OmegaPC ™ Scientific Summary October 2013 Overview The correlation between fish consumption as part of a balanced diet and its health benefits has been known for many years. Fish are a rich source of high quality protein, vitamins and minerals, and are the main dietary source of omega-3 fatty acids. The capacity of omega-3 fatty acids (FA), mainly EPA and DHA, to protect humans from a variety of diseases such as cardiovascular diseases (CVD), depression, inflammation and other ailments, is well established. Studies of Greenland Inuit, as well as in other populations whose daily diets are rich in marine sourced foods, demonstrated this fact many years ago. Ever since these early observations, scientific evidence of the health protecting properties of fish in general, and omega-3 FA in particular, has been accumulating. Unfortunately, modern day diet, especially what is known as “Western diet”, is lacking both fish and omega-3 FA, and CVD has become the primary cause of mortality in the Western world. Omega PC™ is a new generation of fish oil extract, comprised of omega-3 fatty acids bound to both phospholipids and triglycerides, thus much closer to the natural form of omega-3 FA found in wild cold water fish. Each of the Omega PC™ components was tested for safety and efficacy by a battery of pre-clinical and clinical trials, which proved its safety and beneficial contribution to human health. These studies revealed that Omega PC™ may be effective for multiple indications, from chronic inflammation to hyperlipidemia, cognitive function, fatty liver disease, joint health and more. In Omega PC™, most of the omega-3 FAs are linked to phospholipids. Studies have shown that when omega-3 FAs are linked to phospholipids they are better absorbed by the target organs such as the heart, brain and liver, where they exert their beneficial effects. Other studies show that phospholipid-bound omega-3 FAs also have better efficacy, for example, in raising the omega-3 index, whose higher levels are indicative of reduced risk of CVD. Finally, in contrast to fish oil supplementation, consumption of Omega-PC does not cause “fishy burps” and fishy aftertaste due to the phospholipids. Enzymotec’s Omega PC™ is manufactured by a propriety MSO™ process which better preserves the natural form of the omega-3 fatty acids. Omega PC™ is produced under ISO22000:2005 requirements, attesting to its high quality, and under Good Manufacturing Practice. -2- Ludwig Andreas Feuerbach was the one who coined the phrase “a man is what he eats” as early as 1862. The vast knowledge we have accumulated on nutrition supports the realization that what we eat relates directly to our lives, and that changes in our diet have a significant impact on our health. Western diet has changed, from natural foods based on fruits, vegetables, whole grains and more, to an industrialized and processed diet, rich in calories and fat, and low in nutrients. Concurrently to these changes in our diets, so are changes in ailments which plague us. The rise in the incidence of diseases such as diabetes, cancer and cardiovascular diseases came hand in hand with the changes in our diet. Nutritional changes are regarded as contributing factors to the increasing rise in obesity, diabetes and heart diseases. Heart attacks and strokes, both part of a group of diseases known as cardiovascular diseases (CVD), are usually acute events and are mainly caused by a blockage that prevents blood from Western diet has changed, flowing to the heart or from natural foods based brain. The most common on fruits, vegetables, whole reason for this is a build- grains and more, to an up of fatty deposits on industrialized and processed the inner walls of the diet, rich in calories and fat, blood vessels that supply and low in nutrients the heart or brain. CVD is now the number one killer in the Western world. In 2008, 30% (!) of all deaths around the world were attributed to CVD, estimated at 17.3 million cases and by 2030 that number is estimated to increase to 23 million people per year1. The Inuit Paradox The fascinating finding that Greenland Inuit and Canadian indigenous people have almost no occurrence of CVD2 further strength- The Inuit paradox ened the role of nutrition How can a typical diet of the in the rising incidence of Inuit, predominantly consisting death from cardiac dis- of fish, seal meat, fat and eases. This was reported blubber and almost completely by Rabinowitch in the void of greens, fruits and 1930s, and was reaf- fibers (so much that some firmed by Bang and Dy- researchers termed this diet erberg during the 1970s “carnivorous”), be preventative and 1980s3-5. When Rab- of the very diseases which inowitch joined the Cana- plague the entire western dian Government East- world due to diets high in ern Arctic Patrol of 1935, saturated fats and cholesterol? in order to survey the indigenous people of northern and eastern Canada, he noticed the absence of heart diseases among these people6. Moreover, he also no- ticed that the rate of diabetes was far below his expectation, and rates of cancer of most types were extremely low6. Even earlier in the 20th century researchers noted that indigenous people of the north suffered from almost no CVD7. Population studies conducted in Greenland between 1950 and 1974 highlighted this notion (figure 1), while raising a very intriguing and important question: How can a typical diet of the Inuit and of Canadian indigenous people, predominantly consisting of fish, seal meat, fat and blubber and almost completely void of greens, fruits and fibers (so much that some researchers termed this diet “carnivorous”3), be preventative of the very diseases which plague the entire western world and for which medical orthodoxy blames diets high in saturated fats and cholesterol? This contradiction has became known as “the Inuit Paradox”8. Heart Disease 45% Percent of deaths attributed to heart diseases (all kinds) Human health and modern diet 40% 35% 30% 25% 20% 15% 10% 5% 0% Greenland Inuit Danes Americans Figure 1: Deaths attributed to heart diseases in various populations (Wollongong University) Most researchers studying indigenous people of the north related the lack of CVD and diabetes with the diet of these people6, 7, 9. This diet changed between locations, but, even in places where modern diet was available, it was always rich in meat and fat of marine mammals and plenty of fish. Health benefits of fish consumption A comparison between Inuit living in Greenland and Inuit who immigrated to mainland Denmark revealed that the levels of various lipids in the plasma of Dane-Inuit were similar to those of healthy Caucasian Danes. However, this was completely different from Greenland-Inuit, who had lower total lipids, lower cholesterol and lower triglycerides7. This finding highlighted the role of nutrition, as the genetic background of both Inuit groups was identical. Bang and colleagues also compared the nutrition of Inuit to that of neighboring Danes. This comparison showed that Inuit consume half of the omega-6 fatty acids (FAs) than the Danes do, and 5 times the omega-3 FAs. Thus, the fact that the Inuit diet is rich in marine-source oils, which are rich in omega-3 FAs, and contrary to western diets which are rich in omega-6 FAs, gained focus3. Correlation Between Fish Consumption and Death from IHD Observations showing health benefit for people whose diet contain high levels of marine-source oils are not unique to the Inuit. Japanese studies compared agricultural villagers to fishermen. Fish- The answer to the paradox: ermen consumed three Inuit diet was always rich times more fish than the in meat and fat of marine farmers did. The impact mammals and plenty of fish on plasma lipid profile was pronounced, with elevated levels of omega-3 FA in the fishermen’s blood. Interestingly, increased time of coagulation was noted in the blood of the fishermen [a factor related to formation of blood clots (thrombosis), and thus to CVD and stroke10]11. Deaths from IHD (per 100,000) 200 USA 150 Korea Japan 100 Inuit 50 0 Epidemiological studies also highlight the importance of fish consumption to our health. Sekikawa and colleagues compared the intake of fish in Japan, Korea, Iceland and the US and correlated this intake to the prevalence of heart diseases in these countries. Japan had the Epidemiological studies highest per capita conhighlight the importance sumption of fish (close of fish consumption to to the fish consumption our health; evidence show of Canadian indigenous benefit of eating fish on heart people12), followed by diseases, inflammation, Korea. The US concognition, risk of stroke, sumption was less than general wellbeing and more 10% than Japans’. In an inverse correlation, mortality from heart diseases was lowest in Japan and highest in the US. Americans, consuming small amounts of fish, had 4 times the mortality rate from ischemic heart diseases (IHD) than did the Japanese (figure 2)13. Interestingly, according to the World Health Organization (WHO), Japan is the nation with the highest life expectancy14. A larger epidemiology study conducted in 36 countries also revealed a clear inverse correlation between fish consumption, death from ischemic heart disease and allcause mortality15. Iceland 0 50 100 Figure 2: Correlation between fish consumption and mortality from ischemic heart disease (IHD) in various countries (adapted from Sekikawa 201213 and Nobmann 199212) Additional observatory and intervention studies highlight the health benefits of eating fish. An American study followed healthy men for 30 years and correlated between fish consumption and deaths from coronary heart disease (CHD). Those eating more than 250 gram of fish per week had 38% less chance of dying from CHD and 44% less chance of dying from heart attack, relative to those not eating fish (figure 3)16. In the Diet and Reinfarction Trial (DART), men after myocardium infarction (MI, “heart attack”) were instructed to increase their fish consumption and were followed up for two years. Those consuming fish (2-3 portions, or 300450 grams per week) in accordance with the instruction, experienced 29% less mortality (all causes, including cardiac related) compared to those not eating fish17. In a recently published study, Harvard researchers followed the levels of omega-3 in the blood of healthy people for 16 Relative Risk (95% CI) 0.62 (0.4-0.94) Coronary heart disease 0.56 (0.33-0.93) Myocardial infarction 0.3 0.4 0.5 150 Fish consumption (g/day) 0.6 0.7 0.8 0.9 1 Figure 3: Correlation between fish consumption and mortality from coronary heart disease and from myocardial infarction (adapted from Daviglus 199716) -4- years. The results suggested that those who had the highest levels of omega-3 FA in their blood at study initiation lived longer (by 2.2 years), died less from all causes (by 27%) and especially from CHD (by 40%). Since participants of the study were not taking omega-3 supplements, and the only dietary source of omega-3 is from fish, the results clearly show a benefit for eating fish18. Thus, eating fish was shown to protect from cardiovascular diseases, for both men and women, significantly reducing mortality from these ailments. Another well-known effect of eating fish is on cognition, as was demonstrated in a study of more than 200 elders, in which the cognitive state of the subjects was monitored throughout the 5 year study. The subjects underwent a Mini-Mental State Examination (MMSE, used to assess general cognition, mostly in elderly21) test and the scores were compared between those eating fish and those who do not. The results clearly showed (figure 5) that consumption of fish protects from cognitive decline22. Consumption of Fish Prevents Cognitive Decline Eating fish asserts many beneficial health effects in addition to CVD. For example, the health benefits of consuming fish were assessed by a joint forum of the United Nations Food The World Health and Agriculture Organiza- Organizationconcluded that tion and the World Health “healthy dietary patterns Organization19. The con- that include fish and are clusions of this assess- established early in life ment were that maternal influence dietary habits and fish consumption during health during adult life” pregnancy lowers the risk of suboptimal neurodevelopment in newborn babies compared to women not eating fish, and that in children “healthy dietary patterns that include fish and are established early in life influence dietary habits and health during adult life”19. Interestingly, another study, this time correlating between fish consumption and depression, reached strikingly similar results. The results of the study gave a pattern (figure 4) similar to the cross national differences in mortality from CVD mentioned above. The author suggests that there may be similar dietary risk factors for CVD and depression20. Correlation Between Fish Consumption and Depression Annual prevalence of depression (rate/100 people) 8 Canada Germany France USA 4 Korea Japan 2 0 0 50 100 MMSE score 26.5 1990 1995 26 25.5 25 * 24.5 *p<0.01 24 Fish consumers Fish nonconsumers Figure 5: Correlation between fish consumption and cognitive decline (adapted from van Gelder 200922) Scientific studies also demonstrate benefits of eating fish in reducing risk of stroke10, 23, reduction of some types of cancer, such as colorectal24 and other types6, as well as general well-being19. The health benefits of omega-3 consumption are scientifically well-substantiated New Zealand 6 27 150 Fish consumption (lbs per person per year) Figure 4: Correlation between fish consumption and depression in various countries (adapted from Hibbeln 199820) While initial studies have shown that there are substantial health benefits to eating fish, there are factors which limit the consumption of fish for many people. The The availability of fish for many availability of fish for inland communities is limited; many inland communi- thus, the use of fish oil, ties is limited, and ship- containing various amounts of ment of frozen fish over omega-3 FAs, remains almost large distances is ex- a sole source of omega-3 for pensive. Additionally, many people many people are concerned with contamination of fish with heavy metal depositions, mainly mercury, as well as with other toxins, and possible detrimental effect of these contaminants25, 26. Personal taste and culinary considerations also prevent people from eating fish. Thus, the use of fish oil, containing various amounts of omega-3 FAs, remains almost a sole source of omega-3 for many people. -5- Omega-3 fatty acids (also termed n-3 or ω-3) are a group of long chain polyunsaturated fatty acids (PUFA) made of at least 16 carbons with multiple unsaturated bonds, in which the first unsaturated bond is on the third carbon (unlike omega-6 FA where the first unsaturated bond is on the sixth carbon). Alpha-linolenic acid (ALA), which is a fatty acid with 18 carbons and 3 unsaturated bonds also named 18:3, is an omega-3 FA from plant sources. This is the only omega-3 fatty acid considered to be an essential fatty acid, meaning it cannot be synthesized in the body and must be obtained through the diet. Eicosapentaenoic acid (EPA, fatty acid with 20 carbons and 5 unsaturated bonds also named 20:5) and Docosahexaenoic acid (DHA, fatty acid with 22 carbons and 6 unsaturated bonds also named 22:6) can either come from the diet or be converted in the body from ALA. Although EPA and DHA are not essential, the conversion of ALA to EPA and DHA is not very efficient27, since the enzymes used for the conversion are also used to convert the essential omega-6 FA linoleic acid (LA) to omega-6 PUFA. Since we consume up to 20 times more LA than ALA in modern diet, the availability of the enzymes to convert ALA to EPA and DHA is very low28, estimated to be less than 2%27. This means that even if we consume the recommended daily amount of ALA, which is between 1-2 gram/day29, we obtain only between 20-40 mg DHA from that source. Therefore, the levels of EPA and DHA are low unless consumed in the diet, so much that some researchers have begun referring to EPA and DHA as “conditionally essential”30. While ALA comes from plants, the dietary sources of EPA and DHA are mainly from the sea, from cold water fatty fish, certain crustaceans and algae. Health benefits of omega-3 FA consumption were tested in a large number of clinical trials, demonstrating beneficial effects on CVD, inflammation, depression and more. The clinical trials tested the effect of fish oil conWhile ALA comes from plants, sumption on various the dietary sources of EPA and populations, such as DHA are mainly from the sea, healthy subjects considfrom cold water fatty fish ered at risk for CVD, subjects with active CVD, and subjects after myocardial infarction (MI, “heart attack”). In the GISSI-prevenzione trial, more than 11,000 patients after MI received either omega-3, vitamin E, a combination of both, or placebo, as part of their treatment. Those in the omega-3 group had lower mortality and lower cardiac death rate31. In a follow-up trial, the GISSI-HF, close to 7,000 patients with chronic heart failure were treated with either omega-3 or placebo for approximately 4 years. Participants in the omega-3 group had lower total mortality and fewer cardiac events compared with participants in the placebo group32. The beneficial effects of fish and omega-3 on cardiovascular health are generally attributed to a number of factors, as noted in most trials where fish or omega-3 were given to healthy subjects, as well as for subjects with various cardiac diseases: • A clear and significant reduction in blood triglyceride levels33-35 (which is important to CVD but also very important for diabetics36) • A small, but significant and consistent elevation in HDL cholesterol (the “good” cholesterol)33, 37, 38 As with eating fish, the consumption of omega-3 FAs has beneficial health effects on many diseases other than inflammation and CVD. These health benefits are backed by substantial scientific data, showing that consump- As with eating fish, the tion of omega-3 fatty ac- consumption of omega-3 FAs ids has positive effects on has beneficial health effects brain development39, be- on inflammation and CVD, on havior, mood and more40. brain development, behavior, Omega-3 FAs seem to mood and more. have cognitive benefits41 and to be vital throughout all entire human life cycle, from embryo development through childhood, adolescence, adulthood and senior years. Omega-3 index – a new prognostic marker for CVD William Harris suggested in 2004 that the sum of EPA+DHA as a percent of total red blood cell (RBC) membrane fatty acids, which he termed “the omega-3 index”, may be used as a prognostic marker to assess the risk of CVD42. Studies which followed assessed the correlation between the omega-3 index and the risk of CVD. The studies indicated a clear independent and inverse correlation “The omega-3 index” may be between the omega-3 used as a prognostic marker index and risk (mea- to assess the risk of CVD sured as relative risk or odds ratio) of various aspects of CVD, such as sudden cardiac death and acute coronary syndromes (figure 6), leading to the development of the omega-3 index scale. The scale (figure 7) has two cutoffs, one at 4% suggesting that levels of omega-3 index that are lower than 4% are undesirable, since this level is correlated with high risk of CVD, while the 8% cutoff indicates a desirable zone, meaning that people with omega-3 index higher than 8% have very low risk of CVD. -6- Relative Risk of Sudden Cardiac Death: Prospective Cohort Odds Ratio for Primary Cardiac Arrest: Case-Control 1 0.9 0.8 * 0.7 0.6 0.4 * 0.3 * RR/OR 0.5 0.2 0.1 *p<0.05 0 3.9% 5.1% 6% 7.3% 3.9% 5.1% Estimated Omega-3 Index 6% 7.3% Omega-3 Index Figure 6: Correlation between omega-3 index and risk of sudden cardiac death (left panel) or cardiac arrest (right panel) (adapted from Harris 200743) Proposed Risk Zones for the Omega-3 Index UNDESIRABLE 0% INTERMEDIATE 4% DESIRABLE 8% Percent of EPA+DHA in RBC Figure 7: William Harris’ omega-3 index suggested zones [Adapted from Harris 200743] Recommendations from official authorities regarding the consumption of fish and omega-3 The many studies showing health benefit of omega-3 FA have led the Technical Committee on Dietary Lipids of the International Life Sciences Institute North America to issue a statement in regards to omega-3 and CVD: “Consistent evidence from multiple research paradigms demonstrates a clear, inverse relation between EPA+DHA intake and risk of fatal (and possibly nonfatal) chronic heart disease, providing evidence that supports a nutritionally achievable recommendation for EPA+DHA of between 250 and 500 mg/day”44. The American Heart Association (AHA), the Food and Drug Administration (FDA) and the US Department of Agriculture (USDA) recommendations suggest that eating 300 grams of cold water fatty fish every week may benefit the lives of healthy persons, those who are at risk of CVD, and those who are suffering from CVD. Below is a list of Many official authorities issued recommended fish and recommendations regarding omega-3 consumption in the consumption of fish and/or various countries. omega-3 -7- Table 1: Recommended fish and omega-3 consumption in various countries Country Recommended fish consumption Recommended omega-3 consumption Recommending organization USA 300 g/week 250-500 mg/day American Heart Association, US Department of Agriculture44-46 Australia / New Zealand 300-450 g/week 318-425 mg/day Australian Heart Foundation47 European Union 150-300 g/week 250 mg/day European Food Safety Authority (EFSA)48, 49 Belgium 300 g/week 1000 mg/day Superior Health Council28 500 mg/day Agence Francaise de Sècurité Sanitaire des Aliments44 France UK 150-300 g/week 450 mg/day Food Standards Agency and the Department of Health50 The Netherlands 300 g/week 450 mg/day Health Council of the Netherlands51 Global 150-300 g/week 200-500 mg/day World Health Organization52 Despite the recommendations, a review of the Dietary Guidelines for Americans46 reflects on the fact that the average intake of fish in the USA is less than 100 grams per week, and many do not eat fish products at all. Australians eat less than 200 grams of fish per week, most of which is composed of non-fatty fish poor in omega-347. Moreover, more than Despite the recommendations, 50% of the fish we eat to- average intake of fish in the day come from farmed USA is less than 100 grams stocks, and this number per week, and many do not eat is rapidly growing53. fish products at all Some of these farmed fish (for example trout54 and halibut55) provide omega-3 levels which are far below the levels known for wild fish of the same species. For the reasons stated above, it seems that a supplementation of omega-3 is both safe and convenient. The difference in composition between fish oil and fish One should always bear in mind that fish and fish oil are not alike. Fish contain large amounts of high quality proteins, various vitamins and minerals, as well as fat, which is extracted in the production of fish oil. The fat in fish (as in all animals) is composed of two different forms of lipids, triglycerides and phospholipids, each with a different chemical structure and with different biological roles. The next section will discuss the differences between triglycerides and phospholipids. Phospholipids and triglycerides: structure and roles Fish fat is made of two forms of lipids, phospholipids and triglycerides. Phospholipids are distinct from triglycerides in both their structure and their role in the Fish fat is made of two forms living organism. of lipids, phospholipids and Phospholipids are triglycerides considered the building blocks of the cell membrane while triglycerides are used by the human body as an energy source and storage molecule. Both triglycerides and phospholipids are comprised of FAs attached to a glycerol (which is a short chain of 3 carbon atoms) backbone (figure 8). However, the triglyceride molecule has three FAs attached to the glycerol backbone (figure 8a), while a phospholipid molecule only has two FAs and a polar head group attached to the glycerol backbone (figure 8b). The polar head group is comprised of a phosphate and an organic (carbon based) molecule, linked to each other. When the organic molecule is choline, the phospholipid is called phosphatidylcholine (PC) (figure 8b). Phospholipids are amphipathic molecules, meaning they have hydrophobic (water fearing, also termed non-polar) FAs on one side and a polar, hydrophilic (water loving), head group on the other. This unique structure allows them to construct the bi-layer of cell membranes. The phospholipids in fish fat are mainly attached to the omega-3 FAs EPA and DHA, both of which have long been recognized as beneficial to human health44. -8- Phospholipid-based omega-3 fatty acids are better absorbed 8A CH3 Brain Tissue Radioactivity content (kBq/gr tissue) H CH3 N CH3 8B H C H H C FATTY ACID Choline FATTY ACID FATTY ACID O are multiple studies, showing that omega-3 fatty acids are better absorbed when bound to phospholipids (PL) rather than to triglycerides (TG). A number of studies used animal models to prove this concept. For example, a Dutch researcher fed radioisotopes of DHA bound to PL or TG to rats and tested their availability in various tissues of the animals. Rats fed with PL-DHA had significantly higher levels of the FA in their brains, hearts and livers (figure 9)64. O O O P H C C O O Polar Head H H H C H GLYCEROL As discussed above, the health supportive effect of omega-3 fatty acids depend on their absorption into the plasma, the RBC and eventually into different organs such as the liver, the kidney, the Phospholipids based omega-3 brain and more. There fatty acids are better absorbed! H C * H O O O TG-DHA PL-DHA Kidney Tissue Radioactivity content (kBq/gr tissue) C O FATTY ACID O H H C H FATTY ACID P O O GLYCEROL 3 2.5 2 1.5 1 0.5 0 Figure 8: The structure of triglycerides and phospholipids: Triglycerides are comprised of a glycerol backbone attached to 3 fatty acids (figure 8a), while phospholipids are comprised of a glycerol backbone attached to 2 fatty acids and a polar head group (figure 8b). * 12 10 8 6 4 2 0 TG-DHA Health benefits of phospholipids Some phospholipids, such as PC, have an additional contribution since they are considered donors of the essential nutrient choline61, which was shown to be important for cognitive development of infants62 and cognitive maintenance of adults63. Choline deficiencies can also lead to liver disease, atherosclerosis and possibly neurological disorders63. Radioactivity content (kBq/gr tissue) Health benefits of phospholipid consumption have been studied extensively, and their beneficial effects on cognitive functions40, 56 and chronic liver diseases57, 58 are well established. Phospholipids, such as phosphatidylcholine (PC), are important to the development of the newborn59, are abundant in human breast milk and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommends adding them to infant formulae60. 80 70 60 50 40 30 20 10 0 PL-DHA Liver Tissue * TG-DHA PL-DHA Figure 9: Delivery of DHA to target tissues in rats fed with either PL- or TG- based DHA supplementation (*p<0.05)64. -9- In a second study, this time in baboons, an American researcher demonstrated that oral administration of PLFA [in this study the FA used was arachidonic acid (ARA)] reaches target tissues such as the heart, lung, brain and red blood cell membranes, better than TG-FA (figure 10)65. ARA (% dose / organ) 6 5 4 3 2 1 0 * Brain Twenty four healthy volunteers were recruited for a double blinded, randomized, placebo-controlled, crossover trial. The study was comprised of three treatment phases including PL-omega-3 oil or TG-omega-3 oil, each providing 600 mg of omega-3 FAs, or a placebo (corn oil) in capsule form. Each treatment lasted 4 weeks and was separated by washout phases of 8 weeks. Lung 0.02 0.016 * 0.012 TG-ARA Results PL-ARA PL-omega-3 oil consumption increased plasma omega-3 FA levels, including EPA and DHA, compared to TG-omega-3 oil consumption (p=0.0043) (figure 12). * 0.008 0.004 0 Plasma Enzymotec has also performed a clinical trial in healthy volunteers aimed to demonstrate the better absorbance of PL-omega-3 over TG-omega-3. The design and results of this trial are presented below67. Trial design * Liver ARA (% dose / organ) * Enzymotec clinical study demonstrates better absorption of PL-omega-3 RBC Figure 10: Delivery of ARA to target tissues in baboons fed with either PL- or TG- based ARA supplementation (*p<0.05)65. The clinical study findings suggest that omega-3 FAs taken as PL-omega-3 are better absorbed compared with TG-omega-3 Plasma Total Omega-3 8 Percent of omega-3 FA/total plasma FA Studies conducted in humans show similar results. Preterm babies were fed for a number of weeks with a formula supplemented with either PL- or TG- omega-3 and the amount of omega-3 in their feces was used as a proxy for bioavailability. The results show that a larger proportion of the omega-3 is absorbed when taken as PLomega-3 over TG-omega-3 (figure 11)66. *,# 7 * 6 5 Intestinal Absorption of DHA 95 Percent DHA absorbed 90 4 * PL-omega-3 TG-omega-3 Corn oil Figure 12: Omega-3 levels in plasma of healthy subjects following supplementation with PL-omega-3, TG-omega-3 or corn oil (placebo). *P<0.001 compared to corn oil, #P<0.01 compared to TG-omega-3. 85 80 75 Conclusion 70 The study findings suggest that omega-3 FAs taken as PLomega-3 are better absorbed compared with TG-omega-3. 65 *p<0.05 60 PL-DHA TG-DHA Figure 11: Absorption of DHA in preterm babies fed with either PL-omega-3 or TG-omega-3 formula66. - 10 - Phospholipid-based omega-3 fatty acids have better efficacy The health benefits of omega-3 FAs come from Phospholipids basedomega-3 a number of different fatty acids have better efficacy! mechanisms. Direct incorporation of PUFA into cell membranes results in an increase in membrane fluidity, leading to better membrane function68, 69. Omega-3 FAs may also assert functions through specific cell membrane receptors, processes which may explain their anti-inflammatory functions70. Of course, in order to assert their effects, omega-3 FAs need to reach their target site. As noted above, omega-3 linked to PL are better absorbed by various tissues. Omega-3 FAs are directly linked to CVD, and can be monitored through the omega-3 index (% omega -3 FA/total FA in RBC membrane42, see page 8 for detailed explanation). In the trial conducted by Enzymotec67, the omega-3 index was shown to be higher following PL-omega-3 intake over TGomega-3 intake, which may be indicative of better efficacy. Figure 13 presents the effect of the omega-3 source on the level of omega-3 index following 4 weeks intervention. Furthermore, because triglycerides are hydrophobic, their digestion requires bile salts which are released into the intestine while eating. This process means triglycerides stay in the gut for a relatively long time leading to more aftertaste and more fishy burps. Contrary to triglycerides, phospholipids have a polar head, making them partly hydrophilic, expediting the digestion process. When digested, phospholipids do not require bile salts and are quickly moved on from the stomach to the small intestine, where they are absorbed. Thus, phospholipids cause less aftertaste and no fishy burps (to read more please see Burri 201271) Digestion of TGs starts in the stomach and so gases are formed and released PLs on the other hand are only hydrolyzed in the small intestine, far from the mouth Omega-3 Index %EPA + DHA / total FA in RBC 7 Figure 14: A schematic diagram showing the difference between phospholipid and triglyceride digestion. *,# 6 * Summary and conclusions Our diet has changed dramatically over the last century, with increases in consumption of processed foods enriched with fat and sugar, and decreased consumption of fresh vegetables, cooked meats and fish, and these changes have direct and significant negative effect on our health. 5 4 PL-omega-3 TG-omega-3 Corn oil Figure 13: Omega-3 index following supplementation with PL-omega-3, TG-omega-3 or corn oil (placebo). *P<0.01 relative to corn oil, #P<0.05 relative to TG-omega-3. Phospholipid-based omega-3 fatty acids don’t cause fishy burps One of the common complaints of people taking fish oil supplementation is about fishy aftertaste and fishy burps. These phenomena Phospholipids based omega-3 come from the digestion fatty acid don’t cause fishy process of triglycerides. burps! Unlike the digestion of triglycerides, which begins in the stomach before moving to the small intestine, phospholipids are solely digested in the small intestine. Health benefits of eating fish and omega-3 FAs have been known for many years. The positive impact of these fatty acids, which usually come from marine sources, such as wild cold-water fatty fish, may be best demonstrated on cardiovascular diseases, the primary cause of human mortality. Moreover, omega-3 FAs are proven to be beneficial for many other health issues, such as stroke prevention, reducing depression, anti-inflammatory properties, cognition improving traits and for a general well-being. All these benefits have motivated many official health authorities to issue recommendations for the consumption of fish and omega-3 FAs (see table 1). Dietary consumption of phospholipids has health benefits by itself, for example on cognition and liver health. The binding of omega-3 FA to phospholipids enhances their absorption and delivery to target tissues, leading to better efficacy. Thus, consuming omega-3 in the form of phospholipids increases their effect on all omega-3 related health issues, as was proven in scientific studies. - 11 - Omega PC™ References Omega PC™ is a wild, fatty fish lipid extract containing omega-3 fatty acids bound to triglycerides and phospholipids - providing for the first time a natural, complete omega-3 product, which better preserves the nutrient profile found in fish. 1. WHO. World Health Organization: Cardiovascular diseases (CVDs) Fact Sheet. 2013 2. O’Keefe JH, Jr., Harris WS. From Inuit to implementation: omega-3 fatty acids come of age. 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