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September 2002

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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

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