Age-related hypertension is there a role for Omega 3 fatty acids in prevention and adjunctive therapy?

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Age-related hypertension is there a role for Omega 3 fatty acids in prevention and adjunctive therapy? Dr Rob Winwood CSci FIFST Nutrition Science and Advocacy Manager EMEA for DSM Nutritional Products and vice chair of CRN UK. 15:40 Thursday, November 22nd, 2018 at Food Matter Live, Gallery Room 4, Excel, London

Programme Nutrition and Heart Health The adverse effects of hypertension on cardiovascular health. The role of Marine Omega 3 Fatty Acids in reducing blood pressure. 1

Nutrition and heart health Nourish your heart Small dietary changes can lead to a large reduction in the burden of CVD Improving your diet is a key factor in preventing and managing cardiovascular diseases Numerous scientific studies showed that nutrients can reduce the risk of CVD and promote a healthy heart Nutritional epidemiology showed that specific nutrients play a key role in maintaining a healthy heart Source: International Osteoporosis Foundation www.iofbonehealth.org 2

Cardiovascular Disease Examples of Risk Factors: Stress Smoking Obesity, Sedentary lifestyle Dyslipidemia Hypertension Genetic predisposition Metabolic syndrome Poor diet (high salt/trans-fats) Infection CVD is a multi-factorial disease. The efficacy of any nutritional intervention thus needs to be determined by a relevant basket of validated biomarkers Proven treatment interventions: Exercise Reduce blood pressure Regularise blood lipid profile Reduce inflammation Reduce blood viscosity/clotting

Hypertension The major risk factor for cardiovascular disease, and stroke in particular Defined as a blood pressure (BP) of greater than 140/90 mmhg (systolic/diastolic BP) Multiple lifestyle, nutritional and genetic factors known to affect BP Antihypertensive drugs are highly effective yet hypertension remains a global problem

Major Causes of Hypertension (high blood pressure) Aging Stress Smoking Genetics Sleep apnoea High salt consumption Obesity Lack of exercise Chronic kidney disease Adrenal and thyroid disorders Higher than average alcohol consumption Family history of high blood pressure 5

Health risks associated with high blood pressure (hypertension) Heart Disease Heart Attacks (Myocardial Infarctions) Stokes Heart Failure Peripheral arterial disease Aortic aneurysms Kidney disease Vascular dementia 6

EU Generic Function Claims relating to cardiovascular health that are valid for the whole life span (art 13.1). Vitamin B1 Vitamin B2 B Vits Conditions of use of the claim apply. e.g. for Vits B6 and B12 foods must contain 15% of the Reference Labelling Value (RLV) per 100g (7.5%/100mL for beverages) EFSA J 2010, 8(10): 1756 & 1759

BBC News 12 th November 2018 Prof John Dearfield, Professor of Cardiology of University College London spoke about the follow up of a a trial measuring carotid blood flow to the brain back in 2002. The 3,191 participants were then regularly checked recently for signs of dementia. Those who originally had poor blood flow (lowest quartile) and hypertension in the 2002 trial had around a 50% innceased risk of developing dementia. This works demonstrates the importance of good blood flow for long term brain health. 8 https://www.bbc.co.uk/news/health-46155607

The role of Marine Omega 3 Fatty Acids in reducing blood pressure.

Principal Omega-3 Fatty Acids -Linolenic Acid (ALA; 18:3n-3) O OH Eicosapentaenoic Acid (EPA; 20:5n-3) O OH Docosahexaenoic Acid (DHA; 22:6n-3) O OH

Key Clinical Modes of Action for EPA and DHA 1. Resolving Inflammation 2. Inter-cell signaling 3. Control of cell lifespan (Apoptosis) 4. Restoring healthy lipid profile to blood and reducing blood pressure and viscosity 11

Ω-3 & Ω-6 METABOLISM + HEALTH BENEFITS Omega-6 Vegetable Oils LA inefficient conversion in humans Omega-3 Green Vegetables ALA 18:3 Skin Health GLA SDA 18:4 ARA 2 Infant Brain Development EPA 20:5 DHA 22:6 Inflammation EPA+DHA: Heart Health, Neurological, Others Brain Health Eye Health

IMPORTANT TO RE-BALANCE 3 6 Hunter/ Gatherer Agriculture 1900 initial industrialized food system 1970 completely industrialized food system = complete imbalance

Update on the evidence for use of higher doses (500mg to 3g/day) of DHA and EPA in the adjunctive treatment of hypertension

O M E G A - 3 % RISK OF SUDDEN DEATH DECLINES WITH HIGHER LEVELS OF OMEGA-3 Relative Risk of Sudden Cardiac Death 100% Physician s Health Study NEJM 2002 346(15), 50% 20% 1113-1118 LC-Omega-3 in Blood % 90% Risk Reduction 10% 2.21-4.32 4.33-5.19 5.20-6.07 6.08-10.2

40% REDUCTION IN SUDDEN DEATH WITH FISH OIL SUPPLEMENTS GISSI Prevenzione: landmark study confirming the cardioprotective effects of EPA+DHA 100% 850mg (Control) -20% EPA/DHA 850mg EPA/DHA -40% Lancet 1999; 354:447-455 Overall Mortality Sudden Death

Theoretical Responses and Clinical Events vs. Fish or Fish Oil Intake Mozaffarian D, Rimm EB. JAMA. 2006

Authorised EU Article 13.1 Health Claims Official Journal of the European Union 25.2.12, Commission regulation (EU) 432/2012 of 16 th May 2012. DHA Contributes to the maintenance of normal brain function (250 mg/d). DHA Contributes to the maintenance of normal vision (250 mg/d). DHA + EPA Contributes to the maintenance of normal function of the heart (250 mg/d). Note: In order to bear the claim, foods should contain 250 mg of DHA in one or more servings Official Journal of the European Union L160/4, Commission regulation (EU) 536/2013 of 12th June 2013. DHA + EPA Contribute to the maintenance of normal blood pressure ( 3 g/d). DHA + EPA Contributes to the maintenance of normal triglyceride concentrations (2g/d). DHA Contributes to the maintenance of normal blood triglyceride levels (2 g/d). 18

VITAL trial results reported at November 2018 American Heart Association Conference in Chicago show benefits for interventions of EPA+DHA and reduction of primary CVD. The results of the VITamin D and OmegA-2 TriaL (VITAL) were presented at the 2018 American Heart Association (AHA) Scientific Session on Saturday, 10 November 2018 (Manson JE et al, 2018, New England Journal of Medicine DOI: 10.1056/NEJMoa1811403). 25,871 healthy men 50 years of age or older and women 55 years of age or older in the USA received a daily dose of 460 mg EPA + 380 mg DHA for an average of 5.3 years The primary outcome of the study, major cardiovascular events (a composite of myocardial infarction, stroke, and death from cardiovascular causes), was not met with statistical significance, rather only an 8% reduction. BUT Omega-3 supplementation was found to reduce total and fatal myocardial infarction risk by 28% and 50% respectively. A 17% risk reduction was recorded for total coronary heart disease. 19

The marine omega 3 fatty acids DHA and EPA can achieve modest reductions in blood pressure when used at higher doses. Mechanism:- Improved arterial compliance Anti-thrombotic effects Theobold et al., 2007 J Nutr 177(4): 973-8. An application for a qualified health claim for omega 3 fatty acids and blood pressure reduction has been under consideration by the US Food and Drug Administration since 2014.

American Journal of Hypertension 2014: 27(7):885-96 Comprehensive meta-analysis of 70 randomised controlled studies Overall reduction in systolic blood pressure: 1.53 mg Hg (95% CI) Overall reduction in diastolic blood pressure: 0.99 mg Hg (95% CI) 21

Summary The marine omega 3 fatty acids EPA and DHA have been shown to reduce blood pressure in hypertensive individuals. Evidence from RCTs indicated clinically useful reductions of systolic and diastolic blood pressure with adjunctive interventions of 2 4g EPA +DHA. Interventions with EPA and DHA are most effective in individuals with underlying and as yet, untreated hyperextension. A meta-analysis (Miller 2014) has indicated a dose response relationship for EPA and DHA and diastolic blood pressure. 22

Acknowledgements My sincere thanks to Professor Helene McNulty of Ulster University for her work and slides on the role of micronutrients and hypertension. My thanks to Dr Ed Nelson MD, formerly with DSM Nutritional Products (now retired), but who still ensures I am kept up to date in relation to Omega 3 Fatty Acids and Cardiovascular Health. 23

Thank you! Diolch! Tapadh leat! Keep up to date at www.nutri-facts.org! This information is based on DSM s current knowledge. Although DSM has used diligent care to ensure that the information provided herein is accurate and up to date, DSM makes no representation or warranty of the accuracy, reliability, or completeness of the information. This information only contains scientific and technical information for business to business use. Use of this information shall be at your discretion and risk. Nothing herein relieves you from carrying out your own suitability determinations and tests. We do not assume any liability in connection with your product and its use. This information does not relieve you of your obligation to comply with all applicable laws and regulations and to observe all third party rights. Country or region-specific information should also be considered when labelling or advertising to final consumers. This information does not constitute or provide scientific or medical advice, diagnosis, or treatment and is distributed without warranty of any kind, either expressly or implied. In no event shall DSM be liable for any damages arising from the reader s reliance upon, or use of, these materials. The reader shall be solely responsible for any interpretation or use of the material contained herein. The content of this document is subject to change without further notice. Please contact your local DSM representative for more details. All trademarks listed in this brochure are either registered trademarks or trademarks of DSM in The Netherlands and/or other countries.