Everyone seems to know about omega-3 nutritional supplements—those over-the-counter capsules, soft gels, powders or liquids that you can easily purchase in your brick-and-mortar pharmacy, supermarket, big box store (e.g., Walmart, Target, etc.) or online, in the same kinds of places. In some cases, you can also purchase directly from a manufacturer, a catalogue or other retailer.
Because they are nutritional (also referred to as “dietary”) supplements, you don’t need a prescription from a healthcare practitioner, although it’s always wise to share with your doctors and others who are guiding your healthcare choices as to what vitamins and other supplements you’re consuming.
Omega-3s are polyunsaturated fatty acids. There are three main omega-3 fatty acids: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA). The most desirable of these fatty acids are usually considered to be EPA and DHA. Your body can convert ALA into EPA and DHA, but not efficiently and only in small amounts.
Omega-3 supplements are popular and are taken by 16% of American adults, according to the 2021 CRN Consumer Survey on Dietary Supplements. You’ve also likely heard omega-3 supplements being called fish oil supplements and that’s because the richest source of EPA and DHA are found in fatty (or oily) fish. Algae (or algal oil) also contain EPA and DHA, but from plant sources.
Here’s something about omega-3 fish oil supplements that you may not be familiar with: they come in at least two molecular or chemical forms, either triglycerides or ethyl esters.
Ethyl Esters Omega-3 Are Found in Different Forms
To start, here is one difference between the two forms: the omega-3 fatty acids EPA and DHA occur naturally in fish in the triglyceride form, while those in the ethyl ester form are synthesized from the triglyceride form.
This article, published in 2008, goes into more detail as to how the different forms come about. In short (so we’re skipping a few steps), when producing a fish oil concentrate for supplements, manufacturers can either use a process called “re-esterification” which involves the use of enzymes to reattach fatty acids to the glycerol backbone—the glycerol having been removed as the first step during the process of making a fish oil concentrate. Then, the fatty acids are reassembled into the natural triglyceride structure. The second option, as the article explains, is to react the fatty acids released from the glycerol backbone with ethanol, resulting in a fatty acid “ethyl-ester,” a form which does not naturally occur in the human diet.
While the majority of omega-3 fatty acids consumed in the human diet are found in the natural triglyceride or phospholipid form (from salmon, sardines, anchovies and more), it’s the opposite when it comes to nutritional supplements where the ethyl-ester form is more prevalent, likely because this form of manufacturing a fish oil concentrate is less expensive to produce than the re-esterified triglyceride forms. The cheapest omega-3 forms are in natural triglycerides isolated directly from fish oils, but they are less concentrated than either the ethyl ester or re-esterified triglyceride forms.
A third form of omega-3 fatty acids is found in krill oil, considered to be an alternative to fish oil supplements. Krill oil comes from Antarctic krill, tiny crustaceans that look similar to shrimp and are regularly feasted upon by seals, whales, penguins and other birds for whom Antarctic krill is a core component of their diets. In the case of krill oil, the EPA and DHA are found in phospholipid form, which some say may have higher bioavailability than the triglyceride or ethyl ester forms. But the science in this area is still evolving.
In a 2019 article on the topic, Dr. Bill Harris, founder and President of the Fatty Acid Research Institute and founder and former President of OmegaQuant, explained that the omega-3 fatty acids in krill oil were “very well absorbed” but that may be due to the free fatty acids in some krill oil preparations, rather than from the phospholipids.
Ethyl ester forms typically have the lowest absorption, while phospholipid and triglyceride forms are better absorbed. However, taking any supplement with a food that contains fat is your best bet for getting the best absorption from your supplement as possible.
Ethyl Esters Vs. Triglycerides? It May Not Really Matter
When it comes to determining whether the triglyceride form of omega-3 is somehow better or safer than the ethyl ester form, this post provides some food for thought, but at the end of the day it does not take sides. The post suggests that after reviewing the scientific literature in terms of bioavailability, safety or efficacy, that the differences are minor and cannot be considered to be significantly different. It should be noted that Scientific Based Health, where the post appears, sells dietary supplements containing omega-3 fatty acids from both forms.
But back to ethyl ester. There is a third way—in addition to conventional diet and nutritional supplements—to access the benefits of omega-3 fatty acids. And that option is prescription drugs.
There are currently two FDA-approved prescription fish oil medications available, both using ethyl esters. Lovaza (and its generic) combines EPA and DHA (a 1-g capsule contains approximately 465 mg EPA and 375 mg DHA), while Vascepa (icosapent ethyl) includes EPA only (a 1-g capsule contains at least 96% EPA). (Epanova and Omtryg, two other prescription brands, have been discontinued in the U.S.)
This article mentions that a medical food derived from fish oil, Vascazen, is also available. Each 1-g Vascazen capsule contains at least 900 mg of ethyl esters of omega-3 fatty acids sourced from fish oils and includes approximately 680 mg of EPA and approximately 110 mg of DHA. (We won’t be addressing medical foods in today’s blog.)
The Goal is Getting the Right Dose
When it comes to ethyl esters, which fish oil should you take, supplements or prescription drugs? That’s an individual decision, and one best considered with your healthcare practitioner, depending on your personal health situation. Side note: you can’t just “get” a prescription— you have to meet certain criteria in order to be eligible for an omega-3 drug like Vascepa.
There are some basic differences between the two options, including:
- Prescription drugs and supplements are regulated differently. Although both are regulated in the U.S. by the FDA, prescription drugs go through a pre-market approval process before they are brought to market. Dietary supplements, on the other hand, are regulated as a category of food and FDA does not approve their entry to market in the same way as it does for drugs. However, dietary supplement manufacturers, under the law, follow regulations that include manufacturing, labeling, quality control and post-market surveillance.
- Prescription drugs are used to treat diseases. In the case of omega-3s, Lovaza and Vascepa (additionally indicated for those at high risk for CVD and on statins) are used to lower very or severely high serum triglyceride levels, usually exceeding 500 mg/dL. As part of the FDA approval process, prescription drugs go through clinical trials to test for efficacy and safety. In general, the recommended doses of omega-3 ethyl esters are higher with prescription drugs than what you would normally expect for typical omega-3 servings of EPA and DHA; however, some doctors may recommend a high-dose supplement. Dietary supplements, including omega-3 supplements, are legally not permitted to be marketed as a treatment, cure or prevention for any disease. Rather, supplements are meant to fill nutrient shortfalls, support body structure or function (e.g., “support heart health” is something you would likely see on an omega-3 supplement bottle) or for general good health. When it comes to supplements and heart health research, some findings include that omega-3 fatty acids EPA and DHA may lower blood pressure, reduce triglycerides, slow development of plaque in the arteries, and more. But not all the research is conclusive in those areas.
- Both prescription fish oil medications and dietary supplements can be used alongside some other cardiovascular therapies, but in consultation with your doctor. Some research has suggested that combining statins with DHA (or DHA alone) may increase LDL, which although it might seem counterproductive, there is no evidence that the small LDL increase has any adverse effects.
- Both prescription fish oils and fish oil supplements may come with some common side effects. According to this article, some of those drug side effects include: joint pain (Vascepa) and burping, unpleasant taste in your mouth, or upset stomach (Lovaza). Common side effects for omega-3 supplements include those listed for Lovaza and may also include loose stools and heartburn. More serious side effects for Lovaza are discussed here and here for Vascepa. Fish oil supplements are generally considered safe.
- Be sure to ask your doctor about potential interactions with other medications, supplement, or foods and find out if there are warnings for certain people who should not be taking omega-3 prescriptions or supplements.
What’s the Bottom Line on Ethyl Esters Fish Oil?
At the end of the day, if health outcomes are your goal, where you choose to get your omega-3 ethyl esters should go hand in hand with making sure you are getting the right dose to meet your particular health goals. For healthy people who likely will not need prescription strength omega-3 fatty acids, the first step is to start by calculating how much omega-3 you actually need. And for those with very high triglyceride levels, it’s also a good idea to know your existing blood levels of omega-3s. Learn more about the Omega-3 Index and how you can manage your Omega-3 goals.