By Wendy Brody, Pharm. D.

Many people take fish oil supplements for cardiovascular health benefits. Fish oil, refers to the two marine omega-3 fatty acids (FAs) EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Recent studies suggest fish oil may not have the cardiovascular benefits we once thought in certain populations. This article will briefly discuss the latest research findings and recommend those who would benefit from the supplements.

There is evidence that fish oil might lower heart rate, inhibit atherosclerosis, reduce clot formation and inflammation1. In addition, some research evidence suggests that fish oil might reduce stroke risk1. A commonly cited description of how omega-3 FAs work to benefit heart health is an antiarrhythmic effect that prevents sudden death (unexpected death that occurs within minutes)1,3. Some research suggests marine omega-3 FAs might lower risk of a fast heart rhythm problem called atrial fibrillation after a heart attack and heart bypass surgery1. The latest research suggest that consuming fish oil by eating fish versus taking supplements can be effective for keeping people with healthy hearts free of heart disease. In people who already have heart disease, it might also be able to lower their risk of dying from heart disease by eating fish or taking a supplement. However, for people who already take heart medications such as “statin, antiplatelet and high blood pressure medications”, adding fish oil might not offer any additional benefit1,2.

Effectiveness of fish oil for other conditions

Information on herbal remedies, dietary supplements, vitamins, minerals and other natural supplements can be found on The Natural Medicines Database (NMCD) and “MedlinePlus Supplements”. The link to the consumer version of NMCD:

http://naturaldatabaseconsumer.therapeuticresearch.com/home.aspx?cs=&s=NDC .

To MedlinePlus:

http://www.nlm.nih.gov/medlineplus/druginfo/natural/993.html#Effectiveness

The databases rate effectiveness of natural substances based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, and Insufficient Evidence to rate. Fish Oil is rated as Effective for reducing triglyceride levels. The effects of fish oil appear to be the greatest in people who have very high triglyceride levels. The usual dose is 2 to 4 grams daily.

Fish oil is listed possibly effective in MedlinePlus for treatment of at least 30 conditions including preventing age related macular degeneration and benefiting rheumatoid arthritis1,4,7.

Should children take fish oil supplements?

Omega-3 FAs are important for neurodevelopment and are added to many prenatal vitamins, infant formulas and foods. Fish oil supplements are often promoted in kids as improving eyesight, brain function or intelligence. There is no proof that supplements will make kids “smarter” or have any cognitive benefit in most kids. They may be worth a try for kids who don’t get enough omega-3 FAs from their diet. There are chewable or liquid supplements for children who cannot swallow. ®In children with behavioral or psychiatric disorders there is evidence that suggest fish oil might benefit kids with Attention Deficit Hyperactivity Disorder (ADHD) symptoms, autism, depression or those at risk of psychosis1. For most children, however, in place of supplements kids should eat about 4 ounces/week of fatty fish, such as canned light tuna, salmon burgers, etc.

Safety

Fish oil is likely safe for most people including pregnant and breastfeeding women when taken in low doses (< 3 grams daily). High doses might keep blood from clotting, thus increasing the chance of bleeding, and could reduce the immune systems activity, thus reducing the body’s ability to fight infection4. This is of concern in people taking medications to reduce the immune system’s activity (organ transplant patients for example) and the elderly. Medical supervision is recommended for those people taking more than 3 grams daily.

Commonly reported side effects are a fishy aftertaste (fishy burp), nausea, loose stools, rash and nosebleeds4. Fish oil with both EPA and DHA has also been found to increase the LDL-C component of cholesterol1,2. An exception is Vascepa® which contains EPA alone2. Surprisingly there is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil; however, until more is known advise patients allergic to seafood to avoid or use fish oil supplements cautiously1.

Consuming fish oil from amounts of some dietary sources may be unsafe. Some fish (especially shark, king mackerel and farm raised salmon) can be contaminated by mercury5. Furthermore, fish in general can also be contaminated with polychlorinated biphenyls (PCBs)5. In 2004 the FDA and US Environmental Protection Agency issued a joint advisory recommending that women who might become pregnant, might be pregnant or nursing, and young children should eat not more than 12 ounces per week (2 meals) of fish such as canned tuna and salmon6. This recommendation falls within the American Heart Association recommended dietary guidelines for prevention of cardiovascular disease. The European Food Safety Authority also stated in 2005 that the risk of exposure to PCBs and related compounds from eating fish is no different than that for other meats and dairy products5. Based on these findings, the benefits of consuming 2 weekly servings of fish outweigh the potential risk. It is also recommended to eat different varieties of fish to reduce risk of toxin exposure1. Furthermore the method of fish preparation makes a difference in how beneficial it is. Broiled or baked fish appears to reduce heart disease risk, but fried fish or fish sandwiches appear to cancel out or increase risk5.

On the other hand, fish oil supplements meeting USP (United States Pharmacopeia) standards do not have these contaminants or at least have acceptable levels of them. The manufacturing process used to deodorize fish oil supplements seems to reduce levels of PCBs and other contaminants1. FDA-approved fish oil supplements Lovaza®, Epanova® and Vascepa® are recommended for patients with high triglycerides. Although they are more expensive than over the counter supplements, they would alleviate the fear of ingesting toxins and insurance may cover part of the cost.

Interactions of fish oil with medications

There is not much literature in regard to interactions of fish oil with medications. However, this is very important to know and consider before you take fish oil while on any medication, as fish oil affects triglyceride levels in blood. So, fish oil will affect the medications affecting blood thinners like Warfarin10. There is no reported literature on interactions of fish oil with medications, but theoretically, fish oil could interact with following medications:

• NSAIDs (Non Steroidal Anti Inflammatory drugs) e.g. ibuprofen, aspirin
• Blood Pressure Medications: Taking both fish oil and blood pressure medications could cause the blood pressure to drop too low
• Beta Blockers e.g. propranolol, sotalol, atenolol
• Anti platelet medications
• Medications for diabetes
• Diuretics (to get rid of excess water from the body)
• Birth control pills, hormone replacements or anything providing estrogen supplementation

In summary, it is very important to consider the medications you are taking before starting fish oil supplements. Thinking that these are ‘all natural’ products or just supplements, and cannot do any harm is a misconception.

Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions. Pharmacists can play a crucial role in identifying possible drug interactions by asking patients taking warfarin about herbal and other alternative medicine product use.

Choosing a supplement

Unfortunately, over-the-counter supplements, vitamins, minerals and herbal remedies in general are not quality controlled through the FDA as are prescription medications. An independent analysis of 24 dietary fish oil supplements showed that the actual omega-3 FA content ranged from <20% to >80% more than the concentrations stated on the label. There were also quality issues such as spoilage at the time of purchase and premature release of oil from soft gel capsules2. Products with a strong fishy or rancid smell or taste should be thrown away as this could be an indication of spoilage or poor product quality1.

It is important to choose a supplement that is USP verified. The USP letters should appear on the product label if it is. One can check the NMCD to help identify USP products, however, there is a required fee to have access to this database. This is one way to assure the purchase of a quality product unless you go with one of the three FDA approved supplements mentioned below.

There are three prescription fish oil products: Lovaza®, Epanova® and Vascepa®. They are FDA approved for treatment of high triglyceride levels. Lovaza® and Epanova® contain a combination of EPA and DHA, whereas Vascepa® contains only EPA. Look for the amount of EPA and DHA, not the total amount of fish oil. There are also supplements derived from krill oil (a small shrimp like crustacean). They may not provide enough EPA and DHA. In addition, DHA that is derived from algae is available, but DHA alone has not been studied for prevention of cardiovascular disease.

In Conclusion

For most healthy people, consuming fish is a better choice than fish oil supplements. The American Heart Association recommends one-gram daily of DHA plus EPA from fatty fish (preferred), or supplements with medical supervision. There is not enough evidence to recommend fish oil supplements for people without heart disease in order to prevent it. They are a good choice for patients who already have cardiovascular disease for secondary prevention or for high triglycerides. They possibly could be used as an alternative option for some cholesterol drugs (fibrates, niacin, cholesterol absorption inhibitors, bile acid sequestrants) when combined drug therapy (a statin + fibrate, niacin, cholesterol absorption inhibitors) is needed to lower cholesterol and a patient cannot tolerate the side effects2. The results of an ongoing study; Reduction in Cardiovascular Events with EPA-intervention Trial (REDUCE-IT) is scheduled to conclude in 2016. This study is assessing cardiovascular benefits of Vascepa® (EPA) in high-risk patients with high triglyceride levels in addition to a “statin”. The results of this study will hopefully shed more light on the role of marine omega-3 FAs in the treatment of heart disease.`

References

1. PL Detail-Document, Omega-3 Fatty Acids. Pharmacists Letter/Prescriber’s Letter, August 2012.

2. Weintraub, Howard. “Update on Marine Omega-3 Fatty Acids: Management of Dyslipidemia and Current Omega-3 Treatment Options.” Atherosclerosis 230 (2013): 381-89.

3. Daan Kromhout, Satoshi Yasda, Johanna M. Geleijnse, and Hiroaki Shimokawa. “Fish Oil and omega-3 fatty acids in cardiovascular disease: do they really work?” European Heart Journal 33 (2012): 436-43. Print.
4. Villani, Anthony M., Maria Crotty, Leslie G. Cleland, Michael J. James, Robert J. Frasier, Lynne Cobiac, and Michelle D. Miller. “Fish Oil Administration in Older Adults: Is There Potential for Adverse Events? A Systematic Review of the Literature.” BMC Geriatrics 13.41 (2013): BMC Geriatrics. BioMed Central. Web. 02 Apr. 2015. <http://www.biomedcentral.com/1471-2318/13/41>.
5. “Omega-3 Fatty Acids, Fish Oil, Alpha-linolenic Acid: MedlinePlus Supplements.” National Library of Medicine – National Institutes of Health. Web. 2 Apr. 2015. http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-fishoil.html
6. Raatz, Susan, Jeffrey Silverstein, Lisa Jahns, and Matthew Picklo. “Issues of Fish Consumption for Cardiovascular Disease Risk Reduction.” Nutrients 5.4 (2013): 1081-097. Web.
7. What You Need to Know about Mercury in Fish and Shellfish: EPA and FDA Advice for Women Who Might Become Pregnant, Women Who Are Pregnant, Nursing Mothers. Available online: http://www.fda.gov/food/foodsafety/product-specificinformation/seafood/foodbornepathogenscontaminants/methylmercury/ucm115662.htm (accessed on 3 April 2015).
8. Miles EA Calder PC. Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr 2012:107(Suppl 2):S171-84.
9. Fish oil and omega-3 fatty acid supplements (EPA and DHA from fish, algae and krill) ConsumerLab; Available from https://www.consumerlab.com/reviews/fish_oil_supplements_review/omega3. [accessed 03.31.15]

10. Buckley, MS, Goff, AD and Knapp WE (2004). Fish oil interaction with warfarin. Ann. Pharmacother. 38 (1): 50-52.