1. Cardiovascular, Metabolic and Mental Health Benefits of Vasoactive Nutrients
Professor Peter Howe
Nutritional Physiology Research Centre
University of South Australia
Newcastle, 11th February, 2011

2. Goal: attain and maintain optimal health
Functional capacity (physical & mental fitness)
Early Life
Growth and development
Adult Life
Maintaining highest level of function
Older Age
Maintaining health and independence
Range of function
in individuals
genes
diet
lifestyle
Disability threshold
Age

3. Preventable Causes of Death in the US in 2005
Danaei G et al. PLoS Med 2009;6(4): e

4. Obese Australians

5. Obesity Inflammation Metabolic Syndrome Heart disease Diabetes
high
blood glucose,
insulin
high
blood
pressure
high blood fats
Heart disease
Diabetes
$1.4B p.a.
$1.2B p.a.
Physical disability
Cancer
$0.9B p.a.
Mental disorders
obese individuals are 74% more likely to have dementia than normal weight individuals
AIHW, 2008

6. Is metabolic syndrome a circulatory disorder?
Endothelial cells
inhibit cell adhesion/aggregation
regulate vasomotor tone
maintain barrier function
(selective permeability)
maintain vascular integrity
(inhibit smooth muscle cell migration, proliferation)

7. % change in diameter of artery Flow mediated dilatation
G Born & C Schwartz Vascular Endothelium
smoking high BP high blood sugar high blood fat obesity NO
% change in diameter of artery
Flow mediated dilatation

8. Impaired Endothelial Function in Obesity
Obese
Lean P
Davison K, Bircher S, Hill A, Coates A, Howe P, Buckley J. J Obes (accepted 29 Dec 2010)

9. reduced fat, glucose metabolism
Circulatory effects of endothelial dysfunction
Cognitive decline
depression
neuro-degenerative disorders
endothelium
Endothelial dysfunction
Obesity
High blood pressure
High blood sugar
High blood fats
(incl cholesterol)
Smoking
high BP
coronary disease
angina
stroke
impaired blood flow
Can be improved/restored by regular aerobic exercise and supplementation with specific bioactive nutrients
physical incapacity
reduced fat, glucose metabolism

10. Bioactive nutrients from plants
Erdman J et al. J Nutr 2007;137:718S
Cocoa flavanols in dark chocolate

11. Effect of Cocoa Intake on Blood Pressure: meta-analysis
Taubert D et al Arch Intern Med 2007;167:
Cocoa flavanols attenuate Davison K, Berry N, Misan G, Coates AM, Buckley JD, Howe PRC
24hr Ambulatory BP Dose-related effects of flavanol-rich cocoa on blood pressure. J Hum Hypertens 2010

12. Flavanol-rich cocoa attenuates BP responses to exercise
Responses to exercise were tested in borderline hypertensives 2 hours after cocoa by continuously monitoring of beat to beat BP for 5 min at rest (Finapres) then for 10 min whilst cycling at 75% of age-predicted max HR.
(Berry NM et al, Br J Nutr 2010)
BP increase
(mmHg)
SBP
MAP
( AUC)
Time (sec)
DBP
 LF 30mg flavanols
 HF 600mg flavanols

13. FMD responses to flavanol-rich cocoa supplementation
Acute response 2hrs after single dose * 1 2 3 4 5 6 7 8 LF HF
FMD
(%)
Before
After
Chronic response measured > 10hrs after previous dose * 1 2 3 4 5 6 7 8 LF HF
FMD
(%)
Week 0
Week 6
Week 12
Davison K, Coates AM, Buckley JD, Howe PRC. Int J Obesity 2008;32:

14. Endothelial functions are dependent on NO production
Cocoa flavanols
reduce LDL oxidation
inhibit platelet aggregation
modulate inflammatory eicosanoids and cytokines
Cocoa flavanol supplementation can lower BP, attenuate BP responsiveness to stress and counteract hypertension
not due to antioxidant activity
attributable to increased production of endothelial NO and enhanced vasodilatation
probably mediated by epicatechin and related flavanols
Endothelial functions are dependent on NO production
l-arginine
l-arginase NO synthase free radical oxidation
urea nitric oxide (NO) NOx

15. Meta-analysis: effects of flavonoids on FMD
Hooper, L. et al. Am J Clin Nutr 2008;88:38-50
Acute
Chronic

16. Effects of Soy on Arterial Function
A Thorp et al. J Hypertens 2009;27(Suppl 4):S153
Soy/Dairy + Iso
Soy + Iso
Dairy
Large Artery Elasticity Index n=91)
Flow mediated vasodilatation (n=55) * *
Normal dilatation
% ▲ in dilatation from baseline diameter
( ml/mmHg x100)
* Sig difference in dilatation compared to Dairy (P<0.05)
Small Artery Elasticity Index (n=91)
Nitroglycerine vasodilatation (n=55)
The second outcome measure we assessed when on the different diets was arterial compliance.
As you can see there was no difference in either large or small arterial elasticity for all out subjects irrespective of what diet they were on
And again equol production appeared to had no effect
% ▲ in dilatation from baseline diameter
( ml/mmHg x100)

17. Flavonoid Intake and Cognitive Decline in men aged 65–70 years
intake quartiles
Letenneur L et al. Am J Epidemiol 2007;165:1364–1371

18. Cognition is linked to endothelial function
in older adults with cardiovascular disease
88 independent, community-dwelling older adults (average 70 years)
with mild to severe CVD but without neurological disease and dementia
significant correlation with FMD
Forman DE et al. Artery Research 2008;2:35-43

19. Can soy isoflavones improve cognitive function?
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
cerebellum
hippocampus
basal forebrain
prefrontal cortex
ER β
ER α
amygdala
pituitary
hypothalamus
ER α & ER β
Limbic System
cerebral cortex
Important in visuospatial tasks & memory recall
Important in spatial working memory
Relative binding affinities
ERα
ERβ
Estradiol
100
Genistein
0.7 13
Daidzein
0.01
0.04
The sex hormone estrogen has since been show to play an integral role in the organisation and maintenance of these cognitive sex differences by acting on estrogen receptors in the brain
There are two types of estrogen receptors in the brain – alpha and beta
And they are shown to be both selectively expressed and co localised in areas such as the limbic system and cerebral cortex which are associated with memory and learning.
Localisation of estrogen beta receptors specifically in the hippocampus and prefrontal cortex which control cogntive functions known to differ between women and men is of particular importance as it suggest estrogen acts on these receptors to induce genomic and non genomic pathways that upregulate neuronal activity
We recently found that isoflavone supplementation enhances spatial working memory in men.
(Thorp A, Sinn N, Buckley J, Coates A, Howe PR. Br J Nutr 2009)

20. Cerebral blood flow
Local regulation of cerebral blood flow critical for brain function
Ongoing supply required for delivery of glucose, oxygen & nutrients in response to requirements
Evidence of reduced cerebral blood flow in psychopathologies
mild cognitive impairment (Sun et al 2007)
dementias including Alzheimer’s Disease (Crawford 1996, 1998; Warkentin et al 2004)
ADHD (Bradley & Golden 2001)
Depression (Yazici et al 1992)
Schizophrenia (Mori et al 1999)
High overlap between coronary heart disease and psychopathology
Relatively little attention has been given to the possibility that omega-3s may also act on cerebral blood flow. We know that local regulation of blood flow in the brain is critical for ongoing brain function. In fact, although the brain only accounts for 2-2.7% of body weight, it needs 25% of the body’s glucose supply and 19% of the blood supply at rest, and these increase by 50% in response to cerebral activity (Haller 2005). Glucose is the brain’s primary source of energy for metabolic activities and the brain has very limited capacity for storing glucose, hence the importance of a continuous reliable supply of blood. The brain also has high requirements for nutrients, which must also be supplied by the blood and cross the blood-brain barrier.
There is ample evidence of reduced cerebral blood flow in psychiatric illness. There is also a high incidence of coronary heart disease in psychopathologies such as depression and dementia. These point to a possible common underlying vascular problem.
healthguide.howstuffworks.com/stroke-in-depth.htm 20

21. The Blood-Brain Barrier Neurovascular Unit in
Health and Disease
Hawkins & Davis, Pharmacol Rev 57:173–185, 2005

22. Impaired Blood Brain Barrier in Alzheimer's Disease?
A generalized mechanism for AD pathogenesis that includes breakdown of the blood-brain barrier, the leak of plasma components including soluble amyloid peptide (Aβ42) and autoantibodies into the brain tissue, the binding of both of these components to the surfaces of neurons, and their internalization and accumulation in neurons. Accumulation of Aβ42 causes loss of dendrites and synapses, impairment of neuronal function and eventual cell death.
Nagele RG, New Jersey Institute for Successful Aging,

23. Cocoa flavanols and brain perfusion
Transcranial Doppler ultrasound
Vasodilator response to breathing 5% CO2
18% increase in flow velocity in the MCA after eating flavanol-rich cocoa for 1 week
Fisher N et al. J Cardiovasc Pharmacol 2006;47:S210

24. Resveratrol & cardiovascular health
Acute dose-related improvement of FMD
*P<0.05 relative to placebo Mean ± SEM. N=18
Trans-resveratrol (3,4,5’-trihydroxystilbene)
(Wong RHX, Howe PRC, Buckley JD, Coates AM, Kunz I, Berry NM. Nutr Metab Cardiovasc Dis 2010)

25. Red wine polyphenol extract (600mg)1
Resveratrol & cardiovascular health
Acute dose-related improvement of FMD
+3.7
+2.5
+2.4
Red wine polyphenol extract (600mg)1
Cocoa flavanols (902mg)2
Tea (450ml)3
EGCG (300mg)4
1Lekakis et al. 2005;Eur J Cardiov Prev Rehab:12: , 2Davison et al. 2008;Int J Obes: 32: , 3Widlansky et al. 2005; Free Rad Bio Med: 38: , 4Widlansky et al. 2007; J Am Coll Nutr: 26:95-102

26. Omega-3

27. Health Benefits of Omega-3 PUFA Infant development & growth
Promoting fitness (physical, mental, reproductive)
Counteracting chronic disease (prevention, treatment)
Health benefits of 3 PUFA
Inflammatory disorders
psoriasis/dermatitis
rheumatoid arthritis
inflammatory bowel disease immune renal disease
periodontal disease
osteoporosis?
asthma?
Behavioural disorders
depression, bipolar disorder
cognitive impairment, ADHD schizophrenia, autism?
Cancer?
Cardiovascular disease
lipids (TG, HDL-C)
blood pressure
arterial compliance
endothelial dilatation
platelet aggregation
heart rate / variability arrhythmia
cardiac hypertrophy
heart failure
kidney damage
stroke
Diabetes
insulin resistance
abdominal adiposity

28. a-Linolenic acid C18:3 LNA
Physiological effects of PUFAs
Omega 6
Omega 3
plants
safflower
sunflower
corn, soy
Plants
linseed,
canola
NUTS
Linoleic acid
C18:2 LA
a-Linolenic acid
C18:3 LNA
Arachidonic acid
C20:4 AA
Eicosapentaenoic acid
C20:5 EPA
fish,
fish oil
animals
Docosahexaenoic acid
C22:6 DHA
Docosapentaenoic acid C22: DPA
fish
fish,
fish oil
EICOSANOIDS
2-series prostaglandins 3-series
4-series leukotrienes 5-series
excess
may
promote
inhibit
Thrombosis
vasoconstriction
inflammation
inhibits thromboxane synthase
Resolvins,Protectins
Nucleus
PPAR
DNA
cardiovascular and inflammatory disorders
Modulates gene expression in regulatory pathways, e.g. metabolism, inflammation

29. Greatest cardiovascular protection
Omega-3 Index - a new marker of health status
Harris and von Schacky, Preventive Medicine 2004
Least Protection
8.1%
Greatest cardiovascular protection
GISSI-P2: 9-10%
CHS3: 8.8%
DART4:  8-9%
SCIMO5: 8.3%
5 epi. studies:  8%
PHS6: 7.3%
Seattle7: 6.5% 4% 8%
PHS6: 3.9%
Seattle7: 3.3% 6%
10%
1Nilsen. AJCN. 74:50, 2001; 2Marchioli. Circulation. 105:1897, 2002; 3Mozaffarian. Circulation.107:1372, 2003; 4Burr. Lancet. 2:757, 1989; 5von Schacky Ann Intern Med 130:554, 1999; 6Albert. NEJM. 346:1113, 2002; 7Siscovick. JAMA. 274:1363, 1995
SCIMO5: 3.4%
EPA + DHA % total fatty acids in red blood cells
Current levels in Australians ~5%

30. Effects of Omega-3 and Exercise on CV risk factors
Hill A, Murphy K, Buckley J, Howe P, Am J Clin Nutr 2007;85:1267
Change in TG
(mmol/L) *
p < 0.05
Change in HDL
(mmol/L) *
p < 0.05 *
FMD
Change in artery diam.
(mm)
p = 0.05
0.000
0.004
0.008
0.012
0.016 FO
FOX SO
SOX *

31. Effects on Energy intake, Weight & Body Composition
Hill A, Murphy K, Buckley J, Howe P, Am J Clin Nutr 2007;85:1267
Change in body weight kg
p = 0.06
Change in fat mass kg
Change in lean mass *
* P < 0.05 for oil x time and FO
FOX SO
SOX
Change in energy intake kJ
When we investigated changes in body composition as measured by DEXA, we could see that changes in body weight was primarily associated with a reduction in fat mass, shown exclusively in the FOX group, and not changes in lean tissue.
exercise x time interactions
Nutritional Physiology Research Group

32. Relationships between erythrocyte LC n-3 PUFA and body composition
Cross sectional analysis
BMI, waist circumference, DEXA (% body fat)
GC analysis of erythrocyte fatty acids
n = 291
BMI WC
% Body Fat
EPA
-0.08
-0.16*
-0.17**
DPA
-0.05
-0.13
-0.14*
DHA
-0.28**
-0.35**
-0.33**
Omega -3 Index
-0.24**
-0.32**
-0.31**
n = 185
BMI WC
% Body Fat
EPA
0.09
-0.06
-0.15
DPA
-0.02
-0.20*
-0.23**
DHA
-0.08
-0.14
-0.19*
Omega -3 Index
-0.04
-0.13
Data for this study was collected at baseline from volunteers who participated in 5 intervention trials conducted between in South Australia. As you can see there were mixed inclusion criteria but for the majority were overweight or obese and there was no restriction of how much fish they ate.
A range of different techniques were used to assess body composition depending on the study with the first 2 studies only using BMI and the latter 3 also including waist circumference and DEXA to determine % body fat.
The fatty acid profiles of erythrocytes membrane were determined using GC

33. Waist Circumference vs Omega-3 Index
women
men
r= P<0.0001
r= P> 0.05

34. Omega-3 and mental health
Omega-3 deficiency is associated with depression, schizophrenia, aggression, Alzheimer’s Disease, bipolar disorder and developmental disorders.
Animal studies: omega-3 supplementation linked to improved learning and behaviour in rats.
Humans trials: increasing evidence of beneficial impact (particularly EPA) on mental health outcomes, especially mood and cognition.
So not surprisingly, researchers have started investigating omega-3 fatty acids in the brain and have found deficiencies in people with a range of mental illnesses like depression, schizophrenia, Alzheimer’s Disease, bipolar disorder and developmental disorders like dyslexia, learning disorders, autism and ADHD. Some animal studies have found improved learning and behaviour in rats after omega-3 supplementation and a small number of clinical trials with humans have started to find evidence that omega-3s can improve symptoms in some of these conditions.

35. ADHD Intervention Trial
ADHD is most commonly diagnosed childhood disorder
Characterised by hyperactivity; poor impulse control; difficulty sustaining attention
Randomised, placebo-controlled, double-blind 30 wk trial
132 children aged 7-12, 2/3rds boys, unmedicated and on upper end of Conners’ ADHD Index
Evaluated effects of omega-3 supplementation on
inattention
hyperactivity
impulsivity
cognition
Outline intervention trial.
Sinn N & Bryan J. J Dev Behav Pediatr 2007

36. Reductions in inattention
Reductions in hyperactivity-impulsivity 10 11 12 13 14 15 16 17 18
Baseline
15 weeks
30 weeks
Parent ratings of Hyperactive-Impulsive
PUFA
Placebo 12 13 14 15 16 17 18 19 20 21
Baseline
15 weeks
30 weeks
Parent ratings of DSM Inattention
PUFA
Placebo
F = 11.24, p < .01 (Effect size .61)
Improvements in both fish oil groups compared to placebo on core symptoms; no additional improvements with micronutrients (therefore have been grouped together). Placebo group represented by orange line - explain results after one-way crossover.
F = 7.68, p < .01 (Effect size .20)

37. Reductions in cognitive problems
Reductions in overall ADHD ratings 16 17 18 19 20 21 22 23 24 25 26
Baseline
15 weeks
30 weeks
Parent ratings of Cognitive Problems
PUFA
Placebo 18 19 20 21 22 23 24 25 26 27 28
Baseline
15 weeks
30 weeks
Parent ratings of ADHD Index
PUFA
Placebo
F = 10.06, p < .01 (Effect size .52)
F = 9.09, p < .01 (Effect size .59)

39. Current studies on omega-3 in mental health collaborative studies at UniSA and QUT
Comparative effects of EPA and DHA in children with ADHD
7-12 year old children with ADHD and learning difficulties
12-month study: 3 x 4 mth crossover
EPA-rich oil, DHA-rich oil, placebo
Baseline red blood cell PUFA results:-
lower n-3 PUFA = poorer literacy
higher DHA = better word reading
Omega-3 and MCI
Emerging evidence that n-3 supplementation slows the rate of cognitive decline in adults with MCI or early AD
(Panza et al 2007, Kotani et al 2006, Freund-Levi et al 2006)
Comparative effects of EPA and DHA in adults with MCI
6-month parallel comparison
Some children with ADHD-related problems with attention and behaviour may benefit from n-3 PUFA: 30-40% improved notably after 15 weeks; 40-50% after continued supplementation over 30 weeks This has very important implications for the treatment of learning and behaviour problems in childhood.
Further research required to determine which children will benefit, longer term outcomes and biological mechanisms via blood analyses and other neuropsychological tests.
Further research is also needed to investigate the effect of other nutrients and nutrients in combination with each other. In my study, the levels might not have been high enough E.g. children with ADHD are often deficient in zinc – one study found cognitive improvements in children after supplementation with 20mg of zinc per day; which also assists in omega-3 metabolism – MVM supplement in this study only contained less than 2mg zinc per day… 39

40. ADHD Study: baseline RBC n-3 PUFA status CM Milte, N Sinn, AM Coates, J Buckley, PRC Howe. ISSFAL June, 2010
% of total fatty acids
N = 74 1 2 3 4 5 6 7 8
EPA
DPA
DHA
EPA+DHA n -
With learning difficulties
Without learning difficulties *
N-3 index is low, but compares to what seen in typical adult population in studies in Adelaide before. LD may represent a subgroup which may benefit from PUFA supplementation.
*p < .03
Controlling for age

41. Change in RBC PUFA status after 4 months
% of total fas

42. DHA predicts improvements in child cognition
Word reading
Switching attention
p Beta .421
p .005
Beta .415
Increase in cognitive measure indicates an improvement

43. DHA predicts improvements in child cognition Learning Difficulties Subgroup (N = 17)
Word reading
Switching attention
p Beta .630
p .018
Beta .611
Divided attention
p .013
Beta .682

44. DHA predicts improvements in parent ratings
Learning Difficulties Subgroup (N = 17)
Hyperactivity
Restless/impulsive
P Beta .658
P Beta .676

45. Memory and brain function
Erythrocyte polyunsaturated fatty acid status, memory and cognition in older adults with mild cognitive impairment and healthy controls
CM Milte, N Sinn, AM Coates, J Buckley, PRC Howe ISSFAL June, 2010
Study measures
Memory and brain function
cognitive tests: RAVLT, Stroop, Boston naming task, letter fluency, digits forward/backward, trail making, letter number sequencing
delayed and immediate recall memory, executive function, attention, information processing speed, mental flexibility, naming
Memory Functioning Questionnaire (MFQ)
Quality of life/mood
Satisfaction with life scale (SWLS)
Geriatric Depression Scale (GDS)
Health Survey (SF-36)
Blood samples
RBCs: PUFA content
Memory and brain function were assessed using various cognitive tests which measured delayed and immediate recall memory, executive function, attention, information processing speed, mental flexibility and naming. Self-reported memory was also measured using the memory functioning questionnaire.
Self-reported quality of life and mood were measured using questionnaires including the geriatric depression scale.
We also took blood samples to assess PUFA content of erythrocytes.

46. PUFAs in MCI compared with healthy controls
Higher omega Lower omega-3 *
We found those with MCI had higher n-6 status than healthy controls including DPA n-6, and lower n-3 status including EPA after controlling for age.
This led to those with MCI also having an elevated AA/EPA and n-6 to n-3 ratio compared with out healthy controls.
Omega-6
Omega-3
*P < .05, **P < .01

47. n-6 PUFA and impaired cognition
↓ verbal paired associates performance
↑ DPA n-6
↓ excluded letter fluency
↑ DPAn-6
↓ RAVLT delayed recall
↑ LCn-6 PUFA
↑ LCn-6 PUFA (20 min)
↓ digits backwards span performance
↑ AA
MCI
Healthy
Beta= P < .05
R² =
We did regression analysis for the whole cohort controlling for age, gender and education. Higher levels of DPAn-6 predicted poorer performance on verbal paired associates,
n=73
Age + gender + education

48. n-6 PUFA and impaired cognition
↓ verbal paired associates performance
↑ DPA n-6
↓ excluded letter fluency
↑ DPAn-6
↓ RAVLT delayed recall
↑ LCn-6 PUFA
↑ LCn-6 PUFA (20 min)
↓ digits backwards span performance
↑ AA
MCI
Healthy
Beta = P < R² =
And excluded letter fluency
n=73
Age + gender + education

49. n-6 PUFA and impaired cognition
↓ verbal paired associates performance
↑ DPA n-6
↓ excluded letter fluency
↑ DPAn-6
↓ RAVLT delayed recall
↑ LCn-6 PUFA
↑ LCn-6 PUFA (20 min)
↓ digits backwards span performance
↑ AA
MCI
Healthy
Beta = P < R² =
Higher levels of LCn-6 PUFA predicted poorer performance on the RAVLT delayed memory recall task.
n=73
Age + gender + education

50. n-6 PUFA and impaired cognition
↓ verbal paired associates performance
↑ DPA n-6
↓ excluded letter fluency
↑ DPAn-6
↓ RAVLT delayed recall
↑ LCn-6 PUFA
↑ LCn-6 PUFA (20 min)
↓ digits backwards span performance
↑ AA
MCI
Healthy
Beta = P < .05 R² =
And higher levels of n-6 AA were associated with poorer performance on the digits backwards.
n=73
Age + gender + education

51. Depressive scores ↑ in MCI7 *
GDS 6
8 MCI volunteers & no controls in possible depression range 5 4
* P < 0.01 3 2 1
MCI
Healthy Controls
And when we compared depressive scores we found those with MCI had worse scores on the geriatric depression scale than healthy controls. And 8 MCI volunteers in the range for a possible diagnosis of depression, whereas no of the healthy controls were. This is expected when we consider we found worse scores on the GDS predicted poorer cognition and self-reported memory functioning.
Our data support previous work relating PUFA intake to dementia:
high n-6 PUFA and low n-3 PUFA in erythrocytes may predict memory problems
relationship of n-3 PUFA status to self-reported health may be due to depression

52. Summary of key findings
Effects of EPA and DHA vs LA on depressive symptoms (N=38; mixed model analysis N=50)
Mixed model analysis
EPA (p=.03) and DHA (p=.01) vs LA
significant after controlling for basal EPA+DHA
Correlated with change in ↑EPA+DHA r=.039* ↑AA r=-.031, ↓AA/EPA r=-0.34*
Summary of key findings
Both EPA and DHA improved depressive symptoms in elderly with MCI
Improvements correlated with increases in erythrocyte EPA+DHA
DHA was associated with improved health-related quality of life, and to a small degree this explained improved mood
Improved mood in elderly with MCI may reduce risk of dementia
This pilot study was one of the first clinical trials with omega-3 and mental illness. 30 inpatients with unstable bipolar disorder were given over 9g omega-3 per day in addition to their existing medication (none were started on any new medication or psychotherapy) – 4 were unmedicated in each group.
There were 10 drop-outs in the placebo group compared with 2 in the treatment group; most due to worsening of their depressed state.
The omega-3 group performed better than placebo on nearly all outcomes, and in those who showed improvements, this was clinically significant.
Sinn, Milte, Street, Buckley, Coates, Howe (in preparation)

53. Conclusions
Increased intakes of bioactive nutrients such as omega-3 PUFA, flavanols and other polyphenols offer multiple physical and mental health benefits
These benefits may be partly attributable to improvements of circulatory function in chronic cardiometabolic and inflammatory disorders
Functional foods enriched with bioactive nutrients have the potential to optimise health status, especially when combined with regular exercise
They may also deliver therapeutic benefits, when used alone or as adjuncts to medication

54. Investigating nutrition and exercise strategies to improve human health and performance