The Remarkable Brain Cell Nutrient
(PS) is a naturally-occurring phospholipid that is 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 body's 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 (Fig. 1). 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 (Fig. 2). 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 Alzheimer's
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 (Fig. 3). 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 phosphatidylcholine (PC).
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
"Who's 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 mediate the release of transmitters via secretory
vesicles; and receptors for NMDA and other transmitters. PS also serves as a reservoir for
fatty acids which 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
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 IIThe Next Gen-eration).5 In 14 double-blind clinical
trials1-4, 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 12 years!
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 volunters, 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 (Table I). Consequently, the cortisol-blocking effects of
phosphatidylserine may have profound effects on delaying many adverse effects of aging.
Double-Blind Studies Determine the
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
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
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 gastro-intestinal 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 ?
|1 Amaducci, L and the SMID
Group. "Phosphatidylserine in the treatment of Alzheimer's 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 phosphatidylserine
administration." Aging (Clin. Exp. Res.), 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 age-associated memory impairment." Neurol, 1991. 41: 644-9.
|4 Crook, T.H., Petrie W, Wells
C, Massari, D.C. "Effects of phosphatidylserine in Alzheimer's disease."
Psychopharmacol. Bulletin,, 1992. 28: 61-6.
|5 Dean, W., Morgenthaler, J.
Fowkes, S. 1993 "Phosphatidylserine" Smart Drugs II, The Next Generation, Health
Freedom Publications. Menlo Park, CA. pp. 75 80.
|6 Delwaide, P.J.,
Gyselynk-Mambourg A.M., Hurlet A. and Ylieff M. "Double-blind randomized controlled
study of phosphatidylserine in demented patients." Acta Neurol. Scand, 1986.
|7 Engel, R.R., Satzger W,
Gunther W, Kathmann N, Bove D, Gerkes, Munch U and Hippius H. "Double-blind
cross-over study of phosphatidylserine vs. placebo in subjects with early cognitive
deterioration of the Alzheimer type." Eur. Neuropsychopharmacol, 1992. 2: 149-55.
|8 Funfgeld, E.W., Baggen, M,
Nedwidek,P, et al. "Double-blind study with phosphatidylserine (PS) in Parkinsonian
patients with senile dementia of Alzheimer's type (SDAT)." Progr. Clin. Biol. Res,
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|9 Gindin, J, et al., 1995. The
Effect of Plant Phosphatidylserine on Age-Associated Memory Impairment and Mood in the
Functioning Elderly. Rehovot, Israel: Geriatric Institute for Education and Research, and
Department of Geriatrics, Kaplan Hospital.
|10 Hershowitz M, et al.
"Long-term treatment of dementia Alzheimer type with phosphatidylserine: effect on
cognitive functioning and performance in daily life." In, Bazan NG, et al (eds)
Phospholipids in the Nervous System: Biochemical and Molecular Pathology, 1989. Padua,
Italy: Liviana Press.
|11 Maggioni, M, Picotti, G.B.,
Bondiolotti ,G.P., Panerai, A. Cenacchi, T. Nobil, P. and Brambilla, F. "Effects of
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|12 Monteleone, P, Beinat, L,
Tanzillo,C, Maj, M, and Kemali, D. "Effects of phosphatidylserine on the
neuroendocrine response to physical stress in humans." Neuroendocrinol, 1990. 52:
|13 Monteleone, P, Maj,M,
Beinat,L, Natale,M, and Kemali,D. "Blunting by chronic phosphatidylserine
administration of the stress-induced activation of the hypothalamos-pituitary-adrenal axis
in healthy men." Eur. J. Clin.Pharmacol ,1992. 41: 385-8.
|14 Nerozzi, D., et al.
"Phosphatidylserine and impaired memory in the elderly." La Clinica Terapeutica,
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|15 Palmieri, G, Palmieri, R,
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|16 Ransmayr, G, Plorer, S,
Gerstenbrand,F, and Bauer,G. "Double-blind placebo-controlled trial of
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Trials J., 1987. 24: 62-72.
|17 Rosadini, G, Sannita ,W.G.,
Nobili, F, and Cenacchi, T. "Phosphatidylserine: quantitative EEG effects in healthy
volunteers." Neuropsychobiol, 1991. 24: 42-8.
|18 Villardita, C, Griolis, S,
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|19 Kidd, P., 1995.
Phosphatidylserine (PS), A Remarkable Brain Cell Nutrient. Lucas Meyer, Inc, Decator, Il.
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