Predicting the effects of supplemental EPA and DHA on the omega-3 index

Authors: WALKER, RACHEL - Pennsylvania State University; HARRIS JACKSON, KRISTINA - Omegaquant, Llc; TINTLE, NATHAN - Dordt College; SHEARER, GREGORY - Pennsylvania State University; BERNASCONI, ALDO - Global Organization For Epa And Dha (GOED); MASSON, SERGE - Mario Negri Institute Of Pharmacology; LATINI, ROBERTO - Mario Negri Institute Of Pharmacology; HEYDARI, BOBAK - University Of Calgary; KWONG, RAYMOND - Brigham & Women'S Hospital; FLOCK, MICHAEL - University Of Pittsburgh; KRIS-ETHERTON, PENNY - Pennsylvania State University; NEDERGAARD HEDENGRAN, ANNE - Copenhagen University; CARNEY, ROBERT - Washington University School Of Medicine; SKULAS-RAY, ANN - University Of Arizona; GIDDING, SAMUEL - Nemours/alfred I Dupont Hospital For Children; DEWELL, ANTONELLA - Stanford University; GARDNER, CHRISTOPHER - Stanford University; GRENON, MARLENE - University Of San Francisco; SARTER, BARBARA - Bastyr University; Newman, John; PEDERSEN, THERESA - University Of California, Davis; LARSON, MARK - Augustana University; HARRIS, WILLIAM - Omegaquant, Llc

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/24/2019
Publication Date: 8/8/2019
Citation: Walker, R.E., Harris Jackson, K., Tintle, N.L., Shearer, G.C., Bernasconi, A., Masson, S., Latini, R., Heydari, B., Kwong, R.Y., Flock, M., Kris-Etherton, P., Nedergaard Hedengran, A., Carney, R.M., Skulas-Ray, A., Gidding, S.S., Dewell, A., Gardner, C., Grenon, M.S., Sarter, B., Newman, J.W., Pedersen, T.L., Larson, M., Harris, W.S. 2019. Predicting the effects of supplemental EPA and DHA on the omega-3 index. American Journal of Clinical Nutrition. 110(4):1034-1040. https://doi.org/10.1093/ajcn/nqz161.
DOI: https://doi.org/10.1093/ajcn/nqz161

Interpretive Summary: Dietary supplementation with long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids, EPA and DHA) can raise blood EPA+DHA levels, an effect associated with a reduced risk of cardiovascular disease. However, no systematic study has yet examined the magnitude or variability in the ability of supplements to increase blood EPA+DHA. This study was designed to model the effects of supplemental EPA+DHA on the EPA+DHA content of red blood cell membranes (i.e. the Omega-3 Index or O3I). To accomplish this task, de-identified data from 1,812 individuals from 15 published omega-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, and duration of treatment. Variables were selected by stepwise regression, using the Bayesian Information Criterion, a tool which limits model complexity. This process was repeated considering the supplement chemical form (ethyl ester vs. triglyceride) in the model. While placebo controls (n =703) took no omega-3 supplements and had a stable O3I, supplemented individuals (n =1,109) took an average ± SD of 2.153 ± 1.173 g/day of EPA+DHA, for an average duration of 12.7 ± 5.4 weeks, and showed their O3I increased from 5.16 ± 1.69% to 8.65 ± 2.73% (p <0.0001). The base model included body mass index (BMI), dose, and baseline O3I and explained 63% of the variance in response (p <0.0001). For an individual with a baseline O3I of 4% given 850 mg EPA+DHA ethyl ester/day, the estimated final O3I (95% prediction interval) was 5.88% (2.80% to 8.95%). Triglyceride supplements increased the O3I by ~0.66 percentage points more than ethyl ester products. In conclusion, the baseline O3I, EPA+DHA dose, BMI and chemical formulation were significant predictors of O3I change in response to EPA+DHA supplementation. The models developed here can be used by clinicians to recommend efficacious EPA+DHA doses to patients and by researchers to help estimate the needed EPA+DHA dose to reach beneficial O3I levels in their study population.

Technical Abstract: Background: Supplemental long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids, EPA and DHA) raise blood EPA+DHA levels, but no systematic study has yet examined the magnitude or variability of this effect. Objective: To model the effects of supplemental EPA+DHA on the Omega-3 Index (O3I, erythrocyte EPA+DHA). Design: De-identified data from 1,812 individuals from 15 published omega-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, and duration of treatment. Variables were selected by stepwise regression, using the Bayesian Information Criterion. This process was repeated with chemical form (ethyl ester vs. triglyceride) included in the model. Results: Supplemented individuals (n =1,109) took an average ± SD of 2153 ± 1173 mg/day EPA+DHA, and the placebo controls (n =703) took none. The average duration of supplementation was 12.7 ± 5.4 weeks. The O3I increased from 5.16 ± 1.69% to 8.65 ± 2.73% in the supplemented individuals (p <0.0001). The base model included BMI, dose, and baseline O3I and explained 63% of the variance in response (p <0.0001). The estimated final O3I (95% prediction interval) for an individual with a baseline O3I of 4% given 850 mg EPA+DHA ethyl ester/day was 5.88% (2.80% to 8.95%). Triglyceride supplements increased the O3I by ~0.66 percentage points more than ethyl ester products. Conclusions: Baseline O3I, dose, BMI and chemical formulation were significant predictors of O3I change. The models developed here can be used by clinicians to recommend efficacious EPA+DHA doses to patients and by researchers to help estimate the needed EPA+DHA dose to reach beneficial O3I levels in their study population.