Krill oil, what’s all the fuss?


Dr Nina Bailey Igennus Healthcare Nutrition - square - CopyKrill are shrimp-like crustaceans, found mostly in the Antarctic and North Pacific oceans.  Krill oil is becoming a popular source of omega-3 fatty acids and is hailed by its manufacturers as superior in health benefits. Whilst krill are an abundant and relatively untapped resource for human health, they also play an important, even critical part in the Antarctic ecosystem, providing food for fish, sea birds and mammals such as whales and seals.

Not surprisingly, the use of krill in the human food chain raises several questions relating to the ethics of krill fishing on the massive scale envisaged, given the significant impact this may have on marine ecosystems. Thus, with the low number of human studies that have been carried out into the benefits of krill oil and with these ecological concerns in mind, is it fair, or correct, to make such statements about krill and encourage its consumption when the known benefits and sustainable sources of fish oil are both well documented and long-standing?

Just like fish oil, krill oil contains both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish and krill oil differ, however, in the structure by which EPA and DHA are joined together – in krill they exist in phospholipid form, in fish they exist as triglyceride – and also in the addition of astaxanthin, a carotenoid present in krill, which gives it its reddish-pink colour. As krill are low in the food chain they are a relatively inferior source of omega-3 when compared to fish, but the ‘hype’ surrounding krill oil is more related to the bioavailability, rather than the amount, of the omega-3.  It is generally accepted that EPA and DHA in phospholipid form offer potentially enhanced bioavailability over that of triglycerides and much of the marketing hype surrounding krill focuses on these benefits compared to standard fish oils.  Due to the reported enhanced bioavailability, marketing also often emphasises the low dosing requirements of krill oil compared to standard fish oil.  To date there have been few human studies that support this claim, and the benefits of krill may be associated with fatty acids in their free form, not with the omega-3 as phospholipid. Whilst EPA and DHA as free fatty acids are the most bioavailable of all forms of omega-3, they are also the most unstable with the highest potential to oxidise, offering a possible explanation for the presence of astaxanthin in krill.

Comparing krill, triglyceride and ethyl-ester at comparative doses of EPA and DHA

A 2011 paper comparing the bioavailability of omega-3 from both fish oil and krill oil found that the krill oil contained high amounts of EPA and DHA as free fatty acids rather than as total phospholipid (22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA).  In this study, twelve healthy young men (mean age 31 y) were randomised to receive 1680mg EPA+DHA and given either re-esterified triacylglycerides [rTAG], ethyl-esters [EE] or krill oil. Fatty acid levels in plasma phospholipids (as a proxy for bioavailability) were analysed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after the capsules were ingested.    Given the differences in fatty acid structure and the effects on bioavailability, it would be expected that krill oil would deliver the highest levels of EPA and DHA level followed by rTAG and then EE.  Whilst the highest incorporation of EPA and DHA into plasma phospholipids was indeed achieved by krill followed by fish oil as rTAG and finally by EE, the differences in uptake were not significant between the three treatments. [1] The authors go on to suggest that any potential ‘superiority’ in regard to bioavailability of krill oil is likely to be due, in part, to krill’s free fatty acid content rather than its phospholipid content.  In addition, whilst each supplement delivered 1680 mg EPA+DHA in total, the authors do not give details on the total volume of oil required to deliver this dose.  Given that both ethyl-ester and rTAG oils can deliver high doses of omega-3 as super concentrates and that krill oil only delivers EPA and DHA at the standard 300mg per 1000mg oil, the volume of krill oil required to deliver 1680 mg EPA+DHA would have been substantially more.  Thus the concept of ‘taking less’ may not, in reality, hold up.

Comparing krill with fish oil

A second study, also published in 2011, compared a set dose of krill oil (3g) with a set dose of standard fish oil (1.8g).  Again, it took the premise that ‘less is more’ and given the superior bioavailability attributed to krill oil and that 40% more krill than standard fish oil was given, supplementation with krill oil would be expected to be superior to fish oil for raising EPA and DHA.  Participants were randomised into three study groups and given either 3g krill oil daily (n = 36; 3.0g/day, EPA + DHA = 543mg), 1.8g fish oil daily (n = 40; 1.8g/day, EPA + DHA = 864mg) or no supplementation (n = 37) for a period of 7 weeks. [2]  A significant increase in plasma EPA and DHA was observed in the subjects supplemented with both fish and krill oil compared with the controls, although there were no significant differences in the changes in any of the omega-3s between the fish oil and the krill oil groups.  The authors state that as the subjects in the krill oil group received 62.8% of the total amount of EPA and DHA received by the subjects in the fish oil group, then the bioavailability of EPA and DHA from krill oil is at least as efficient as EPA and DHA from fish oil.  In reality, however, subjects had to take 40% more in total volume to achieve the same level of erythrocyte EPA and DHA as that delivered by the fish oil;  given the marked difference in price (krill oil is substantially more expensive than standard fish oil) this may not be practical for the consumer.  Supplementation with both krill and fish oil groups reduced the AA to EPA ratio – a biomarker of inflammation. Interestingly, there was a statistically significant increase in the pro-inflammatory omega-6 arachidonic acid (AA) from baseline in the krill group, whereas a decrease was observed in the fish oil group; reduction was shown, therefore, to be more favourable in the fish oil group (a reduction in AA to EPA of 3.8 for the fish oil group against 3.4 for the krill group).

Krill vs fish oil in ‘like for like’ dosing

An earlier study published in 2009 made a direct comparison dosing 2g krill oil against 2g fish oil (menhaden oil) in overweight and obese individuals. [3]  In addition to reporting changes in plasma fatty acid levels, the authors also reported change in a variety of metabolic and cardiovascular functions and the frequency of adverse events relating to tolerability of the oils.   In regard to EPA and DHA content, 2 grams krill oil supplement provided 216mg/d EPA and 90mg/d DHA, and 2 grams of the menhaden oil supplement provided 212mg/d EPA and 178mg/d DHA.  The authors reported that compared to supplementation with menhaden oil, plasma EPA and DHA concentrations were significantly higher after supplementation with krill oil despite delivering 20% less total omega-3. When looking at changes in EPA and DHA as individual fatty acids, the change in EPA from baseline was higher for krill oil (178.4 ± 38.7 vs 131.8 ± 28.0 μmol/L) but lower for DHA (90.2 ± 40.3 vs. 149.9 ± 30.4 μmol/L), reflecting the differing concentrations of EPA and DHA in the oils.  At the end of the treatment period, the mean plasma EPA concentration was somewhat higher in the krill oil group compared with the menhaden oil group (377 vs 293 μmol/L), whereas the mean plasma DHA concentrations were comparable (476 vs 478 μmol/L). The authors therefore suggest that the EPA and DHA from krill oil are absorbed at least as well as that from menhaden oil.

Changes in the metabolic and cardiovascular effects

Triglycerides (TG), cholesterol levels and C-reactive protein levels (a marker for systemic inflammation) and urinary F2-isoprostane levels (as an indicator of lipid peroxidation and oxidative stress) did not differ across treatments. A significant reduction in systolic blood pressure response was observed, however, in the menhaden oil group but not the krill oil group.   In summary, whilst an equivalent dose (gram for gram) of krill oil raised EPA and DHA levels comparatively if not slightly better than that of fish oil, no significant changes in lipid responses, TG levels and markers of inflammation or peroxidation products were observed for either the krill or fish oil group when compared to the control group.

In a similar study carried out by Ramprasath et al., in 2014 twenty four healthy volunteers took part in a double blinded, randomised, placebo controlled crossover trial. The study consisted of three treatment phases including capsules containing krill or fish oil providing 600mg of n-3 polyunsaturated fatty acids each or placebo in the form of corn oil. Each treatment phase lasted four weeks and was separated by an eight-week washout period. The study found that krill oil significantly increased both plasma and red blood cell omega-3 PUFA levels and omega-3 to 6 ratio in comparison to fish oil and placebo. Lipid profile changes were not significantly different between the fish and krill oil treatments. On first analysis the results look good in favour of krill; however, heavy criticism of this study has been expressed as a result of a number of misleading methodological issues.  Firstly the authors state that both the fish oil and the krill oil treatments delivered 600mg of EPA and DHA when, in fact, the krill oil capsules delivered 114mg more than the fish oil, which itself delivered 664mg. When taking a closer look at the formulations of the oils used, the fish oil was not pure fish oil but a mixture of fish and corn oil. Krill oil as discussed above generally contains much lower levels of EPA and DHA than standard fish oil and therefore for the authors to deliver a similar EPA and DHA dose in both treatment regimes, the fish oil had to be diluted so that the 3g of ‘fish oil’ given was in fact 1.7g fish oil plus 1.3g of corn oil. As a result, the dominant fat given to both the placebo and the fish oil group was omega-6. In light of these methodological issues, the study findings of enhanced EPA and DHA uptake and improved omega-3 to 6 ratio when taking krill compared to fish oil are hardly surprising and the reported results of this study have subsequently been deemed both unjustified and highly misleading (Nicols 2014).

Is krill oil more tolerable than fish oil?

Another marketed benefit associated with krill oil is an apparent lack of gastrointestinal side-effects that are sometimes experienced with high-dose fish oil consumption.  Yet, in the paper by Maki et al (2009), [3] after 4 weeks of supplementation, 20% of the krill group reported gas or bloating, with no individuals within the fish oil group reporting similar symptoms.  In addition, 36% of the krill oil group reported flatulence, with 20% reporting diarrhoea or loose stools (compared to just 8% of the fish oil group experiencing any of these issues).  In summary, those individuals taking 2 grams krill oil were more likely to report an increase in frequency and severity of gastrointestinal disturbance compared to those individuals taking 2 grams fish oils.

Summary

Marketing hype around krill oil focuses on its potentially superior bioavailability and, based on this, the consumer is told to take less oil whilst deriving comparable health benefits attributed to larger doses of fish oil.  Results from the few human intervention studies published suggest that the concept of ‘less is more’ may be misleading.  When supplementing with comparable doses of oil, EPA and DHA from krill oil appear to be absorbed at least as well as that from fish oil [3].  In reality, however, the amount of krill oil required to achieve the same level of erythrocyte EPA and DHA as that delivered by fish oil is 40% more in total volume. [2] Comparing the bioavailability of different forms of omega-3, the phospholipid complex of EPA and DHA within krill oil does appear to be superior when compared to rTAG or EE, which would be expected given the transport mechanism through the gut.  However since krill oil is high in free fatty acids, it raises questions about the claims that the phospholipid content of krill oil is responsible for its high bioavailability. [1] Furthermore, many of the health benefits attributed to krill may simply be due to the high content of astaxanthin, ‘nature’s natural antioxidant’ which, alone, offers significant protection against oxidative stress and inflammation [4] and may be responsible for the anti-inflammatory health benefits observed in some animal studies. [5, 6]  In conclusion, whilst the bioavailability of krill oil (as phospholipid or free fatty acid) may offer additional clues to its health benefits, given the established need for high doses of omega-3 fatty acids and in particular EPA in the treatment of a variety of health conditions [7-10], krill oil is neither practical nor cost effective when compared to rTAG and ethyl-EPA.  Use of highly concentrated rTAG and ethyl-ester oils can easily deliver therapeutic doses in lower volume and any potential bioavailability issues are easily overcome by taking the capsules with food and as a split dose.

References

1. Schuchardt JP, Schneider I, Meyer H, Neubronner J, von Schacky C, Hahn A: Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations–a comparative bioavailability study of fish oil vs. krill oil. Lipids in health and disease 2011, 10:145.

2. Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, Pedersen JI: Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids 2011, 46:37-46.

3. Maki KC, Reeves MS, Farmer M, Griinari M, Berge K, Vik H, Hubacher R, Rains TM: Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women. Nutrition research 2009, 29:609-615.

4. Kidd P: Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Alternative medicine review : a journal of clinical therapeutic 2011, 16:355-364.

5. Deutsch L: Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms. Journal of the American College of Nutrition 2007, 26:39-48.

6. Grimstad T, Bjorndal B, Cacabelos D, Aasprong OG, Janssen EA, Omdal R, Svardal A, Hausken T, Bohov P, Portero-Otin M, et al: Dietary supplementation of krill oil attenuates inflammation and oxidative stress in experimental ulcerative colitis in rats. Scandinavian journal of gastroenterology 2012, 47:49-58.

7. Sublette ME, Ellis SP, Geant AL, Mann JJ: Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. The Journal of clinical psychiatry 2011, 72:1577-1584.

8. Ballantyne CM, Braeckman RA, Soni PN: Icosapent ethyl for the treatment of hypertriglyceridemia. Expert opinion on pharmacotherapy 2013, 14:1409-1416.

9. Bloch MH, Qawasmi A: Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry 2011, 50:991-1000.

10. Martins JG: EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. Journal of the American College of Nutrition 2009, 28:525-542.

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Dr Nina Bailey

About Dr Nina Bailey

Nina is a leading expert in marine fatty acids and their role in health and disease. Nina holds a master’s degree in Clinical Nutrition and received her doctorate from Cambridge University. Nina’s main area of interest is the role of essential fatty acids in inflammatory disorders. She is a published scientist and regularly features in national health publications and has featured as a nutrition expert on several leading and regional radio stations including SKY.FM, various BBC stations and London’s Biggest Conversation. Nina regularly holds training workshops and webinars both with the public and health practitioners.