Comparison of Fish Oil Products For Pharmacists

The interest surrounding fish oil products has been around for decades, and we are still learning about many of their mechanisms and potential benefits. In the post below, we provide a comparison of fish oil products and break down the family of omega fatty acids.

Omega-3 fatty acids in particular have been researched with regards to cardiovascular disease, type 2 diabetes, depression, brain development, asthma, ADHD, and perhaps most recently, autoimmune disease. The VITAL trial’s ancillary study showed a trend of reduced incidence of autoimmune disease (i.e., rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis) over a 5 year period of supplementing with omega-3 fatty acids, however, the results were not statistically significant, similar to other trials to-date which has left much debate over omega-3 fatty acids. 

Omega-3 fatty acids are an essential amino acid, which means we have to obtain it from the diet. The 3 most abundant types are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA). ALA is a precursor to EPA/DHA, however, the body is inefficient at converting them. These are the fatty acids found in supplements and prescription products, most notably used for cardiovascular and brain health. Food sources that contain high amounts of omega-3 fatty acids include chia seeds (ALA), flax seeds (ALA), walnuts (ALA), and salmon (EPA/DHA).

Omega-6 fatty acids are also essential and need to be obtained from the diet. They are beneficial in providing energy, however are known to be pro-inflammatory at high amounts. There is some debate on what omega-6 to omega-3 ratio is most beneficial. Suggestions have been recommended to aim for somewhere between a 1:1 or 4:1 ratio. Those who follow the typical Western diet often have well over this (about 15:1). Food sources of omega-6 fatty acids include soy oil, corn oil, safflower oil, and avocado oil. 

Omega-9 fatty acids are non-essential and can be produced by the body. They have been shown to help with inflammation and insulin sensitivity when used in place of saturated fats. Some evidence even suggests a beneficial role in cardiovascular health. This is the primary component in olive oil. A few other food sources of omega-9 fatty acids include peanuts, almonds, and avocado. 

Supplements and prescription products consist of omega-3 fatty acids. Fish oil (EPA/DHA) and krill oil (EPA/DHA) are both available over-the-counter (OTC). Krill oil has been gaining popularity in recent years and differs from fish oil as it is derived from crustaceans rather than fatty fish such as tuna, herring, anchovies, or mackerel. This results in fatty acids presenting as triglycerides in fish oil products and as phospholipids in krill oil products. Some experts believe that fatty acids found as phospholipids are absorbed better, however, more research is needed to draw any conclusions on this topic. Additionally, krill oil contains astaxanthin, which is an antioxidant suspected to carry further health benefits and gives it a reddish color. 

  • Fish oil (EPA/DHA); fatty acids found as triglycerides, derived from fatty fish
  • Krill oil (EPA/DHA); fatty acids found as phospholipids, derived from crustaceans

Prescription products are also available and are currently only indicated to treat hyperlipidemia in adults with high triglycerides (≥ 500 mg/dL). These fish oil products are highly purified to remove isomers and heavy metals, which is not a requirement for OTC fish oil (look for 3rd party testing). Additionally, prescription products contain >90% omega-3 fatty acids vs. only 30-50% in OTC products. Fatty acid preparations are generally considered safe with only mild side effects such as fishy taste, burping, upset stomach, and arthralgias. Available FDA-approved omega-3 prescription products are summarized below. 

ProductCompositionIndicationsDoseClinical Notes
Lovaza & generics EPA/DHASevere hypertriglyceridemia (>500 mg/dL) adjunct to diet4 g PO once daily OR 2 g PO twice dailyDHA associated with increase in LDL, monitoring required
VascepaEPAPrimary ASCVD prophylaxis adjunct to maximally tolerated statin in patients with triglycerides >150 mg/dL AND
Severe hypertriglyceridemia (>500 mg/dL) adjunct to diet
2g PO twice dailyEvidence for heart attack/stroke prevention
Typically more expensive than Lovaza
Comparison of fish oil products (prescription)

As we are still learning the mechanisms behind omega-3 fatty acids, it is worth mentioning the results of the EVAPORATE trial, a novel study aiming to seek mechanistic data of omega-3 fatty acids. In ASCVD patients who took the prescription product Vascepa, containing icosapent ethyl (IPE; ether estyl of EPA), they found a reduced plaque burden in vessels when measured by CT scans. This is an interesting finding to pay attention to as it was previously thought before that vessel plaques were permanent.

Omega-3 fatty acids can be confusing as there are multiple types, formulations, and health claims. Hopefully this comparison of fish oil products helps provide a little clarity. Pharmacists should remain aware of the current literature behind omega-3 fatty acids and the differences between OTC and prescription products, especially as new indications may potentially be on the verge in upcoming years. 

Article written by; Hannah Wetter, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

References: 

Budoff, M., et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. European Heart Journal. Published 2020; 41: 3925-3932. 

Hahn, J., et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. Published 2022; 376.

Hilleman, D., et al. Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review. Advances In Therapy. Published 2020; 37(2): 656-670. 

Matos Medeiros-de-Moraes, I., et al. Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis. Oxidative Medicine and Cellular Longevity. Published 2018: 6053492. 

Novotny, K., et al. Omega-3 Fatty Acids. StatPearls [Internet]. Last updated January 26, 2022. Accessed via https://www.ncbi.nlm.nih.gov/books/NBK564314/

Ulven, S., and Holven, K. Comparison of bioavailability of krill oil versus fish oil and health benefit. Vascular Health and Risk Management. Published 2015; 11: 511-524. Schwalfenberg, G. Omega-3 fatty acids: Their beneficial role in cardiovascular health. Canadian Family Physician. Published June 2006; 52(6): 734-740.

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Written By Eric Christianson

February 16, 2022

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