The following is a collection of phosphatidylserine abstracts from published scientific research and papers. Integratedhealth.com has designed PS-100 with phosphatidylserine research in mind.
REFERENCE 1 of 14
Maggioni M, Picotti GB, Bondiolotti GP, Panerai A, Cenacchi T, Nobile P, Brambilla F
Effects of phosphatidylserine therapy in geriatric patients with depressive disorders.
In: Acta Psychiatr Scand (1990 Mar) 81(3):265-70
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-Br~ane-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.
Institutional address: Clinica Zucchi Universita Milano Italy.
REFERENCE 2 of 14
Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC
Effects of phosphatidylserine in age-associated memory impairment.
In: Neurology (1991 May) 41(5):644-9
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.
Institutional address: Memory Assessment Clinics Inc. Bethesda MD 20814.
REFERENCE 3 of 14
Pepeu G, Spignoli G
Nootropic drugs and brain cholinergic mechanisms.
In: Prog Neuropsychopharmacol Biol Psychiatry (1989) 13 Suppl:S77-88
1. This review has two aims: first, to marshal and discuss evidences demonstrating an interaction between nootropic drugs and brain cholinergic mechanisms; second, to define the relationship between the effects on cholinergic mechanisms and the cognitive process. 2. Direct or indirect evidences indicating an activation of cholinergic mechanisms exist for pyrrolidinone derivatives including piracetam, oxiracetam, aniracetam, pyroglutamic acid, tenilsetam and pramiracetam and for miscellaneous chemical structures such as vinpocetine, naloxone, ebiratide and phosphatidylserine. All these drugs prevent or revert scopolamine-induced disruption of several learning and memory paradigms in animal and man. 3. Some of the pyrrolidinone derivatives also prevent amnesia associated with inhibition of acetylcholine synthesis brought about by hemicholinium. Oxiracetam prevents the decrease in brain acetylcholine and amnesia caused by electroconvulsive shock. Oxiracetam, aniracetam and pyroglutamic acid prevent brain acetylcholine decrease and amnesia induced by scopolamine. Comparable bell-shaped dose-effect relationships result for both actions. Phosphatidylserine restores acetylcholine synthesis and conditioned responses in aging rats. 4. The mechanisms through which the action on cholinergic systems might take place, including stimulation of the high affinity choline uptake, are discussed. The information available are not yet sufficient to define at which steps of the cognitive process the action on cholinergic system plays a role and which are the influences of the changes in cholinergic function on other neurochemical mechanisms of learning and memory.
Institutional address: Department of Preclinical and Clinical Pharmacology University of Florence Italy.
REFERENCE 4 of 14
Khalsa DS
Integrated medicine and the prevention and reversal of memory loss.
In: Altern Ther Health Med (1998 Nov) 4(6):38-43
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.
Institutional address: Alzheimer’s Prevention Foundation Tucson Ariz. USA.
REFERENCE 5 of 14
Guarcello V, Triolo G, Cioni M, Morale MC, Farinella Z, Scapagnini U, Marchetti B
Phosphatidylserine counteracts physiological and pharmacological suppression of humoral immune response.
In: Immunopharmacology (1990 May-Jun) 19(3):185-95
Phosphatidylserine (PS) is a necessary cofactor for protein kinase C (PKC) activation, and changes in the synthesis of PS have been shown to participate in the mechanism(s) involved in the transmembrane signaling of interleukin 1 (IL-1). In view of the age-associated defects in T-cell functions, in the present study we have addressed the question of whether an in vivo treatment with PS might interfere with such processes. Furthermore, the effect of an in vitro treatment with PS in human peripheral blood monocytes (PBMC) or splenocytes activated with a lectin mitogen, on the expression of IL-2 receptor, was assessed. While the process of ageing was accompanied by a marked decline of humoral response monitored by anti-BSA antibodies (of the IgG class) production, following immunization with BSA in complete Freund adjuvant, chronic treatment with PS (50 mg/kg, in drinking water), reversed this effect, raising specific antibody titers to levels practically indistinguishable from those measured in young animals. Pharmacological depression of humoral immune response induced by a treatment of adult animals with dexamethasone was similarly reversed by a chronic treatment with PS. While only a pharmacological concentration (10(-5) M) of PS significantly increased IL-2 receptor expression in activated human PBMC, simultaneous treatment of PBMC with inactive doses of PS and the pharmacological activator of PKC (phorbol myristate acetate, PMA, 10(- 8) M) resulted in a synergistic stimulation of Tac+ cells. Furthermore, in cultures of rat splenocytes PS (10(-6) M) significantly stimulated the expression of IL-2 receptor, and concomitant addition of PS (10(-7) M) to Con A-stimulated splenocytes produced a significant potentiation of IL-2 receptor induction. The present results indicate that in vivo treatment of ageing animals with the specific phospholipid PS is able to reverse the physiological decline of the humoral immune response induced by the ageing process. Moreover, treatment of young rats with PS reversed the pharmacological associated depression of specific antibody production. The in vitro effects of the phospholipid on human PBMC and rat splenocytes might suggest that PS is implicated in T-cell activation through its action on IL-2 receptor.
Institutional address: Department of Pharmacology Medical School University of Catania Italy.
REFERENCE 6 of 14
Monteleone P, Maj M, Beinat L, Natale M, Kemali D
Blunting by chronic phosphatidylserine administration of the stress- induced activation of the hypothalamo-pituitary-adrenal axis in healthy men.
In: Eur J Clin Pharmacol (1992) 42(4):385-8
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 9 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.
Institutional address: Institute of Psychiatry First Medical School University of Naples Italy.
REFERENCE 7 of 14
Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D
Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans.
In: Neuroendocrinology (1990 Sep) 52(3):243-8
The activity of brain cortex-derived phosphatidylserine (BC-PS) on the neuroendocrine and neurovegetative responses to physical stress was tested in 8 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 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 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.
Institutional address: Institute of Medical Psychology and Psychiatry First Medical School University of Naples Italy.
REFERENCE 8 of 14
Mori TA, Codde JP, Vandongen R, Beilin LJ
New findings in the fatty acid composition of individual platelet phospholipids in man after dietary fish oil supplementation.
In: Lipids (1987 Oct) 22(10):744-50
Nine healthy male volunteers were given 15 Max EPA fish oil capsules providing 2.67 g of eicosapentaenoic acid (EPA, 20:5 omega 3) and 1.72 g of docosahexaenoic acid (DHA, 22:6 omega 3) daily for 3 wk. Measurements were taken at baseline, at the end of the fish-oil period, and at 2 and 6 wk postsupplementation. The effect of fish oil on plasma lipids and the fatty acid composition of individual platelet phospholipids was studied. In general, the proportions of 20:5 omega 3 and 22:6 omega 3 in platelet phosphoglycerides were substantially increased mainly at the expense of arachidonic acid (AA, 20:4 omega 6). A large and significant increase in the relative EPA content of phosphatidylcholine (PC) (P less than 0.001) and phosphatidylethanolamine (PE) (P less than 0.001) was noted at the end of the 3 wk supplementation. We have also shown for the first time a small but significant (P less than 0.001) incorporation of EPA in phosphatidylserine (PS). Incorporation of DHA was also detected in PC, PE and PS, whereas the relative AA content of these phospholipids was significantly reduced. Fish oil supplementation led to a significant increase of 22:5 omega 3 in PS and decreases of 20:3 omega 6 in PC and 22:4 omega 6 in PE. Postsupplementation measurements showed a gradual return of all fatty acids to baseline levels. The fatty acid composition of the phosphatidylinositol (PI) fraction remained unchanged throughout the trial period. We conclude that in humans omega 3 fatty acids are incorporated into platelet membrane phospholipid subclasses with a high degree of specificity.
Institutional address: Department of Medicine University of Western Australia Royal Perth Hospital.
REFERENCE 9 of 14
Corwin J, Dean RL 3d, Bartus RT, Rotrosen J, Watkins DL
Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: amelioration of passive avoidance deficits without changes in psychomotor task performance.
In: Neurobiol Aging (1985 Spring) 6(1):11-5
A series of studies was conducted to evaluate the effects of phosphatidylserine (PS) in aged Fischer 344 rats. No effects were observed in any of four psychomotor tasks in which aged rats normally show deficits, nor on measures of shock sensitivity. However, significant dose-related effects on retention of passive avoidance were observed when PS was given both 30 min prior to training and retention. Further, in a second experiment similar positive effects were observed when PS was given only 30 min prior to training, as well as only 5 min following training. These results suggest that one effect of PS may include an ability to enhance neural events involved in the encoding or consolidation of new information into memory.
REFERENCE 10 of 14
Dyatlovitskaya EV, Lemenovskaya AF, Bergelson LD
Use of protein-mediated lipid exchange in the study of membrane-bound enzymes. The lipid dependence of glucose-6-phosphatase.
In: Eur J Biochem (1979 Sep) 99(3):605-12
The ability of liver lipid-exchange proteins to introduce foreign phospholipids into microsomes was used in a study of the lipid dependence of glucose-6-phosphatase. Supplementation of intact rat liver and hepatoma microsomes with exogeneous aminophospholipids prevents the decline of glucose-6-phosphatase activity during incubation, whereas the introduction of exogeneous phosphatidylcholine has no protective effect. On the contrary with deoxycholate-disrupted hepatoma microsomes, introduction of additional phosphatidylcholine causes activation while phosphatidylethanolamine has only little effect. The results are explained by assuming that the transport unit and the catalytic moiety of the glucose-6-phosphatase system have different lipid requirements, the activity of the former protein depending mainly on phosphatidylethanolamine and phosphatidylserine and that of the catalytic protein depending on phosphatidylcholine. In deoxycholate- disrupted liver microsomes (in which both the glucose-6-phosphatase activity and the phosphatidylcholine content are much higher than in hepatoma microsomes) incubation with phosphatidylcholine and lipid- exchange proteins alters neither the phospholipid composition nor the enzyme activity. THis suggests that the diminished activity of glucose-6-phosphatase in hepatomas may be partly due to a low level of phosphatidylcholine.
REFERENCE 11 of 14
Nishikawa T, Yoshida A, Tamura Y, Yoshida S
Involvement of protein kinase C in the regulation of cortisol production by guinea pig adrenocortical cells.
In: Horm Metab Res (1990 Jan) 22(1):29-32
Cytosol of the guinea pig adrenals was found to contain a protein kinase which was dependent on the presence of both calcium and phospholipids (phosphatidylserine and diolein), i.e., calcium/phospholipid-dependent protein kinase (protein kinase C). The peak of protein kinase C was separated from type II cAMP-dependent protein kinase by DE-52 chromatography. 12-0-Tetradecanoylphorbol-13- acetate (TPA) caused dose-dependent increments of cortisol formation without affecting cAMP formation by guinea pig adrenocortical cells as well as angiotensin II did. TPA-activated cortisol production was blocked by the addition of aminoglutethimide and cycloheximide, suggesting that the site of action of TPA might be located at a point before the production of pregnenolone in the mitochondria. Since TPA showed an increase in the cortisol production, protein kinase C may be involved in modulating steroidogenesis in the guinea pig adrenals in addition to the classical cAMP-dependent protein kinase pathway.
Institutional address: Department of Internal Medicine (II) School of Medicine Chiba University Japan.
REFERENCE 12 of 14
Melby JM, Wennhold AR, Nelson DH
Corticosteroid-induced lipid changes in rat liver microsomes.
In: Endocrinology (1981 Sep) 109(3):920-3
An influence of corticosteroids on the phospholipid composition of several tissues has been demonstrated previously. Increases in the activity of rat liver microsomal cytochrome c reductase and aryl hydrocarbon hydroxylase after corticoid administration were also demonstrated. The phospholipid composition of liver microsomes is now reported to be altered by similar corticosteroid treatment. Phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin levels in rat liver microsomes were decreased significantly after in vivo cortisol administration. The levels of palmitic, stearic, oleic, linoleic, and arachidonic acids in phosphatidylcholine and of palmitic acid in phosphatidylserine-phosphatidylinositol were also affected. Cholesterol was increased after adrenalectomy and decreased to control levels after the administration of cortisol. Some of the microsomal enzymes which are affected by corticosteroids or adrenalectomy are known to require phospholipids for full activity. The alteration of enzyme activities and membrane phospholipid composition by similar dosage schedules of corticosteroids suggests a possible relation between the two effects. By affecting the lipid composition of the membranes, corticosteroids may regulate or modulate the activity of the lipid-requiring enzyme systems.
REFERENCE 13 of 14
Knapp HR, Hullin F, Salem N Jr
Asymmetric incorporation of dietary n-3 fatty acids into membrane aminophospholipids of human erythrocytes.
In: J Lipid Res (1994 Jul) 35(7):1283-91
Dietary supplementation with different classes of polyunsaturate fatty acids is known to result in their incorporation into cell membranes, but the effects of this on eicosanoid formation and other cell functions frequently does not correspond to the degree of alteration in total membrane fatty acids. This phenomenon may be related to the compartmentalization of polyunsaturate fatty acids both within the organelles and within membranes. Aminophospholipids are asymmetrically distributed across the membrane bilayers of most human cells. These phospholipids are highly enriched in polyunsaturated fatty acids, and are known to have specific interactions with a number of membrane proteins. To determine whether dietary n-3 fatty acids are preferentially incorporated into membrane lipids in a particular spatial pattern, we have utilized the nonpermeant aminophospholipid probe, trinitrobenzenesulfonic acid, to study the transmembrane molecular species distribution of human erythrocyte ethanolamine phospholipids and phosphatidylserines before and at the end of 4 weeks of dietary supplementation with n-3 fatty acids. Selective incorporation of n-3 fatty acids occurred in the inner membrane leaflet ethanolamine phospholipids, particularly into the alkenyl-acyl species. The n-3 species in phosphatidylserines, particularly 18:0 and 22:6 n-3 (sn-1 and sn-2, respectively), replaced n-6 and n-9 species. These data may provide a basis for different cell responses to n-3 fatty acid enrichment, and for different degrees of diet-induced alteration in responses involving inner and outer membrane leaflet functions.
Institutional address: Department of Internal Medicine University of Iowa.
REFERENCE 14 of 14
Barre DE, Holub BJ
The effect of borage oil consumption on the composition of individual phospholipids in human platelets.
In: Lipids (1992 May) 27(5):315-20
The effect of supplementation with borage oil containing gamma- linolenic acid (GLA, 18:3n-6) on the levels and fatty acid compositions of individual human platelet phospholipids was evaluated. For this purpose, male volunteers were given an average daily intake of 5.23 g of GLA (as borage oil) for 42 days, after which the supplement was withdrawn for an additional 42-day period. No significant differences were found in the relative amounts of the choline phospholipids (PC), ethanolamine phospholipids (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and sphingomyelin (SPH) at days 0, 22, 43, 64, and 85. However, marked differences were observed in the fatty acid compositions of all the phospholipids including a marked, and reversible, rise in the level of dihomo-gamma- linolenic acid (DGLA, 20:3n-6), without a significant elevation in arachidonic acid (AA, 20:4n-6) and decreases in n-3 polyunsaturated fatty acids. In the case of PC, a net rise in DGLA of 1.8 mol% was observed by day 22 (from 2.1 to 3.9 mol%). The DGLA/AA ratios at day 43 exhibited considerable variability across phospholipids with PC greater than PS greater than PE = PI; the PC, PE, PS, and PI accounted for 67.6, 16.7, 12.9, and 2.6%, respectively, of the total DGLA in platelet phospholipids. Interestingly, despite the lack of DGLA in SPH, this phospholipid exhibited a marked enrichment in nervonic acid (NA, 24:1n-9) from 16.2 to 24.7 mol% upon borage oil consumption. The observed alterations may represent biochemical strategies for adaptation to dietary fatty acid modifications and the regulation of platelet membrane functioning.
Institutional address: Department of Nutritional Sciences University of Guelph Ontario Canada.