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Omega-3 wax esters from Calanus finmarchicus

This white paper is written by our trusted partner Springfield.

The availability of omega-3 fatty acids with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is under threat. Fish quotas have been tightened and fish management has improved. Another reason is the increasing demand for pelagic fish or fish oil. The production of fish oil can no longer meet the demands of the growing market. This has led to the search for alternative and sustainable sources of lipids containing omega-3 polyunsaturated fatty acids. A new source of ecologically responsible and sustainable omega-3 fatty acids for humans is Calanus® Oil.





Motor ecosystem in the Norwegian Sea

Calanus® Oil is an unrefined natural oil derived from the crustacean Calanus finmarchicus. The organisms floating in the water are part of zooplankton and belong to the class of Copepods.

Calanus finmarchicus is present in large quantities in the cold water of the Arctic Ocean. The animal (3-5 mm in length) is very popular because of the particular lipid composition and the relatively high content of astaxanthin, a carotenoid with anti-oxidative effect, responsible for the dark red colour [1].

Asbjørn Selsbane on it´s way to unload a fresh batch of Calanus finmarchicus

Unique composition: wax esters

Calanus® Oil has a chemical composition different from that of fish or krill oil. The peculiarity is that fatty acids occur at over 80 percent in the form of wax esters. These are long chains of fatty acids linked to fatty alcohols. As a result, the oil has specific health benefits that are absent from fish or krill oil, or are present to a lesser extent. 

High omega-3 fatty acid content including SDA

Calanus® Oil is a rich source of omega-3 fatty acids (20 percent), composed mainly of [2]

alpha-linolenic acid        ALA, 1.1%

eicosapentaenoic acid   EPA, 6.6%

docosahexaenoic acid    DHA, 4.5%

stearidonic acid              SDA, 7.0%

Research shows that this oil with essential fatty acids has a high bioavailability. This means that the fatty acids are well absorbed by the digestive tract, whereby the EPA and DHA plasma levels increase significantly [2]. 

Noteworthy is the high level of the omega-3 fatty acid stearidonic acid (SDA) that can be converted into EPA relatively easy  in the body [11]. In addition, this conversion is approximately 4.5 times more efficient than from alpha-linolenic acid [12]. 

A clinical study of 18 healthy volunteers showed that the EPA levels in the blood increased to a significant higher level after oral ingestion of Calanus® Oil in comparison with omega-3 fatty acids derived from fish oil, despite the twice higher dose of EPA from the fish oil capsules. It is plausible that the greater increase of the EPA blood level may be explained, at least in part, by the conversion of the SDA present in Calanus® Oil into EPA [1].

Wide application

In addition to the already known mechanisms of action of omega-3 fatty acids, Calanus® Oil can also contribute through a newly discovered mechanism, to the prevention or treatment of obesity, insulin resistance and low-grade inflammation. These symptoms and mechanism are associated with the metabolic syndrome but also with chronic conditions such as cardiovascular disease, diabetes, cancer or inflammatory bowel disease. In addition, the wax esters from Calanus® Oil increase aerobic capacity which is favourable for oxygen uptake and cellular energy supply [7].

Obesity and inflammation

Preclinical studies show that Calanus® Oil counteracts the effects of excessive fat consumption. To this end, groups of mice were compared.

One half of the group was deliberately fattened up through a high-fat diet (45 percent of the energy requirement from fat). The other half of the group followed a normal diet (10 percent of the energy requirement from fat). The body weight of the mice on the high-fat diet increased considerably, as did the amount of accumulated abdominal fat. The glucose tolerance of this group also decreased.

Subsequently, the group that followed the high-fat diet, was supplemented with 1-1.5% (w/w) Calanus® Oil. This showed that increased body weight, accumulated abdominal fat, fatty liver, insulin resistance and inflammatory processes in the abdominal fatty tissue decreased.

Calanus® Oil supplementation reduced the size of the fat cells (adipocytes) and increased the amount of adiponectin (measured at mRNA level), a protein hormone that plays a role in regulating glucose levels and the breakdown of fatty acids.

The anti-inflammatory effect was demonstrated by reduced infiltration of macrophages. Moreover, the production of inflammatory cytokines, tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 decreased [3].

A follow-up study compared the metabolic effects of wax esters obtained from Calanus® Oil with those of purified EPA and DHA ethyl esters in a mouse model of diet-induced obesity. Mice that initially followed a high-fat diet were supplemented with either wax esters or a combination of EPA / DHA after seven weeks. A third group received a high-fat diet without supplementation throughout the 27-week feeding period.

Again, the wax esters decreased the increase in body weight, abdominal fat and fatty liver by 21%, 34% and 52%, respectively.

Both glucose tolerance and aerobic capacity improved significantly. This time too, the inflammatory processes in the abdominal tissue decreased. Thus, the wax esters obtained from Calanus® Oil have virtually the same effects as the complete crude oil. In addition, the ethyl esters of EPA and DHA showed none of these metabolic effects, with the exception of the anti-inflammatory effect [4].

Interestingly, the effects of Calanus® Oil are not only preventative but also therapeutic. The oil also seemed beneficial, regardless of whether the supplementation was started before or after the onset of obesity and glucose intolerance [3-4].

Good for the heart and blood vessels 

Other preclinical (animal experimental) research indicates that Calanus® Oil may possibly be used in the prevention of atherosclerosis. The process of arteriosclerosis could be delayed [5]. Other animal experimental studies discuss the possible role of Calanus® Oil in hypertension [6].

The mechanism of action: fatty acid sensors in the intestines

The difference in activity between omega-3 fatty acids from Calanus® Oil and fish oil is probably due to the slower degradation and absorption of wax esters, compared to ethyl esters or triglycerides (fats) from fish oil supplements. In the digestion of wax esters, the free fatty acids are released in the lower part of the intestine: in the distal part of the small intestine (ileum) and the of the large intestine (colon) [1,3]. These intestinal regions are rich in receptors, the free fatty acid receptor 4 (FFA4), to which free fatty acids, including the omega-3 fatty acids, bind. FFA4 is a G-protein coupled receptor involved in the signal transfer of hormones, neurotransmitters and other messenger substances. It is also called GPR120.

Research on these receptors is relatively new and is expanding rapidly related to obesity and metabolic syndrome.

These receptors appear to be involved in the homeostatic regulation of systemic (generalised) metabolic and inflammatory processes via cells of the immune system (macrophages) and fat cells (adipocytes). When fatty acids are absorbed via the intestinal wall, the FFA4 receptors, also known as fatty acid sensors, are activated. Both EPA and DHA as well as SDA are potent stimulators of FFA4 which can may inhibit the development of obesity and diabetes.

After activation of FFA4 receptors, hormones are released that play a role in digestion (cholecystokinin), glucose homeostasis (glucagon-like peptide-1 and gastric inhibitory polypeptide), gastric emptying and signal transfer related to hunger and satiety (ghrelin and leptin).

Researchers observed that reduced FFA4 function, due to gene-variants, may play a role in the development of obesity, insulin resistance and the accompanying low-grade inflammatory processes (9). Also in obese people, it has been shown that FFA4 was present to a lesser extent. This means, the gene expression of FFA4 is reduced and a lower activity is shown [9, 10].

The study of Calanus® Oil shows that the digestion of wax esters and the release of free fatty acids occur mainly in FFA4-rich parts of the intestines. Here, the fatty acids bind to the FFA4 receptors present on enteroendocrine cells.

Then hormones are released that regulate the metabolism and the conversion of fats and sugar. In addition, Calanus® Oil inhibits the production (gene expression) of pro-inflammatory cytokines [3,7].

Summary

In summary, Calanus® Oil appears promising for the prevention and / or treatment of overweight. The fat deposits in and around the abdomen decrease, as well as the associated inflammatory processes. This is important for general health, including metabolic diseases, cardiovascular diseases and possibly joint disorders. Glucose tolerance and insulin sensitivity may improve. This is beneficial in the fight against diabetes. The overall energy level also increases due to increased aerobic capacity.

It should be emphasized that most study results are currently based on preclinical research. This implies that the effects found have not yet been demonstrated in humans. At the same time, follow-up clinical studies are underway. In the Czech Republic, for example, the effects of Calanus® Oil on muscle strength and insulin sensitivity are studied in 51 elderly people. In Norway, there is a clinical study on Calanus® Oil, ADHD and cognitive abilities in children. Other Norwegian research concerns inflammatory bowel disease [13].

Suggested applications

Calanus® Oil can potentially be of benefit in the prevention and / or treatment of obesity, metabolic syndrome, insulin resistance, inflammatory (bowel) disorders, aerobic capacity and endurance.


REFERENCES

1. Cook CM, Larsen TS, Derrig LD, et al. Wax Ester Rich Oil From The Marine Crustacean, Calanus finmarchicus, is a Bioavailable Source of EPA and DHA for Human Consumption. Lipids. 2016 Oct;51(10):1137-1144.

2. Application for the Approval of Calanus® Oil as an Ingredient for Use in Food Supplements, 2011.

3. Höper AC, Salma W, Khalid AM, et al. Oil from the marine zooplankton Calanus finmarchicus improves the cardiometabolic phenotype of diet-induced obese mice. Br J Nutr. 2013 Dec;110(12):2186-93.

4. Höper AC, Salma W, Sollie SJ, et al. Wax esters from the marine copepod Calanus finmarchicus reduce diet-induced obesity and obesity-related metabolic disorders in mice. J Nutr. 2014 Feb;144(2):164-9.

5. Eilertsen KE, Mæhre HK, Jensen IJ, et al. A wax ester and astaxanthin-rich extract from the marine copepod Calanus finmarchicus attenuates atherogenesis in female apolipoprotein E-deficient mice. J Nutr. 2012 Mar;142(3):508-12.

6. Salma W, Franekova V, Lund T, et al. Dietary Calanus oil antagonizes angiotensin II-induced hypertension and tissue wasting in diet-induced obese mice. Prostaglandins Leukot Essent Fatty Acids. 2016 May;108:13-21.

7. Höper AC. Calanus oil and its lipid constituents. Impact on obesity and obesity-related metabolic disorders in rodents. Dissertation, The Arctic University of Norway, December 2013.

8. Anbazhagan AN, Priyamvada S, Gujral T, et al. A novel anti-inflammatory role of GPR120 in intestinal epithelial cells. Am J Physiol Cell Physiol. 2016 Apr 1;310(7):C612-21.

9. Oh DY, Olefsky JM. Omega 3 fatty acids and GPR120. Cell Metab. 2012 May 2;15(5):564-5.

10. Cvijanovic N, Isaacs NJ, Rayner CK, et al. Lipid stimulation of fatty acid sensors in the human duodenum: relationship with gastrointestinal hormones, BMI and diet. Int J Obes (Lond). 2017 Feb;41(2):233-239.

11. Whelan J. Dietary stearidonic acid is a long chain (n-3) polyunsaturated fatty acid with potential health benefits. J Nutr. 2009 Jan;139(1):5-10. Epub 2008 Dec 3.

12. James MJ, Ursin VM, Cleland LG. Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids. Am J Clin Nutr. 2003 May;77(5):1140-5

13. Ulven T., Christiansen E. Dietary fatty acids and their potential for controlling metabolic diseases through activation of FFA4/GPR120. Annu. Rev. Nutr. 2015. 35:239–63

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