Omega PC™ - Scientific Summary

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.
Mayo Clinic proceedings. Mayo Clinic. 2000;75:607-614
3. Bang HO, Dyerberg J, Sinclair HM. The composition
of the Eskimo food in north western Greenland. The
American journal of clinical nutrition. 1980;33:2657-2661
4. Bjerregaard P, Dyerberg J. Mortality from ischaemic
heart disease and cerebrovascular disease in
Greenland. International journal of epidemiology.
1988;17:514-519
5. Dyerberg J, Bang HO, Stoffersen E, et al.
Eicosapentaenoic acid and prevention of thrombosis
and atherosclerosis? Lancet. 1978;2:117-119
6. Rabinowitch IM. Clinical and Other Observations on
Canadian Eskimos in the Eastern Arctic. Canadian
Medical Association journal. 1936;34:487-501
7. Bang HO, Dyerberg J, Nielsen AB. Plasma lipid
and lipoprotein pattern in Greenlandic West-coast
Eskimos. Lancet. 1971;1:1143-1145
8. Lee KW, Lip GY. The role of omega-3 fatty acids in
the secondary prevention of cardiovascular disease.
QJM : monthly journal of the Association of Physicians.
2003;96:465-480
9. Dyerberg JM, J. Z. Nielsen, A.H. Schmidt, E.B.
Omega-3 polyunsaturated fatty acids and ischaemic
heart disease. Lancet. 1982;320:614
10. Bouzan C, Cohen JT, Connor WE, et al. A quantitative
analysis of fish consumption and stroke risk. American
journal of preventive medicine. 2005;29:347-352
11. Hirai A, Hamazaki T, Terano T, et al. Eicosapentaenoic
acid and platelet function in Japanese. Lancet.
1980;316:1132-1133
12. Nobmann ED, Byers T, Lanier AP, et al. The diet
of Alaska Native adults: 1987-1988. The American
journal of clinical nutrition. 1992;55:1024-1032
13. Sekikawa A, Steingrimsdottir L, Ueshima H, et al.
Serum levels of marine-derived n-3 fatty acids in
Icelanders, Japanese, Koreans, and Americans--a
descriptive epidemiologic study. Prostaglandins,
leukotrienes, and essential fatty acids. 2012;87:11-16
14. WHO. World Health Organization: Life expectancy. 2011
15. Zhang J, Sasaki S, Amano K, et al. Fish consumption
and mortality from all causes, ischemic heart
disease, and stroke: an ecological study. Preventive
medicine. 1999;28:520-529
16. Daviglus ML, Stamler J, Orencia AJ, et al. Fish
consumption and the 30-year risk of fatal myocardial
infarction. The New England journal of medicine.
1997;336:1046-1053
17. Burr ML, Fehily AM, Gilbert JF, et al. Effects of
changes in fat, fish, and fibre intakes on death and
myocardial reinfarction: diet and reinfarction trial
(DART). Lancet. 1989;2:757-761
• Omega PC™ is superior to fish oil for four primary
reasons:
1. Better absorption –it is clinically proven that omega-3
fatty acids bound to phospholipids are better absorbed
into the brain and heart.
2. Better efficacy–phospholipid-based oils have been
clinically proven to increase levels of omega-3 in the
membranes of RBC more efficiently than regular fish oil,
attesting to the higher efficacy of PL-omega-3.
3. Omega PC™ offers a natural nutrient profile - unlike
fish oil, Omega PC™ is manufactured by a cold extraction
process preserving the natural nutrient profile found in
fish, bringing it closer to nature.
4. No fishy burps - because phospholipids are digested
in the intestine, Omega PC™ means no fishy burps.
- 12 -
18. Mozaffarian D, Lemaitre RN, King IB, et al. Plasma
phospholipid long-chain omega-3 fatty acids
and total and cause-specific mortality in older
adults: a cohort study. Annals of internal medicine.
2013;158:515-525
19. FAO/WHO. Joint FAO/WHO Expert Consultation on the
Risks and Benefits of Fish Consumption. 2010
20. Hibbeln JR. Fish consumption and major depression.
Lancet. 1998;351:1213
21. Straus E, Sherman MSE, Spreen O. A Compendium of
Neuropsychological Tests. Oxford Press; 2006.
22. van Gelder BM, Tijhuis M, Kalmijn S, et al. Fish
consumption, n-3 fatty acids, and subsequent 5-y
cognitive decline in elderly men: the Zutphen Elderly
Study. The American journal of clinical nutrition.
2007;85:1142-1147
23. Larsson SC, Orsini N, Wolk A. Long-chain omega-3
polyunsaturated fatty acids and risk of stroke: a
meta-analysis. European journal of epidemiology.
2012;27:895-901
24. Gonzalez CA, Riboli E. Diet and cancer prevention:
Contributions from the European Prospective
Investigation into Cancer and Nutrition (EPIC) study.
European journal of cancer. 2010;46:2555-2562
25. Foran JA, Carpenter DO, Hamilton MC, et al. Riskbased consumption advice for farmed Atlantic and
wild Pacific salmon contaminated with dioxins
and dioxin-like compounds. Environmental health
perspectives. 2005;113:552-556
26. Lichtenstein AH, Appel LJ, Brands M, et al.
Summary of American Heart Association Diet
and Lifestyle Recommendations revision 2006.
Arteriosclerosis, thrombosis, and vascular biology.
2006;26:2186-2191
27. Sugasini D, Lokesh BR. Uptake of alpha-linolenic
acid and its conversion to long chain omega-3 fatty
acids in rats fed microemulsions of linseed oil.
Lipids. 2012;47:1155-1167
28. Superior Health Council: Recommendations and
claims made on omega-3-fatty Acids. 2004
29. ISSFAL. Recommendations for intake of
polyunsaturated fatty acids in healthy adults 2004
30. Cunnane SC. Problems with essential fatty acids:
time for a new paradigm? Progress in lipid research.
2003;42:544-568
31. GISSI. Dietary supplementation with n-3
polyunsaturated fatty acids and vitamin E after
myocardial infarction: results of the GISSIPrevenzione trial. Gruppo Italiano per lo Studio
della Sopravvivenza nell’Infarto miocardico. Lancet.
1999;354:447-455
32. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect
of n-3 polyunsaturated fatty acids in patients
with chronic heart failure (the GISSI-HF trial): a
randomised, double-blind, placebo-controlled trial.
Lancet. 2008;372:1223-1230
33. Davidson MH, Stein EA, Bays HE, et al. Efficacy and
tolerability of adding prescription omega-3 fatty acids
4 g/d to simvastatin 40 mg/d in hypertriglyceridemic
patients: an 8-week, randomized, double-blind,
placebo-controlled study. Clinical therapeutics.
2007;29:1354-1367
34. Montori VM, Farmer A, Wollan PC, et al. Fish oil
supplementation in type 2 diabetes: a quantitative
systematic review. Diabetes care. 2000;23:1407-1415
35. Schuchardt JP, Neubronner J, Kressel G, et al.
Moderate doses of EPA and DHA from re-esterified
triacylglycerols but not from ethyl-esters lower
fasting serum triacylglycerols in statin-treated
dyslipidemic subjects: Results from a six month
randomized controlled trial. Prostaglandins,
leukotrienes, and essential fatty acids. 2011;85:381386
36. Kaushik M, Mozaffarian D, Spiegelman D, et al. Longchain omega-3 fatty acids, fish intake, and the risk
of type 2 diabetes mellitus. The American journal of
clinical nutrition. 2009;90:613-620
37. Bernstein AM, Ding EL, Willett WC, et al. A metaanalysis shows that docosahexaenoic acid from algal
oil reduces serum triglycerides and increases HDLcholesterol and LDL-cholesterol in persons without
coronary heart disease. The Journal of nutrition.
2012;142:99-104
38. Dawczynski C, Martin L, Wagner A, et al. n-3 LCPUFA-enriched dairy products are able to reduce
cardiovascular risk factors: a double-blind, crossover study. Clinical nutrition. 2010;29:592-599
39. Carlson SJ, Fallon EM, Kalish BT, et al. The role of the
omega-3 fatty acid DHA in the human life cycle. JPEN.
Journal of parenteral and enteral nutrition. 2013;37:15-22
40. Kidd PM. Omega-3 DHA and EPA for cognition,
behavior, and mood: clinical findings and
structural-functional synergies with cell membrane
phospholipids. Alternative medicine review : a journal
of clinical therapeutic. 2007;12:207-227
41. Stonehouse W, Conlon CA, Podd J, et al. DHA
supplementation improved both memory and
reaction time in healthy young adults: a randomized
controlled trial. The American journal of clinical
nutrition. 2013;97:1134-1143
42. Harris WS, Von Schacky C. The Omega-3 Index: a new
risk factor for death from coronary heart disease?
Preventive medicine. 2004;39:212-220
43. Harris WS. Omega-3 fatty acids and cardiovascular
disease: a case for omega-3 index as a new risk
factor. Pharmacological research : the official journal
of the Italian Pharmacological Society. 2007;55:217223
44. Harris WS, Mozaffarian D, Lefevre M, et al.
Towards establishing dietary reference intakes for
eicosapentaenoic and docosahexaenoic acids. The
Journal of nutrition. 2009;139:804S-819S
- 13 -
45. American Heart Assocation: Fish 101. 2013
46. USDA. Dietary Guidelines for Americans 2010. 2010
47. Heart Foundation Australia: Fish, fish oils, n-3
polyunsaturated fatty acids and cardiovascular health
- position statement. 2008
48. EFSA. EFSA provides advice on the safety and
nutritional contribution of wild and farmed fish. 2005
49. EFSA. EFSA sets European dietary reference values
for nutrient intakes. 2010
50. Committee on Toxicity: Advice on fish consumption:
benefits & risks. 2004
51. Health Council of the Netherlands: Guidelines for a
healthy diet 2006. 2006
52. WHO. World Health Organization: Population nutrient
intake goals for preventing diet-related chronic
diseases. Nutrition Topics.
53. Naylor RL, Hardy RW, Bureau DP, et al. Feeding
aquaculture in an era of finite resources. Proceedings
of the National Academy of Sciences of the United
States of America. 2009;106:15103-15110
54. Dewailly E, Ayotte P, Lucas M, et al. Risk and benefits
from consuming salmon and trout: a Canadian
perspective. Food and chemical toxicology : an
international journal published for the British Industrial
Biological Research Association. 2007;45:1343-1348
55. Holub BJ. Omega-3 Levels in Fish: Data Quality,
Quantity, and Future. 2009
56. Vakhapova V, Cohen T, Richter Y, et al.
Phosphatidylserine containing omega-3 fatty acids
may improve memory abilities in non-demented
elderly with memory complaints: a double-blind
placebo-controlled trial. Dementia and geriatric
cognitive disorders. 2010;29:467-474
57. Grimstad T, Berge RK, Bohov P, et al. Salmon diet
in patients with active ulcerative colitis reduced the
simple clinical colitis activity index and increased
the anti-inflammatory fatty acid index--a pilot
study. Scandinavian journal of clinical and laboratory
investigation. 2011;71:68-73
58. Hayashi H, Tanaka Y, Hibino H, et al. Beneficial
effect of salmon roe phosphatidylcholine in chronic
liver disease. Current medical research and opinion.
1999;15:177-184
59. Harzer G, Haug M, Dieterich I, et al. Changing
patterns of human milk lipids in the course of the
lactation and during the day. The American journal of
clinical nutrition. 1983;37:612-621
60. Koletzko B, Baker S, Cleghorn G, et al. Global
standard for the composition of infant formula:
recommendations of an ESPGHAN coordinated
international expert group. Journal of pediatric
gastroenterology and nutrition. 2005;41:584-599
61. Zeisel SH, Da Costa KA, Franklin PD, et al. Choline,
an essential nutrient for humans. FASEB journal:
official publication of the Federation of American
Societies for Experimental Biology. 1991;5:2093-2098
62. Zeisel SH. Nutrition in pregnancy: the argument for
including a source of choline. International journal of
women’s health. 2013;5:193-199
63. Zeisel SH, da Costa KA. Choline: an essential nutrient
for public health. Nutrition reviews. 2009;67:615-623
64. Graf BA, Duchateau GS, Patterson AB, et al. Age
dependent incorporation of 14C-DHA into rat brain
and body tissues after dosing various 14C-DHAesters. Prostaglandins, leukotrienes, and essential
fatty acids. 2010;83:89-96
65. Wijendran V, Huang MC, Diau GY, et al. Efficacy of
dietary arachidonic acid provided as triglyceride or
phospholipid as substrates for brain arachidonic acid
accretion in baboon neonates. Pediatric research.
2002;51:265-272
66. Carnielli VP, Verlato G, Pederzini F, et al. Intestinal
absorption of long-chain polyunsaturated fatty acids
in preterm infants fed breast milk or formula. The
American journal of clinical nutrition. 1998;67:97-103
67. Ramprasath VR, Eyal I, Zchut s, et al. Assessment
of bioavailability of krill oil compared to fish oil in
healthy individuals. Unpublished data. 2013
68. Oh IS, Shimizu H, Sato T, et al. Molecular
mechanisms associated with leptin resistance:
n-3 polyunsaturated fatty acids induce alterations
in the tight junction of the brain. Cell metabolism.
2005;1:331-341
69. Salem N, Jr., Litman B, Kim HY, et al. Mechanisms
of action of docosahexaenoic acid in the nervous
system. Lipids. 2001;36:945-959
70. Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an
omega-3 fatty acid receptor mediating potent antiinflammatory and insulin-sensitizing effects. Cell.
2010;142:687-698
71. Burri L, Hoem N, Banni S, et al. Marine omega-3
phospholipids: metabolism and biological activities.
International journal of molecular sciences.
2012;13:15401-15419
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