The Big Debate: EE or TG?
By Annalouise O’Connor, PhD, RD
What’s the controversy?
Ethyl ester (EE) or triglyceride (TG)? Is there a difference in absorption and bioavailability? This is a frequently debated, often polarizing question when it comes to fish oil supplementation and one that has continued to receive research focus over the past 30 years.
What’s the difference?
Fatty acids in an EE form are attached to an ethanol backbone. Fatty acids in a TG form are attached to a glycerol backbone. In food, the majority of fatty acids are in the TG form.
EE forms became popular because higher daily intakes of EPA and DHA, the predominant fatty acids of interest in fish oil supplements, are often desired. As natural nonconcentrated fish oil is typically 20-30%1 EPA and DHA, it can become impractical to obtain sufficiently high EPA and DHA intakes through these lower concentrated oils. To avoid pill burden and increase compliance, methods to concentrate EPA and DHA within marine oils have been developed. As part of this concentration process, natural TG molecules are broken apart and the glycerol backbone removed and replaced with an ethanol backbone to form a fatty acid EE (a process known as transesterification). EE-rich oil can be consumed as is, or further work can be done to re-esterify these back to a TG molecule. For this to happen, EE molecules are broken down, and the released EPA and DHA free fatty acids can be then re-esterified back to a TG (re-esterified TG [rTG] form), allowing for concentrated TG oils.
What’s the evidence for absorption?
Acute intake studies: Much of the evidence driving the debate around EE vs. TG absorption and bioavailability comes from acute intake studies, where researchers looked at appearance of EPA and DHA in plasma after a one-time intake. Studies have demonstrated that the appearance of EPA and DHA is greater following TG compared with EE in these studies;2,3 however, not all show differences.4,5 Differences in study design and study subjects may explain some of these differences, but the fat content of the accompanying meal may also explain some of the discrepancy between results, as coconsumption of dietary fat with EPA and DHA in EE form has been shown to increase plasma levels.6,7
Longer-term intake studies: Acute intake studies provide insight into acute absorption but don’t indicate how any postprandial variation in EPA and DHA bioavailability impacts longer-term status. Several long-term intake studies have been conducted to try to shed light on this issue. In an early study in healthy men and women, circulating EPA and DHA was seen to be higher after two weeks’ supplementation of a matched intake of EPA+DHA in TG form compared with EE.8 In a six-month study of daily intake of EPA (1.01g) and DHA (0.67g) in a rTG or EE form in men and women, omega-3 index (representing EPA and DHA status) was seen to increase in both groups, but the rTG group continued to have a light advantage at six months (change from 7.0 to 13.25 in the rTG group vs. 7.42 to 12.42 in the EE group).9 In a later study over three months comparing unmodified TG, EE, free fatty acid, or rTG in healthy men and women, the results identified that lipid structure did not have a notable and consistent impact on EPA and DHA status.4
- Clearly after 30 years of debate and research, there is still more to understand. What is understood now is that both EE and TG forms are safe and are present in high-quality formulas. Both have been shown to improve EPA and DHA status.
- EPA and DHA, whatever the form, may be needed to fill a nutrient gap for many. On average, the daily intake of EPA and DHA, plus estimated EPA equivalents (endogenous biosynthesis from other fatty acids) from food and supplements, among American adults is 170 mg per day.11 Ninety percent of people consumed less than the minimally recommended 500 mg per day,12 and reported consumption is markedly below amounts that promote therapeutic benefits.
- To reach goals, consuming fish oil every day (rather than the same overall weekly amount delivered as two large bolus doses) leads to faster improvement in EPA and DHA status and higher status after one year.13 So taking your fish oil supplement when you remember is better than not taking them, but consistent everyday habits are best.
- Whatever form you are taking, make sure you are getting the most from it. Taking fish oil with a fat-rich food such as avocado, nut butters, or healthy oils is advisable, as this has been shown to increase absorption of both EE6,7 and TG forms7 of EPA and DHA.
- USDA Nutrient Database. EPA+DHA in Salmon Oil (NDB ID: 04593), Sardine Oil (NDB ID: 04594), and Menhaden Oil (NDB ID: 04591). https://ndb.nal.usda.gov. Accessed July 26, 2018.
- El Boustani et al. Lipids. 1987;22(10):711-714.
- Lawson LD et al. Biochem & Biophys Res Comm. 1988;152(1):328-335.
- West et al. Br J Nutr. 2016;116:788-797.
- Nordoy et al. Am J Clin Nutr. 1991;53:1185-1190.
- Lawson LD et al. Biochem & Biophys Res Comm. 1988;156(2):960-963.
- Davidson et al. J Clin Lipid 2012;6:573-584.
- Dyerberg et al. Prost Leuko Essen Fatty Acids 2010;83:137-141.
- Neubronner et al. Eur J Clin Nutr. 2011;65:247-254.
- Hansen et al. Eur J Clin Nutr. 1993;47:497-507.
- Richter et al. Lipids. 2017;52(11):917-927.
- Vannice et al. J Acad Nutr Diet. 2014;114(1):136-153.
- Browning et al. J Nutr. 2014;144(5):667-672.