Earlier this month, researchers presented two important omega-3 research papers at the National Lipid Association (NLA) 2011 Scientific Sessions in New York City.
Both studies relate to the differing effects of omega-3 EPA and DHA – the fish-source omega-3s essential to human health – on blood levels of cholesterol and triglycerides.
In short, both sets of results reaffirm the generally beneficial nature of both omega-3s’ effects, and show that EPA and DHA bring distinct, valuable cardiac health benefits.
This affirmation matters because there’s been a growing trend toward “pharmaceutical” supplements that contain only EPA or DHA – especially EPA – based on erroneous perceptions that EPA is more important to heart health.
The findings underscore the heart-health advantages of seafood – and “whole”, unrefined, non-manipulated fish or krill oil supplements – which provide EPA and DHA in roughly equal proportions.
Study #1: EPA excels at preventing oxidation of LDL cholesterol
Having a high level of total or LDL cholesterol is not risky by itself, and this persistent medical myth has long been refuted by overwhelming evidence.
Instead, the real cholesterol danger occurs when the lipid “packages” that carry LDL and other kinds of cholesterol become oxidized by free radicals.
Among other things, this oxidative damage initiates the process of atherosclerosis … a key feature of cardiovascular disease.
Researchers from Brigham and Women’s Hospital in Boston reported their finding that supplemental EPA inhibits oxidation of LDL cholesterol – with or without supplemental DHA – while DHA doesn’t seem to prevent LDL oxidation (Mason RP et al. 2011).
This is not very surprising, since EPA is the omega-3 the body needs to produce anti-inflammatory messenger compounds (eicosanoids), and inflammation can generate LDL-oxidizing free radicals.
This clinical trial was one of a number of studies that tried to determine why LDL cholesterol levels tend to rise slightly in patients given omega-3s to lower their triglyceride levels.
The Brigham team compared the effects of EPA and DHA – alone or in combination with statin drugs – on oxidation of LDL cholesterol within vesicles … small “sacks” the body uses to store or transport fatty compounds.
As senior investigator Dr. Preston Mason told heartwire.org, “We know that EPA and DHA have different effects on LDL cholesterol levels. One of the things that affect LDL clearance [from the blood] is its oxidative state. Oxidized LDL is not cleared. One of the concepts is that EPA might preferentially prevent LDL oxidation, so even though it's not affecting its synthesis, it would help its clearance.” (O'Riordan M 2011)
EPA reduced the formation of oxidized LDL cholesterol by 42 percent and 54 percent in vesicles with normal and elevated cholesterol levels, respectively.
DHA also inhibited formation of oxidized LDL cholesterol, but to a lesser extent (28 percent), and only in vesicles with elevated cholesterol levels.
The separate anti-oxidation effects of taking EPA, DHA, and EPA+DHA supplements were enhanced when used in combination with statin drugs, including atorvastatin, atorvastatin metabolite, simvastatin, or rosuvastatin.
As Dr. Mason told heartwire, they detected “excellent [antioxidant] effects” with all the statins tested, so, “…there might be some opportunity for synergy [between statin drugs and EPA].” (O’Riordan M 2011)
Study #2: EPA and DHA raise LDL levels slightly to modestly … and it doesn’t matter
Omega-3 fish oil lowers blood levels of triglycerides and non-HDL cholesterol … blood-fat effects of unrivaled importance when it comes to reducing heart-health risks.
While fish oils often raise levels of LDL-cholesterol slightly to modestly, it has long been scientifically obsolete to focus on LDL levels alone as a heart-risk factor.
(For more on this topic, see “Does Fish Oil Lower Cholesterol? Does it Matter?,” “Switch to Fish Yields Statin-Like Benefits,” and “Cholesterol Fiasco Undermines Accepted Theory.”)
However, an obsession with LDL levels persists, thanks to decades of sadly misguided public health messages.
So it’s good to see the results of a new evidence review, which details the differing effects of EPA and DHA on LDL cholesterol levels, and affirms the distinct and generally beneficial effects that both kinds of omega-3s exert on people’s blood fats.
A team led by Dr. Terry Jacobson reviewed 21 clinical trials that had tested the effects of EPA and DHA on blood levels of LDL cholesterol, HDL cholesterol, triglycerides, and non-HDL-cholesterol (Jacobson T et al. 2011).
In studies that directly compared separate DHA and EPA supplements, participants’ average triglyceride levels dropped by 22.4 percent with DHA and by 15.6 percent with EPA.
In head-to-head comparisons, DHA supplements raised LDL cholesterol by 2.6 percent, while EPA lowered LDL cholesterol levels by 0.7 percent.
In trials separately comparing each omega-3 to a placebo, 10 of the 14 trials testing DHA showed LDL cholesterol increases ranging from 5.4 percent to 16 percent, while none of the EPA trials showed any increase.
It’s important to understand that, by themselves, LDL cholesterol increases in this slight-to-modest range have little clinical meaning.
This is especially true when such increases are considered in the context of a person’s overall cholesterol profile, which DHA is known to improve in more important ways.
As we’ve said, DHA lowers blood levels of triglycerides and non-HDL cholesterol: blood-fat effects of preeminent importance to reducing heart-health risks.
Interestingly, the rises in LDL cholesterol levels among DHA-treated patients correlated significantly with their triglyceride levels … that is, LDL rose the most among those with high triglyceride levels at the outset of the trial.
Commenting on the LDL increase, Dr. William Harris of the University of South Dakota said, “… LDL-cholesterol levels can often be abnormally low to start with, so it goes up to normal. It often looks like a large relative increase … [so] … I'm not too concerned about it.”
And Dr. Roger Blumenthal at Johns Hopkins has previously noted that while omega-3s can raise LDL cholesterol, they do not affect blood levels of apolipoprotein B, which are a much better measure of the formation of “atherogenic” (plaque-forming) blood particles (O'Riordan M 2011).
Like Harris, he’s previously expressed a lack of concern about the clinical implications of fairly small omega-3-induced increases in LDL cholesterol (O’Riordan M 2011).
Jacobson T et al. Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Low-Density Lipoprotein Cholesterol: A Critical Review. Poster 106. 2011 NLA Annual Scientific Sessions, New York City, May 19-21, 2011.
Mason RP et al. Comparative Lipid Antioxidant Effects of Omega-3 Fatty Acids in Combination with HMG-CoA Reductase Inhibitors. Poster 107. 2011 NLA Annual Scientific Sessions, New York City, May 19-21, 2011
O'Riordan M. Data suggest DHA and EPA have differential effects on LDL-cholesterol levels. theheart.org by WebMD. May 22, 2011. Accessed at http://www.theheart.org/article/1229499.do