LE Magazine September 2002
Page 2 of 4
Brain
function—Phosphatidylserine
A review of nutrients and botanicals
in the integrative management of cognitive dysfunction.
Dementias and other severe cognitive dysfunction states
pose a daunting challenge to existing medical management
strategies. An integrative, early intervention approach seems
warranted. Whereas, allopathic treatment options are highly
limited, nutritional and botanical therapies are available
which have proven degrees of efficacy and generally favorable
benefit-to-risk profiles. This review covers five such
therapies: phosphatidylserine (PS), acetyl-l-carnitine (ALC),
vinpocetine, ginkgo biloba extract (GbE) and bacopa monniera
(Bacopa). PS is a phospholipid enriched in the brain,
validated through double-blind trials for improving memory,
learning, concentration, word recall and mood in middle-aged
and elderly subjects with dementia or age-related cognitive
decline. PS has an excellent benefit-to-risk profile. ALC is
an energizer and metabolic cofactor which also benefits
various cognitive functions in the middle-aged and elderly,
but with a slightly less favorable benefit-to-risk profile.
Vinpocetine, found in the lesser periwinkle Vinca minor, is an
excellent vasodilator and cerebral metabolic enhancer with
proven benefits for vascular-based cognitive dysfunction. Two
meta-analyses of GbE demonstrate the best preparations and
offer limited benefits for vascular insufficiencies and even
more limited benefits for Alzheimer’s, while
“commodity” GbE products offer little benefit, if
any at all. GbE (and probably also vinpocetine) is
incompatible with blood-thinning drugs. Bacopa is an Ayurvedic
botanical with apparent anti-anxiety, anti-fatigue and
memory-strengthening effects. These five substances offer
interesting contributions to a personalized approach for
restoring cognitive function, perhaps eventually in
conjunction with the judicious application of growth
factors.
Altern Med Rev 1999
Jun;4(3):144-61
Double-blind randomized controlled
study of phosphatidylserine in senile demented patients.
A double-blind randomized controlled study was conducted in
42 hospitalized demented patients to evaluate the
therapeutical effect of phosphatidylserine (BC-PS). Half of
the patients received 3 X 100 mg of this product, and the
other half a placebo of the same appearance. After a wash-out
period, prescription lasted for six weeks. To evaluate the
patients, two distinct rating scales were used: the Crichton
Scale and an original one (Peri Scale) designed in our
geriatric unit (see Appendix). A circle crossing test was
added. Out of the 35 patients who completed the trial, 18 had
received placebo and 17 BC-PS. The results indicated a trend
toward improvement in the BC-PS treated patients and an
analysis of covariance showed a significant (p less than 0.05)
treatment effect on the Peri Scale. The results at the end of
the treatment period were compared with those obtained three
weeks later. Here again there was a statistically significant
difference in the Peri Scale results, indicating that
modifications are drug-related. The behavioral improvement
shown in this study is in agreement with experimental studies
on aged animals.
Acta Neurol Scand 1986
Feb;73(2):136-40
Effects of phosphatidylserine in
age-associated memory impairment.
We treated 149 patients meeting criteria for age-associated
memory impairment (AAMI) for 12 weeks with a formulation of
phosphatidylserine (100 mg BC-PS tid) or placebo. Patients
treated with the drug improved relative to those treated with
placebo on performance tests related to learning and memory
tasks of daily life. Analysis of clinical subgroups suggested
that persons within the sample who performed at a relatively
low level prior to treatment were most likely to respond to
BC-PS. Within this subgroup, there was improvement on both
computerized and standard neuropsychological performance
tests, and also on clinical global ratings of improvement. The
results suggest that the compound may be a promising candidate
for treating memory loss in later life.
Neurology 1991 May;41(5):644-9
Cognitive decline in the elderly: a
double-blind, placebo-controlled multicenter study on efficacy
of phosphatidylserine administration.
This double-blind study assesses the therapeutic efficacy
and the safety of oral treatment with phosphatidylserine
(BC-PS) vs placebo (300 mg/day for six months) in a group of
geriatric patients with cognitive impairment. A total of 494
elderly patients (age between 65 and 93 years), with moderate
to severe cognitive decline, according to the Mini Mental
State Examination and Global Deterioration Scale, were
recruited in 23 Geriatric or General Medicine Units in
Northeastern Italy. Sixty-nine patients dropped out within the
six-month trial period. Patients were examined just before
starting therapy, and three and six months thereafter. The
efficacy of treatment compared to placebo was measured on the
basis of changes occurring in behavior and cognitive
performance using the Plutchik Geriatric Rating Scale and the
Buschke Selective Reminding Test. Statistically significant
improvements in the phosphatidylserine-treated group compared
to placebo were observed both in terms of behavioral and
cognitive parameters. In addition, clinical evaluation and
laboratory tests demonstrated that BC-PS was well tolerated.
These results are clinically important since the patients were
representative of the geriatric population commonly met in
clinical practice.
Aging (Milano) 1993
Apr;5(2):123-33
Double-blind study with
phosphatidylserine (PS) in parkinsonian patients with senile
dementia of Alzheimer’s type (SDAT).
Experimental and clinical studies showed that
phosphatidylserine—special preparation from cow’s
brain by FIDIA, Abano Terme, Italy—is able to influence
cerebral changes contributed to the symptoms of senile
dementia of Alzheimer’s type. The application of the
computerized EEG (CEEG) method Dynamic Brain Mapping (HZI
Research Center, Tarrytown, New York) is able to proof the
therapeutic effect of phosphatidylserine: the acceleration of
a slowed EEG in Parkinsonian patients with SDAT. These
reactions were seen previous to the favorable clinical
influence documented by the Sandoz Clinical Assessment
Geriatric Scale (SCAG), which showed a significant
amelioration in anxiety, motivation and affectivity by the
verum drug. Acute and long-term CEEG results—till 18
months—showed that the so-called theta anteriorization
can be reduced or even abolished; this is replaced by alpha
waves. Even in preclinical cerebral changes this method open
the possibility to show incipient alterations of the brain
metabolism. Preliminary therapeutic results leads to this and
not proven hypothesis that prevention or retardation of
cerebral aging might be possible.
Prog Clin Biol Res
1989;317:1235-46
Phosphatidylserine in the treatment of
clinically diagnosed Alzheimer’s disease. The SMID
Group.
Modifications in cellular membranes can be observed in
aging and Alzheimer’s disease (AD). These mainly concern
the degree of the membrane’s viscosity, with consequent
reduction of the activity of some protein structures, such as
enzymes, receptors and membrane carriers. Moreover, dendritic
spine loss, found in aging and AD brain, is one of the most
characteristic findings. BC-PS, a phospholipid, purified from
bovine brain, is found to be able to influence positively the
above cited modifications. Moreover, BC-PS administration to
old rats improves the performances in some memory tests. In
humans, the effects of BC-PS have been studied by some
controlled trials in AD and related cognitive disorders. The
most recent of these trials, conducted on an Italian
population of AD patients is presented here, emphasizing in
particular its methodological aspects.
J Neural Transm Suppl
1987;24:287-92
Effects of phosphatidylserine in
Alzheimer’s disease.
We studied 51 patients meeting clinical criteria for
probable Alzheimer’s disease (AD). Patients were treated
for 12 weeks with a formulation of bovine cortex
phosphatidylserine (BC-PS; 100 mg tid) or placebo, and those
treated with the drug improved on several cognitive measures
relative to those administered placebo. Differences between
treatment groups were most apparent among patients with less
severe cognitive impairment. Results suggest that
phosphatidylserine may be a promising candidate for study in
the early stages of AD.
Psychopharmacol Bull
1992;28(1):61-6
Double-blind cross-over study of
phosphatidylserine vs. placebo in patients with early dementia
of the Alzheimer type.
Thirty-three patients with mild primary degenerative
dementia according to DSM-III (MMS between 15 and 27) took
part in a double-blind cross-over study of phosphatidylserine
(Fidia 300 mg/d) versus placebo. Both treatment phases lasted
for eight weeks with an eight week washout phase in between
and a four week washout phase before treatment phase one.
Clinical global improvement ratings showed significantly more
patients improving under phosphatidylserine (BC-PS) than under
placebo during treatment phase one. The improvement carried
over to the following wash-out and treatment phases. There
were no significant improvements in GBS dementia rating scale,
psychometric tests or P300-latency. 16-channel EEG mapping
findings indicated that the patients initially showed higher
power values in all frequency bands (except alpha), when
compared to a younger, healthy control group. BC-PS reduced
the higher power values compared to placebo, shifting EEG
power more towards the normal level.
Eur Neuropsychopharmacol 1992
Jun;2(2):149-55
Effects of phosphatidylserine therapy
in geriatric patients with depressive disorders.
The effects of phosphatidylserine (BC-PS) on cognitive,
affective and behavioural symptoms were studied in a group of
10 elderly women with depressive disorders. Patients were
treated with placebo for 15 days, followed by BC-PS (300
mg/day) for 30 days. The Hamilton Rating Scale for Depression,
Gottfries-Brane-Steen Rating Scale, Nurse’s Observation
Scale for Inpatient Evaluation and Buschke Selective Reminding
Test were administered before and after placebo and after
BC-PS therapy to monitor changes in depression, memory and
general behavior. At the same time, basal plasma levels of
noradrenaline, MHPG, DOPAC, HVA and 5-HIAA, and
GH/beta-endorphin/beta-lipotropin responses to clonidine
stimulation were measured. BC-PS induced consistent
improvement of depressive symptoms, memory and behavior. No
changes in amine metabolite levels or in hormonal responses to
alpha 2-adrenoceptor stimulation were observed.
Acta Psychiatr Scand 1990
Mar;81(3):265-70
Blunting by chronic phosphatidylserine
administration of the stress-induced activation of the
hypothalamo-pituitary-adrenal axis in healthy men.
The effect of chronic administration of phosphatidylserine
derived from brain cortex on the neuroendocrine responses to
physical stress has been examined in a placebo-controlled
study in nine healthy men. Phosphatidylserine 800 mg/d for 10
days significantly blunted the ACTH and cortisol responses to
physical exercise (P = 0.003 and P = 0.03, respectively),
without affecting the rise in plasma GH and PRL. Physical
exercise significantly increased the plasma lactate
concentration both after placebo and phosphatidylserine. The
results suggest that chronic oral administration of
phosphatidylserine may counteract stress-induced activation of
the hypothalamo-pituitary-adrenal axis in man.
Eur J Clin Pharmacol
1992;42(4):385-8
Effects of phosphatidylserine on the
neuroendocrine response to physical stress in humans.
The activity of brain cortex-derived phosphatidylserine
(BC-PS) on the neuroendocrine and neurovegetative responses to
physical stress was tested in eight healthy men who underwent
three experiments with a bicycle ergometer. According to a
double-blind design, before starting the exercise, each
subject received intravenously, within 10 min, 50 mg or 75 mg
of BC-PS or a volume-matched placebo diluted in 100 ml of
saline. Blood samples were collected before and after the
exercise for plasma epinephrine (E), norepinephrine (NE),
dopamine (DA), adrenocorticotropin (ACTH), cortisol, growth
hormone (GH), prolactin (PRL) and glucose determinations.
Blood pressure and heart rate were also recorded. Physical
stress induced a clear-cut increase in plasma E, NE, ACTH,
cortisol, GH and PRL, whereas no significant change was
observed in plasma DA and glucose. Pretreatment with both 50
mg and 75 mg BC-PS significantly blunted the ACTH and cortisol
responses to physical stress.
Neuroendocrinology 1990
Sep;52(3):243-8
The influence of phosphatidylserine
supplementation on mood and heart rate when faced with an
acute stressor.
There have been previous reports that supplements of
phosphatidylserine (PS) blunted the release of cortisol in
response to exercise stress and that it improved mood. The
present study extended these observations by considering
whether PS supplementation influenced subjective feelings of
stress and the change in heart rate when a stressful mental
arithmetic task was performed. In young adults with
neuroticism scores above rather than below the median, the
taking of 300 mg PS each day for a month was associated with
feeling less stressed and having a better mood. The study for
the first time reports an improvement in mood following PS
supplementation in a sub-group of young healthy adults.
Nutr Neurosci 2001;4(3):169-78
Continued on Page 3 of
4
Back to
the Magazine Forum
|