Hosted by with Sophie Tully BSc MSc, 10th October This presentation addresses the role of cholesterol in CVD and the latest evidence into nutritional strategies to manage and treat high cholesterol and support healthy CVD function. Sophie covers the aetiology of CVD and why cholesterol has long been considered an important marker of CVD health and the emergence of newly identified CVD risk factors which may offer a more effective diagnostic tool. Finally she discusses new opinions on nutritional approaches to keep cholesterol levels healthy and prevent CVD events.

1. Nutritional approaches to managing
cholesterol and CVD.
Key messages from the research.
Sophie Tully BSc MSc DIPPT

2. What is CVD?
Cardiovascular disease (CVD) is a general term that describes a disease of the
heart or blood vessels.
• Blood flow to the heart, brain or body can be reduced as a result of a:
– blood clot (thrombosis)
– build-up of fatty deposits inside an artery, leading to the artery hardening
and narrowing (atherosclerosis)
Types of CVD:
• Coronary heart disease
• Stroke
• Peripheral arterial disease
• Aortic disease
www.NHS.uk/conditions

5. Risk factors
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Smoking
Being physically inactive
Being overweight or obese
Diabetes
Family history of heart disease
Ethnic background
Sex - men are more likely to develop CVD at an earlier age than women
Age - the older you are, the more likely you are to develop CVD
• High blood pressure
• High blood cholesterol
• Stress, alcohol, the type of job you do may also influence your risk of
developing CVD
www.bhf.org.uk

6. Traditional management methods
Antihypertensives:
- diuretics
- angiotensin-converting enzyme (ACE) inhibitors
- beta blockers
Blood-thinning medications:
- aspirin therapy
- warfarin
Cholesterol-lowering medications:
- statins
- fibrates

7. • Today 6-7million UK inhabitants are on daily statins!
• In the US between 2005-2009 nearly 20% of the population
were taking antihypertensive medication
• Approximately 2 million US inhabitants take blood thinners
daily
• Common side effects of these drugs include: water
retention, depression+/anxiety, headache, dry mouth,
insomnia, chest pain, impotence, hair loss, skin rash,
nausea / diarrhoea, kidney & liver damage……….

8. Recommended risk reduction
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Exercise
Lose weight
Reduce stress
Stop smoking
Eat a low fat diet
Reduce cholesterol intake
Ideal lipid profile (according to the BHF):
Total cholesterol
HDL cholesterol
LDL cholesterol
Triglycerides
4 mmol/L
>1 mmol/L
< 2 mmol/L
<1.7 mmol/L

9. The truth about fat
Fat-free =
• flavour, texture and satisfaction free
• sugar and artificial ingredients added to make product
edible!
Fat is:
• an essential membrane component of every single cell in the
body (including saturated fat!)
• a highly efficient source of fuel that humans are designed to
thrive on
• an energy store, insulator to protect our vital organs, acts as a
messenger, aids protein function, contributes to normal growth,
immune function, reproduction and other aspects of basic
metabolism

10. The truth about Cholesterol
Low cholesterol intake =
• Inadequate supply of the building blocks for hormones
• Inability to produce bile acids
• Inability to synthesise Vitamin D
Now widely recognised that dietary intake of cholesterol has very
little impact on the body’s cholesterol levels
The body requires a continuous supply of cholesterol and
possesses the ability to synthesise cholesterol itself

11. Per
Nutrition information medium
size egg
Per 100g
What about eggs?
66kcal
131kcal
Protein
6.4g
12.6g
Carbohydrate
of which sugars
trace
trace
Cutting out eggs cuts out a cheap,
healthy and widely available source
of lots of nutrients that contribute to
reaching vital RDAs
Fat
of which saturates
monounsaturates
polyunsaturates
4.6g
1.3g
1.7g
0.7g
9.0g
2.5g
3.4g
1.4g
Sodium
78mg
154mg
Energy
Delicious, nutritious
and filling!
http://healthyegg.co.uk/nutritionalcomposition

12. The ‘evidence’ for fat and cholesterol
• Early studies (1980) by Ancel and Keys found:
– total fat does not affect CHD death
– but % energy from saturated fat does correlate with CHD
• Replacing saturated fat with any nutrient = reduced LDL = good for CVD
• However, 2 studies in 2010 say otherwise:
– meta-analysis, just under 350,000 subjects found NO link between saturated fat intake
and coronary events
– Japanese cohort following 58,453 women over 14 years found those eating ‘ideal’ 2.511g saturated fat daily had 45% increased stroke risk and 22% increased CVD vs those
eating more (18g) daily
• Today ~50% of our calories come from carbohydrate but CVD risk is still on
the rise!

13. The ‘evidence’ for fat and cholesterol
• 1% increased energy intake from sat fat vs CHO = increased LDL by 0.03 mmol/L
• 5% increased energy CHO vs sat fat = 7% increased CHD
• Increased sat fat intake = increased LDL particle size
• Increased CHO intake = increased triglycerides and reduced HDL and reduced LDL
particle size = increased atherosclerosis risk
– small LDL particles = increased vessel wall damage and penetration
– reduced binding capacity of LDL particles to receptors = remain in circulation
for longer
– more susceptible to oxidative damage

14. The ‘evidence’ for fat and cholesterol
• GI of CHO source very important:
– high GI = 33% increased heart attack risk, med GI = no effect, low GI =
small reduced risk
– low GI diet is typically high in vegetables, fruit, legumes and
unprocessed grains = high in vitamins, minerals, phytonutrients and
fibre – all essential for CV health
The Health delusion: a big fat mistake, Glen Matten and Aidan Goggins

15. What really works?
Polyunsaturated fatty acids (PUFAs)
• A 5% switch from sat fat to PUFA = 10% reduced CHD
• Replacing CHO with PUFA = most favourable CHD outcomes
• Thus increasing PUFA = CHD benefits
• But two types of PUFA
– omega-6s are abundant in plant oils, animal protein, nuts and
grains
– omega-3s found in small amounts in foods, mainly fish

16. PUFAs continued…
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Omega-6 intake already around upper recommended limits
but omega-3 intake generally low
• Studies looking at increasing omega-6 only vs omega-3&6
intake found:
– increasing omega-6 intake only = small increase CHD risk
•
Thus benefits of PUFA intake mainly down to omega-3s
– specifically EPA & DHA found in fish
Why?

17. PUFAs continued…
EPA and DHA have been shown to be/offer:
– anti-inflammatory
– vasodilator activity
– triglyceride lowering
– reduced platelet aggregation
– plaque stabilisation
– antiarrhythmic
– hypotensive effects
(Halcox, 2010)
Importance of omega-3s in CV function:
• The omega-3 index is an indicator of cardiovascular disease risk
• RBC omega-3 levels and the AA to EPA ratio may be a more potent risk
factor for sudden cardiac death than high blood cholesterol levels or creactive protein (Dawczynski et al., 2010)

18. Inflammation and CVD
• PUFAs – strongly linked to control of the inflammatory response
• Optimal EPA (and DHA) levels = healthy inflammatory control
• AA intake important for inflammatory control
• AA to EPA ratio = very useful biomarker of inflammation and chronic
disease risk
• Stress and high GI foods – linked to CVD and both increase inflammation
• Inflammation leads to increased susceptibility to damage of blood vessel
walls and reduced cellular communication
(Boer, Van Wetten and Pruiboom, 2012)

19. AA to EPA ratio is a direct measure of inflammation
By modifying diet we can influence the ratio of pro-inflammatory (from AA)
to anti-inflammatory eicosanoids (from EPA)

20. Conditions associated with a high AA to EPA ratio
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Depression
Bipolar disorder
Schizophrenia
Myalgic encephalomyelitis
Fibromyalgia
Chronic pain syndromes
Diabetes
Cardiovascular disease
Cancer
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Inflammatory disorders
Inflammatory bowel disease:
(Crohn’s disease, ulcerative colitis)
Neurodevelopmental disorders:
(autism, dyslexia, dyspraxia, ADHD)
Alzheimer’s disease
Huntington’s disease
Skin conditions:
(eczema, psoriasis, dermatitis)

21. EPA, DHA and CVD – the research
• Red blood cell omega-3 levels strongly inversely associated with sudden
cardiac death
• Daily fish oil associated with reduced risk of all cause mortality and
secondary coronary events in post-myocardial infarction cohorts
• Fish oil supplementation resulted in reduced risk of death or
hospitalisation due to CV events
• Recommended minimum 1g daily intake of fish oil from supplements
predominantly EPA or oily fish intake
– fish consumption associated with high toxin levels and large volumes needed
(Weitz et al., 2010)

23. EPA and DHA benefits shared or different?
• 2011 two very comprehensive reviews were published
• EPA alone = reduced TGs and risk of coronary events and conditions
• DHA alone = reduced TGs, increased LDL particle size and reduced BP and
HR
• Either alone or in combination, contribute differentially to reduced
inflammation, oxidative stress and platelet aggregation, enhanced cardiac
and arterial function seen with omega-3 intake
• Both reviews concluded evidence on the whole for the enhanced effects of
one fat over the other on any CV marker was poor due to low number of
studies, under-powered and poor design

24. EPA and DHA benefits shared or different?
Overall conclusions:
In order to determine which type of omega-3 and dose would be optimal
requires many more studies, as response varies dependant on the
individual and their specific CVD profile.
It was noted however that EPA levels were more impacted by increasing
intakes than DHA, suggesting DHA in the cell may be more stable and
thus potentially the need to supplement is not so great.

25. A new wave of pure omega-3 studies
Following these reviews numerous pure oil studies were carried out:
1) JELIS study found
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1.8g/day of ethyl-EPA in just under 20,000 hypercholesterolemic
subjects randomised to EPA + statins or statins alone = 19%
reduced incidence of major CVD
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that increasing EPA and reducing AA:EPA ratio were both useful
in preventing coronary artery disease

26. A new wave of pure omega-3 studies
2)
Tani et al., 2013
– Hypertriglyceridaemia patients randomised to 2 x 900mg ethyl-EPA for
6 months had significantly increased LDL particle size, reduced serum
TGs and non-HDL cholesterol vs no significant changes in controls
– LDL particle size at 6 months positively correlated with serum EPA and
negatively correlated with AA:EPA ratio
– 6 month AA:EPA ratio was found to be better than any other marker at
predicting LDL particle size

27. What next?
• Importance of EPA as stand alone and co-therapy for CVD now well
established
• In 2012 the FDA approved a high purity ethyl-EPA product for use in
treating hypertriglyceridaemia
• Phase III placebo controlled clinical trials using ‘Vascepa™’ further
support the benefits of ethyl-EPA in managing and treating CVD

28. Vascepa™ trials:
• ANCHOR & MARINE looked at role of EPA on inflammatory markers
associated with CVD and atherosclerosis in hypertriglyceridaemic
patients taking statins for cholesterol control.
• Both studies randomised subjects to 12 weeks of taking 4 or 2g EPA or
placebo daily
• Results showed 4g EPA reduced TGs, non-HDL cholesterol and other
markers of atherosclerosis without increasing total LDL
• The ANCHOR study used predominantly (>70%) diabetic subjects and
showed 4g EPA daily significantly improved lipid profiles and lipid related
markers without negatively impacting glycaemic control

29. There’s more to come!
• REDUCE-IT study currently ongoing
• Aim is to determine efficacy of IPE in preventing CV events in high risk
patients on statins
• Overall Vascepa™ has been hailed as safe, effective and a new
alternative with potential benefits over existing treatments

30. Igennus CVD support protocol
Pharmepa Step 1: Restore
2 capsules = 1g pure ethyl EPA
Vitamin E for antioxidant protection
Designed to
• Increase cellular EPA levels quickly
• Restore a healthy AA:EPA ratio
• Reduce the production of pro-inflammatory products
• Increase the production of anti-inflammatory products
• Support cardiovascular health and cholesterol levels

31. VESIsorb Ubiquinol-QH
CoQ10 and cholesterol-lowering drugs
• Igennus is the only independent manufacturer
of reductase is an enzyme that plays critical role Based in
• HMG-CoAspecialist Fatty Acid ina the UK. in the
regulation of cholesterol synthesis, as well as CoQ10 synthesis hub for the
Cambridge the medical innovation
UK:
• HMG-CoA reductase inhibitors, generally known as statins (such as
atorvastatin, cerivastatin, lovastatin, pravastatin, simvastatin), are
- Seven elevated
commonly used to treat Seas blood Merck Pharma blocking
cholesterol levels by Germany
cholesterol biosynthesis; in doing so, they also block CoQ10 Canada
- Minami
Atrium Pharma
biosynthesis
- Biocare
Elder Pharma India
• Taking ubiquinol supplements can correct the deficiency causedSweden
- Eskimo 3
Bringwell Pharma by
such medications without affecting the medication's positive effects
- Equizen
Vifor Pharma Swiss
on cholesterol levels and can improve statin-induced myopathy

32. Acetyl-CoA
HMG-CoA synthase
HMG-CoA
HMG-CoA reductase
inhibitors (statins)
HMG-CoA reductase
Mevalonate
Cholesterol
Coenzyme Q10
(ubiquinone)

33. VESIsorb Ubiquinol-QH
Faster acting, stronger plasma concentration and longer lasting effects
• Igennus is the only independent manufacturer
 Unprecedented bioavailability Acid in the UK. Based in
of specialist Fatty
 Fully reduced ‘bioactive’ form
Cambridge the medical innovation hub for the
 Solubilised for maximum absorption
 NovelUK:
VESIsorb® delivery system mimics the natural transport system
of the intestine, providing significantly higher plasma concentrations†
- delivery Seas
Merck Pharma
than any other Seven system offering a comparable dose Germany
 One capsule Minami a therapeutic dose (100 mg)
- daily delivers
Atrium Pharma Canada
- Biocare
Elder Pharma India
Enhances energy production
Potent antioxidant
Supports antioxidant turnover
- Eskimo
Bringwell Pharma Sweden
Enhances cellular communication3Cell cycle support
Reduces statin-associated myopathy
Cardioprotective
Neuroprotective
Anti-inflammatory
- Equizen
Vifor Pharma Swiss

34. Homocysteine Control
Sustained Release
Homocysteine is an amino acid derivative of methionine, anmanufacturer
• Igennus is the only independent
essential amino acid obtained from protein-rich foods
of specialist Fatty Acid in the UK. Based in
The amount of homocysteine in medical a predictive marker
Cambridge the the blood is innovation hub for the
of cardiovascular health status
UK:
High levels are Seven Seas
- a reliable risk factor for cardiovascular diseaseGermany
Merck Pharma
- lowers levels
Atrium Pharma Canada
Homocysteine Minami of nitric oxide, a gas that is critical to
maintaining healthy and flexible arterialElder Pharma India
walls
- Biocare
- Eskimo 3
Bringwell affecting
Elevated homocysteine directly damages cholesterol, Pharma Sweden
arterial walls, causing them to thicken which can lead to
- Equizen
Vifor Pharma Swiss
atherosclerosis

35. Homocysteine Control
Sustained Release
• Igennus is the only independent manufacturer
of specialist Fatty Acid in the UK. Based in
for the
UK:
 Formulated at proven dosages for efficacy
Homocysteine ControlTM Sustained Release tablets contain a
synergistic blend of bioavailable vitamins B6, B12 and folic acid at
precise dosages for maintaining healthy homocysteine levels.
Cambridge the medical innovation hub
 Highly bioavailable actives
- Seven
Merck Pharma Germany
 Easy-to-swallow tabletsSeas
 Suitable for vegetarians & vegans
- Minami
Atrium Pharma Canada
 Sustained release tablets to maintain optimal blood
Elder Pharma India
concentrations Biocare
 Split dosing overcomes bioavailability issues associated with Sweden
- Eskimo 3
Bringwell Pharma
B12 supplementation
- Equizen
Vifor Pharma Swiss

36. www.igennus.com
01223 421434
• Igennus is the only independent manufacturer
info@igennus.com
of specialist Fatty Acid in the UK. Based in
Cambridge the medical innovation hub for the
UK:
- Seven Seas Sophie Tully
Merck Pharma Germany
Nutrition education manager
- Minami
Atrium Pharma Canada
sophiet@igennus.com
- Biocare
Elder Pharma India
education@igennus.com
- Eskimo 3 07908683174 Pharma Sweden
Bringwell
- Equizen
Vifor Pharma Swiss