Phosphatidy-L-Serine is used for Alzheimer's disease and other dementias, age-related decline in mental function, improving cognitive function in young people, attention deficit-hyperactivity disorder (ADHD) and for improving athletic performance. It has been shown to improve attention, verbal fluency and memory in aging people with cognitive deterioration. It is the most abundant fat soluble phospholipid in the human brain and is important in nervous system and brain function.
Phosphatidy-L-Serine has been shown to increase acetylcholine, norepinephrine, serotonin and dopamine levels in animal models and patients with Alzheimer's disease. In animal models of multiple sclerosis Phosphatidy-L-Serine reduces tremor, spasticity and urinary incontinence.
Published Clinical Studiescltop
"Brain-specific" nutrients: a memory cure?1
McDaniel MA, Maier SF, Einstein GO.
Department of Psychology, University of New Mexico, Albuquerque, New Mexico 87131, USA. mcdaniel@umn.edu
OBJECTIVE: We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E). RESULTS: In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. CONCLUSIONS: In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.
PMID: 14624946 [PubMed - in process]
Metabolism and functions of phosphatidylserine in mammalian brain.2
Mozzi R, Buratta S, Goracci G.
Department of Internal Medicine, Division of Biochemistry, University of Perugia, Perugia, Italy.
Phosphatidylserine (PtdSer) is involved in cell signaling and apoptosis. The mechanisms regulating its synthesis and degradation are still not defined. Thus, its role in these processes cannot be clearly established at molecular level. In higher eukaryotes, PtdSer is synthesized from phosphatidylethanolamine or phosphatidylcholine through the exchange of the nitrogen base with free serine. PtdSer concentration in the nervous tissue membranes varies with age, brain areas, cells, and subcellular components. At least two serine base exchange enzymes isoforms are present in brain, and their biochemical properties and regulation are still largely unknown because their activities vary with cell type and/or subcellular fraction, developmental stage, and differentiation. These peculiarities may explain the apparent contrasting reports. PtdSer cellular levels also depend on its decarboxylation to phosphatidylethanolamine and conversion to lysoPtdSer by phospholipases. Several aspects of brain PtdSer metabolism and functions seem related to the high polyunsaturated fatty acids content, particularly docosahexaenoic acid (DHA).
Publication Types:
PMID: 12608694 [PubMed - indexed for MEDLINE]
3
Apoptotic PC12 cells exposing phosphatidylserine promote the production of anti-inflammatory and neuroprotective molecules by microglial cells.
De Simone R, Ajmone-Cat MA, Tirassa P, Minghetti L.
Laboratory of Pathophysiology, Istituto Superiore di Sanita, Rome, Italy. desimone@iss.it
The interaction of phosphatidylserine (PS), exposed on the surface of apoptotic cells and with its specific receptor (PtdSerR) expressed by microglia, is a crucial event in the recognition and clearance of apoptotic neurons. Here, we extend our previous studies in which PS-liposomes mimicking apoptotic cells were used to investigate the functional role of PS-PtdSerR interactions on microglial functional state. Purified rat microglial cells were either incubated with PC12 cells maintained in complete medium (healthy), exposed to staurosporine or serum deprivation (apoptotic), or treated with hydrogen peroxide (necrotic). After 24 hours, supernatants from co-cultures and single cell type cultures were analyzed for nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), prostaglandin E2 (PGE2), transforming growth factor-beta1 (TGF-beta1), and nerve growth factor (NGF). When lipopolysaccharide (LPS)-activated microglia was cultured with apoptotic PC12 cells, NO and TNF-alpha levels significantly decreased, IL-10 was not affected, and PGE2 levels were substantially increased. In addition, TGF-beta and NGF syntheses increased when resting microglia was cultured with apoptotic but not healthy or necrotic PC12 cells. We proposed that upon interaction with PS-expressing apoptotic neurons, microglia no longer act as a promoter of the inflammatory cascade and that the specific microglial functional state induced by PS-PtdSerR may be relevant for the final outcome of neurodegenerative diseases.
PMID: 12578230 [PubMed - indexed for MEDLINE]
Safety of soy-derived phosphatidylserine in elderly people.4
Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ.
Department of Psychiatry and Neuropsychology, Brain and Behaviour Institute, Universiteit Maastricht, The Netherlands. b.jorissen@np.unimaas.nl
Phosphatidylserine (PS) is a phospholipid which has been claimed to enhance neuronal membrane function, and can be derived from several sources. Earlier studies used brain cortex derived PS, of which the human tolerability of 300mg daily in 130 patients has been shown. The human tolerability of PS derived from soybean has not been reported, although it is widely sold as a nutritional supplement which may improve cognitive function in the elderly. We report the results of a study of the safety of two dosages of soy-phosphatidylserine (S-PS) in elderly. Subjects were 120 elderly of both sexes who fulfilled the more stringent criteria for age-associated memory impairment; some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300 or 600 mg S-PS daily. Standard biochemical and hematological safety parameters, blood pressure, heart rate and adverse events were assessed at baseline, after 6 and 12 weeks of treatment. No significant differences were found in any of the outcome variables between the treatment groups after Bonferonni-Holme correction. In conclusion, soy derived PS is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily.
Publication Types:
PMID: 12385596 [PubMed - indexed for MEDLINE]
5
Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats.
Suzuki S, Yamatoya H, Sakai M, Kataoka A, Furushiro M, Kudo S.
Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi, Tokyo 186-8650, Japan.
Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) was prepared from soybean lecithin and L-serine by a transphosphatidylation reaction, and its effect on age-related memory impairment was evaluated in rats by the Morris water maze test. Continuous oral administration of SB-tPS (60 mg x kg(-1) x d(-1) for 60 d) to male aged rats (24-25 mo) significantly improved performance in the water maze escape test (P < 0.01 vs. control aged rats) similar to bovine brain cortex-derived phosphatidylserine, which restores cognitive function in patients with senile dementia. SB-tPS also increased acetylcholine release and the Na(+), K(+)-ATPase activity of the synaptosomes prepared from these aged rats to the level in young rats. The nootropic actions of SB-tPS in the present study can be partly explained by the changes in these biochemical activities.
PMID: 11694624 [PubMed - indexed for MEDLINE]
6
An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline.
Schreiber S, Kampf-Sherf O, Gorfine M, Kelly D, Oppenheim Y, Lerer B.
Department of Psychiatry C, Chaim Sheba Medical Center, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel. shaulsch@post.tau.ac.il
We assessed whether the efficacy of plant-source derived phosphatydilserine (one of the phospholipids which play an important functional role in membrane-related processes in the brain) for treatment of age related cognitive decline is consistent with previous (placebo controlled) positive findings with bovine derivative of PS (BC-PS). Eighteen healthy elderly volunteers meeting Age Associated Memory Impairment inclusion and exclusion criteria were treated for 12 weeks with plant-source derived phosphatydilserine (PS) (100 mg x 3/day p.o.) and evaluated at base line, after 6 weeks of treatment and at the end of the trial. Fifteen concluded the study. All but two outcome measures elicited a significant drug over time effect. Post-hoc paired t-tests showed that the significant effect was attributable to an improvement from base line to week 6 and that effect was maintained at week 12. These results are encouraging. However, they await double-blind controlled verification in a large sample before suggesting that this may be a viable approach to the treatment of age-related cognitive decline, without exposing the patients to possible hazards involved in the treatment with bovine derivative of PS (BC-PS).
PMID: 11201936 [PubMed - indexed for MEDLINE]
Phosphatidylserine reverses reserpine-induced amnesia.7
Alves CS, Andreatini R, da Cunha C, Tufik S, Vital MA.
Laboratorio de Fisiologia e Farmacologia do SNC-Centro Politecnico, Department of Pharmacology, Federal University of Parana, Jardim das Americas--PR, Caixa Postal 19.031, CEP 81.531-990, Curitiba, Brazil.
The effects of phosphatidylserine (PS) were studied in rats treated with reserpine (1 mg/kg) immediately after training in the passive avoidance task. In experiment I, phosphatidylserine (25 mg/kg) was administered 30 min before or immediately after training. Acute pre- or post-treatment with phosphatidylserine was effective in reversing the amnestic effect of reserpine in test trials performed 24 h and 1 week after training. Experiment II was performed to determine if the long-term pretreatment with phosphatidylserine (25 mg/kg) for 7 days is able to protect the rats against the amnestic effects of reserpine in this task. The data show that phosphatidylserine reverses the impairment induced by reserpine in trials performed 24 h and 1 week after training. These results indicate that the memory deficits associated with catecholamine depletion caused by reserpine can be attenuated by acute pre- or post-training or by long-term pretreatment with this phospholipid.
PMID: 10980275 [PubMed - indexed for MEDLINE]
Integrated medicine and the prevention and reversal of memory loss.8
Khalsa DS.
Alzheimer's Prevention Foundation, Tucson, Ariz., USA.
This article, based on scientific research and clinical observations, suggests that memory loss is not an inevitable consequence of aging and that Alzheimer's disease can be prevented and reversed using an integrated medical approach. Three new associations with memory loss other than age, heredity, and genetics are described. They include a high-fat diet, chronic unbalanced stress with its attendant risk in the adrenal hormone cortisol, and the presence of cardiovascular disease. A 4-pillar integrative medical program on brain longevity is presented. The program includes a diet consisting of 15% fat and supplementation with brain-specific nutrients such as vitamin B complex, vitamin E, ubiquinone, ginkgo biloba, and phosphatidylserine. In addition, stress-relieving meditation, mind-body and cognitive exercise, antiaging drugs like L-deprenyl citrate, as well as hormones such as dehydroepiandrosterone and pregnenolone complete the program. Patient benefits such as greater wisdom and spiritual happiness are also explored.
Publication Types:
PMID: 9810066 [PubMed - indexed for MEDLINE]
Effects of phosphatidylserine in age-associated memory impairment.9
Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC.
Memory Assessment Clinics, Inc., Bethesda, MD 20814.
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.
Publication Types:
PMID: 2027477 [PubMed - indexed for MEDLINE]
Effects of phosphatidylserine therapy in geriatric patients with depressive disorders.10
Maggioni M, Picotti GB, Bondiolotti GP, Panerai A, Cenacchi T, Nobile P, Brambilla F.
Clinica Zucchi, Universita Milano, Italy.
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 behaviour. 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 behaviour. No changes in amine metabolite levels or in hormonal responses to alpha 2-adrenoceptor stimulation were observed.
Publication Types:
PMID: 1693032 [PubMed - indexed for MEDLINE]
11
Phosphatidylserine in the treatment of clinically diagnosed Alzheimer's disease. The SMID Group.
[No authors listed]
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. The 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.
PMID: 3479526 [PubMed - indexed for MEDLINE]