resveratrol consumption may also boost perceptions of well-being in postmenopausal women. Further investigation to elucidate underlying mechanisms is warranted.

Purpose: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. Methods: This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. Results: AC treatment for four cycles (weekly intravenous injection of 2¿mg/kg doxorubicin and 20¿mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase. Reductions in densities of osteocytes and bone lining cells were also observed. In addition, bone marrow was severely damaged, including a severe reduction in bone marrow cellularity and an increase in marrow adipocyte content. Accompanying these changes, there were increases in mRNA expression of adipogenesis regulatory genes (PPAR¿ and FABP4) and an inflammatory cytokine (TNFa) in metaphysis bone and bone marrow. Conclusions: This study indicates that AC chemotherapy may induce some bone loss, due to reduced bone formation, and bone marrow damage, due to increased marrow adiposity. Preventive strategies for preserving the bone and bone marrow microenvironment during anthracycline chemotherapy warrant further investigation.

Aim Cognitive deficits in type 2 diabetes mellitus (T2DM) may be partly attributable to stiffness in cerebral arteries and impaired vasodilator function, limiting the ability to increase blood flow in brain regions to meet cognitive demands. We undertook a comparison of cerebrovascular responsiveness (CVR) and cognitive performance in adults with and without T2DM. Methods Older adults with (50) and without (Herath, Cherbuin, Eramudugolla, & Anstey, 2016) T2DM underwent transcranial Doppler ultrasound measurements of basal cerebral mean blood flow velocity (MBFV) and pulsatility index (PI), a measure of arterial stiffness, in the middle cerebral arteries (MCA). A battery of tasks assessing domains of working memory, executive function and information processing/motor speed was then administered while MBFV was recorded. CVR to cognitive tasks was calculated as a percentage increase in MBFV from the basal level. Results There was no difference in basal MBFV between groups. However, PI was 14% higher in the T2DM group (P¿<¿0.05), who performed poorer across all cognitive domains assessed and displayed poorer CVR in three tasks. Cognitive performance was inversely related to the PI/MBFV ratio, an indicator of intracranial stenosis. Discussion Impaired cerebral perfusion during mental tasks is accompanied by poor cognitive performance and stiffness in the cerebral vessels.

Growth factors can be isolated from bovine milk to form a whey growth factor extract (WGFE). This study examined whether WGFE promoted activation of the AKT/mTOR pathway enabling increased lean tissue mass and strength in resistance trained men. Forty six men with >6 months of resistance training (RT) experience performed 12 weeks of RT. Participants consumed 20 g/day of whey protein and were randomised to receive either 1.6 g WGFE/day (WGFE; n = 22) or 1.6 g cellulose/day (control, CONT; n = 24). The primary outcome was leg press one-repetition maximum (LP1-RM) which was assessed at baseline, 6 and 12 weeks. At baseline and 12 weeks body composition was assessed by dual energy x-ray absorptiometry, and muscle protein synthesis and gene expression were assessed (vastus lateralis biopsy) in a sub-sample (WGFE n = 10, CONT n = 10) pre- and 3 hr post-training. RT increased LP1-RM (+34.9%) and lean tissue mass (+2.3%; p < 0.05) with no difference between treatments (p > 0.48, treatment x time). Post-exercise P70s6k phosphorylation increased acutely, FOXO3a phosphorylation was unaltered. There were no differences in kinase signalling or gene expression between treatments. Compared with CONT, WGFE did not result in greater increases in lean tissue mass or strength in experienced resistance trained men.

Background Obese children are typically less physically active than their normal-weight peers and are often assumed to be 'unfit'. Objective Investigate the relationships between adiposity, physical activity levels and cardiorespiratory fitness (CRF) in obese and normal-weight children. A secondary aim was to examine obese/normal-weight differences in CRF. Methods Obese (N = 107) and normal-weight (N = 132) 10-13-year-olds participated. Fat-free mass (FFM), percent fat, physical activity and peak oxygen uptake (VO2peak) were assessed. Analyses were adjusted for socioeconomic status (SES). Results Higher percent fat was inversely associated with VO2peak normalized for mass (r = -0.780, P < 0.001) even after controlling for physical activity (r = -0.673, P < 0.001). While higher percent fat was also inversely associated with VO2peak normalized for FFM, this was only significant in males (r = -0.247, P = 0.004) and did not persist after controlling for physical activity (r = -0.059 P = 0.526). Compared with normal-weight children, obese children had higher absolute VO2peak, lower VO2peak corrected for mass (P = 0.009) and lower VO2peak corrected for FFM (P = 0.041) that did not persist after controlling for SES (P = 0.086). Conclusion Obesity-related inefficiencies in CRF were evident. Higher adiposity was associated with poorer CRF relative to mass, irrespective of physical activity levels. However, low physical activity levels may be responsible for associations between adiposity and CRF relative to FFM seen in boys, indicating the importance of encouraging physical activity.

Background: This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. Method: Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. Conclusion: This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Background and aims: Progressive microvascular dysfunction in type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby increasing risks of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol could similarly benefit the cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM. Methods and results: In a double-blind, placebo-controlled, balanced crossover intervention, 36 dementia-free, non-insulin dependent T2DM older adults (49-78 years old) consumed single doses of synthetic trans-resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, both before and 45 min after treatment. CVR, measured bilaterally in the middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), was expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during hypercapnia. Resveratrol consumption increased CVR in the MCA; mean within-individual changes for each dose from placebo were 13.8 ± 3.5% for 75 mg (P = 0.001), 8.9 ± 3.5% for 150 mg (P = 0.016), and 13.7 ± 3.3% for 300 mg (P < 0.001); only the 75 mg dose was efficacious in the PCA (13.2 ± 4.5%, P = 0.016). Conclusions: Our results provide the first clinical evidence of an acute enhancement of vasodilator responsiveness in cerebral vessels following consumption of resveratrol in this population who are known to have endothelial dysfunction and sub-clinical cognitive impairment. Importantly, maximum improvement was observed with the lowest dose used. Clinical trial registration: ACTRN12614000891628 (. www.anzctr.org.au).

Objectives: Reductions in maximal rate of heart rate increase (rHRI) correlate with performance reductions when training load is increased. This study evaluated whether rHRI tracked performance changes across a range of training states. Design: Prospective intervention. Methods: rHRI was assessed during five min of cycling at 100 W (rHRIcyc) and running at 8 km/h (rHRIrun) in 13 male triathletes following two weeks of light-training (LT), two weeks of heavy-training (HT) and a two-day recovery period (RP). A five min cycling time-trial assessed performance and peak oxygen consumption (VO2peak). Results: Performance likely decreased following HT (Effect size ± 90% confidence interval = -0.18 ± 0.09), then very likely increased following RP (0.32 ± 0.14). rHRIcyc very likely decreased (-0.48 ± 0.24), and rHRIrun possibly decreased (-0.33 ± 0.48), following HT. Changes in both measures were unclear following RP. Steady-state HR was almost certainly lower (-0.81 ± 0.31) during rHRIcyc than rHRIrun. A large correlation was found between reductions in performance and rHRIrun (r ± 90%; CI = 0.65 ± 0.34) from LT to HT, but was unclear for rHRIcyc. Trivial within-subject correlations were found between rHRI and performance, but the strength of relationship between rHRIrun and performance was largely associated with VO2peak following LT (r = -0.58 ± 0.38). Conclusions: Performance reductions were most sensitively tracked by rHRIrun following HT. This may be due to rHRIrun being assessed at a higher intensity than rHRIcyc, inferred from a higher steady-state HR and supported by a stronger within-subject relationship between rHRIrun and performance in individuals with a lower VO2peak, in whom the same exercise intensity would represent a greater physiological stress. rHRI assessed at relatively high exercise intensities may better track performance changes.

Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM.We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR) to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli), cognitive performance and correlations with plasma resveratrol concentrations. Methods: Thirty-six T2DM adults aged 40¿80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV) during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task) and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. Results: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. Conclusion: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted.

The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10¿mg/kg, epirubicin at 2.5¿mg/kg and 5-flurouracil at 10¿mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation.

Introduction Impairment of cerebrovascular function becomes evident after menopause. No study has yet explored relationships between deficits in cerebrovascular function, cognitive performance, and mood in postmenopausal women. Method Cerebrovascular function was assessed in 80 healthy postmenopausal women by monitoring blood flow velocity (BFV) in the middle and posterior cerebral arteries using transcranial Doppler ultrasound at rest, following a hypercapnic challenge, and during performance of a cognitive test battery; the latter assessed domains of memory and executive functions. Various measures of mood (i.e., Profile of Mood States and Center for Epidemiological Studies Depression Scale) were also assessed. Results Cerebral artery elasticity and BFV responsiveness to cognitive tests (neurovascular coupling) correlated with cognitive performance but not with depressive symptoms or mood states. Mood deficits were related to poor cognitive performance. Conclusion These results highlight the importance of adequate cerebral perfusion for optimized cognitive function in healthy postmenopausal women. Preventative strategies to attenuate accelerated cognitive decline should also consider restoring cerebrovascular function.

Different mathematical models were used to evaluate if the maximal rate of heart rate (HR) increase (rHRI) was related to reductions in exercise performance resulting from acute fatigue. Fourteen triathletes completed testing before and after a 2-h run. rHRI was assessed during 5 min of 100-W cycling and a sigmoidal (rHRIsig) and exponential (rHRIexp) model were applied. Exercise performance was assessed using a 5-min cycling time-trial. The run elicited reductions in time-trial performance (1.34 ± 0.19 to 1.25 ± 0.18 kJ · kg-1, P < 0.001), rHRIsig (2.25 ± 1.0 to 1.14 ± 0.7 beats · min-1 · s-1, P < 0.001) and rHRIexp (3.79 ± 2.07 to 1.98 ± 1.05 beats · min-1 · s-1, P = 0.001), and increased pre-exercise HR (73.0 ± 8.4 to 90.5 ± 11.4 beats · min-1, P < 0.001). Pre-post run difference in time-trial performance was related to difference in rHRIsig (r = 0.58, P = 0.04 and r = 0.75, P = 0.003) but not rHRIexp (r = -0.04, P = 0.9 and r = 0.27, P = 0.4) when controlling for differences in pre-exercise and steady-state HR. rHRIsig was reduced following acute exercise-induced fatigue, and correlated with difference in performance.

Objectives: The recovery of heart rate (HRR) after exercise is a potential indicator of fitness which has been shown to respond to changes in training. This study investigated the within-individual association between HRR and exercise performance following three different training loads. Design: 11 male cyclists/triathletes were tested after two weeks of light training, two weeks of heavy training and two days of rest. Methods: Exercise performance was measured using a 5-min maximal cycling time-trial. HRR was measured over 60 s during supine recovery. Results: Exercise performance decreased 2.2 ± 2.5% following heavy training compared with post-light training (= 0.01), and then increased 4.0 ± 4.2% following rest (= 0.004). Most HRR indices indicated a more rapid recovery of heart rate (HR) following heavy training, and reverted to post light training levels following two days of rest. HRR indices did not differ between post-light training and after the rest period (> 0.6). There were inverse within-subject relationships between indices of HRR and performance (= -0.6, p = 0.004). Peak HR decreased 3.2 ± 5.1 bpm following heavy training (= 0.06) and significantly increased 4.9 ± 4.3 bpm following recovery (= 0.004). There was a moderate within-subject relationship between peak HR and exercise performance (= 0.7, p = 0.001). Controlling for peak HR reduced the relationships between HRR and performance (= -0.4-0.5, p < 0.05). Conclusions: This study demonstrated that HRR tracks short-term changes in exercise performance within-individuals, such that increases in HRR are associated with poorer exercise performance following heavy training. Peak HR can be compromised under conditions of fatigue, and needs to be taken into account in HRR analyses.

Background: This study examined relationships between adiposity, physical functioning, and physical activity. Methods: Obese (N = 107) and healthy-weight (N = 132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry); knee extensor strength (KE, isokinetic dynamometry); cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry); physical health-related quality of life (HRQOL); and worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. Results: Moderate relationships were observed between %BF and (1) 6MWT, (2) KE strength corrected for mass, and (3) CRF relative to mass (r -0.36 to -0.69, p = 0.007). Weak relationships were found between %BF and physical HRQOL (r -0.27, p = 0.008); CRF relative to mass and physical HRQOL (r -0.24, p = 0.003); physical activity and 6MWT (r 0.17, p = 0.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain, and CRF relative to mass; while 28.0% variance in 6MWT was explained by %BF and physical activity. Conclusions: It appears that children with a higher body fat percentage have poorer KE strength, CRF, and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, reductions in pain, and improvements in physical activity and CRF may assist physical functioning.

The metabolic syndrome is a pathological state whereby cardiovascular and metabolic dysfunction coexist and typically progress in a mutual feed-forward manner to further dysfunction and ultimately disease. The health and function of the vascular endothelium is integral in this phenomenon and thus represents a logical target for intervention. Consumption of foods high in cocoa flavanols has demonstrated a capacity to markedly improve endothelial function and key markers of the metabolic syndrome including blood pressure and insulin sensitivity. The typically high energy content of foods containing sufficient doses of cocoa flavanols has caused some reservations around its therapeutic use, but this is dependent upon the particulars of the food matrix used. Further to this, the food matrix appears to influence the dose response curve of cocoa flavanols, particularly on blood pressure, with dark chocolate appearing to be 8 times more effective in systolic blood pressure reduction than a cocoa powder drink for the equivalent dose of flavanol. Cocoa flavanol consumption conclusively demonstrates a positive impact on cardiometabolic function; however, more research is needed to understand how best to consume it to maximize the benefit while avoiding excessive fat and sugar consumption.

© 2015. Context: The anti-inflammatory activity of long-chain n-3 polyunsaturated fatty acids (PUFAs) has been established in several chronic inflammatory diseases but has yet to be demonstrated in inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD). Objective: The aim of this systematic review was to investigate, using PRISMA guidelines, the relationship between the intake of long-chain n-3 PUFAs and the prevalence, severity, and health outcomes of COPD. Data Sources: Eight health databases and the World Health Organization's international clinical trial registry were searched for relevant studies. Study Selection: Experimental or observational studies that were published in English and that assessed long-chain n-3 PUFA intake (by determining habitual consumption and/or tissue levels) in adults with COPD were included. Data Extraction: Publication demographics, participant characteristics, type of intervention or exposure, long-chain n-3 PUFA intake, pulmonary function, COPD mortality, and COPD severity were independently extracted from each article by 2 authors using a prospectively designed data extraction tool. Data Synthesis: All 11 of the studies included in the review were observational. Approximately equal numbers of studies reported significant (n=6, 5 inverse) relationships or no significant relationships (n=5) between either consumption of long-chain n-3 PUFAs or levels of long-chain n-3 PUFAS in tissue and a COPD outcome. Conclusions: Current evidence of a relationship between long-chain n-3 PUFA intake and COPD is limited and conflicting, with studies having wide methodological variation. Registration number: PROSPERO 2013:CRD42013004085.

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage.

Objective: The purpose of this study was to determine if vibration therapy is more effective than the standard treatment of stretching and massage for improving recovery of muscle strength and reducing muscle soreness after muscle damage induced by eccentric exercise. Design: A randomized, single-blinded parallel intervention trial design was used. Setting: Research laboratory. Participants: Fifty untrained men aged 18 to 30 years completed the study. Interventions: Participants performed 100 maximal eccentric muscle actions (ECC<inf>max</inf>) of the right knee extensor muscles. For the next 7 days, 25 participants applied cycloidal vibration therapy to the knee extensors twice daily and 25 participants performed stretching and sports massage (SSM) twice daily. Main Outcome Measures: Changes in markers of muscle damage [peak isometric torque (PIT), serum creatine kinase (CK), and serum myoglobin (Mb)], muscle soreness (visual analog scale), and inflammation [serum C-reactive protein (CRP)] were assessed. Results: After ECC<inf>max</inf>, there was no difference in recovery of PIT and muscle soreness or serum CK, Mb, and CRP levels between vibration and SSM groups (P > 0.28). Conclusions: Cycloidal vibration therapy is no more effective than the standard practice of stretching and massage to promote muscle recovery after the performance of muscle-damaging exercise. Clinical Relevance: Prescription of vibration therapy after maximal exercise involving eccentric muscle damage did not alleviate signs and symptoms of muscle damage faster than the standard prescription of stretching and massage.

© 2015, the authors; licensee MDPI, Basel, Switzerland. Epidemiological evidence indicates an inverse association between nut consumption and obesity, inflammation, hyperlipidaemia and glucose intolerance. We investigated effects of high oleic peanut consumption vs. a nut free diet on adiposity and cardio-metabolic risk markers. In a randomised cross-over design, 61 healthy subjects (65 ± 7 years, body mass index (BMI) 31 ± 4 kg/m²) alternated either high oleic peanuts (15%¿20% of energy) or a nut free diet for 12 weeks. Body composition and mass, waist circumference, C-reactive protein (CRP), lipids, glucose and insulin were assessed at baseline and after each phase. Repeated measures analysis of variance (ANOVA) compared the two diets. Consistent with other nut studies, there were no differences in lipids, CRP, glucose and insulin with peanut consumption. In contrast, some reports have demonstrated benefits, likely due to differences in the study cohort. Energy intake was 10% higher (853 kJ, p < 0.05), following peanut consumption vs. control, attributed to a 30% increase in fat intake (p < 0.001), predominantly monounsaturated (increase 22 g, p < 0.05). Despite greater energy intake during the peanut phase, there were no differences in body composition, and less than predicted increase (0.5 kg) in body weight for this additional energy intake, possibly due to incomplete nutrient absorption and energy utilisation.

Objective: To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. Method: Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners¿ Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. Results: Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r =.365, p <.001) and attention (r = -.540, p <.001) and reduced oppositional behavior (r = -.301, p <.003), hyperactivity (r = -.310, p <.001), cognitive problems (r = -.326, p <.001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = -.270, p =.002) and DSM-IV inattention (r = -.343, p <.001). Conclusion: Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD.

© 2015 . Background: Hypocaloric low-fat diets, high in protein with moderate carbohydrate (HP) can enhance weight loss, improve glycaemic control and improve cardiometabolic health risk factors in type 2 diabetes mellitus (T2DM). However, it is unclear whether the metabolic benefits observed during weight loss are sustained during energy-balance and weight maintenance. Furthermore, there is a lack of evidence regarding the effect of HP diets on food cravings, cognitive function and psychological wellbeing in T2DM, despite carbohydrate food cravings, cognitive impairment and depression being associated with hyperglycaemia. Methods/design: Overweight/obese adults with T2DM were randomised to consume either a HP diet (n. = 32, ~. 32% protein, 33% carbohydrate, 30% fat) or a higher-carbohydrate diet (HC, n. = 29, ~. 22% protein, 51% carbohydrate, 22% fat) for 24 weeks with 30 min of moderate intensity exercise five days/week for the study duration. There were 2 phases: a 12 week weight loss phase followed by a 12 week weight maintenance phase. Primary outcome was glycaemic control (glycosylated haemoglobin; HbA1c). Secondary outcomes were cardiometabolic risk factors (body composition, fasting blood pressure, blood lipids, glucose, insulin and C-reactive protein), food cravings, cognitive function (memory; psychomotor and executive function and psychological well-being. Outcomes were measured at baseline and the end of each 12-week intervention phase. Data will be analysed as intention-to-treat using linear mixed effects models. Conclusion: This study will examine the effects of two dietary interventions on health outcomes in T2DM during weight loss and notably following weight maintenance where there is a paucity of evidence.

Cross-sectional studies have reported positive relationships between serum lutein concentrations and higher physical activity levels. The purpose of the study was to determine whether increasing plasma lutein levels increases physical activity. Forty-four older adults (BMI, 25.3 ± 2.6 kg/m2; age, 68.8 ± 6.4 year) not meeting Australian physical activity guidelines (150 min/week of moderate to vigorous activity) were randomized to consume capsules containing 21 mg of lutein or placebo with 250 mL of full-cream milk per day for 4 weeks and encouraged to increase physical activity. Physical activity was assessed by self-report, pedometry and accelerometry (daily activity counts and sedentary time). Exercise self-efficacy was assessed by questionnaire. Thirty-nine participants competed the study (Lutein = 19, Placebo = 20). Lutein increased plasma lutein concentrations compared with placebo (p < 0.001). Absolute and percentage changes in plasma lutein were inversely associated with absolute (r = -0.36, p = 0.03) and percentage changes (r = -0.39, p = 0.02) in sedentary time. Percentage change in plasma lutein was positively associated with the percentage change in average daily activity counts (r = 0.36, p = 0.03). Exercise self-efficacy did not change (p = 0.16). Lutein increased plasma lutein, which was associated with increased physical activity and reduced sedentary time in older adults. Larger trials should evaluate whether Lutein can provide health benefits over the longer term. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Epidemiological evidence of an inverse association between consumption of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) and obesity has been conflicting, even though studies in animal models of obesity and limited human trials suggest that LC n-3 PUFA consumption may contribute to weight loss. We used baseline data from a convenience sample of 476 adults (291 women, 185 men) participating in clinical trials at our Centre to explore relationships between erythrocyte levels of LC n-3 PUFA (a reliable indicator of habitual intake) and measures of adiposity, viz. body mass index (BMI), waist circumference (WC) and body fat (BF) assessed by dual-energy X-ray absorptiometry. Means ± SD of assessments were BMI: 34 ± 7 and 31 ± 5 kg/m2; WC: 105 ± 16 and 110 ± 13 cm; BF: 48 ± 5 and 35% ± 6% in women and men respectively. Erythrocyte levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were similar in men and women while docosapentaenoic acid (DPA) was higher and EPA + DHA (Omega-3 Index) slightly lower in men than in women. Both DHA and EPA + DHA correlated inversely with BMI, WC and BF in women while DPA correlated inversely with BF in men. Quartile distributions and curvilinear regression of the Omega-3 Index versus BMI revealed a steep rise of BMI in the lower range of the Omega-3 Index in women, but no association in men. Thus the results highlight important gender differences in relationships of specific LC n-3 PUFA in erythrocytes to markers of adiposity. If these reflect causal relationships between LC n-3 PUFA consumption and risk of obesity, gender specific targeted interventions should be considered. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

© 2014 by the authors; licensee MDPI, Basel, Switzerland. Osteoporosis is a highly prevalent skeletal disorder in the elderly that causes serious bone fractures. Peak bone mass achieved at adolescence has been shown to predict bone mass and osteoporosis related risk fracture later in life. Resveratrol, a natural polyphenol compound, may have the potential to promote bone formation and reduce bone resorption. However, it is unclear whether it can aid bone growth and bone mass accumulation during rapid growth and modulate bone metabolism during ageing. Using rat models, the current study investigated the potential effects of resveratrol supplementation during the rapid postnatal growth period and in late adulthood (early ageing) on bone microarchitecture and metabolism. In the growth trial, 4-week-old male hooded Wistar rats on a normal chow diet were given resveratrol (2.5 mg/kg/day) or vehicle control for 5 weeks. In the ageing trial, 6-month-old male hooded Wistar rats were treated with resveratrol (20 mg/kg/day) or vehicle for 3 months. Treatment effects in the tibia were examined by µ-computer tomography ((J.-CT) analysis, bone histomorphometric measurements and reverse transcription-polymerase chain reaction (RT-PCR) gene expression analysis. Resveratrol treatment did not affect trabecular bone volume and bone remodeling indices in the youth animal model. Resveratrol supplementation in the early ageing rats tended to decrease trabecular bone volume, Sirt1 gene expression and increased expression of adipogenesis-related genes in bone, all of which were statistically insignificant. However, it decreased osteocalcin expression (p = 0.03). Furthermore, serum levels of bone resorption marker C-terminal telopeptides type I collagen (CTX-1) were significantly elevated in the resveratrol supplementation group (p = 0.02) with no changes observed in serum levels of bone formation marker alkaline phosphatase (ALP). These results in rat models suggest that resveratrol supplementation does not significantly affect bone volume during the rapid growth phase but may potentially have negative effects on male skeleton during early ageing.

© 2014 Elsevier Ltd. Snack foods can contribute a high proportion of energy intake to the diet. Peanuts are a snack food rich in unsaturated fatty acids, protein and fibre which have demonstrated satiety effects and may reduce total energy intake, despite their high energy density. This study examined the effects of consuming Hi-oleic (oleic acid ~75% of total fatty acids) peanuts and regular peanuts (oleic acid ~50% and higher in polyunsaturated fatty acids) compared with a high carbohydrate snack (potato crisps) on satiety and subsequent energy intake. Using a triple crossover study design, 24 participants (61 ± 1 years) consumed iso-energetic amounts (56-84 g) of Hi-oleic or regular peanuts or (60-90 g) potato crisps after an overnight fast. Hunger and satiety were assessed at baseline, 30, 60, 120 and 180 minutes following snack consumption using visual analogue scales, after which a cold buffet meal was freely consumed and energy intake measured. The same snack was consumed on 3 subsequent days with energy intake assessed from dietary records. This protocol was repeated weekly with each snack food. Total energy intake was lower following consumption of Hi-oleic and regular peanuts compared with crisps, both acutely during the buffet meal (-21%; p <.001 and -17%; p <.01) and over the 4 days (-11%; p <.001 and -9%; p <.01). Despite these reductions in energy intake, no differences in perceived satiety were observed. The findings suggest peanuts may be a preferred snack food to include in the diet for maintaining a healthy weight.

Methotrexate (MTX) chemotherapy is known to cause bone loss which lacks specific preventative treatments, although clinically folinic acid is often used to reduce MTX toxicity in soft tissues. This study investigated damaging effects of MTX injections (0.75 mg/kg/day for 5 days) in rats and potential protective benefits of fish oil (0.25, 0.5, or 0.75 ml/100 g/day) in comparison to folinic acid (0.75 mg/kg) in the tibial metaphysis. MTX treatment significantly reduced height of primary spongiosa and volume of trabecular bone while reducing density of osteoblasts. Consistently, MTX reduced osteogenic differentiation but increased adipogenesis of bone marrow stromal cells, accompanied by lower mRNA expression of osteogenic transcription factors Runx2 and Osx, but an up-regulation of adipogenesis-related genes FABP4 and PPAR-¿. MTX also increased osteoclast density, bone marrow osteoclast formation, and mRNA expression of proinflammatory cytokines IL-1, IL-6, TNF-a, and RANKL/OPG ratio in bone. Fish oil (0.5 or 0.75 ml/100 g) or folinic acid supplementation preserved bone volume, osteoblast density, and osteogenic differentiation, and suppressed MTX-induced cytokine expression, osteoclastogenesis, and adipogenesis. Thus, fish oil at 0.5 ml/100 g or above is as effective as folinic acid in counteracting MTX-induced bone damage, conserving bone formation, suppressing resorption and marrow adiposity, suggesting its therapeutic potential in preventing bone loss during MTX chemotherapy. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:587-596, 2014. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

OBJECTIVES:: To investigate whether obesity is associated with musculoskeletal pain in children. MATERIALS AND METHODS:: Obese (n=107) and healthy-weight (n=132) 10-to 13-year-old children (132 males, 107 females) participated in an observational case-control study. Children self-reported pain location (excluding abdominal pain), pain intensity (current and prior week), and pain prevalence (overall and lower limb) using the Pediatric Pain Questionnaire. Body composition was assessed (dual-energy x-ray absorptiometry) and children wore an accelerometer for 8 days. RESULTS:: After adjustment for accelerometry (weekly average counts per hour) and socioeconomic status, obese children had more intense pain (worst pain, P=0.006), pain in more locations (P=0.005), and a higher prevalence of lower limb pain (60% vs. 52% respectively, P=0.012) than healthy-weight children. Significant relationships were observed between body mass index and total pain locations (P=0.004, unadjusted and adjusted) and worst pain intensity (P=0.009, adjusted for socioeconomic status/accelerometry). There were no significant relationships between percent body fat and pain variables (unadjusted/adjusted analyses, P=0.262 to 1.0). DISCUSSION:: Obesity in children was associated with increased overall and lower limb musculoskeletal pain, for which body mass index was a stronger predictor than adiposity. Clinicians treating obese children should screen for pain and prescribe exercise programs that take their symptoms into account. Copyright © 2013 by Lippincott Williams & Wilkins.

Nuts are rich in many nutrients that can benefit multiple cardiometabolic functions, including arterial compliance, blood pressure, inflammation, glucoregulation and endothelial vasodilatation. Impaired vasodilatation may contribute to impaired cognitive performance due to poor cerebral perfusion. The present narrative review examines associations between nut consumption, vascular health and cognitive function. It includes a systematic search which identified seventy-one epidemiological or intervention studies in which effects of chronic nut consumption on blood pressure, glucoregulation, endothelial vasodilator function, arterial compliance, inflammatory biomarkers and cognitive performance were evaluated. Weighted mean changes were estimated where data were available; they indicate that nut consumption reduces blood pressure and improves glucoregulation, endothelial vasodilator function and inflammation, whilst a limited number of studies suggest that nut consumption may also improve cognitive performance. Further clinical trials are warranted to explore relationships between nut consumption, endothelial function and cognitive function. © 2014 The Authors.

A number of intervention studies have reported that the prevalence of obesity may be in part inversely related to dairy food consumption while others report no association. We sought to examine relationships between energy, protein and calcium consumption from dairy foods (milk, yoghurt, cheese, dairy spreads, ice-cream) and adiposity including body mass index (BMI), waist (WC) and hip circumference (HC), and direct measures of body composition using dual energy X-ray absorptiometry (% body fat and abdominal fat) in an opportunistic sample of 720 overweight/obese Australian men and women. Mean (SD) age, weight and BMI of the population were 51 ± 10 year, 94 ± 18 kg and 32.4 ± 5.7 kg/m2, respectively. Reduced fat milk was the most commonly consumed dairy product (235 ± 200 g/day), followed by whole milk (63 ± 128 g/day) and yoghurt (53 ± 66 g/day). Overall dairy food consumption (g/day) was inversely associated with BMI, % body fat and WC (all p < 0.05). Dairy protein and dairy calcium (g/day) were both inversely associated with all adiposity measures (all p < 0.05). Yoghurt consumption (g/day) was inversely associated with % body fat, abdominal fat, WC and HC (all p < 0.05), while reduced fat milk consumption was inversely associated with BMI, WC, HC and % body fat (all p < 0.05). Within a sample of obese adults, consumption of dairy products, dairy protein, and calcium was associated with more favourable body composition. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

The aim of this study was to determine if changes in omega-3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression. A total of 95 volunteers receiving treatment for major depression were randomised to consume 8 × 1 g capsules per day of HiDHA (2 g DHA, 0.6 g EPA and 10 mg Vitamin E) or olive oil (placebo) for 16 weeks, whilst undergoing weekly counseling sessions by trained clinical psychologists using a standard empirically validated psychotherapy. Depression status was assessed using the 17 item Hamilton rating scale for depression and the Beck Depression Inventory by a psychodiagnostician who was blind to the treatment. Blood was taken at baseline and 16 weeks (n = 48) for measurement of erythrocyte fatty acids. With HiDHA supplementation, erythrocyte DHA content rose from 4.1 ± 0.2 to 7.9 ± 0.4 % (mean ± SEM, p < 0.001) of total fatty acids but did not change (4.0 ± 0.2 to 4.1 ± 0.2 %) in the olive oil group. The mean changes in scores of depression did not differ significantly between the two groups (-12.2 ± 2.1 for tuna oil and -14.4 ± 2.3 for olive oil). However, analysis of covariance showed that in the fish oil group there was a significant correlation (r = -0.51) between the change in erythrocyte DHA and the change in scores of depression (p < 0.05). Further study of the relationship between DHA and depression is warranted. © 2013 AOCS.

Background: We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation (FMD) in the brachial artery after resveratrol consumption in mildly hypertensive, overweight/obese adults. Resveratrol supplementation has also been shown to increase cerebral blood flow acutely, without affecting cognition. Objectives: To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance. Method: Twenty-eight obese but otherwise healthy adults (BMI: 33.3±0.6kg/m 2) were randomized to take a single 75 mg capsule of trans-resveratrol (Resvida) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial. Blood pressure, arterial compliance, FMD, and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule. An additional capsule of the same supplement was then taken. FMD assessment was repeated 1 h later. Results: Chronic resveratrol supplementation for 6 weeks was well tolerated and resulted in a 23% increase in FMD compared with placebo (P = 0.021, paired t-test). The extent of increase correlated negatively with baseline FMD (r= -0.47, P=0.01). A single dose of resveratrol (75 mg) following chronic resveratrol supplementation resulted in a 35% greater acute FMD response than the equivalent placebo supplementation. These FMD improvements remained significant after adjusting for baseline FMD. Blood pressure, arterial compliance, and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation. Conclusion: Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.