Fish oil supplements do not raise LDL-cholesterol levels: New analysis

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While the cardiovascular benefits of omega-3 fatty acids have been known for decades, there was disagreement about whether fish oil supplements may raise LDL-cholesterol levels. A new analysis provides reassurance about the safety of these products.

Data from a predominantly male, normolipidemic, middle-aged cohort of 9,253 individuals indicated that fish oil supplementation was not associated with increases in LDL-cholesterol levels.

In addition, fish oil supplementation was associated with increases in red blood cell (erythrocyte) levels of DHA.

“[I]ncreases in the omega-3 index and in erythrocyte DHA over time were associated with modestly decreased levels of LDL-C,” wrote the researchers, led by Dr William Harris from the Fatty Acid Research Institute (FARI).

“These findings can reassure individuals who, in making healthier lifestyle choices, want to increase their intake of omega-3 fatty acids (through dietary sources or supplementation), that clinically significant adverse effects on LDL-C are unlikely to occur.”

The question…

The potential cardiovascular benefits of omega-3s date were first reported about 50 years ago when Dyerberg, Hans Olaf Bang, and Aase Brøndum Nielsen published landmark papers on the topic in the The Lancet in 1971 The American Journal of Clinical Nutrition in 1975.

To date, the polyunsaturated fatty acids (PUFAs) have been linked to a range of cardiovascular benefits, from improving in blood lipid levels to reducing the tendency of thrombosis, and from improving blood pressure and heart rate to reducing the risk of coronary heart disease (CHD) and cardiac death.

While the triglyceride (TG)-lowering effects of omega-3s are well established for doses between 3 and 4 grams per day, there exists disagreement in the scientific literature regarding the effects of DHA-containing products on LDL-cholesterol levels.

Indeed, a 2018 meta‐analysis of 110 randomized placebo‐control human clinical trials found that EPA and DHA supplements produced increases in both LDL- and HDL-cholesterol (AbuMweis et al. J Hum Nutr Diet. Vol. 31, pp. 67–84).

“Some of this inconsistency in results may have been due to study populations having varying baseline TG levels as was observed for other TG-lowering agents,” explained Dr Harris and his co-authors. “Nevertheless, a recent Science Advisory from the American Heart Association concluded that ‘there is no strong evidence that DHA-containing prescription omega-3 fatty acid agents used as monotherapy or in combination with statins raise LDL-C in patients with HTG [high triglyceride levels].’”

Study details

For the new paper, Dr Harris and his co-workers performed a prospective observational study of 9,253 individuals and analyzed erythrocyte DHA levels and LDL-C levels.

Dr Harris explained to NutraIngredients-USA that statins were being used by 29% of the cohort, which is like the general US population over age 40. In addition, smoking rates were the same as in VITAL, as was BMI.

“So, I’d say they were pretty representative of the typical American. So, the findings should apply generally,” he added.

The analysis revealed that, “independent of a concurrent change in the use of cholesterol-lowering medications, a rise in DHA was associated with a small, but statistically significant decrease in LDL-C levels”, they wrote.

Indeed, a 1% increase in red blood cell DHA levels was associated with a 1.9 mg/dL decrease in LDL-cholesterol, they said.

Importantly, the association between increased DHA and decreased LDL-C was observed in people who taking omega 3 and in non-supplement users who most likely increased their DHA levels via dietary changes.

“Most people taking dietary fish oil supplements don’t take doses big enough to move the LDL needle (1-2 g DHA per day),” Dr Harris told us. “It’s the routine health conscious consumer that may take 1-2 fish oil pills per day that we are studying here.”

Source: Journal of Clinical Lipidology

Published online ahead of print, doi 10.1016/j.jacl.2020.11.011

“Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study”

Authors: W.S. Harris et al.