Clinical evidence for the use of krill oil in the treatment and prevention of cardiovascular disease

The n-3 polyunsaturated fatty acids, EPA and DHA, have been reported to have a variety of beneficial effects in cardiovascular diseases, notes Dr Inge Bruheim, Research Director, Rimfrost Group

Krill oil is a rich source of phospholipid-derived EPA/DHA, whereas the EPA and DHA in fish oils are bound in triglycerides. The difference between the chemical binding of EPA and DHA is thought to affect their bioavailability in favour of krill oil. Rimfrost has shown that EPA/DHA in krill oil has a higher 72-hour bioavailability than in krill meal compared with fish oil. However, longer-term studies using a parameter reflecting tissue fatty acid composition such as erythrocyte EPA plus DHA are needed.

Changes in dietary intake play a major role in the prevention and treatment of cardiovascular disease. The health of the Nordic populations has substantially improved during the last 30 years, partly as a result of the marked decline in cardiovascular morbidity and mortality. However, cardiovascular disease (CVD) caused by atherosclerosis is still the main cause of mortality worldwide.1

There are convincing links between the reduced risk of CVD and the consumption of marine omega-3 fatty acids such as EPA and DHA.2,3 This reduced CVD risk can partly be explained by the fact that the intake of omega-3 fatty acids is associated with a decrease in serum triglycerides (TG) and an increase in high density lipoprotein (HDL).4,5 In addition, studies have shown that omega-3 fatty acids reduce blood pressure, improve platelet activation and endothelial function, and reduce inflammation.6–9

Fish is a good source of EPA/DHA. However, fish production can’t easily be increased and, therefore, other sources are being explored. One of them is Antarctic krill, a shrimp-like crustacean that feeds on algae in deep ocean waters. In krill, EPA/DHA is bound to phospholipids, whereas in fish or fish oil, EPA and DHA are mainly found in triglycerides.

Phospholipids are amphiphilic and, as such, they have emulsifying features that can contribute to enhanced absorption. It has been debated whether or not these differences in the structure of n-3 fatty acids contribute to the bioavailability of fatty acids; that is, the incorporation of fatty acids into different lipid fractions in the systemic circulation and target tissues. So far, only Rampsrath has shown that krill oil supplementation increased the proportion of EPA+DHA in total plasma and erythrocytes more than fish oil after 4 weeks of consumption.10

New data on acute krill oil bioavailability

We compared the acute bioavailability of two different krill oil products, krill meal (Rimfrost Genuine, 40% oil content) and krill oil (Rimfrost Sublime), with fish oil. Each sample provided an equal amount (about 1700mg) of n-3 fatty acids.

Bioavailability was measured using different lipid fractions: plasma triglycerides (TG) and phospholipids (PL), all of which have slightly different lipid turnover rates (TG having the shortest and PL the longer one). The study was a randomised, single-blind, active-reference study with repeated measurements.

The largest EPA+DHA incremental area under the 72h response curve in plasma phospholipids (iAUCPL) was detected after krill oil ingestion (mean = 89.08 ± 33.36% x h). The iAUCPL post-krill oil ingestion was significantly larger than after krill meal ingestion (mean = 44.97 ± 18.07% x h, p<0.001) or fish oil supplementation (mean = 59.15 ± 22.22% x h, p=0.003).11

The krill meal food matrix was different from the other capsule formulations used in the study and that may have adversely affected the bioavailability of the fatty acids in that particular formulation. Therefore, the krill meal results are not shown. One explanation for the better bioavailability of EPA and DHA in krill oil is that krill oil contains substantial concentrations of EPA and DHA as free fatty acids.12

The content of free fatty acids in the krill oil used in this study, however, was low (2.6% of EPA and DHA as free fatty acids), supporting the view that the phospholipids in krill oil, and not the free fatty acids, are responsible for the higher recorded bioavailabilities.

Smaller AUCs in response to all three forms of EPA+DHA were detected in the triglyceride fraction than in the phospholipid fatty acids, and there was no significant difference between them. Clearly, however, the incorporation of fatty acids into plasma phospholipids or triglyceride fatty acids is not a random phenomenon, but rather a regulated process affected by the ratios of fatty acids present, endogenous production and individual status.

Conclusion

According to the primary endpoint, EPA plus DHA had a higher bioavailability in krill oil compared with fish oil. However, this was less consistently reflected in the secondary endpoints measured. To substantiate these findings, Rimfrost Group has initiated a new study, together with the University of Oslo and Akershus University College of Applied Sciences.

By comparing fish intake (fat and lean) with krill oil and applying longer-term parameters of omega-3 fatty acid bioavailability, such as plasma lipids, and other markers of cardiovascular health, including inflammatory, haemostatic and endothelial dysfunction markers, the company aims to provide further evidence to support these initial results.

References

1. World Health Organization (WHO), The Top 10 Causes of Death (www.who.int/mediacentre/factsheets/fs310/en/).

2. H.C. Bucher, et al., 'n-3 Polyunsaturated Fatty Acids in Coronary Heart Disease: A Meta-Analysis of Randomized Controlled Trials,' Am. J. Med. 112(4), 298–304 (2002).

3. W.S. Harris, 'n-3 Fatty Acids and Serum Lipoproteins: Human Studies,' Am. J. Clin. Nutr. 65(5 Suppl.), 1645–1654 (1997).

4. R. Buckley, et al., 'Circulating Triacylglycerol and apoE Levels in Response to EPA and Docosahexaenoic Acid Supplementation in Adult Human Subjects,' Br. J. Nutr. 92(3), 477–483 (2004).

5. J. Dyerberg, et al., 'Effects of Trans- and n-3 Unsaturated Fatty Acids on Cardiovascular Risk Markers in Healthy Males. An 8 Week Dietary Intervention Study,' Eur. J. Clin. Nutr. 58(7), 1062–1070 (2004).

6. J.M. Geleijnse, et al., 'Blood Pressure Response to Fish Oil Supplementation: Metaregression Analysis of Randomized Trials,' J. Hypertens. 20(8), 1493–1499 (2002).

7. E.M. Hjerkinn, et al., 'Influence of Long-Term Intervention with Dietary Counseling, Long-Chain n-3 Fatty Acid Supplements, or Both on Circulating Markers of Endothelial Activation in Men with Long-Standing Hyperlipidemia,' Am. J. Clin. Nutr. 81(3), 583–589 (2005).

8. O. Johansen, et al., 'The effect of Supplementation with Omega-3 Fatty Acids on Soluble Markers of Endothelial Function in Patients with Coronary Heart Disease,' Arterioscler. Thromb. Vasc. Biol. 19(7), 1681–1686 (1999).

9. P.C. Calder, 'n-3 Polyunsaturated Fatty Acids, Inflammation and Inflammatory Diseases,' Am. J. Clin. Nutr. 83(6 Suppl.), 1505–1519 (2006).

10. V.R. Ramprasath, et al., 'Enhanced Increase of Omega-3 Index in Healthy Individuals with Response to 4-Week n-3 Fatty Acid Supplementation from Krill Oil Versus Fish Oil,' Lipids Health Dis. 12, 178 (2013).

11. A. Köhler, et al., 'Bioavailability of Fatty Acids from Krill Oil, Krill Meal and Fish Oil in Healthy Subjects: A Randomized, Single-Dose, Crossover Trial,' Lipids Health Dis. 14(1), 19 (2015).

12. J.P. Schuchardt, et al., 'Incorporation of EPA and DHA into Plasma Phospholipids in Response to Different Omega-3 Fatty Acid Formulations: A Comparative Bioavailability Study of Fish Oil Versus Krill Oil,' Lipids Health Dis. 10(145), 1–7 (2011).

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