As health practitioners, the decisions we make need to be based on the best available evidence. This process involves doing research, reading the pertinent studies, and critically analysing them. Only then, we can make an educated and informed decision.
But often, that process takes a very long time. And as a busy practitioner, time is limited. So we take shortcuts. We listen to colleagues. We listen to company reps. We quickly read the news headlines and move on. All of these cognitive shortcuts are to the detriment of our patients.
One common myth is that the mystical triglyceride form of fish oil is better as compared to the ethyl ester form. I’ve already encouraged you not to take my word for it and to do your own research, but I’ll attempt to guide you through a few questions you should be asking and to summarize some of the evidence.
What exactly does it mean to have omega-3 fish oil in the triglyceride form?
The triglyceride form of omega-3 fish oil is, chemically and structurally, an ester form. Hold the phone. Here’s the difference. In the triglyceride form, the omega-3s are esterified to glycerol, while in the ethyl ester form, the omega-3s are esterified to an ethyl group. Both forms are classified as esters.
What important differences could arise from different forms of fish oil?
In short, what actually matters? What would make you use one form over another? Based on good evidence, one form would have to be superior from another in the realms of manufacturing, bioavailability, safety, or efficacy. If you have improvements in one or more of those domains, it’s highly worth considering because it indicates a meaningful difference.
Are there important differences in manufacturing different forms?
No. The manufacturing process can vary, but there are more important elements to consider in the identification of quality. A high quality manufacturing process involves using a high-quality source of fish (such as small wild fish) and processing them in a GMP facility. Some manufacturing processes are better than others. But the form of fish oil has a very small role to play in this domain.
What about differences in bioavailability?
A few studies have been conducted which compared absorption, metabolism, and overall bioavailability. The results of these studies show that the differences are minor, inconsequential, and cannot be judged to be physiologically or clinically significant. Both forms are well-absorbed and metabolized and are bioavailable.
What about differences in safety?
The long term safety of the ethyl ester form of omega-3 fish oils has been established in the medical literature. The most common adverse events are mild gastrointestinal concerns, but there are no major safety issues. The long term safety of the triglyceride form has not been established, but the short term safety is demonstrably good, and it is highly probable that the long term safety will follow. So it is likely that both forms are very safe.
What about differences in efficacy?
According to the body of evidence, the answer is a resounding yes. Clinical trials have virtually all been done using the ethyl ester form of EPA and DHA, the most prominent key ingredients in fish oil. All the biggest trials have been conducted using the ethyl ester form. This means that efficacy can be confirmed with the ethyl ester form, but the same cannot be said of the triglyceride form. That would just be bad science.
To illustrate this point, if a well-conducted study showed that olive oil was effective for improving mood, you cannot conclude that a different form of oil, like peanut oil, would be equally effective, even though they both may contain omega-9 fatty acids. We have evidence of efficacy for the ethyl ester form. We do not have anywhere near the same amount of evidence for the triglyceride form. That’s not to say it doesn’t work, but only that the evidence does not justify superiority.
If you look at pharmaceutical companies who have large R & D budgets, the omega-3 products they offer are in the ethyl ester form. These companies are not stupid. They have teams of researchers and deep pockets. They have very high incentives to develop the absolute best products and they’ve opted for the ethyl ester form. That’s certainly not scientific proof by any stretch, but it is a strong vote of confidence.
So what’s the bottom line?
The triglyceride myth has gone on long enough. It’s important that health practitioners perform their due diligence, examine the body of evidence, and use critical thinking. Both forms are esters. Both forms are manufactured similarly. Both forms are bioavailable. Both forms are safe. But only ethyl ester has a large time-tested body of evidence supporting its efficacy. At the end of the day, we are likely to find that this discussion isn’t really clinically meaningful and that you simply shouldn't worry about what form your fish oil is. There are many more significant factors to review instead.
Jump DB. The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem. 2002;277:8755-8758.
Hu FB, et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. J Am Med Assoc. 2002;287:1815-1821.
Burr ML, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989;2:757-761.
Harris WS, et al. Safety and efficacy of Omacor in sever hypertriglyceridemia. J Cardiovasc Risk. 1997;4;385-391.
Bays HE, et al. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther. 2008;6:391-409.
Bays, H. Rationale for prescription omega-3-acid ethyl ester therapy for hypertryglyceridemia: a primer for physicians. Drugs Today (Barc). 2008;44:205-246.
Sadovsky R, et al. Prescription omega-3-acid ethyl esters for the treatment of very high triglycerides. Postgrad Med. 2009;121:145-153.
Nordoy A, et al. Absorption of the n-3 eicosapentaenoic acid and docosahexaenoic acids as ethyl esters and triglycerides by humans. Am J Clin Nutr. 1991;53:1185-1190.