Event Type Home Study Webcast freece Expiration Date 8/30/2013 ACPE Expiration Date 8/30/2015 Credits 1 Contact Hour Target Audience Nurses, Pharmacists, Pharmacy Technicians Program Overview The benefits of increasing intake of omega-3 fish oil and possibly other good fats are heavily touted in the lay literature and on the internet. But what conditions are these "good" fats helpful for? This program will provide information on the mechanism of action of omega-3 fish oil and role of EPA and DHA in human health. Nurse Educational Objectives Understanding the biochemistry and dietary sources of two classes of essential fatty acids, Omega-3 and Omega-6 Explain the biologic function of two critical Omega-3's, EPA/DHA promote human health Outline the cellular and physiological mechanisms behind how Omega-3 EPA/DHA promote neurophysiologic health Review the scientific evidence demonstrating importance of Omega-3 EPA/DHA on cardiovascular health and discuss the importance of the Omega-3 Index State dose ranges for total Omega-3 EPA/DHA from fish oil in the clinical setting and for general health promotion
Pharmacist Educational Objectives Understanding the biochemistry and dietary sources of two classes of essential fatty acids, Omega-3 and Omega-6 Explain the biologic function of two critical Omega-3's, EPA/DHA promote human health Outline the cellular and physiological mechanisms behind how Omega-3 EPA/DHA promote neurophysiologic health Review the scientific evidence demonstrating importance of Omega-3 EPA/DHA on cardiovascular health and discuss the importance of the Omega-3 Index State dose ranges for total Omega-3 EPA/DHA from fish oil in the clinical setting and for general health promotion Pharmacy Technician Educational Objectives List sources of Omega-3 fatty acids Activity Type Knowledge Accreditation Nurse Pharmacist Pharmacy Technician N-789 0798-0000-12-066-H01-P 0798-0000-12-066-H01-T PharmCon, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. PharmCon, Inc. has been approved as a provider of continuing education for nurses by the Maryland Nurses Association which is accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center s Commission on Accreditation. Faculty Daniel Johnston, MD Stratcam, LLC. Financial Support Received From Supported by an education grant from Ocean Nutrition - Canada (MEG-3)
Disclaimer PharmCon, Inc. does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, authors may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient or pharmacy management. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this activity and other unrelated sources.
Page 1 Omega-3 Fish Oil The role of EPA & DHA In Human Health OBJECTIVES Essential Fatty Acid Biochemistry Basics Essential Fatty Acid Families Omega-3 family Omega-3 EPA/DHA Biochemistry Basics Omega-3 family Essential Fatty Acid Families Alpha Linoleic Acid (ALA) H 3 C H 3 C H 3 C COOH Alpha Linoleic Acid (ALA) Flaxseed Oil Canola Oil Soybean Oil Eicosapentaenoic (EPA) Oily Fish/Fish Oil Docosahexaenoic (DHA) Oily Fish/ Fish Oil COOH COOH Flaxseed Oil Canola Oil Soybean Oil Eicosapentaenoic (EPA) Docosahexaenoic (DHA) Oily Fish / Fish Oil Meats/Eggs
Page 2 Omega-3 EPA & DHA play critical roles in health through hormonal & structural mechanisms Omega-6 Omega-3 EPA & DHA play critical roles in health through hormonal & structural mechanisms Omega-3 LA American Diet very high in LA C-OH Competition for desaturase & elongation enzymes Inefficient conversion Inhibited by high LA) (less than 5%) ALA COOH AA C-OH Series 2 Prostaglandins / Thromboxanes Series 4 Leukotrienes Series 3 Prostaglandins Thromboxanes Series 5 Leukotrienes COOH EPA Fish / Fish Oil COOH DHA Structural Role: Brain, Retina, Testis Imbalance in American Diet High Omega-6 to Omega-3 ratio leads to imbalance of Inflammatory Eicosanoids Imbalance in American Diet High Omega-6 to Omega-3 ratio leads to imbalance of Inflammatory Eicosanoids Pro-Inflammatory Pro-Inflammatory Anti-Inflammatory Anti-Inflammatory 25:1 Western Diet High Omega-6 arachidonic acid Low Omega 3 EPA/DHA Western Diet High Omega-6 arachidonic acid Addition of: EPA DHA
Page 3 Summary on Key Omega-3s: ALA, EPA, DHA Well known Omega-3 EPA/DHA Effects ALA Alpha-linolenic Primarily from plant sources is considered heart healthy EPA Eicosapentaenoic Acid Primarily from oily fish DHA Docosahexaenoic Acid Primarily from oily fish EPA and DHA are longer, highly unsaturated and have the most clinical evidence for cardiac health, and CNS normal growth and development. FDA approved drugs contain EPA/DHA, not ALA Reduced platelet aggregation Lower triglyceride levels Reduced susceptibility to cardiac arrhythmias Lower inflammation Decrease telomere attrition All mediated by: Altered cell membrane physiochemical properties Shifts in eicosanoid production Altered gene expression The Oxford Durham Study Clinical and Scientific Evidence for the importance of Omega-3 EPA/DHA in healthy function of the Central Nervous System 117 children (ages 5 to 12) with Developmental Coordination Disorder (DCD) Daily dose of 6 capsules Richardson, A.J., et al. Pediatrics 2005:115:1360-66
Page 4 Reading and Spelling Decrease in teacher-rated ADHD-related symptoms Active treatment (N=55) Compared with expected rate of progress for normal children, gains were : Increase 3 x for reading Increase 2 x for spelling Placebo (N=57) Gains were: 1 x normal rate for reading Decrease 0.5x for spelling Statistical Significance Reading p < 0.004 Spelling p < 0.001 Improvements in Literacy Skills DSM Combined-typeDSM Hyperactivity DSM Inattention Conners Global Index CG Emotional Lability CG restless-impulsive Conners Index Social Problems Perfectionism Anxiety Hyperactivity Cognitive Problems Opposition Reading Spelling gain (months) Mean -0.10 0.00 0.10 0.20 0.30 0.40 0.50 0.60 Richardson, A.J., et al. Pediatrics 2005:115:1360-66 Treatment Effect Size (Mean change 0-3m/Pooled Baseline SD) Human Brain Omega-3 Accumulation Human Brain Omega-3 Accumulation 10000 µmol 10000 µmol 8000 8000 6000 4000 DHA Omega-3 6000 4000 Preterm Term DHA Omega-3 2000 2000 A 20 40 60 80 100 120 140 Gestational Age (Weeks) Martinez 1992 J Pediatrics 120:s129 2005 A 20 40 60 80 100 120 140 Gestational Age (Weeks) Martinez 1992 J Pediatrics 120:s129 2005
Page 5 Avon Longitudinal Study of Parents and Children (ALSPAC) Recruited 14,541 pregnant mothers, largest & most complete longitudinal study in the world. Enrollment included every pregnancy between April 1 st 1991 & December 31 st 1992 in Avon (Southwest of London, UK) Children now between 11.5 and 15 years of age Participants mail questionnaires every 6 months 1,500 children seen in clinics every year since birth 85% of children seen in clinics every year since age 7 Higher maternal seafood consumption optimal scoring increases 34 32 30 28 26 24 22 20 Percentage of 14 children with low verbal IQ,WISC-III uk, 8y r = 0.97 r 2 = 0.95 F=27.2 p<0.02. 0 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 Estimated omega-3 fatty acids from seafood (en %) Mother at 32 wk gestation Collaboration with John M. Davis, M.D. Univ. of Illinois Jean Golding, Ph.D., Pauline Emmett, Ph.D.- ALSPAC study group Hibbeln et al, Lancet 2007: 369: 578-585 Omega-3 EPA/DHA in Maternal and Pediatric Health In view of the mounting evidence implicating omega-3 fatty acid deficiency as a determinant of various maternal and pediatric afflictions, physicians should consider recommending purified fish oil supplementation during pregnancy and lactation. S J Genuis, et al Journal of Perinatology, 2006 Cumulative Incidence Dementia / Alzheimer s and Plasma PC DHA 0.16 0.14 0.12 0.10 0.08 0.06 0.02 DHA content of plasma phosphatidylcholine measured in 899 subjects (76 yrs) from Framingham Heart Study Incidence of dementia/ad tracked over 9.1 yrs 0 2 4 6 8 10 12 Years Follow-up Quartiles 1-3 Quartile 4 RR Q4 vs Q1-3 = 0.53 (p=0.04) Schaefer et al. Arch Neurol. 2006 Nov;63(11):1545-50.
Page 6 Summary of Proposed Mechanisms of Omega-3 EPA/DHA on CNS Decrease the production of AA-derived eicosanoids Decrease neuroinflammation and inflammatory cytokines IL-1 beta, IL-12, IL-6, IF & TNF-a Alter neuronal fluidity, increase dendritic arborization Modify dopminergic and serotonergic neurotransmission Increase dopamine levels in the frontal cortex and increase dopamine binding to D2 receptor sites Omega-3 EPA/DHA in Cardiovascular Health Relations between EPA/DHA intake and risk for CHD death in US-based prospective cohort and case-control studies Physician s Health Study (Relative risk of sudden death declines with higher levels of Omega-3 in the blood) Relative risk 1.2 1.0 0.8 0.6 0 All studies (n=6) Studies MRFIT Nurse s Health Health Professionals Physician s Health Cardiovascular Health Seattle Primary Cardiac Arrest Relative risk 100% 80% 60% 40% 20% 90% reduction 25 78 159 290 560 (34) (56) (85) (146) (224) 0% 2.21-4.32 4.33-5.19 5.20-6.07 6.08-10.2 Omega-3 EPA/DHA in Blood (%) Mean (SD) EPA + DHA intake, mg/d Harris, Kris-Etherton, Harris. Curr Athero Repts 2008;10:503-509 NEJM 2002: 346(15), 1113-1118
Page 7 Relative risk CHD Death (%) 100% 80% 60% 40% 0% Nurse Health Study (Omega-3 lowers CHD risk in women) < 1/month 1-3/month 1/week 2-4/week > 5/week Intake of Fish Relative risk CHD Death (%) GISSI-Prevenzione: time course of clinical events More than 11,300 post-mi patients given usual care with or without 850mg EPA + DHA (1 cap/d Omega-3 acid ethyl esters) for 3.5 years Overall Survival Effects of Omega-3 at 3.5 years Days 0 180 360 540 720 900 1080 1260 Total mortality reduced by 21% Probability 1.00 0.99 0.98 0.96 Freedom from Sudden Death Effects of Omega-3 at 3.5 years Days 0 180 360 540 720 900 1080 1260 Sudden death reduced by 45% NEJM 2002: 346(15), 1113-1118 No Omega-3 EPA/DHA Omega-3 EPA/DHA Marchioli R et al. Circulation 2002; 105:1897-1903 Japan EPA Lipid Intervention Study-JELIS 18,645 Japanese (70% women, 61 yrs) randomized to statin alone or statin+epa (1.8 g/d) and followed for 5 years JELIS: Effects of EPA on Incidence of Stroke 15 Entire Cohort N= 18,645 1 a Prevention = 14,981 2 a Prevention = 3,664 4 2.0 12. 10 No EPA EPA Major coronary events (%) 3 2 0 1.5 1.0 0 0 8.0 0 Hazard ratio: 0.80 (0.64-0.997) P=0.047 0 1 2 3 4 5 Years 0 1 2 3 4 5 Control Years EPA 0 0 1 2 3 4 5 MCE = Major coronary events were considered to be sudden cardiac death, fatal and nonfatal MI, unstable AP, and angioplasty/stenting or CABG Years 0 1 2 3 4 5 Years 20% reduction in risk for stroke in those with a history of stroke Adjusted for age, gender, smoking, diabetes and hypertension Yokayama et al. Lancet 2007;369:1090-98 Tanaka et al. Stroke 2008;39:2052-2058
Page 8 Omega-3 EPA/DHA in Prevention of Heart Disease Measuring Omega-3 Index A measure of the amount of EPA+DHA in red blood cell membranes expressed as the percent of total fatty acids The totality of evidence supports a strong role for Omega-3 EPA/DHA fatty acids derived from fish oil in prevention of heart disease through a presumptive role as an antiarrythmic agent and through an ability to promote plaque stabilization. American Journal of Cardiology Example: 64 fatty acids in this model membrane, 3 of which are EPA and DHA 3/64 = 4.6% Omega-3 Index = 4.6% Harris WS and von Schacky. Prev Med 2004;39:212-220 Omega-3 Index risk Zones Relative Risk for death from Coronary Heart Disease Omega-3 Index risk Zones Relative Risk for death from Coronary Heart Disease USA/EU Japan Undesirable Intermediate Desirable Undesirable Intermediate Desirable 4% 8% Percent of EPA+DHA in RBC 4% 8% Percent of EPA+DHA in RBC Harris WS and von Schacky. Prev Med 2004;39:212-220; Itomura, et al. in vivo 2008;22:131-6 Harris WS and von Schacky. Prev Med 2004;39:212-220; Itomura, et al. in vivo 2008;22:131-6
Page 9 Rationale for Selecting Omega-3 Index Targets for Cardiovascular Disease Least Protection PHS: 3.9% SCIMO: 3.4% Seattle: 3.3% 10% 8% 6% 4% Greatest Protection GISSI-P: ~ 9-10% CHS: 8.8% DART: ~ 8-9% SCIMO: 8.3% 5 epi studies: ~ 8% PHS: 7.3% Seattle: 6.5% 8.1% Summary of key roles of Omega-3 EPA/DHA 2% 0% Harris WS and von Schacky. Prev Med 2004;39:212-220; Itomura, et al. in vivo 2008;22:131-6 EPA Summary of key roles of Omega-3 EPA/DHA Decreases inflammation, vasoconstriction Decreases platelet aggregation Reduces susceptibility to cardiac arrhythmias DHA Structural importance in CNS Critical during early stages of life Possibly decreases risk of dementia later in life Omega-3 EPA + DHA total dosage for optimal wellness Average N. American intake: 80 150mg/day Minimum intake for health promotion: 1,000mg/day Amount for clinical conditions: 1,000-4,000mg/day Note: must eat 2-3 servings of fatty fish per week to reach minimum of recommended 500mg EPA + DHA per day by the AHA Mood Sources: Oily Fish, Fish Oil Cognition Sources: Oily Fish, Fish Oil Note: One 1,000mg fish oil soft gel is not 1,000mg of EPA + DHA. Labels must be read carefully to determine EPA + DHA content per capsule
Page 10 What do other health agencies recommend Closing Comments American Heart Association: 500mg/day minimum with 1,000 to 3,000 mg EPA and DHA per day for groups with high heart risk. Health Canada: To reduce serum triglycerides: 1,000 3,000 mg EPA/DHA per day British Nutrition Foundation (BNF) Task Force: 1,250 mg EPA/DHA per day Norwegian Directorate for Health and Social Services: 1,000 mg EPA + DHA per day (for infants) UK Scientific Advisory Committee on Nutrition (SACN) and Food Standards Agency: At least 1,500 mg/day Omega-3 EPA + DHA supplementation is required to produce beneficial effects on cardiovascular factors. Omega-3 EPA and DHA from oily fish or fish oil work synergistically to improve human health within a variety of clinical areas such as heart disease, neurodevelopment, and prevention of cognitive decline Physicians should be aware when recommending to increase Omega-3 intake that EPA and DHA from oily fish or fish oil supplements have the most robust scientific support Newer areas of research include depression, traumatic brain injury, post surgical care and various inflammatory arthritic conditions such as rheumatoid arthritis and are showing promise. Notes Notes