Risks associated with omega-3 supplementation

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During my preoperative visit, my surgeon handed me a list of no less then 165 medications and supplements that I should stop taking 14 days prior to my surgery. Fish and krill oil were on the list, as were aspirin and nonsteroidal anti-inflammatory drugs

(NSAIDs)-as expected.

Being the over-achiever that I am, I ceased taking my krill oil and NSAIDs 18 days prior to surgery and proceeded to complain about my aches and pains until those aches and pains were replaced by postoperative pain.

At my follow-up visit on Day 18, I inquired when I could resume my daily intake of supplements and NSAIDs. The surgeon’s response surprised me. I could take my NSAIDs as needed for pain but should refrain for an extended period of time from omega-3 supplementation due to its blood-thinning properties.

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I was surprised when my surgeon said he equated omega-3s to Plavix (clopidogrel, Bristol-Myers Squibb), a medication used to prevent platelets from clotting in patients with a history of heart attack or stroke. My surgeon reported patients losing skin grafts and suffering excessive bruising due to fish oil supplementation-most often when patients did not report taking it preoperatively.

He asked if I supported taking supplements, particularly fish oil, in my patients, and I said that I did. He said he was unconvinced about the positive cardiac effects of fish oil and did not think that the risk was warranted. My recommendation of fish oil for my dry eye patients, and those with arthritis and elevated cholesterol, was also discussed.

Upon clearing my head from my postoperative pain medication regime, I looked into the side effects and contraindications for omega-3 fatty acids.

Omega-3 fatty acid benefits

As you probably know, omega-3 fatty acids are found in the form of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-lipoic acid (ALA). Depending on how much Lifetime television you watch, you will be familiar with these acronyms.

EPA and DHA are the most beneficial, and they are available from marine animal sources. ALA is converted to EPA and DHA, and is found in plant-based sources such as flax seeds, walnuts, chia, and hemp. (I am not sure about you but I am not a fan of eating chia or hemp.)

Advantages to supplementation as reported by the national Center for Complementary and Integrative Health include benefits to infant brain development, ocular inflammation, and rheumatoid arthritis.

Improved cardiac health appears to be less supported by literature reports. Recent reports of the benefits for cognitive impairment,¹ concussion, and traumatic brain injury² are intriguing to those with a family history of dementia-and parents of football players.

The U.S. Food and Drug Administration (FDA) suggests taking dietary supplements containing omega-3 fatty acids provided they do not consume more than 3 grams per day.³

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Side effects of omega-3 fatty acids

I looked into the side effects. The FDA has listed increased bleeding time and increases in the frequency of atrial fibrillation or flutter in the first few months of taking Lovanza (omega-3-acid ethyl esters, GlaxoSmithKline), a 4-gm dose prescription fish oil preparation. Increased bleeding time can be a concern even in healthy patients not taking blood thinners prior to surgery or invasive procedures.⁴

I had a discussion about this with my own primary care physician (PCP), who voiced concern over taking baby aspirin relative to blood thinning. She said increased bleeding can be a problem in healthy adults who suffer from trauma in accidents and require emergency surgery. If baby aspirin usage is unreported to their medical provider, there may be complications.

Literature reports regarding complications related to intake of omega-3 supplements are few. One report describing a subdural hematoma after a fall in an elderly woman taking warfarin and omega-3s⁵ substantiates my PCP’s concern with accidents and blood-thinners.

One case describes a sudden spike in international normalized ratio (INR, also called standardized prothrombin time) in a patient taking warfarin (Coumadin, Bristol-Myers Squibb), omega-3s, and trazadone (Oleptro, Labopharm).⁶ Another reports an increase in INR in a patient taking 1.5 mg daily of warfarin after doubling her fish oil dose from 1000 to 2000 mg daily.

A study describes development of a duodenal ulcer in a 60-year-old athlete who consumed 20 g of omega-3s daily for a year to increase athletic performance.⁷ The diagnosis occurred after he took cortisone and antibiotics, although he had no previous history of gastrointestinal problems.

The study authors suspected the bleeding ulcer resulted from the high dose of omega-3 fatty acids and its effect on bleeding-compounded by the fact that cortisone increases the fatty acids oxidation and may render it pro-inflammatory. Other antithrombotic microconstituents included in the supplements and diet may also have been related.

Another study compared bleeding risk in patients taking aspirin and clopidogrel (Plavix, Bristol-Myers Squibb) when fish oil was added. This retrospective review compared 182 medical records of primarily coronary artery disease patients being treated with high-dose fish oil (mean dose 3 +/- 1.25 g), aspirin (mean dose 161 +/- 115 mg), and clopidogrel (mean dose 75 mg), to 182 controls treated with aspirin and clopidogrel alone.

During a mean follow-up period of 33 months, one major bleeding episode occurred in the group taking fish oil and another medication, while no major bleeding episodes occurred in the non-fish oil group (P =1.0). During follow-up, four minor bleeding episodes (2.2 percent) occurred in the fish oil group, and seven (3.9 percent) in the non-fish oil group. Authors concluded the high-dose fish oil was safe in combination with aspirin and clopidogrel and does not increase the risk of bleeding compared with that seen with aspirin and clopidogrel alone.⁸

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My research confirms

Based on my research, my opinion is that you could run into problems with omega-3 supplements, but you may be safe at my preferred therapeutic dosage. I continue to recommend 2000mg of fish oil, or two capsules of krill oil, for dry eye. I also continue to suggest it to those with autoimmune conditions, arthritis, and ocular inflammation.

Though I continue to recommend omega-3s, I have added a disclaimer, “These supplements are powerful, and I need you to inform your doctors that you are taking them. If you have surgery, taking these may affect your surgical outcome.”

For my patients who are currently under the care of a cardiologist or with a bleeding disorder, I discuss taking these supplements with their doctors prior to making the recommendation.

References

1. Cederholm T. Fish consumption and omega-3 fatty acid supplementation for prevention or treatment of cognitive decline, dementia or Alzheimer's disease in older adults-any news? Curr Opin Clin Nutr Metab Care. 2017 Mar;20(2):104-109.

2. Lewis MD. Concussions, Traumatic Brain Injury, and the Innovative Use of Omega-3s. J Am Coll Nutr. 2016 Jul;35(5):469-75.

3. U.S. Food & Drug Administration (FDA). Guidance for Industry: A Food Labeling Guide (12. Appendix D: Qualified Health Claims). http://www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/labelingnutrition/ucm064923.htm. Accessed February 10, 2017.

4. Y. L. Chee,  J. C. Crawford,  H. G. Watson and M. Greaves.   Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures.  British Committee for Standards in Haematology, British Journal of Haematology, 2008, 140, 496–504)

5. McClaskey EM, Michalets EL. Subdural hematoma after a fall in an elderly patient taking high-dose omega-3 fatty acids with warfarin and aspirin: case report and review of the literature. Pharmacotherapy. 2007 Jan;27(1):152-60.

6. Jalili M, Dehpour AR. Extremely prolonged INR associated with warfarin in combination with both trazodone and omega-3 fatty acids.  Arch Med Res. 2007 Nov;38(8):901-4.

7. Detopoulou P, Papamikos V. Gastrointestinal bleeding after high intake of omega-3 fatty acids, cortisone and antibiotic therapy: a case study. Int J Sport Nutr Exerc Metab. 2014 Jun;24(3):253-7.

8. Watson PD1, Joy PS, Nkonde C, Hessen SE, Karalis DG.  Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel--versus--aspirin + clopidogrel in patients with cardiovascular disease.  Am J Cardiol. 2009 Oct 15;104(8):1052-4. 

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