Are Re-Esterified Omega-3 Products Better for Dry Eyes?

When Bo and I attended the CE Sarasota optometry conference last week, we got a lot of questions about a new dry eye study. This particular study, sponsored by PRN, concluded that consuming four PRN-brand softgels daily resulted in a significant improvement in dry eye signs and symptoms (1).

For those following the scientific literature on omega-3, this research is more good news. The study reconfirmed the importance of using omega-3 supplements as part of dry eye treatments. Of note, however, this study had used a concentrated and re-esterified triglyceride based fish oil to achieve its results.

What did we think of this re-esterified triglyceride form, the optometrists asked? And how did it compare to our Omega Cure® cod liver oil?

What Are Re-Esterified Fish Oils?

Before we can address what re-esterified triglyceride-based fish oils (rTGs) are, let’s go back and explain the reason for their origin.

A natural fish oil or cod liver oil contains a certain percentage of omega-3s, including the main EPA and DHA variety. The percentage of omega-3s can fluctuate, depending on the season, the type of fish harvested and if the fish oil has started to oxidize.

But on average, a natural fish oil will contain no more than 30% combined EPA/DHA (2). Since most regular fish oil capsules contain only 1000 mg of total oil per softgel, each capsule delivers at most 300 mg of EPA and DHA – a far cry from the dose featured in most studies showing positive results with omega-3 supplements.

The omega-3 concentrate market developed as an alternative for consumers frustrated with swallowing the approximate 10 capsules required to get an effective EPA/DHA dose. In creating concentrates, the manufacturers artificially pump up the concentration of EPA and DHA in an oil, altering the molecules into new chemical structures known as ethyl esters. Using this technique, the manufacturers can get between 50%-90% EPA and DHA in an oil (3, 4). For the consumer, this means swallowing only four capsules, instead of the handfuls described above.

These Concentrates Have Consequences Though

Studies have shown that ethyl ester oils are not as bioavailable as natural triglyceride-based fish oils (4, 5). Furthermore, scientists have questioned their safety, since ethyl esters are synthetic molecules, not found in nature. In fact, pregnant women and children are recommended against using ethyl ester products for safety concerns (6).

This negative response to ethyl esters has ushered in an interest in rTG fish oils. In making the rTG oils, the manufacturer still creates an ethyl ester omega-3 oil. But instead of stopping there, the manufacturer adds an extra step and removes the ethanol molecules from the oil, thus converting it to the re-esterified triglyceride form (6, 7). The point here is to achieve the same high EPA/DHA volume found in the ethyl ester products. But since it’s in a triglyceride form, it’s supposed to be more acceptable to the body.

spoon full of fish oil capsules
Re-esterified omega-3 products were created as an alternative to swallowing larger numbers of regular fish oil capsules. But their purpose and benefits are not apparent when compared to fresh and natural liquid fish oils.

Rancidity and Safety Questions

While rTG oils, like PRN’s products, address some of the ethyl ester bioavailability and safety concerns, they leave plenty of questions still on the table.

First and foremost, there’s the question of rancidity. Biochemists will tell you that the more you work and alter an oil, the more trans fats and rancidity-linked byproducts you risk creating. This is a concern for rTG oils, where the omega-3 molecules have not just been chemically manipulated to create the ethyl ester form, but also further processed.

In addition, rTG oils are most commonly sold in capsules. People have the misconception that putting fish oil into a capsule somehow protects the integrity of the oil. Nothing is further from the truth. During the encapsulation process, the oil is exposed to heat and oxygen, and within a month, the oxidation level of the oil can increase significantly (8). The concern is that long term consumption of rancid fish oils can be unsafe. Indeed, researchers speculate that oxidized oil may contain carcinogens and cause arteriosclerosis (8).

Why Are Omega-3 Concentrates Problematic

The manufacturers of concentrated omega-3 products may also be throwing out the baby with the bathwater, so to speak. The pumped up EPA and DHA levels replace the other omega-3 members and nutrients found in natural oils. So while fresh fish or cod liver oil contain dozens of different fatty acids and vitamins, as well as important nutrient co-factors, the concentrated fish oil leaves you with basically just two chemically-modified nutrients.

While it’s true the majority of omega-3 research has concentrated on EPA and DHA as the main workhorses of the omega-3 family, some of the latest brain research indicates it’s not just those two molecules at play. Other types of omega-3s, like DPA, and nutrient co-factors also seem to be important for brain health (9) and fighting cancer (10). We still have a lot to learn about how these molecules work in the body. But it may well be that these nutrient co-factors or the synergy of the fatty acids together can explain why studies suggest eating fish or natural fish oil provide greater benefits.

concentrated omega 3 products vitamins fish fruit vegetables
Concentrated omega-3 products are to fish as vitamins are to fruits and vegetables. They provide a particular nutrient, but they often miss the other important components that make fish (or fruits and vegetables) nutritious to eat.

Are Re-Esterified Omega-3 Products Worth It?

Given the concerns above, it merits asking if rTG omega-3 products are worth it. To answer that, it depends on what we are comparing them against. Compared to expensive dry eye treatments like Restasis, rTGs are certainly more cost effective. And looking at regular fish oil capsules, rTGs provide the advantage of delivering a higher EPA/DHA dose per serving.

But the very purpose of these concentrated products becomes obsolete if you compare them against a truly fresh omega-3 oil, like Omega Cure.

There is no reason to put fish oil in a softgel, other than to disguise a rancid, bad-tasting product. If you simply start with a fresh, high quality fish oil, there ought to be no fishy taste or smell.  In addition, one tablespoon of a fresh liquid cod liver oil delivers as much EPA and DHA as 10 regular fish oil capsules and five PRN softgels. In other words, truly fresh liquid cod liver oil solves the problems that started people chemically modifying their oils, while also avoiding the safety concerns voiced above.

Dry Eye Study Shows Promising Development

In the PRN dry eyes study, the researchers measured the omega-3 index score of its 105 participants. This was a welcome addition, since it allowed them to assess whether the patients were compliant with swallowing four capsules every day for 12 weeks. (As a side note, it is interesting that the omega-3 index they reported was significantly lower than what we’ve measured in people using one tablespoon of Omega Cure daily, but that’s a separate point!)

There were many positive aspects to the research. The study brought more attention to omega-3 supplements as a positive tool for helping people with dry eyes caused by meibomian gland dysfunction. The researchers also showed clear benefits in evaluating tear osmolarity and tear break-up time.

For all its positive findings, the study still leaves many unanswered questions about the long-term use of rTG oils for patients with dry eyes. We ask ourselves, why choose a chemically modified product when you can have a better omega-3 experience with our fresh and natural Omega Cure?

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1. Epitropoulos AT, Donnenfeld ED, Shah ZA et al. Effect of Oral Re-esterified Omega-3 Nutritional Supplementation on Dry Eyes. Cornea. 2016; 35 (9): 1185–1191. doi: 10.1097/ICO.0000000000000940.

2. Omega-3 Fatty Acid, Fish Oil, DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid).WorldHealth.Net. American Academy of Anti-Aging Medicine. December 30, 2005.

3. Alexander LJ. Is There a Difference Between Re-esterified Triglyceride and Ethyl Ester Fish Oil? Advanced Ocular Care. January/February 2011: 20 -21.

4. Dyerberg J, Madsen P, Moller JM, et al. Bioavailability of Marine N-3 Fatty Acid Formulations. Prostaglandins Leukot Essent Fatty Acids. 2010;83:137–141.

5. Fish Oils as Triglycerides vs. Ethyl Esters: Why This Matters. Ascenta Health.

6. Opperman M, Bennade S. Analysis of the Omega-3 Fatty Acid Content of South African Fish Oil Supplements: A Follow-Up Study. Cardiovascular Journal of Africa. 2013 Oct; 24(8): 297–302. Doi: 10.5830/CVJA-2013-074.

7. Why PRN? PRN Omega Health.

8. Albert BB, Cameron-Smith D, Hofman PL, Cutfield WS. Oxidation of Marine Omega-3 Supplements and Human Health. BioMed Research International, vol. 2013, Article ID 464921, 8 pages, 2013. doi:10.1155/2013/464921.

9. Dyall SC. Long-Chain Omega-3 Fatty Acids and the Brain: A Review of the Independent and Shared Effects of EPA, DPA and DHA. Frontiers in Aging Neuroscience. 2015; 7: 52. doi: 10.3389/fnagi.2015.00052. 

10. UC Davis Researchers: Key Discovery Involving Omega-3 Fatty Acids and Cancer. UC Davis Department of Entomology and Nematology. April 1, 2013

Anne-Marie Chalmers, MD

Anne-Marie Chalmers, MD

Born and raised in the United States, Dr. Chalmers graduated from Brown University and completed her medical training at the University of Oslo in Norway. Dr. Chalmers practiced medicine for many years, serving both at high-tech hospitals and as a community health worker in rural Norway. Together with Dr. Martinsen, she later co-founded Wellpride LLLP dba Omega3 Innovations and is the joint holder of several patents that facilitate the ingestion of multiple medication combinations. Today, she serves as the president of Omega3 Innovations.

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