Physicians' Academy for Cardiovascular Education

Effect of fish oil supplementation on serum triglycerides, LDL cholesterol

Literature - Oelrich B, et al., Nutrition, Metabolism & Cardiovascular Diseases (2011),

Effect of fish oil supplementation on serum triglycerides, LDL cholesterol and LDL subfractions in hypertriglyceridemic adults,

Oelrich B, et al., Nutrition, Metabolism & Cardiovascular Diseases (2011), doi:10.1016/j.numecd.2011.06.003

Background and aims

The well-established triglyceride (TG) lowering effect of fish oil is accompanied by an increase in LDL-cholesterol (LDL-C) concentration. Less is known about the differential impact on LDL particle distribution - the smaller particles being associated with a greater risk for atherosclerosis. We aimed to examine the changes in serum concentrations of four subclasses of LDL particles as well as shifts in LDL phenotype patterns (A, B, AB) among hypertriglyceridemic adults.

Methods and results

This was a secondary analysis from a double-blind, parallel design, placebo controlled trial with 42 adults that experienced significant TG lowering and modest increases in total LDL-C concentrations after 12 weeks of 4 g/d EPA + DHA. Reduction in serum TG concentrations (mean ± SEM) was -26 ± 4% (-0.81 ± 10.12 mmol/L), p < 0.0001. Total LDL-C concentration increased by 13 ± 3% (+0.31 ± 0.08 mmol/L), p < 0.0001. The 12-week changes in concentrations of LDL1, LDL2, LDL3 and LDL4 were +0.06 ± 0.02 mmol/L [+2.2 ± 0.7 mg/dL], +0.07 ± 0.03 mmol/L [+2.6 ± 1.0 mg/dL], +0.16 ± 0.05 mmol/L [+6.3 ± 1.8 mg/dL], and +0.04 ± 0.04 mmol/L [+1.4 ± 1.7 mg/dL], respectively (+20 ± 5%, +64 ± 13%, +26 ± 6%, and +17 ± 9%), p < 0.05 for all but LDL4. Changes in LDL phenotype patterns A, B and A/B were negligible and not statistically significant.


In this population of hypertriglyceridemic adults, dietary supplementation with fish oil resulted in an increase in total LDL-C concentration which was distributed relatively evenly across the range of smaller and more atherogenic as well as larger and less atherogenic LDL particles.


Hypertriglyceridemia affects around 30% of the US population [1,2], but only 1.3% of the affected in the US population use a pharmacologic intervention to reduce TG. The approach and timing when to initiate pharmacological treatment is still a source of debate, especially for isolated hypertriglyceridemia (i.e. hypertriglyceridemia in the absence of additional cardiovascular risk factors). The cardiovascular benefits of marine omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) [3,4] are well established. For the treatment of hypertriglyceridemia, the American Heart Association issued a recommendation of 2 to 4 g/day of EPA/DHA [5]. The most established of cardiovascular benefit of fish oil is its hypotriglyceridemic effect [6].

Results and therapeutic perspectives

Forty-two, hypertriglyceridemic adults without a history of CVD disease or other CV risk factors were included in the study and exposed to active therapy in three fish oil supplementation arms with 4 g/day of combined EPA and DHA.

Effect of fish oil supplements on triglycerides and LDL-cholesterol

All active treatment arms experienced a statistically significant blood TG lowering of 26%. Mean LDL-C increased significantly with a concomitant increase for all LDL particle sizes (p<0,05) but the LDL4 particle class. Nevertheless, fish oil supplements may provide what for many individuals would be an easier behavior modification to make (i.e., taking dietary supplements vs. changing overall dietary patterns). While the TG lowering effect of these two hygienic/lifestyle measures is similar, the mechanism is quite likely different.


Dietary fish oil supplementation, has a beneficial impact on lowering blood TG concentrations. Nevertheless, a modest LDL-C increasing effect has also been demonstrated in this study. It may be argued that the adverse increase in total LDL-C might be moderated to some extent by a shift in LDL particle distribution, but this shift seems modest in the current study. To lower TG concentrations effectively, strategies to address the overall lipid profile seem preferable.


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