Nutrients and Circulatory Function

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1 Clinical Nutrition Research Centre Nutrients and Circulatory Function Peter Howe Clinical Nutrition Research Centre University of Newcastle Nutritional Physiology Research Centre University of South Australia Sydney, 3 rd September, 2012

2 Health optimisation throughout life Functional capacity (physical & mental fitness) Early Life Growth and development Adult Life Maintaining highest level of function Older Age Maintaining health and independence healthy diet and lifestyle Disability threshold Age medical treatment

Prevalence of obesity in older Australians AIHW, 2005 Diabetes Cardiovascular

3 Obesity is increasing Metabolic Syndrome Obesity Inflammation Mental disorders are increasing high blood glucose, insulin high blood pressure high blood fats Prevalence of obesity in older Australians AIHW, 2005 Diabetes Cardiovascular disease Mental disorders (depression, dementia) Prevalence of self-reported mental disorders AIHW, 2008

4 Metabolic syndrome is a circulatory disorder Functions of endothelium inhibits cell adhesion inhibits platelet aggregation regulates vasomotor tone maintains selective permeability maintains vascular integrity (inhibits cell migration, proliferation) endothelium Obesity High blood pressure High blood sugar High blood fats (incl cholesterol) Smoking endothelial dysfunction impaired blood flow hypertension stroke coronary disease angina heart failure

5 Progression from endothelial dysfunction to arterial disease advancing age Non-invasive assessment of endothelial function flow mediated dilatation (FMD) expressed as % change in diameter

Circulatory effects of endothelial dysfunction endothelium

Obesity High blood pressure High blood sugar High blood fats

blood flow hypertension stroke coronary disease angina heart

6 Circulatory effects of endothelial dysfunction endothelium Cognitive decline depression neurodegenerative disorders Obesity High blood pressure High blood sugar High blood fats (incl cholesterol) Smoking endothelial dysfunction impaired blood flow hypertension stroke coronary disease angina heart failure physical incapacity reduced fat, glucose metabolism tissue inflammation

Cerebral blood flow and mental health Local regulation of cerebral blood flow critical for brain function Essential for supply of glucose, oxygen, nutrients on demand and removal of toxic metabolites

7 Cerebral blood flow and mental health Local regulation of cerebral blood flow critical for brain function Essential for supply of glucose, oxygen, nutrients on demand and removal of toxic metabolites Evidence of reduced cerebral blood flow in psychopathologies:- o Mild cognitive impairment (Sun et al 2007) o Dementias including Alzheimer s Disease (Crawford 1996, 1998; Warkentin et al 2004) o ADHD (Bradley & Golden 2001) o Schizophrenia (Mori et al 1999) o Depression (Yazici et al 1992) o coronary heart disease is strongly associated with depression Flow mediated dilatation is correlated with cognitive performance Flow mediated dilatation declines with age and cognitive impairment

8 Circulatory effects of endothelial dysfunction endothelium Cognitive decline depression neurodegenerative disorders Obesity High blood pressure High blood sugar High blood fats (incl cholesterol) Smoking endothelial dysfunction impaired blood flow Can be improved/restored by regular aerobic exercise and supplementation with certain vasoactive nutrients hypertension stroke coronary disease angina heart failure physical incapacity reduced fat, glucose metabolism tissue inflammation

10 Health benefits of Long Chain Omega-3 PUFA Enhancing early infant development & growth Preventing/counteracting chronic disease Cardiovascular risk factors lipids (TG, HDL, not LDL) blood pressure (modest) heart rate variability platelet aggregation arterial compliance endothelial dilatation (FMD) Cardiovascular disease arrhythmia (sudden death) stroke heart failure hypertension coronary heart disease renal disease Inflammatory disorders psoriasis/dermatitis rheumatoid arthritis inflammatory bowel disease periodontal disease osteoporosis? asthma? Behavioural disorders depression bipolar disorder cognitive impairment ADHD autism? schizophrenia?

11 Cardiovascular benefits of cocoa flavanols lower ambulatory blood pressure Davison K et al, J Hum Hypertens 2010 reduce blood pressure response to stress Berry N et al, Br J Nutr 2010 increase endothelial vasodilatation Davison K et al, Int J Obesity 2008 FMD (%) acute response before 2 hrs after * chronic response measured > 10hrs after previous dose Week 0 Week 6 Week 12 * * low flavanol high flavanol 0 low flavanol high flavanol

12 Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials Hooper et al. AJCN Feb 2012 acute FMD response chronic FMD response

13 The Panel notes that cocoa flavanols consumed for 12 weeks have been shown to increase fasting ED-FMD significantly in the target population (Davison et al, 2008) The following wording reflects the scientific evidence: Cocoa flavanols help maintain endothelium-dependent vasodilation, which contributes to normal blood flow.

14 Cocoa flavanols increase cerebral blood flow Fisher N et al (J Cardiovasc Pharmacol 2006;47:S210) reported an 18% increase of blood flow velocity in the middle cerebral artery after one week of daily intake of flavanol-rich cocoa. Cerebral blood flow is reduced in cognitive impairment Sun Z et al (Eur J Neurol 2007;14:150) found that blood flow velocity was significantly lower in both the middle and anterior cerebral arteries of elderly with mild cognitive impairment compared to age-matched controls. Cocoa flavanols enhance cognition Scholey et al (J Psychopharmacol : 1505) were the first to report acute cognitive improvements in healthy adults taking cocoa flavanols. Field et al (Physiol Behav 2011;103:255) confirmed acute cognitive benefit of cocoa flavanols and also reported improved visual contrast sensitivity. Desideri et al (Hypertension 2012;60:794) have now reported cognitive improvements with regular consumption of cocoa flavanols for 8 weeks. These improvements were associated with increases in insulin sensitivity.

Effects of soy isoflavones on FMD and cognitive function Soy isoflavones enhance FMD chronically (6 weeks), possibly via ERβ The main soy isoflavone, genistein, is a selective ERβ agonist ERβ are

(n=55) P<0.05 * * prefrontal cortex important in spatial working memory ER β Limbic System cerebral cortex ER α & ER β 0 Dairy S/D Soy A Thorp et al.

15 Effects of soy isoflavones on FMD and cognitive function Soy isoflavones enhance FMD chronically (6 weeks), possibly via ERβ The main soy isoflavone, genistein, is a selective ERβ agonist ERβ are localised in brain regions associated with learning and memory (Resnick et al 2004) Estrogen acts on ERβ to increase cerebral blood flow (Duckles & Krause 2007) % Flow mediated dilatation (n=55) P<0.05 * * prefrontal cortex important in spatial working memory ER β Limbic System cerebral cortex ER α & ER β 0 Dairy S/D Soy A Thorp et al. AJCN 2008;88:298 J Hypertens 2009;27(Suppl 4):S153 basal forebrain ER β hypothalamus ER α pituitary ER α & ER β amygdala ER α cerebellum ER β hippocampus ER β important in visuospatial tasks & memory recall We have shown that isoflavone supplementation for 6 weeks can enhance spatial working memory in men Thorp A, Sinn N, Buckley J, Coates A, Howe P. Br J Nutr 2009

16 Can we assess vasodilator function in the brain? We can measure blood flow in middle cerebral artery by Transcranial Doppler Ultrasound Vasodilator response to breathing 5% CO 2 Fisher N et al. J Cardiovasc Pharm 2006;47:S210

Wild green oat Wild green oat extract Neuravena (Frutarom, Switzerland) is an extract of Avena

It can acutely enhance cognitive performance.

% 20 4 15 2 10 5 0 Placebo WGOE Placebo WGOE Chronic supplementation (1600 mg/day for 12 wks)

17 Wild green oat Wild green oat extract Neuravena (Frutarom, Switzerland) is an extract of Avena sativa (oat herb) containing avenanthramides, phytoalexin and flavonoids (vitexin and isovitexin). It can acutely enhance cognitive performance. - Berry et al J Alt Compl Med 2010 WGO Extract 8 6 FMD % Cerebrovascular responsiveness % Placebo WGOE Placebo WGOE Chronic supplementation (1600 mg/day for 12 wks) resulted in a sustained improvement of FMD and cerebral vasodilator function in healthy older adults; both increased by 41%. 0 - Wong et al (under review)

Resveratrol & cardiovascular health Acute dose-related improvement of

4% Cocoa flavanols (902mg) 2 Tea (450ml) 3 +1.5% EGCG (300mg) 4 1.

Obes: 2008;32:1289 3 Widlansky et al Free Rad Bio Med: 2005;38:499 4

18 Resveratrol & cardiovascular health Acute dose-related improvement of FMD Wong RHX, Howe PRC, Buckley JD, Coates AM, Kunz I, Berry NM Nutr Metab Cardiovasc Dis % Trans-resveratrol (3,4,5 -trihydroxystilbene) % +2.4% +3.4% FMD response (%) % Red wine polyphenol extract (600mg) % Cocoa flavanols (902mg) 2 Tea (450ml) % EGCG (300mg) 4 1. Lekakis et al Eur J Card Prev Rehab 2005;12:596 2 Davison et al Int J Obes: 2008;32: Widlansky et al Free Rad Bio Med: 2005;38:499 4 Widlansky et al J Am Coll Nutr: 2007;26: Resveratrol dose (mg) Sustained improvement in FMD with Resveratrol (75mg/day) for 6 weeks Wong et al (unpublished)

Conclusions A healthy circulation is vital for physical and mental health. Impaired endothelial function may link age-related deficits in mood and cognition with obesity and metabolic syndrome.

19 Conclusions A healthy circulation is vital for physical and mental health. Impaired endothelial function may link age-related deficits in mood and cognition with obesity and metabolic syndrome. Selected vasoactive nutrients have the potential to optimise cardiometabolic and mental health status by improving endothelial function in both systemic and cerebral arteries. Further research is needed to identify mechanisms of action of vasoactive nutrients and optimal delivery in the diet. Health claims for nutrients and foods should place greater emphasis on health-promoting rather than disease reduction benefits.

8/06/2015. The Good News we are living longer! - but are we living healthier? National Research Priority: Preventive Healthcare

8/06/2015. The Good News we are living longer! - but are we living healthier? National Research Priority: Preventive Healthcare // The Good News we are living longer! Clinical Nutrition Research Centre University of Newcastle, Australia 7 th June Life Expectancy in (CIA World Factbook) - but are we living healthier? National Research