Fish Oils Denesh, Alan. Shane, Vince

What are Fish Oils? Fish oils provides the essential fatty acids needed for important biological compounds They are essential because they must be consumed through the diet The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essential nutrients that enhance quality of life and lower the risk of premature death. They function via the cell membrane, and anchored by phospholipids molecules Omega-3 phospholipids demonstrated anti-inflammatory activity. DHA and EPA are used together in a wide variety of clinical applications

Mechanism Of Action in Fish Oils -EPA AND DHA GET INTO THE PHOSPHOLIPIDS MEMBRANE -ENZYMATIC OXIDATION OF THESE COMPOUNDS SIGNAL MOLECULES CALLED EICOSANOIDS -EPA AND DHA IN THE MEMBRANE LOWERS PLATELET AGGRESSION AND GENES THAT PROMOTE INFLAMMATION AND ACCUMULATION IF FAT IN THE ARTERIES. -EICOSANOIDS MEDIATE THE EFFECT OF OMEGA 3, WHICH HELP TO REDUCE INFLAMMATION AT SPECIFIC DESTINATIONS scientist.com/?articles.view/artic leNo/32901/title/Omega-3s-- Fishing-for-a-Mechanism/

Fish Oil Claims - SUPPORTS JOINT, BRAIN AND VISION HEALTH - AIDS IN EXERCISE RECOVERY - SUPPORTS DAILY HEALTH FOR SEDENTARY INDIVIDUALS -PROMOTES HEALTH IMMUNE SYSTEM FUNCTION - PROMOTES CARDIOVASCULAR HEALTH -MAY REDUCE RISK OF CARDIOVASCULAR DISEASE

How is Fish Oils Marketed? Fish Oil is marketed to target individuals wanting to support joint health and exercise recovery and overall immune system function and cardiovascular health

Fish Oil Sources Food Sources: Lake Trout Mackerel Tuna Salmon Flax seeds Supplement Sources: Pills Liquids

Are Fish Oils Safe For Me to take?  Safe for MOST people including pregnant and breast feeding women  It is safe for most if taken in low doses, under 3g per day  Side effects can include belching, bad breath, nausea, rash and nose bleeds  Taking Fish Oils with meals can reduce the above side effects More serious potential side effects include:  Increase risk of bleeding in liver disease  Allergies to seafood may lead to allergies in supplement  May increase symptoms of bipolar disorder and depression  Higher dosages may make managing diabetes more difficult  Cause blood pressure to drop too low for people on blood pressure lowering medications

Fish Oil Supplement Recommendations Do not exceed more than 2g of EPA and DHA omega-3 fatty acids from supplementation as recommended by the FDA As directed on the label It can be taken 1 to 3 times daily with a meal

Questions to Consider… Do Fish oils help with preventing cardiovascular disease? Can fish oils be used in the treatment of cardiovascular disease? Who should take this supplement?

Effect of marine n-3 fatty acids on circulating inflammatory markers in health subjects and subjects with cardiovascular risk factors Mari C. W. Myhrstad, Kjetil Retterstol, Vibeke H. Telle-Hansen, Inger Ottestad, Bente Halvorsen, Kirsten B. Holven, Stine M. Ulven (December 2010) Methodology: Study type: Systematic Literature Review (based in PubMed Database from 2009) Search terms included: DHA or EPA or DPA or Omega-3 or fish oil or cod liver oil AND inflammation Limitations: studies within 10 years, in humans, clinical trials, English language

Willerson and Ridker, 2004 Measuring inflammatory markers in the plasma and serum may detect inflammation. Elevated levels of C-Reactive Proteins (CRPs), more so than Interleukin-6 (IL-6), may suggest inflammation. Inflammation is a precursor to the development of atherosclerosis, and symptoms associated with metabolic syndrome are also “associated” with high levels of CRPs. Studies have shown that elevated levels of CRPs were also able to predict cases of Type-2 diabetes. Previously stated disorders may be associated with cardiovascular disease risk, however whether or not reduction of CRPs actually lowers CVD risk is unknown.

Methodology (continued):  Intervention studies examining the effects of marine n-3 fatty acids on circulating inflammatory markers in the plasma and serum of HEALTHY SUBJECTS, SUBJECTS WITH HIGH RISK OF CVD & PATIENTS WITH CVD.  Exclusion criteria: 1. Interventions assessing inflammatory markers with ex vivo methods 2. Interventions with children 3. Animal or cell culture studies.  Of 91 articles identified, 22 were selected (and another 13 based on their references) [total: 35 articles] Myrhstad et al, 2010

Myhrstad et al, 2010

Myrhstad et al, 2010

CONCLUDING… The effects of marine n-3 on inflammation are INCONCLUSIVE

EPA & DHA In many foods - mostly profound in various types of fish - (hence why they are called marine omega-3s) Experts have found that people who eat foods with high levels of two of the omega- 3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have low rates of CHD - (Atherosclerosis) Prescription Omega-3 drugs are known to lower very high levels of triglycerides. Although these drugs are more expensive to buy than fish oil supplements, the drug contains about three times the dose found in supplements

DOSE! Recommendations show that people with heart disease can take 1 gram of a supplement of EPA+DHA a day. People who need to lower triglycerides to decrease their risk for CHD can take either 2 to 4 grams a day or 4 to 6 grams a day. IS this true? Does Dosage Really Matter? If so, which guideline?

Dose-Response (Study) N=55 – RCT Time = 2+ weeks -Change in plasma triglycerides from baseline for each individual -Each 1-g/day increase of EPA_DHA reduced triglycerides by _5.9 mg/dl This effect was significantly greater in trials of individuals with higher starting triglyceride levels -Among trials of individuals with mean baseline triglycerides below the median (_83 mg/dl), each 1 g/day EPA_DHA decreased triglycerides by _1.7 mg/dl -Among trials of individuals with mean baseline triglycerides above the median (_83 mg/dl), each 1 g/day EPA_DHA decreased triglycerides by _8.4 mg/dl Dariush Mozaffarian et al. Study (Boston, Massachusetts)

Dose-Response Does Dose Really Matter? Appears so

n–3 Fatty Acids and Cardiovascular Events after Myocardial Infarction -placebo-controlled trial -n=4837 -Men and Women -Ages Subjects are people who have had a myocardial infraction up to 10 years before the study

procedures Were split into 4 groups Baseling data ( Hr,BP was measured and other conditions and medications were known thorugh questionarie placebo group, 400 mg of EPA–DHA per day, 2 g of ALA per day, Any combination of the 3. Were given in the form of margarine. Followed up with patients 12 and 24 months after intervention

Results EPA–DHA (either alone or in combination with ALA), as compared with placebo and ALA only, had no effect on the rate of major cardiovascular events (Fig. 2) ALA did not have significantly lower rates of major cardiovascular events than did the two groups that received no ALA ALA had rate of major cardiovascular events that was 9% lower

Study Conclusion In conclusion, in this trial involving patients who had had a myocardial infarction and who were receiving good clinical care, low doses of n−3 fatty acids did not significantly reduce the rates of cardiovascular end points.

DISCUSSION

References Kidd, P.M. (2007). Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural- functional synergies with cell membrane phospholipids. University of California, 12(3): Myhrstad, M., Retterstol, K., Telle-Hansen, V., Ottestad, I., Halvorsen, B., Holven, K., & Ulven, S. (2011). Effect of marine n-3 fatty acids on circulating inflammatory markers in health subjects and subjects with cardiovascular risk factors. Inflammation Research: The European Histamine Research Society, 60(4), Willerson, J., & Ridker, P. (2004). Inflammation as a cardiovascular risk factor. Circulation, 109(21), Kromhout, D. (2010). N-3 fatty acids and cardiovascular events after myocardial infractions. The New England Journal of Medicine. 363:2015­26. Anderson E.J., & Tylor D.A. (2012). Omega-3: fishing for a mechanism. The Scientist. Retrieved from Mozaffarian, D., & Wu, J. (2011). Omega- 3 Fatty Acids and Cardiovascular Disease. American College of Cardiology.Vol 58. Doi.10.16