The Remarkable Brain Cell Nutrient
Parris M. Kidd, Ph.D. and Ward Dean,
Phosphatidylserine (PS) is a
naturally-occurring phospholipid found in all cells of the body,
with particularly high concentrations in the brain. PS is an
essential cell membrane building-block for nerve cells. Of all
the bodys organs, the brain, without question, performs the most
complex and most energy-demanding functions. Healthy nerve cell
membranes are essential to generate optimum energy and to
produce, package and release numerous chemical neurotransmitters
in their proper amount and balance. Cell membranes are also the
sites where nerve cells react to these neurotransmitters and
where neurotransmitters are then recycled for later use for
clearance from the brain.
The site where nerve cells perform most of their specialized
functions is on or within their membranes. These membranes are
composed mainly of phospholipids and proteins. Among the causes
of memory decline and other cognitive impairment are: (1) the
death of nerve cells, or (2) the decreased density of their
interconnected networks due to loss of dendrites, the tiny
filaments which connect one nerve cell to another. These changes
may be due to aging or damage to the brain from such insults as
alcohol consumption, cigarette smoking, toxic chemicals, chronic
emotional stress, stroke, trauma or hypoglycemia.
Supplementation of the diet with PS has been proven to slow,
halt, or in many cases, even reverse cognitive degeneration due
to age-related cognitive decline (ARCD) (2, 3, 9) and dementing
illnesses like Alzheimers disease.(1,4, 6, 7, 8, 10) PS has been
scientifically established to be among the most effective
substances to consistently result in dramatic cognitive
improvements and enhancements of other higher brain functions.
Until recently, however, PS was available in the U.S. only as a
very minor constituent of lecithin. Now, new technology has made
it possible to greatly enhance the PS content of lecithin,
making phosphatidylserine readily available in effective amounts
for the first time.
Structure and Biochemistry of PS
The PS molecule has a head, a middle piece, and two tail groups.
The head piece consists of serine and phosphate, the middle
piece is derived from glycerol, and the tails are fatty acids.
PS is extremely bioavailable and crosses the blood-brain barrier
with ease. Once in the brain, the PS molecule as a unit merges
smoothly into the nerve cell membrane where it is available to
facilitate cell-level energetics and homeostasis, as well as
enhance neurotransmitter production, release, and action. PS
also serves as a precursor reservoir for the related
phospholipids, phosphatidylethanolamine (PE) and
As a unique phospholipid constituent of all known cell
membranes, PS helps to ensure membrane integrity (in conjunction
with the other phospholipids: PE, PC and phosphatidylinositol
[PI]). This demarcates the living cell interior from the
nonliving outer environment. This demarcation is absolutely
necessary for life to exist. PS also helps support the functions
of a number of membrane proteins. A list of these membrane
proteins reads like a Whos Who of important proteins for the
cell: Na/K ATPase; Ca ATPase; Mg ATPase (for ion transport);
protein kinase C; adenylate cyclase (for processing signals that
reach the cell from the environment); NADPH-cytochrome C
reductase (for mitochondrial energy production); proteins that
www.e the release of transmitters via secretory vesicles; and
receptors for NMDA and other transmitters. PS also serves as a
reservoir for fatty acids that are the sources of messenger
molecules which carry signals from the cell membrane to the
surroundings (the prostanoids or prostaglandins).
PS occurs in all tissues of the body. In addition to its many
nerve cell functions, it is also known to be involved in red
cell recycling, bone matrix formation, testicular function,
generation and regulation of the heartbeat, and hormone
secretion by the adrenal glands.
Clinical Findings of Memory Improvement
Findings from many controlled clinical trials indicate that PS
consistently ameliorates memory loss and other cognitive decline
related to aging (many of these findings have been cited and
described in Smart Drugs II - The Next Generation).(5) In 14
double-blind clinical trials(1-4, 6-11, 14-16,18) conducted with
subjects aged 50 and older, PS benefited all degrees of
cognitive impairment. In one U.S. trial by Crook, et al (1991)
on subjects with age-related cognitive decline (ARCD),(3) PS
reversed the decline of name-face acquisition skills by a
statistical 12 years, i.e., from average scores attained by
64-year-old subjects, to average scores attained by
52-year-olds. This is a reduction in cognitive biological age of
In double-blind trials conducted with more severely afflicted
subjects, PS brought about statistically and clinically
significant improvements in measures of recall, learning,
concentration, adaptability, mood and sociability. In other
double-blind trials, PS improved neuro-physiological measures
such as EEG (electroencephalogram) and reflexes (as judged by
flicker-fusion response time).(17)
In another human trial conducted with young male volunteers, PS
significantly improved EEG alpha rhythm (which often declines
with aging and memory loss).(17) In older subjects with severe
cognitive impairment, PS dramatically enhanced brain glucose
consumption (assessed via positron emission tomographic [PET]
imaging) and partially restored the 24-hour rhythm of TSH
(thyroid-stimulating hormone) secretion in aged men.(19) Also,
in elderly subjects, PS enhanced the
hypothalamic-pituitary-adrenal (HPA) stress-coping axis, as
assessed by the dexamethasone suppression test.(13)
PS as a Cortisol Blocker
PS also ameliorated elevations of stress hormones (ACTH and
cortisol) associated with strenuous exercise in young
men.(12,13) This is an extremely important finding, as
age-related increases in the cortisol/DHEA ratio (due to both
prolonged elevated cortisol levels due to stress and/or aging
and decreased DHEA levels due to aging) are a significant
biomarker of aging. This changing ratio reflects the toxic
effects on the body of prolonged relative hypercortisolemia
(elevated blood levels of cortisol). These effects can
ultimately manifest as the Cushingoid appearance of many people
over the age of 50. Consequently, the cortisol-blocking effects
of phosphatidylserine may profoundly delay many adverse effects
Double-Blind Studies Determine the Right Dose
The dosing strategy for PS has been elucidated from more than 40
clinical studies (many of them double-blind) with over 2,000
subjects in Europe and the USA during the past two decades.
Clinically effective oral intakes ranged from 200 to 800 mg per
day, taken in divided doses with meals. Most of the trials were
conducted at 300 mg per day but for subjects with motor
impairment, higher doses may be necessary.
A Proven Track Record of Safety
The incidence of side effects from PS is very low. This is best
illustrated by the largest double-blind trial (Cenacchi and
others, 1993),(2) in which one subject (of 494) dropped out
because of an adverse PS effect, as compared with seven
drop-outs from the placebo group.
After some 20 years of clinical use, PS has exhibited no known
negative interactions with drug therapies. In the Cenacchi, et
al. trial cited above,(2) the subjects were elderly (65-93
years) and were allowed to continue on their prescribed drug
regimens for the full six months of the trial. Of the 494
subjects who began the trial, 425 completed it. Other drop-outs
were due to deaths or other reasons not related to PS. Over the
full six months, no adverse interactions were noted between PS
and the assortment of drugs that were being taken by this
typically elderly population (diuretics, anti-thrombotics, anti-diabetogenics,
anti-arrhythmics, anti-hypertensives, anti-inflammatories,
anti-acids, anti-ulcers, mucolytics, insulin, calcitonin, and
calcium channel blockers).
PS has an extremely favorable benefit-to-risk profile which
stands to reason since it is a major intrinsic constituent of
all human cells. Lecithin, the plant extract source of PS, is
rated GRAS (Generally Recognized As Safe). Human subjects have
safely tolerated up to 800 mg of PS per day. PS has safely been
administered to dogs at 70 gm per day for one year, without any
toxicity or adverse effects. Furthermore, no clinical blood
abnormalities have ever been seen after long-term intake.
Toxicological assessments indicate that PS is neither mutagenic
nor carcinogenic; it is not teratogenic in animals, and there
are no indications it would be unsafe during human pregnancy.
Contraindications for the use of PS include soy allergy, known
intolerance to lecithin preparations, and rare cases of
antiphospholipid autoimmune syndromes. PS has infrequently
caused gastrointestinal upset and can cause insomnia if taken in
a large dose (600 mg) just before going to bed.
Over Two Decades of Studies Validate the Efficacy of PS
PS has been studied exhaustively for over twenty years. During
this time, it has demonstrated in study after study that it has
a significant effect on enhancing memory and other brain
functions in both normal and cognitively impaired individuals.
These studies confirm that PS is a highly effective agent for
enhancing brain function, with a remarkable safety profile.
Whether the impaired mental function is linked to aging, toxic
or traumatic damage, cerebral insufficiency, or nonspecific
causes; diverse measures of brain performance indicate that PS
is rarely, if ever, surpassed for its clinical benefits to the
brain as a whole.
source of nutrients and supplements.
did we qualify them ?
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treatment of Alzheimers disease: results of a multicenter study.
Psychopharmacol. Bulletin, 1988, 24: 130-4.
2. Cenacchi, B, Bertoldin T, Farina C, Fiori M.G., Crepaldi G.
Cognitive decline in the elderly: a double-blind,
placebo-controlled multicenter study on efficacy of
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1993, 5: 123-33.
3. Crook, T.H., Tinklenburg, J, Yesavage J, Petrie W, Nunzie M.G.,
and Massari, D.C. Effects of phosphatidylserine in
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[Translated from the Italian]
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Cell Nutrient. Lucas Meyer, Inc, Decator, Il.
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