Review of the Health Benefits of Antarctic Krill

Author: Mikko Griinari and Inge Bruheim (Clanet Oy, Finland and Olympic Seafood AS, Norway)

Abstract

Clinical studies demonstrate that krill oil is an effective omega-3 source at a low level of dietary supplementation. A number of different factors appear to contribute. Phospholipid bound omega-3 fatty acids in krill are more bioavailable than fish oil omega-3 and the phospholipid binding also increases the bioefficacy of omega-3 fatty acids. Further evidence on possible mechanisms is provided by krill oil studies in experimental animal models. Krill oil alters lipid metabolism in dyslipidemia and modulates the inflammatory response. Some of the krill oil effects appear to be mediated through endocannabinoids and at the level of gene transcription. In addition to the highly bioactive omega-3 phospholipids of the lipid fraction, krill proteins have come into focus. Initial investigations on the potential health effects of krill protein have been successfully conducted.

Introduction

Antarctic krill (Euphausia superba) is a small crustacean that has generated a lot of research interest during the past several years. This review focuses on krill derived products and their uses as health promoting nutritionals. Krill oil is, by far, the most widely studied krill product. Potential health promoting effects of other products derived from krill, including krill protein, have only recently been examined. Krill oil is characterized by its phospholipid bound omega-3 fatty acid content and red colour coming from the carotenoid antioxidant astaxanthin. These compositional features make krill oil different from any other omega-3 source. There is increasing evidence that the phospholipid form of the krill oil omega-3 fatty acids enhances its efficacy.

The history of omega-3 research expands over three decades and today the health promoting effects of long chain omega-3 fatty acids are well characterized. During the past 30 years, the evidence of the positive health effects of omega-3 fatty acids has been published in thousands of research papers. Over 200 scientific reviews summarizing omega-3 research were published last year alone. Most of this research involves fish oil omega-3 fatty acids. The areas of health and physiological function covered in these reviews include mental health and cognitive function, management of inflammatory conditions (gastrointestinal tract, joints, brain etc.), obesity and metabolic syndrome, neuroprotection, allergies and many more.

The area of omega-3 nutrition and health is very broad and the potential uses of krill oil omega-3 phospholipids are equally broad. This review will provide an overview of research performed, thus far, with krill oil and other krill derived products.

Clinical studies – efficacy at a low dose

Early studies demonstrated pronounced effects at low doses of krill oil supplementation. A daily dose of 0.3 g of krill oil reduced inflammation and alleviated arthritic symptoms within a short treatment period of 7 and 14 days in patients with cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis (Deutsch 2007). A multiple dose study (1 to 3 g/d) in hyperlipidemic patients compared krill oil and fish oil and found that krill oil was effective in management of hyperlipidemia by significantly reducing total cholesterol, LDL-cholesterol, and triglycerides, as well as increasing HDL-cholesterol levels. At lower or equal doses, krill oil was
significantly more effective than fish oil in reducing blood glucose, triglyceride, and LDL-cholesterol levels (Bunea et al. 2004).  Furthermore, a study in patients diagnosed with premenstrual syndrome (PMS) compared the effects of krill oil and fish oil supplemented at a daily dose of 2 g. Krill oil reduced emotional symptoms of PMS and pain associated with dysmenorrhea. Krill oil was shown to be more effective than fish oil (Sampalis et al. 2003).  These documented clinical responses are remarkable considering that the daily dose of omega-3 fatty acids, EPA and DHA, ranged from only 72 mg/d to 720 mg/d. It is a commonly held view that significant improvement in pain and mobility of arthritic joints as well as alleviation of hypertriglyceridemic condition can be produced only with high fish oil supplement doses providing 2000 to 4000 mg/d EPA and DHA.

Recent studies performed at similar doses of krill oil (2 to 3 g/d) have demonstrated safe use of krill oil in obese subjects (Maki et al. 2009), more effective enrichment of EPA and DHA in plasma lipids from krill oil compared to fish oil (Ulven et al. 2010) and positive changes in metabolic regulation involving the endocannabinoid system (Banni et al. 2011). Two studies (Maki et al. 2009, Ulven et al. 2010) examined the effect of omega-3 supplementation on serum lipids and found no changes between the study groups. These studies were performed in relatively small group of healthy volunteers, which may have influenced the outcome of the studies. Examination of individual responses in serum TG levels in the study by Ulven et al. (2010) revealed a close inverse correlation between baseline serum TG levels and change in TG levels after 7 weeks of intervention in the krill oil group, but not in the fish oil group. This observation suggests that krill oil may be effective in reducing serum TG levels in hypertriglyceridemic individuals at relatively low dose of omega-3 intake (543 mg/d).

Study demonstrates superior bioavailability of krill oil omega-3

A recent study by Schuchardt et al. (2011) determined the bioavailability of omega-3 fatty acids based on plasma phospholipid incorporation for a high dose of omega-3 fatty acids from three different sources: fish oil triglycerides, fish oil ethyl esters and krill oil. This was a single dose study with a 72 h follow up. The omega-3 dose for all oil supplements was 2100 mg and in the case of krill oil this meant ingestion of 14 capsules at one time and 7 g of oil. Although, 7 g of krill oil represents a very high level of intake and outside the range of doses tested in clinical studies, the observations are still noteworthy. Bioavailability of krill oil EPA and DHA was found to be highest, although the differences between krill oil and fish oil products were only borderline significant. Clearly the bioavailability of dietary omega-3 fatty acids improves when they are bound to phospholipids. However, the improvement in bioavailability may not be sufficiently large to explain the pronounced differences in clinical responses in studies comparing krill oil and fish oil. Postabsorptive
metabolism of the krill oil omega-3 fatty acids is likely to be influenced by the association with the phospholipids.

Increased bioefficacy of omega-3 phospholipids and astaxanthin

Another possible contributing factor to the observed efficacy of krill oil as a source of omega-3 fatty acids is the effective post-absorptive transfer of phospholipid bound omega-3 fatty acids to target tissues. Previous research has examined the metabolism of dietary DHA and found that the metabolic fate of DHA differs substantially when ingested as triglycerides compared to phosphatidylcholine, both in terms of bioavailability of DHA in plasma and accumulation in target tissues (Lemaitre-Delaunay et al., 1999). Phospholipids have also been suggested to facilitate a more efficient transfer of omega-3 fatty acids to target tissues such as brain, liver and kidney (Lagarde et al. 2001; Wijendran et al. 2002; Graf et al. 2010). Bioefficacy describes a function of a nutrient, much deeper into the metabolic process than bioavailability. Bioavailability and bioefficacy are intrinsically related as bioefficacy describes the efficacy of use of a bioavailable nutrient. In a way, bioefficacy can also be viewed as the efficiency of conversion of a nutrient to active form. In the case of krill oil, omega-3 phospholipid represents an active form of omega-3 fatty acids. Incorporation of long chain omega-3 fatty acids to cell membranes requires that the fatty acid is associated with a phospholipid. No other form of fatty acid can be incorporated to cell membrane. It is possible that an omega-3 fatty acid in krill oil, preformed as a phospholipid, can be more easily recognized by the target tissue and thus improves the efficiency of use of this particular nutrient. Metabolism of krill oil astaxanthin is another example where bioavailability and bioefficacy are intrinsically linked. Astaxanthin is known to be highly potent antioxidant supporting the stability of cell membranes. As for all carotenoids, the bioavailability of astaxanthin is quite low. However, in association with krill oil phospholipids, the bioavailability of astaxanthin is increased. The formation of lyso-phospholipids during the digestive process of krill oil improves, through their detergent like action, the absorption of astaxanthin. Thus, the bioefficacy of astaxanthin is improved through the synergistic effect of nutrients present in krill oil.

Krill oil performs better than fish oil in experimental animal studies

Further evidence on a possible mechanism of action of krill oil in physiological processes is provided by experimental animal studies. In these studies the effects of krill oil are often contrasted with the effects of fish oil, both treatments providing equal amount of omega-3 fatty acids. Invariably, krill oil supplemented experimental animals perform better. Krill oil supplementation has corrected dyslipidemias and decreased lipid accumulation in the liver of high fat diet fed mice and obese rats (Tandy et al. 2009; Batetta et al. 2009), altered metabolic signalling via the endocannabinoid system and hepatic gene expression (Piscitelli et al. 2011; Burri et al. 2011), alleviated collagen induced rheumatoid arthritis and dextran sulfate sodium induced ulcerative colitis (Ierna et al. 2010; Grimstad et al. 2012). Results in the experimental animal models suggest that krill oil alters lipid metabolism in dyslipidemia and modulates the inflammatory response in disease conditions involving inflammation. Some of the krill oil effects appear to be mediated through endocannabinoids and at the level of gene transcription.

Future krill products contain protein

Krill oil has been the predominant krill derived nutritional product on the market for several years and therefore the primary target for research investigations. A limited number of experiments have been performed using krill protein as a treatment. Proteins from fish and other marine species have been shown to influence lipid metabolism in rodent models; reduce triglyceride and cholesterol levels compared to a casein diet (Jaques et al. 1995; Liaset et al. 2009), as well as reduce inflammation in response to feeding high-fat diets
(Pilon et al. 2011). Importantly, the combination of omega-3 fatty acids and marine protein appear to have a synergistic effect on plasma lipid lowering (Wergedahl et al 2009; Hosomi et al. 2011). Only a few studies have examined the potential health effects of krill protein. Krill protein concentrate was shown to be a good source of EPA and DHA in growing rats (Bridges et al. 2010), and to prevent renal injury in female Sprague–Dawley rats (Gigliotti et al. 2011). Fat-free krill powder consisting of hydrolyzed protein demonstrated antihypertensive effects in spontaneously hypertensive rats. Two peptides with angiotensin I-converting enzyme inhibitory effects were subsequently isolated from this hydrolysate (Hatanaka et al. 2009). Recently, a krill meal product containing lipid and protein (55 and 37%, respectively) demonstrated a broad range of effects in a mouse model of dyslipidemia and chronic inflammation (Bjorndal et al. (in press)). An anti-inflammatory effect was confirmed as a reduction of the levels of inflammatory mediator, TNFα, in the liver.  Furthermore, plasma triglyceride and cholesterol levels were reduced and a number of hepatic genes involved in lipid, cholesterol and glucose synthesis were down regulated. These recent studies in experimental animals point the direction of future clinical studies. Combinations of krill oil and krill protein clearly have potential to act synergistically to promote human health.