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Exploring the effects of resveratrol supplementation on cerebrovascular function in hormonal migraineurs: A pilot study.
Dzator, JSA, Coupland, KG, Howe, PRC
IBRO neuroscience reports. 2023;:310-319
Abstract
BACKGROUND Past research suggests that hormonal migraineurs may have poorer cerebrovascular function than women who do not suffer from migraine. Resveratrol, a vasoactive phytoestrogen, has been shown to improve cerebrovascular function in several populations but has never been tested in hormonal migraineurs. AIM: To investigate the effects of 3-month resveratrol supplementation on the cerebrovascular function of hormonal migraineurs. METHODS We conducted a randomised, double-blind, placebo-controlled, crossover intervention pilot study with resveratrol (150 mg/d for 3 months) in ten hormonal migraineurs (mean age: 37.2 ± 2.6 years). Participants visited the University of Newcastle's Clinical Nutrition Research Centre where quality of life and disability, and cerebrovascular function were assessed. Quality of life and disability were examined using Migraine-Specific Quality of Life, Headache Impact Test-6 and the Migraine Disability Assessment. Cerebrovascular function was determined using transcranial Doppler ultrasound to bilaterally measure blood flow velocity in the middle and posterior cerebral arteries at rest and in response to a hypercapnic stimulus. Cerebrovascular responsiveness to a cognitive task battery was also measured bilaterally in the middle cerebral arteries. RESULTS Compared to placebo, blood flow velocity in the right posterior cerebral artery was significantly higher (P = 0.041) following resveratrol supplementation. No other significant differences in cerebrovascular function between resveratrol and placebo treatments were observed. Baseline correlation analyses revealed higher blood flow velocities in the middle and posterior cerebral arteries were associated with better quality of life and less disability. However, higher cerebrovascular responsiveness to hypercapnia in the posterior circulation was associated with higher migraine-related disability and poorer migraine-related quality of life. CONCLUSION In this pilot we found evidence that resveratrol may increase blood flow velocity in the right posterior cerebral artery in hormonal migraineurs. Larger cohorts are required confirm this effect and its potential relationship to migraine in premenopausal women.
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A Randomised, Double-Blind, Placebo-Controlled Crossover Trial of Resveratrol Supplementation for Prophylaxis of Hormonal Migraine.
Dzator, JSA, Howe, PRC, Coupland, KG, Wong, RHX
Nutrients. 2022;(9)
Abstract
Resveratrol, a vasoactive phytoestrogen, has beneficial effects on cerebrovascular function. 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 conducted 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 participant'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.
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3.
Long-term resveratrol supplementation improves pain perception, menopausal symptoms, and overall well-being in postmenopausal women: findings from a 24-month randomized, controlled, crossover trial.
Thaung Zaw, JJ, Howe, PRC, Wong, RHX
Menopause (New York, N.Y.). 2020;(1):40-49
Abstract
OBJECTIVE Following concerns about hormone therapy, postmenopausal women need alternative options to manage menopause-related symptoms and improve their well-being. A 14-week pilot study has shown that supplementation with resveratrol, a phytoestrogen with circulatory benefits, can improve aspects of well-being including chronic pain, which is a common complaint in postmenopausal women. We aimed to confirm these benefits in a larger, long-term study. METHODS The Resveratrol for Healthy Ageing in Women study, a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention trial of resveratrol supplementation (75 mg BID) was conducted in 125 healthy postmenopausal women to evaluate effects on cognitive performance (results published elsewhere). Aspects of well-being including pain perception, mood and depressive symptoms, menopausal symptoms, sleep quality, and quality of life were assessed with questionnaires as secondary outcomes of the study. Cerebrovascular responsiveness to hypercapnia was measured as a surrogate marker of cerebrovascular function. RESULTS Resveratrol supplementation reduced composite pain score (P < 0.001), especially in overweight individuals; this was associated with improvements in cerebrovascular responsiveness to hypercapnia (R = -0.329, P = 0.014). Somatic menopausal symptoms (P = 0.024) and general well-being (P = 0.010) were also improved after resveratrol supplementation. CONCLUSIONS These results confirm the pilot study finding that resveratrol supplementation can reduce chronic pain in age-related osteoarthritis and improve menopause-related quality of life in postmenopausal women. These improvements are sustained by supplementation for at least 12 months and are associated with enhancement of circulatory function. CLINICAL TRIAL REGISTRATION ACTRN12616000679482p.
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4.
Postmenopausal health interventions: Time to move on from the Women's Health Initiative?
Thaung Zaw, JJ, Howe, PRC, Wong, RHX
Ageing research reviews. 2018;:79-86
Abstract
Menopause is a critical period during which, without timely interventions, increased risks of cardiovascular and metabolic diseases, osteoporosis, sexual dysfunction and premature cognitive decline will contribute to diminished quality-of-life in women. Hormone therapy (HT) used to be the standard of care for managing vasomotor symptoms and prevention of chronic diseases until publication of the Women's Health Initiative (WHI) in 2002. Concerned about risks highlighted in WHI publications, many symptomatic women promptly ceased HT which resulted in increased vasomotor symptoms, osteoporosis-related-fractures and insomnia. Data from post-hoc WHI analyses and newer clinical trials consistently show reductions in coronary heart disease and mortality when estrogen therapy is initiated soon after menopause, whereas administration in later years and/or in combination with progesterone carries increased risks. However, no validated primary preventive strategies are available for younger postmenopausal women (<60 years), highlighting the need to re-evaluate the use of estrogen alone for which the risk-benefit balance appears positive. In contrast, in older women (>60 years), risks associated with oral HT exceed benefits; however transdermal estrogen may offer a safer alternative and should be further evaluated. Alternative therapies such as phytoestrogens and non-hormonal prescriptions may be beneficial for older women or those who are unsuitable for HT. Long-term head-to-head comparisons of HT with alternative interventions are warranted to confirm their efficacy for chronic disease prevention.
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Comparison of two low-fat diets, differing in protein and carbohydrate, on psychological wellbeing in adults with obesity and type 2 diabetes: a randomised clinical trial.
Watson, NA, Dyer, KA, Buckley, JD, Brinkworth, GD, Coates, AM, Parfitt, G, Howe, PRC, Noakes, M, Murphy, KJ
Nutrition journal. 2018;17(1):62
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The psychological burden of living with type 2 diabetes (T2D) has far reaching effects, negatively impacting quality of life, physical health and emotional wellbeing. It has been suggested that health-related quality of life (HRQoL) changes in response to weight status however this has not yet been explored in individuals with T2D. The aim of this randomised controlled study was to compare the effects of high protein and high carbohydrate diets, combined with moderate intensity exercise, on psychological wellbeing and HRQoL in 61 overweight adults with T2D. Participants enrolled in a 12-week weight loss period followed by a 12-week weight maintenance phase and blood glucose levels and various quality of life factors were assessed. This trial found in overweight adults with T2D, improvements in several psychological wellbeing and HRQoL were seen in response to modest weight loss and improvements in blood sugar levels. Improvements were seen in both high protein and high carbohydrate group, though a high protein diet may be better for maintaining control of blood glucose levels thus improving feelings of vitality. Based on this study, the authors conclude that it is imperative to address and support the psychological aspects of patients managing T2D.
Abstract
BACKGROUND Although higher-protein diets (HP) can assist with weight loss and glycemic control, their effect on psychological wellbeing has not been established. The objective of this study was to compare the effects of a HP and a higher-carbohydrate diet (HC), combined with regular exercise, on psychological wellbeing both during weight loss (WL) and weight maintenance phases (WM). METHODS In a parallel RCT, 61 adults with T2D (mean ± SD: BMI 34.3 ± 5.1 kg/m2, aged 55 ± 8 years) consumed a HP diet (29% protein, 34% carbohydrate, 31% fat) or an isocaloric HC diet (21%:48%:24%), with moderate intensity exercise, for 12 weeks of WL and 12 weeks of WM. Secondary data evaluating psychological wellbeing was assessed using: Problems Areas in Diabetes (PAID); Diabetes-39 Quality of Life (D-39); Short Form Health Survey (SF-36); Perceived Stress Scale-10 (PSS-10) and the Leeds Sleep Evaluation Questionnaire (LSEQ) at Weeks 0, 12 and 24 and evaluated with mixed models analysis. RESULTS Independent of diet, improvements for PAID; D-39 diabetes control; D-39 severity of diabetes; SF-36 physical functioning and SF-36 general health were found following WL (d = 0.30 to 0.69, P ≤ 0.04 for all) which remained after 12 weeks of WM. SF-36 vitality improved more in the HP group (group x time interaction P = 0.03). Associations were seen between HbA1c and D-39 severity of diabetes rating (r = 0.30, P = 0.01) and SF-36 mental health (r = - 0.32, P = 0.003) and between weight loss and PAID (r = 0.30, P = 0.01). CONCLUSION Several improvements in diabetes-related and general psychological wellbeing were seen similarly for both diets following weight loss and a reduction in HbA1c with most of these improvements remaining when weight loss was sustained for 12 weeks. A HP diet may provide additional increases in vitality. TRIAL REGISTRATION The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12613000008729 ) on 4 January 2013.
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Reductions in food cravings are similar with low-fat weight loss diets differing in protein and carbohydrate in overweight and obese adults with type 2 diabetes: A randomized clinical trial.
Watson, NA, Dyer, KA, Buckley, JD, Brinkworth, GD, Coates, AM, Parfitt, G, Howe, PRC, Noakes, M, Murphy, KJ
Nutrition research (New York, N.Y.). 2018;:56-66
Abstract
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/m2; 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.
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Effects of Long-Chain Omega-3 Polyunsaturated Fatty Acids on Endothelial Vasodilator Function and Cognition-Are They Interrelated?
Kuszewski, JC, Wong, RHX, Howe, PRC
Nutrients. 2017;(5)
Abstract
Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain functions by acting on endothelial cells in the cerebrovasculature to facilitate vasodilatation and perfusion. The aim of this review is to explore this hypothesis by analyzing the effect of LCn-3 PUFA supplementation on systemic vasodilator and cognitive function and finding evidence to link LCn-3 PUFA intake, vasodilator function and cognition. Forty randomized controlled trials examining the effect of LCn-3 PUFA supplementation in humans on either endothelial vasodilator function or cognition were identified and pooled effects measured with a weighted analysis. Compared to placebo, LCn-3 PUFA tended to increase flow-mediated dilatation and significantly improved cognitive function. Emerging evidence links vasodilator dysfunction to cognitive impairment, but evidence that LCn-3 PUFA can improve cognition through enhancements of vasodilator function is still lacking. Further research is needed to determine: (1) whether LCn-3 PUFA can enhance dilatation of cerebral vessels; (2) if improvements in cerebrovascular responsiveness by LCn-3 PUFA are accompanied by cognitive benefits; and (3) the target population groups.
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The addition of peanuts to habitual diets is associated with lower consumption of savory non-core snacks by men and sweet non-core snacks by women.
Barbour, JA, Stojanovski, E, Moran, LJ, Howe, PRC, Coates, AM
Nutrition research (New York, N.Y.). 2017;:65-72
Abstract
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±7years, body mass index 31±4kg/m2) consumed their habitual diet with or without peanuts (56g/d for 32 women, 84g/d for 29 men) for 12weeks 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±0.2kg (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.
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Does phytoestrogen supplementation improve cognition in humans? A systematic review.
Thaung Zaw, JJ, Howe, PRC, Wong, RHX
Annals of the New York Academy of Sciences. 2017;(1):150-163
Abstract
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.
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Cerebrovascular and cognitive benefits of high-oleic peanut consumption in healthy overweight middle-aged adults.
Barbour, JA, Howe, PRC, Buckley, JD, Bryan, J, Coates, AM
Nutritional neuroscience. 2017;(10):555-562
Abstract
OBJECTIVE Peanuts contain bioactive nutrients beneficial for vascular function. This study investigated whether consumption of unsalted peanuts (with skins) would enhance cerebrovascular perfusion and cognitive performance. METHOD In a randomized crossover trial, 61 volunteers (29 males/32 females, 65 ± 7 years, BMI 31 ± 4 kg/m2) consumed their habitual diet ± high-oleic peanuts (56-84 g/day), each for 12 weeks. Nutrient intakes, vascular and cognitive function were assessed at baseline and at the end of each 12-week phase. Differences between the ends of each phase were compared by general linear repeated measures ANOVA controlling for baseline. Pearson's correlation analyses determined relationships between differences in cerebrovascular reactivity (CVR) and cognitive function. RESULTS Intakes of bioactive nutrients increased during the peanut phase. CVR was 5% greater in the left middle cerebral artery (MCA) and 7% greater in the right MCA. Small artery elasticity was 10% greater after peanut consumption; large artery elasticity and blood pressure did not differ between phases. Measures of short-term memory, verbal fluency, and processing speed were also higher following the peanut phase; other cognitive measures did not change. Differences in CVR in the left MCA correlated with differences in delayed memory and recognition. DISCUSSION Regular peanut consumption improved cerebrovascular and cognitive function; increased intakes of bioactive nutrients may have mediated these improvements. This clinical trial was registered with the Australian Clinical Trials Registry (ACTRN 12612000192886).