Those familiar with our work know that we have spent quite a bit of time evaluating the therapeutic outcomes of marine-derived omega-3 fatty acids. Our recent review of the topic has been downloaded and widely circulated amongst healthcare providers and the general public, worldwide. In that review, we covered the types of fish used, how fish oil is made, sustainability issues, bioavailability differences, quality control concerns and much more; including the research comparing omega-3 fatty acid from fish oil and krill oil. You can get the article as a PDF file here.
Just a month after publishing our paper online, a few more studies comparing fish oil and krill oil were published that initially appeared to suggest that omega-3 fatty acids from krill oil may indeed have a slightly better bioavailability than those from fish oil and/or had triglyceride lowering effects similar to fish oil; but after only a month of scrutiny, these studies are exposed as epic failures of how marketing-driven research leads to bad science and confusing outcomes.
First- as a brief review for those who haven’t read our whitepaper. Our position was that the EPA and DHA in krill oil should function in much the same way as EPA and DHA from fish oil- assuming equal amounts of the fatty acid become bioavailable after consumption. The typical claims made by the marketers of krill oil is that, because krill oil omega-3s are delivered as phospholipids (PL, rather than triglycerides), they will have (or have been shown to have) higher bioavailability than fish oil omega-3s. Our whitepaper clearly shows that the studies used by marketers to “prove” such assertions are either not clinically or statistically significant; or are not appropriately designed to make such comparisons. However, the biggest issue is not their failure to prove better bioavailability, or the fact that krill oil appears to be nearly ¼ free fatty acids upon analysis (not all PL as claimed); but the fact that commercially available krill oil products are extremely low in EPA and DHA, while still costing much more than fish oil products (containing much more EPA and DHA). In fact, in the only trial comparing equivalent doses, researchers needed to use 14 krill oil capsules to get the same amount of EPA and DHA as 4 capsules of fish oil.
This is where the first of the new studies fits in. Published in December of 2013 in the open access Lipids in Health and Disease, this paper has such a hopeful title: Enhanced increase of omega-3 index in healthy individuals with response to 4-week n-3 fatty acid supplementation from krill versus fish oil [Free Download]. The cross-over designed trial appears to compare an equal amount of EPA and DHA from krill oil and fish oil (and a corn oil placebo); and indeed reports a higher increase in the omega-3 index (the percent of EPA and DHA within RBC phospholipids) during the time subjects were taking krill (compared to fish oil); although both fish and krill oil were better than placebo. They report that the various oils were provided in six- 500 mg capsules (3 with breakfast, 3 with dinner); describing the fish oil as a “TG 18/12” oil. Going one step further; they analyze and report the fatty acid composition of each of the three oil products; and this is where things get fishy.
They claim the fish oil to which they compared the krill oil was a TG 18/12, which is the usual designation for un-concentrated fish body oil providing 180 mg of EPA and 120 mg of DHA per 1000 mg of oil. However, their fatty acid composition lists a very unusual fatty acid profile for this fish oil: including 32% linoleic acid- an omega-6 fatty acid. Normally, fish oil contains about 2-3% omega-6 fatty acids; so what is going on with this oil? Well, we were not the only ones to wonder about this. In early January of 2014, a commentary of the above trial was also published in the same journal, asking about the strange fatty acid profile of this fish oil, along with a few other points of contention. You can find that Commentary Here.
Incredibly, the authors of the original paper explained it this way in their rebuttal [Found Here]: Our primary objective was to compare effects of consumption of same amount of n-3 fatty acids from krill or fish oil. When designing a double blinded placebo controlled randomised cross over trial, it was felt that the amounts of treatment products as well as the bioactives of interest be maintained consistent across different interventions. However, the n-3 PUFA content of the krill oil fell below that of fish oil. In order to match the concentrations of n-3 PUFA and volumes between krill and fish oil, the fish oil was diluted with the placebo, corn oil at a ratio of 1.3:1.0.[Emphasis added] Yes, you read that correctly. They used the lowest dose of fish oil they could find (one shown to have lower bioavailability than the concentrated TG forms) and still needed to dilute it with corn oil so they could reduce its omega-3 content for a head-to-head comparison to krill oil. The authors also admit: We agree that we could have included the information about dilution of fish oil in the original manuscript itself. While we will avoid the obvious question about motive usually entertained when a manufacturer of krill is involved in such a study; this begs the question of the type of expertise used in the peer-reviewing process that missed the obvious questions about the fatty acid profile of the fish oil.
This report, with the commentary and rebuttal, only solidifies our view that krill oil simply cannot deliver a cost-effective payload of EPA and DHA to be considered as a therapeutic alternative to fish oil. Krill oil products do not even have the amount of EPA and DHA found in the lowest concentrations of fish oil, while their cost is sometimes double or triple the same. From a therapeutic standpoint, concentrated TG forms can deliver 4-8 times more EPA and DHA per capsule, at an affordable price.
This brings us to the second paper, published in the February 2014 edition of Nutrition Research. Again, the title of this article (written by scientist employed by the manufacturer of the krill product used) was deceptively hopeful: Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels. Unfortunately, the data proved to be anything but a straight-forward TG-lowering effect from krill oil- although their analysis is so flawed that it almost defies explanation.
The study was designed much like TG-lowering studies of fish oil. Three-hundred patients with high triglycerides were recruited and given placebo or 3 to 4 grams of krill oil providing 0, 100, 200, 400 or 800 mg of EPA/DHA over 12 weeks. Blood lipids and omega-3 index were measured at baseline, six weeks and 12-weeks after consuming the krill products. The data speaks for itself; after 12-weeks of krill oil consumption the change in TG levels in these individuals with a mean TG at baseline=231 was as follows: Placebo (+3.9%), 100 mg (-10%), 200 mg (-3.8%), 400 mg (-6.7%), 800 mg (+0.9%)- none of these reached statistical significance. The authors claim that the lack of efficacy and dose-response was due to the overwhelming intra-individual TG measurements and high standard deviation- making it impossible to measure fasting TG as an outcome. How then, with these numbers (even showing an increase in TG using 800 mg of EPA and DHA) were they able to declare a TG-lowering effect in the title?
The reviewers of the paper allowed these authors to circumvent the “limitations” of the study and use “an explorative data analysis approach to increase the statistical power of the study.” In essence what they did was to pool together all the doses, including the 6-week data points which happened to be better for nearly all the doses, and analyzed the data as if a theoretical average EPA/DHA content of 385 mg was given to all the subjects. The authors then boldly declare that “Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%.” Even if we accepted this flawed explorative data analysis, this data showed only a 6.3% reduction from baseline TG levels- a level that even if achieved in this study, represents a small clinical difference. In contrast, fish oil studies routinely see drops in TG (from baseline) of >25%, show clear dose-response and are maintained or even continue to improve between 6 and 12 weeks.
The fact that such a flawed study that failed to reach any statistical-significant reductions in TG based on the primary objective (12-weeks) and initial statistical plan was permitted to use statistical manipulation to imply a positive outcome is incomprehensible. Clinicians and patients would read the title and abstract of this paper thinking that krill oil was able to reduce TG levels in these subjects- when in fact, at the end of 12 weeks the data shows that it did not. This paper should be retracted, rewritten to describe it as a failure to meet its TG-lowering objective and republished.
While I am certain the marketing departments of krill manufacturers and distributors are eager to share with you their “latest success stories”- now you have the rest of story- revealing krill oil’s epic failure as a therapeutic contender in the omega-3 world.
[Dr. Guilliams discussed this and many more issues related to fish oil (from the whitepaper) in a discussion with Dr. Hoffman’s on his Intelligent Medicine podcast. Download and Listen Here.]
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