Benefits
Absorption compared with ethyl ester fish oil
In a two-week comparison in 72 adults given about 3.3 grams of EPA plus DHA a day, the amount reaching blood fats was higher from re-esterified triglycerides than from ethyl esters, and similar to or higher than from natural fish oil. Short trials like this measure uptake into the blood, not a health outcome.
Omega-3 index rise over six months
In a six-month trial in 150 adults taking identical daily doses of EPA plus DHA, the omega-3 index, the share of these fats in red blood cell membranes, rose faster and higher with the re-esterified triglyceride form than with the ethyl ester form. The index is a status marker rather than a health outcome on its own.
Fasting triglyceride change in a six-month trial
In the same six-month trial, in statin-treated adults with abnormal blood fats, fasting serum triglycerides fell from the start with the re-esterified triglyceride form but not with the ethyl ester form, and only the re-esterified form was below placebo at six months. The gap between the two fish oil forms was not statistically significant.
Degree of re-esterification varies between products
Products labeled rTG differ in how completely they are re-esterified; some are only about half to two-thirds triglyceride. In a sixteen-week trial in 60 young adults, a product that was over 95% re-esterified raised EPA and DHA in red blood cells more than one that was under 70%. This trial was run by a fish oil maker.
Food narrows the absorption gap between forms
The uptake advantage of triglyceride forms over ethyl esters is largest when capsules are taken with little dietary fat. Human studies show ethyl ester absorption climbs sharply when the same dose is taken with a high-fat meal, which narrows the gap. Taking any fish oil with a meal that contains fat supports absorption.
Mechanism of action
What re-esterified triglycerides are
Concentrated fish oil usually starts as ethyl esters or free fatty acids, made by breaking natural fish triglycerides apart to raise the EPA and DHA content. In the re-esterified form these concentrated fatty acids are joined back onto a glycerol backbone, recreating a triglyceride that carries a higher dose of EPA and DHA than the original oil.
Why the chemical form affects uptake
Fat-digesting enzymes in the gut, mainly pancreatic lipase, cleave triglycerides readily. Ethyl esters are broken down more slowly and lean more heavily on bile and dietary fat to be absorbed. This is why triglyceride forms, natural or re-esterified, tend to deliver EPA and DHA into the blood more completely than ethyl esters in short studies.
Why short-term differences may shrink
Taking capsules with a fatty meal raises ethyl ester absorption toward that of triglyceride forms. Over weeks of daily use, the level of EPA and DHA in cell membranes is driven mostly by the total amount absorbed, so fast uptake measured after a single dose does not always translate into a lasting difference between forms.
Clinical trials
Double-blind comparison of ethyl ester, free fatty acid and re-esterified triglyceride concentrates against placebo oil, with single-blind fish body oil and cod liver oil arms, about 3.3 g EPA plus DHA a day for two weeks (Dyerberg et al. 2010, Prostaglandins Leukot Essent Fatty Acids)
72 volunteers.
Measured as the rise in EPA and DHA in fasting serum fractions, bioavailability from re-esterified triglycerides was about 124% of natural fish oil, while ethyl esters were about 73% and free fatty acids about 91%. The study measured uptake into the blood over two weeks, not a health outcome, and the stereochemistry of the fatty acids did not change the result.
Double-blind, placebo-controlled trial of fish oil as re-esterified triacylglycerides or as ethyl esters, both supplying 1.01 g EPA plus 0.67 g DHA a day, versus corn oil, for six months (Neubronner et al. 2011, Eur J Clin Nutr)
150 adults randomized across the three groups.
The omega-3 index rose in both fish oil groups. It increased more with the re-esterified triglyceride form than with the ethyl ester form at three months and again at six months. The omega-3 index is a marker of omega-3 status in red blood cells rather than a clinical outcome.
Double-blind, placebo-controlled trial of fish oil as re-esterified triacylglycerides or ethyl esters (1.01 g EPA plus 0.67 g DHA a day) versus corn oil in statin-treated adults with abnormal blood fats, for six months (Schuchardt et al. 2011, Prostaglandins Leukot Essent Fatty Acids)
150 statin-treated adults with dyslipidemia (the same cohort as the omega-3 index trial).
Total, HDL and LDL cholesterol did not change in any group. Fasting serum triglycerides fell from baseline with the re-esterified triglyceride form, but not with the ethyl ester form, after three and six months. Only the re-esterified form was significantly lower than placebo at six months, and the two fish oil forms did not differ significantly from each other.
Double-blind trial comparing two re-esterified triglyceride fish oils, one over 95% and one under 70% re-esterified, over sixteen weeks; run by a fish oil manufacturer (Minton et al. 2023, PLoS One)
60 young, healthy adults taking about 2.5 to 2.75 g EPA plus DHA a day.
EPA, DPA and DHA as a share of red blood cell phospholipids were higher at week 16 with the product that was over 95% re-esterified than with the one under 70%. The authors suggest the percentage of true re-esterified triglyceride could serve as a quality marker, since products labeled rTG vary.
Randomized, open-label, single-dose crossover comparing a free fatty acid omega-3 formulation with a prescription ethyl ester formulation during low-fat and high-fat meals, 4 g doses (Davidson et al. 2012, J Clin Lipidol)
54 overweight adults.
With a low-fat meal, EPA plus DHA in the blood was about four times higher from the free fatty acid form than from the ethyl ester form. With a high-fat meal the difference shrank to about 1.3 times. This shows ethyl ester absorption depends heavily on how much fat is eaten with the dose.