Nutritional approaches to managing cholesterol and CVD. Key messages from the research.

Sophie Tully BSc MSc DIPPT

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

Risk factors• 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

Antihypertensives:- diuretics - angiotensin-converting enzyme (ACE) inhibitors - beta blockers

Blood-thinning medications: - aspirin therapy

- warfarin Cholesterol-lowering medications:

- statins - fibrates

Traditional management methods

• 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……….

Recommended risk reduction• Exercise• Lose weight• Reduce stress• Stop smoking• Eat a low fat diet• Reduce cholesterol intake

Ideal lipid profile (according to the BHF):

Total cholesterol 4 mmol/LHDL cholesterol >1 mmol/LLDL cholesterol < 2 mmol/LTriglycerides <1.7 mmol/L

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

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

The truth about Cholesterol

Nutrition information

Per medium size egg

Per 100g

Energy66kcal 131kcal

Protein 6.4g 12.6g

Carbohydrateof which sugars trace trace

Fatof which saturates    monounsaturates    polyunsaturates

4.6g1.3g1.7g0.7g

9.0g2.5g3.4g1.4g

Sodium 78mg 154mg

What about eggs?

Cutting out eggs cuts out a cheap, healthy and widely available source of lots of nutrients that contribute to reaching vital RDAs

Delicious, nutritious and filling!

http://healthyegg.co.uk/nutritional-composition

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’ 2.5-

11g 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!

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

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

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

PUFAs continued…

• 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?

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 c-reactive protein (Dawczynski et al., 2010)

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)

AA to EPA ratio is a direct measure of inflammationBy modifying diet we can influence the ratio of pro-inflammatory (from AA)

to anti-inflammatory eicosanoids (from EPA)

• Depression• Bipolar disorder• Schizophrenia• Myalgic encephalomyelitis• Fibromyalgia• Chronic pain syndromes• Diabetes• Cardiovascular disease• Cancer

• 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)

Conditions associated with a high AA to EPA ratio

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)

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

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.

A new wave of pure omega-3 studies

Following these reviews numerous pure oil studies were carried out:

1) JELIS study found

– 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

– that increasing EPA and reducing AA:EPA ratio were both useful in preventing coronary artery disease

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

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

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

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

Igennus CVD support protocol

Pharmepa Step 1: Restore2 capsules = 1g pure ethyl EPAVitamin 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

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

VESIsorb Ubiquinol-QH

CoQ10 and cholesterol-lowering drugs

• HMG-CoA reductase is an enzyme that plays a critical role in the regulation of cholesterol synthesis, as well as CoQ10 synthesis

• HMG-CoA reductase inhibitors, generally known as statins (such as atorvastatin, cerivastatin, lovastatin, pravastatin, simvastatin), are commonly used to treat elevated blood cholesterol levels by blocking cholesterol biosynthesis; in doing so, they also block CoQ10 biosynthesis

• Taking ubiquinol supplements can correct the deficiency caused by such medications without affecting the medication's positive effects on cholesterol levels and can improve statin-induced myopathy

Acetyl-CoA

Cholesterol

HMG-CoA

Mevalonate

HMG-CoA reductase inhibitors (statins)

Coenzyme Q10(ubiquinone)

HMG-CoA reductase

HMG-CoA synthase

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

VESIsorb Ubiquinol-QH

Faster acting, stronger plasma concentration and longer lasting effects

Unprecedented bioavailability Fully reduced ‘bioactive’ form Solubilised for maximum absorption Novel VESIsorb® delivery system mimics the natural transport system

of the intestine, providing significantly higher plasma concentrations†

than any other delivery system offering a comparable dose One capsule daily delivers a therapeutic dose (100 mg)

Enhances energy production Potent antioxidant Supports antioxidant turnoverEnhances cellular communication Cell cycle support Reduces statin-associated myopathyCardioprotective Neuroprotective Anti-inflammatory

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

Homocysteine ControlSustained Release

• Homocysteine is an amino acid derivative of methionine, an essential amino acid obtained from protein-rich foods

• The amount of homocysteine in the blood is a predictive marker of cardiovascular health status

• High levels are a reliable risk factor for cardiovascular disease

• Homocysteine lowers levels of nitric oxide, a gas that is critical to maintaining healthy and flexible arterial walls

• Elevated homocysteine directly damages cholesterol, affecting arterial walls, causing them to thicken which can lead to atherosclerosis

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

Homocysteine ControlSustained Release

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.

Formulated at proven dosages for efficacy Highly bioavailable actives Easy-to-swallow tablets Suitable for vegetarians & vegans Sustained release tablets to maintain optimal blood

concentrations Split dosing overcomes bioavailability issues associated with

B12 supplementation

• Igennus is the only independent manufacturer of specialist Fatty Acid in the UK. Based in Cambridge the medical innovation hub for the UK:

- Seven Seas Merck Pharma Germany- Minami Atrium Pharma Canada- Biocare Elder Pharma India- Eskimo 3 Bringwell Pharma Sweden- Equizen Vifor Pharma Swiss

www.igennus.com01223 421434

info@igennus.com

Sophie TullyNutrition education manager

sophiet@igennus.comeducation@igennus.com

07908683174