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PhosphatidylserineThink Smart. Think Sharp.
A Breakthrough Solution for Brain Health
Scientific Summary
2Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
Executive SummaryPhosphatidylserine (PS), a structural component of cells, is
found in all biological membranes of plants, animals and
other forms of life. The human body contains about 30g
of phosphatidylserine, about half (~13 g) of which is found
in the brain. Phosphatidylserine plays a vital role in several
metabolic processes, such as activation of cell-membrane
bound enzymes, and is involved in neuronal signaling.
Pre-clinical and clinical studies demonstrated that oral
administration of phosphatidylserine improves cognitive
functions.
This scientific summary reviews the many facts and
published research findings on phosphatidylserine, and
presents results from Enzymotec’s clinical trial which tested
the effects of its Sharp●PS® product on cognition.
The qualitative and quantitative scientific evidence,
including human and animal data, is sufficient to determine
that phosphatidylserine supplementation is beneficial
to cognition and to establish that consumption of
phosphatidylserine is safe and well tolerated.
3 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
Background During the last few decades, life expectancy has
been rising sharply and is expected to continue
to rise in nearly all populations worldwide.
According to the United Nations Population
Division, the worldwide proportion of elders,
aged 65 and above, increased from 5% to 7%
from 1950 to 2000, and is expected to grow up
to 16% by 2050. In some countries, China for
example, an even greater extent of population
aging is expected. Due to the Chinese “one
child policy”, which was introduced in 1979 to
alleviate social, economic, and environmental
problems, it is expected that a threefold
increase in the elderly population will occur
between 2000 and 2050, from 7% to 23% of
the population. In Japan, the country with the
highest life expectancy, the elderly population
is projected to increase to more than a third of
the total population by 2050 (figure 1)1.
Aging is not a uniform process, and we must
distinguish between aging and healthy aging. An
increase in life expectancy does not necessarily
mean an increase in the quality of life or health of
the individuals. Therefore, today, one of the main
concerns of the aging population is to maintain
high physical activity and mobility, as well as
mental capacity, all required to maintain high
quality of life and active, healthy, aging.
Among cognitive difficulties of the elderly
population, age associated memory decline,
defined as normal deterioration of memory
which is unrelated to any pathology, may be the
most documented in the scientific literature. In
humans, this decline may start already at 30 years
of age, and may become evident by middle age2,
and experimental findings are in agreement with
people’s subjective reports of memory problems
as they age. Healthy aging is characterized by
slow, but constant, decrease in cognitive functions
Figure 1: Global picture of aging
World USA Japan China
1950 1975 2000 2050
Australia
Perc
ent
of p
opul
atio
n ov
er 6
5
5% 5% 5% 4%
7%8% 8%
9%8%
6%7%
10% 11%
12% 13% 12%
19%
22%
19%
29%
23%
36%
21%
16%
17%
2025
40%
35%
30%
25%
20%
15%
10%
5%
0%
4Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
which is completely different from pathological
cognitive deterioration. Pathological deterioration
includes faster changes in brain structure, such
as formation of brain plaques and neuronal
degeneration, manifesting first as Mild Cognitive
Impairment (MCI) and other types of dementia. A
seven year-follow-up clinical study demonstrated
that subjects with subjective memory complaints
had 4.5 times higher risk to further deteriorate to
pathological MCI or dementia than subjects free
of these symptoms3 (figure 2).
Clinical evidence suggests that dietary deficit
of important nutrients may contribute to the
development of brain pathologies during aging.
Thus, supplementation of nutrients with clinically
proven cognitive benefits may give answer to the
customer quest for cognitive enhancers. With better
understanding of the consequences of cognitive
deterioration, aging consumers turn more and
more to nutrition solutions for cognitive support.
This trend is on the rise and, with the aging of the
population, is expected to grow in coming years.
The importance of nutritionGlobalization and industrialization processes have
led to dramatic changes in our daily diet, resulting
in deficiency of many vital minerals, vitamins
and certain lipids. Western diet is characterized
by accumulating more energy than we need
and spending less than we should, by increased
trans-fat consumption and by reduced intake
of vegetables and other food products related
to healthier diets4. In some instances, transition
from traditional diets to Western diets (as in some
Asian countries) resulted in dramatic nutritional
changes which led to severe impact on the health
Cog
nitiv
e D
eclin
e
Mild CognitiveImpairment
Pathological Cognitive Decline
Time (Years)
Mild
Moderate
ModeratelySevereDementia
Severe
Normal Age Associated Memory Decline
Figure 2: Normal gradual decline of cognitive functions during aging (red line) in comparison
with pathological cognitive decline (Adapted and modified from Golomb et al., 2004³).
Our diets today lack many
vitamins, minerals and lipids
which are vital for proper brain
function
5 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
in general, and phospholipids in particular, is
affected by our diet. This, in turn, may affect
the structure of the brain. For example, the
hippocampus, a brain region which is responsible
for certain aspects of learning and memory, is
particularly susceptible to disruption by dietary
factors16. Findings that show association between
aging and alterations in brain lipid composition
may explain, at least in part, the deterioration in
cognitive abilities of elderly18.
Phospholipids – The building blocks of cell membranes Phospholipids (PLs) are an important family of lipids
which are distinct from triglycerides, the main
lipid group in our diet, in both form and function.
Phospholipids are the main building blocks of cell
membranes while triglycerides are used by the
human body mainly as a source of energy, or as
energy storage molecules. Both triglycerides and
phospholipids are comprised of fatty acids (FAs)
attached to a glycerol backbone, which is a short
chain of 3 carbons. However, the triglyceride
molecule has three FAs attached to the glycerol
backbone, while a phospholipid molecule has
the glycerol backbone attached to only two FAs
and to a polar, water soluble, head group (Figure
3). Phospholipids are considered amphipathic
of the population5.
Nutrition is known to play a major role in
the function of the nervous system. Thus,
administration of essential brain nutrients, for
support of healthy brain function, is a good
strategy to maintain or restore neuronal functions.
Studies have shown that nutrition affects
cognitive functions and mental performances
early in life6-12, with effects persisting throughout
adulthood and old age13.
Insufficient consumption of important nutrients
may be restored by supplementing it from
external sources. Consequently, more than half
of US adults use dietary supplements to balance
their diets, improve various daily functions and
maintain a healthier lifestyle14.
The brain is influenced by nutritionThe ability of nutrition to affect the brain is limited
by a barrier in the brain known as the Blood-
Brain-Barrier (BBB). Nonetheless, compounds
which are required for proper brain function are
actively transferred from the blood to the brain.
Thus, vitamins, minerals, amino acids and various
lipids are actively carried into the brain by special
protein transporters. The brain is one of the
organs richest in lipid content. Actually, brain lipid
content makes up to 50% of brain dry weight15.
Lipids are an essential component of the diet. Our
diet contains different forms of lipids, such as free
fatty acids, triglycerides, phospholipids and others.
The roles of lipids in our body are diverse, from
structural to functional. In addition to their use
for energy storage, lipids are important building
blocks of the body’s cellular membranes and serve
as precursors for hormones and other biologically
functional molecules. The composition of lipids
Phospholipids are used as cellular
membrane building blocks, unlike
triglycerides which are used for
storage of energy
6Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
molecules, meaning they have non-polar FAs on
one side and a polar head group on the other.
This unique characteristic of phospholipids is what
allows their function as building blocks of biological
membranes. The polar head group is comprised of
a phosphate group and an organic molecule linked
to each other. Phospholipids in cellular membrane
differ in composition from one cell type to another,
with phosphatidylcholine (PC) being the most
abundant PL in all cell types. Compared to most
tissues, the brain is enriched with another member
of the phospholipid family, phosphatidylserine (PS).
PhosphatidylserineLevels of PS vary significantly between tissues. In
most tissues, PS accounts for only about 3% of
total membrane phospholipids17, while in brain
tissues its amount is closer to 18%18. Variations
in phospholipid composition from one cell type to
another emphasize the importance of biological
membrane composition for proper function; thus,
the importance of PS to proper brain function is
underlined.
Neuronal cells do not readily regenerate, thus it
is important that these cells will have a superior
survival mechanism. High levels of PS in neuronal
membranes were shown to be important for
neuronal survival by facilitating several important
cellular processes19. Maintaining PS levels in
neuronal tissues has been associated with normal
and efficient signal transduction processes,
efficient neuronal glucose consumption and other
biological pathways which are crucial for normal
and healthy cognitive and mental functions2, 20-22.
Thus, PS is informally characterized as a brain-
specific nutrient because of its possible importance
for proper neuronal function2.
Figure 3: Structure of PS molecule (top), the localization of PS
within the inner layer of cell membrane (middle) and its utilization in
formation of tissues (bottom)
7 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
effect of dietary supplementation of PS on cognition Supplementing the diet with PS is known to affect
a large number of cognitive functions, among them
memory, learning and attention. Dietary PS was first
isolated from bovine cortex (BC-PS), and studies
demonstrated its beneficial effects both in pre-
clinical and clinical trials. Based on the large body
of clinical evidence demonstrating the beneficial
effects PS asserts on cognition, the American Food
and Drug Administration (FDA) has authorized in
April 2003 two qualified health claims for PS25:
“Consumption of Phosphatidylserine may reduce
the risk of cognitive dysfunction in the elderly”; and
“Consumption of Phosphatidylserine may reduce
the risk of dementia in the elderly”. However, FDA
also added a disclaimer indicating that “very limited
and preliminary scientific research suggests that
phosphatidylserine may reduce the risk of dementia
in the elderly. FDA concludes that there is little
scientific evidence supporting this claim.”
Phosphatidylserine in the dietPhosphatidylserine is a normal constituent of
human diet23, found in small amounts in human
breast milk and in natural food sources such as:
1) Animals – PS was first identified in bovine
brain which is known to date as a good source for
PS. Other internal animal parts and various fish
are also good sources for PS.
2) Plants – the amount of PS found in plants is
very limited. PS can be found in certain beans,
whole grains and rice, though levels are low.
PS is an example of a nutrient whose intake
levels have dropped in recent years. Changes in
consumer tastes, increased awareness to health
issues (e.g. reduced fat and cholesterol diets, mad
cow disease), as well as advances in technological
processing of fats and oils in the food industry, all
resulted in reduction in the amount of PLs in our
food. PS consumption todays is reduced by nearly
50% (Figure 4) compared to its consumption
during the early 80s’. It is estimated that the current
intake of PS is rather low, about 130 mg per day for
adults consuming “regular” diet, and even lower
for those on a reduced fat or vegetarian diet23.
Figure 4: Dietary trends suggest that PS intake has declined over the
past few decades (adapted from Hamm 200224).
PS is the only cognitive solution with
FDA health claims:
*”Consumption of PS may reduce
the risk of cognitive dysfunction in
the elderly”; and *”Consumption of
PS may reduce the risk of dementia
in the elderly”
Estim
ated
PS
daily
inta
ke (m
g/da
y)
Pre 1980 Current Vegetarian
300
250
200
150
100
50
0
8Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
treated with PS for periods of up to 6m, participated
in the studies. The doses used in these trials
ranged from 100 to 800 mg/day, but the most
prevalent regimen was 300 mg/day for 3 months.
The majority of the clinical studies conducted in
the early 80’s, using BC-PS, demonstrated the
clear benefit of PS supplementation on memory30,
concentration31 and other cognitive functions
in elderly population with various degrees of
cognitive deterioration, from Age-Associated
Memory Decline (AAMD) to Alzheimer’s’ disease
(AD)34, 35. Providing BC-PS to elderly patients was
also found to significantly enhance behavioral
parameters33. Importantly, BC-PS supplementation
to patients with AD had positive effect on their
cognitive performance34, 35.
In recent years, due to safety concerns regarding
the risk of contamination by bovine spongiform
encephalopathy prions (“mad cow disease”), BC-
PS is no longer used for human consumption and
alternative sources, such as marine derived PS
or soy PS (S-PS), have been developed. Soybean
derived PS has been available commercially
worldwide for more than a decade and has been
clinically tested during this period.
Clinical evidence of soy derived PSGindin and colleagues36 were the first to test the
cognitive effects of S-PS in a clinical trial. In their
randomized, double blind, placebo controlled
study, 57 elders aged 60-80 with complaints of
memory decline (AAMD) were given 300 mg S-PS
Beneficial effects of PS – Scientific evidence: Pre-clinical studies
PS was shown to have behavioral and cognitive
effects in numerous pre-clinical studies.
Administration of PS to rats was shown to
antagonize the amnesic effects of scopolamine.
The effect was similar regardless of the source
of PS [soy PS (S-PS) and BC-PS]26. Comparable
effects on cognition were also observed in a pre-
clinical study evaluating the cognition-enhancing
properties of S-PS and BC-PS (as well as PS from
eggs) in three different behavioral tests27. Another
study found that dietary supplementation of PS is
able to ameliorate impaired learning behavior28.
Nunzi et al29 demonstrated the capability of BC-
PS treatment to maintain dendritic spine density
(known to reduce with age and neurocognitive
diseases) of neurons in the hippocampus of old
rats. In 27-month-old rats, equal to human elderly
age, spine density showed a significant decrease
in dendrites compared to a 3-month-old animal.
However, in 27-month-old rats treated with BC-PS
values of spine density were not statistically different
when compared to those of 3-month-old animals.
Clinical studies
The clinical database of phosphatidylserine
intake includes over 46 clinical trials of which 27
have been conducted as double-blind, placebo-
controlled studies. The objective of the majority
of these studies was to examine the effects of
PS administration in reducing the symptoms of
dementia and cognitive dysfunction in elderly
individuals. Overall, more than 1500 subjects,
9 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
In another study, the clinical effects of 300 mg/day
S-PS were compared to those of BC-PS following 12
weeks of supplementation. The results demonstrated
a similar extent of improvement in cognitive function
following intake of both products37.
Although most of the studies demonstrated the
beneficial effect of PS following consumption of
300 mg/day, several studies suggested that a dose
of 100 mg/day of PS may be effective and sufficient
for demonstrating improvement of cognitive
measures such as memory and concentration.
In a pilot study, with only 12 patients, the
effective dosage of PS was examined. The aim
was to examine whether a dose of 100 mg PS
had a similar effect as 300 mg PS/day. Results of
this study demonstrated that following 12 weeks
of treatment, 100 mg/day PS showed a similar
improvement in various aspects of memory as did
the 300 mg/day dose37.
In a randomized, double-blind, placebo control
study, conducted in 79 Japanese elders with
memory complaints (defined as MCI), the efficacy
of S-PS (100 mg/day or 300 mg/day) was evaluated
over 6 month’s supplementation, followed by 3
months of non-supplemented follow-up period.
PS was found to be safe and no adverse events
were reported. In subjects with relatively low
cognitive score at baseline, the memory scores
following PS treatment were significantly increased
compared to baseline, while memory scores of
the placebo group remained unchanged (Figure
6). The memory improvements in the S-PS-treated
groups were mostly attributed to the increase in
delayed verbal recall and memory abilities38.
per day or placebo for a period of 3 months. Using
the Wechsler test (for memory) and the List of
Depression Symptoms score (for mood), the main
findings of the study were that both memory
and mood were significantly improved following
administration of S-PS (Figure 5).
effect on Memory
effect on Mood
Placebo
Placebo
S-PS
S-PS
Chan
ge in
Wec
hsle
r mem
ory
test
sco
reCh
ange
in L
ist o
f Dep
ress
ion
Sym
ptom
s sc
ore
Figure 5: Effect of soy PS on memory (top, higher score means better
memory) and mood (bottom, higher score means worsening of mood)
in subjects with AAMD supplemented with 300 mg/day PS for 3
months (Gindin 199336).
4
2
0
-2
3
2
1
0
10Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
A dose of 100 mg/day PS was also demonstrated
to improve cognitive performance in 120 students
aged 17-18 who were randomized to receive
either 250ml milk supplemented with 100 mg
PS or 250ml un-supplemented milk (placebo)
for 40 days. Memory was assessed by clinical
memory scale with computerized tests. Various
aspects of memory and learning were improved
in the PS supplementation group. Improved
domains included directed memory, associative
learning, free memory of images, recognition of
meaningless figures and portrait features-linked
memory (Figure 7)39. This study demonstrated
that PS beneficial effect is not limited to the
elderly population but may improve cognitive
performance and academic achievements in
young population as well.
Figure 6: Effect of PS in subjects with MCI. Shown are the effects of 100 mg/day S-PS on demented state (left) and on general
cognitive state (right) (Kato-Kataoka 201038).
0
6
3
9 Follow up
Months oftreatment
3
2
1
0
-1
Test for Dementia (HDS-r)
Chan
ge in
DW
R sc
ore
Placebo PS
2
1
0
-1
Test for Cognitive Function (MMSe)
Chan
ge in
DW
R sc
ore
Placebo PS
Even in teenagers, a group whose
cognitive performance is at its peak,
supplementation of 100 mg/day
PS for 40 days improved cognitive
performance.
* p<0.05
**p<0.01
** *
*****
11 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
by a computerized cognitive assessment tool (at
baseline, following 6 weeks of treatment and at
study termination).
Enzymotec’s Sharp●PS® Clinical study Sharp●PS® is a high grade soybean derived
PS produced by Enzymotec. The efficacy of
Sharp●PS® in improving cognitive abilities of
elderly participants was evaluated in an open
label study40. Twenty-six subjects (mean age: 74.6
years, 73% females) with memory complaints
were treated with 300 mg/day Sharp●PS® for 12
weeks. Participants’ cognitive performance was
evaluated by verbal and visual neuropsychological
tests, including Rey Auditory Verbal Learning Test
(AVLT) (at baseline and at study termination) and
*
*
*
*
*
Directedmemory
Associativelearning
Free memoryof images
Recognition of meaningless
figures
Portrait features-linked
memory
40
35
30
25
20
15
10
*p<0.05
Before PS intake
After PS intake
Figure 7: Improvement in cognitive functions of high school students following 40 days supplementation with 100 mg/day
PS in milk (Tang Yong 201139)
Test
Sco
re
Supplementation of Enzymotec’s
Sharp●PS® improves many aspects
of cognition such as memory,
learning and more
12Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
respectively). This improvement was enhanced
following 12 weeks of treatment (change
from mean baseline score: +8% and +12%,
respectively). Moreover, after 12 supplementation
weeks, mean scores of executive function and
mental flexibility were improved by 14% and
13%, respectively.
ResultsSeveral parameters of cognitive performance were
improved following Sharp●PS® supplementation
(Figures 8 and 9). The results of the computerized
test (Figure 8) show that following only 6 weeks
of Sharp●PS® administration, memory recognition
and memory recall were significantly improved
(change from mean baseline: +7% and +10%,
Memoryrecognition
Memoryrecall
Executivefunctions
Mentalflexibility
95
90
85
80
75
70
65
60
Figure 8: Effect of Sharp●PS® on memory recognition, memory recall, executive functions and mental flexibility following 6
and 12 weeks of supplementation. Significant improvements are presented (change from baseline to 6 and to 12 treatment
weeks). * p<0.01, ** p<0.006.
Baseline
12 weeks
6 weeks
*p<0.01**p<0.006
**
*
**
** ** *
Mea
n Sc
ore
(Poi
nts)
13 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
recognition tasks, though these improvements
did not reach statistical significance (data not
shown). Sharp●PS® treatment was well tolerated
and no major treatment-related adverse events
were reported during the course of the study.
The study findings suggest that Sharp●PS® has
a beneficial impact on cognitive abilities of the
elderly and that it is safe for use.
Similarly, significant beneficial effects were
observed in Rey-AVLT test (Figure 9). Following
12 weeks of Sharp●PS® supplementation, verbal
immediate recall and total learning scores improved
significantly (change from mean baseline: +24%
and +10%, respectively). An improvement was
also detected in the best learning score, in the
performance of the verbal delayed recall and
Figure 9: REY-AVLT results following 12 weeks of Sharp●PS® administration.
*p<0.05, **p<0.01 based on Student’s t-test comparison for dependent samples of the change between baseline and
endpoint.
6
5
4
3
2
1
0
45
43
41
39
37
35
33
**
*
Baseline Baseline12 weeks 12 weeks
immediate recall Total Learning
Mea
n Sc
ore
(# w
ords
cor
rect
ly re
calle
d)
14Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
in neuronal cells and tissues, translocation
of Akt to the membrane, resulting in its
activation, is PS-dependent43. Increase in brain
PS was accompanied by reduction of apoptosis
(programed cell death) of neurons which is
critical for the maintaining of normal brain
function43. Humans are equipped with the same
number of neurons in their brains from birth till
adulthood44. Thus, keeping the neurons in good
health is of utmost importance.
• Activation of cellular enzymes such as protein
kinase C (PKC): activation of PKC is known to be
PS-dependent45, and its activity is essential for
cognitive processes such as memory and learning.
PKC is known to phosphorylate a number of
proteins, such as MARCKS, GAP-43, and the
NMDA receptor, all of which are known to be
involved in information storage processes. In a
pre-clinical study, PKC activity within the brain
was found to diminish with age46, parallel to age
associated deterioration in cognitive abilities.
Pharmacologic intervention, with PKC inhibitors
and activators, has been shown to modulate
cognition47. A pre-clinical study demonstrated
that intake of PS increases PKC levels in the brain49,
which may partly explain the positive effects of PS
on memory and cognition. The dependence of
PKC activation on PS is schematically presented
in Figure 10.
Summary and conclusions of clinical studiesStudies using S-PS in elders tested effects of 100-
300 mg PS per day, for a period of up to 6 months
supplementation. Improvement could be seen
within 6 weeks, increasing even more following
longer use. In these studies the main benefit of S-PS
in patients with cognitive decline was improvement
of memory. Additional improvements were found
in learning abilities, mental flexibility, mood and
general improvement of daily life. PS was shown
to be safe for consumption and no adverse events
were reported.
Suggested mechanisms of action of PSUnlike most other phospholipids, PS is a negatively
charged molecule (see Figure 10), and many of
the mechanisms by which PS is thought to act are
based on that fact. PS was shown to participate
in key signaling pathways in the neuronal system.
Furthermore, PS was also shown to function
as a component of the membrane which binds
and activates cytosolic (=intracellular) proteins
involved in neuronal signaling and other functions
of neurons43. There are a number of mechanisms
described in the scientific literature for the function
of PS41, though no conclusive evidence points to a
single mechanism. Suggested mechanisms include:
• Activation of signal molecules such as Akt:
Activity of Akt within neurons is mediated
through PS43, and its activation promotes the
survival of neurons. Studies have shown that
15 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
nerve cells and an indicator of brain activity.
Measurements of cerebral metabolic rate of
glucose by Position Emission Tomography (PET)
have shown that PS causes a significant increase
in glucose metabolism of defined cortical and
subcortical structures of the brain52.
• Reduction of cortisol levels: Administration
of PS may counteract stress-induced activation
of the hypothalamic-pituitary-adrenal axis in
humans, as shown by reduction in blood cortisol
and ACTH levels following administration of PS53.
All of these suggested PS mechanisms eventually
impacts the subjects’ cognitive functioning as well
as mood and behavior.
• Influence on synaptic plasticity: As PS directly
activates PKC49, increased phosphorylation of
brain PKC following PS supplementation results in
activation of a PKC substrate called GAP4350. GAP43
is known to be involved directly in synaptic plasticity.
• Effect on brain waves (intensity and
frequencies): Administration of PS was shown
to affect quantitative Electroencephalography
(EEG) measurements and profile51, causing a
15-20 percent average power incrementing at
all frequency bands (except Alpha).
• Improvement of glucose utilization and induction of superior metabolic activation: Glucose is the preferred energy substrate for
Figure 10: PKC activation is PS dependent. PKC activation requires the following steps: 1. Ions of calcium bind to PKC,
charging it with a positive charge and opening a cleft for PS binding; 2. the now positively charged PKC is attracted to the
negatively charged PS. When PS binds to PKC, it anchors it to the membrane; 3. PS-dependent membrane anchoring leads to
binding of another lipid member, DAG, which leads to release of an inhibitory domain of PKC, making it active.
16Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
Summary• PS is an essential constituent of brain membranes
and an important player in brain-related
biochemical pathways.
• Clinical studies demonstrate that oral
supplementation of PS leads to improvement
in brain functions such as memory, attention,
mood, behavior and more.
• Sharp●PS® is a high quality soy-derived
phosphatidylserine produced by Enzymotec.
• Sharp●PS® efficacy in improving cognitive
abilities of elderly was demonstrated in a clinical
study.
17 Enzymotec Ltd. Sagi 2000 Industrial Zone | Kfar Baruch. Israel, 23106 | Tel: 972 74 7177177 | Fax: 972 74 7177001
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