DHA-enriched phosphatidylserine ameliorates non-alcoholic fatty liver disease and intestinal dysbacteriosis in mice induced by a high-fat diet.

Docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) has attracted increasing attention because of its unique health benefits. In this study, DHA-PS was biosynthesized from DHA-enriched phosphatidylcholine (DHA-PC), which was extracted from herring roe, Clupea harengus. The ameliorating effect of DHA-PS on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) was investigated using a mouse model. The DHA-PS treatment ameliorated NAFLD and effectively decreased the serum total cholesterol, triglyceride, non-esterified fatty acid, and low-density lipoprotein cholesterol levels and considerably increased the serum high-density lipoprotein cholesterol levels. Moreover, the DHA-PS treatment reduced the levels of liver-function enzymes and pro-inflammatory cytokines and also the oxidative stress indices. Furthermore, DHA-PS increased the diversity and richness of the beneficial intestinal microorganisms, suggesting its potential as a dietary supplement and functional food to combat HFD-induced NAFLD.

Phosphatidylserine modulates response to oxidative stress through hormesis and increases lifespan via DAF-16 in Caenorhabditis elegans.

Phosphatidylserine is one of the phospholipids present in cell membranes, especially in brain and nervous system. The phosphatidylserine content is reduced with aging and age-related decrease in phosphatidylserine is known to contribute to cognitive impairment and Alzheimer's disease in the elderly. In the present study, we examined the effect of supplementation with phosphatidylserine on the response to oxidative stress and aging using C. elegans as a model system. Dietary supplementation with phosphatidylserine significantly increased resistance to oxidative stress and extended lifespan accompanying reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with phosphatidylserine. The cellular levels of reactive oxygen species and the expression of stress-responsive genes were increased by phosphatidylserine treatment, suggesting a hormetic effect. The extension of lifespan by phosphatidylserine overlaps with reduced insulin/IGF-1-like signaling and requires DAF-16. The effect of phosphatidylserine on age-related diseases was examined using animal model of disease. Supplementation with phosphatidylserine significantly suppressed amyloid beta-induced toxicity in Alzheimer's disease model. Reduced survival in diabetes mellitus due to high-glucose diet was reversed by supplementation with phosphatidylserine. This study reports the anti-oxidative stress and anti-aging effect of phosphatidylserine for the first time at the organismal level and proposes possible underlying mechanisms.

A simple and rapid-acting approach for the reduction of C-reactive protein.

C-reactive protein (CRP) is an acute-phase protein which can bind to and aggregate oxidized low-density lipoprotein (ox-LDL) particles, thereby enhancing the uptake of oxLDL by macrophages. This finally leads to the formation of foam cells that are a typical characteristic of atherosclerotic plaques. Serum CRP has been shown to bind to phospholipids such as phophatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylserine (PS). Owing to the rapid and efficient clearance of nanoliposomes from the circulation by the liver, we hypothesized that nanoliposomes composed of the mentioned phospholipids can serve as a potential tool to lower elevated serum CRP levels following acute inflammation. To evaluate this hypothesis, nanoliposomal formulations containing hydrogenated soy phosphatidylcholine (HSPC), a combination of HSPC and 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG), and a combination of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS) were prepared using lipid film hydration method followed by extrusion at the final concentration of 20 mM. To elevate circulating CRP levels in mice, 0.1 ml of Freund's complete adjuvant (CFA) containing 5 mg/ml heat-killed Mycobacterium tuberculosis was subcutaneously injected into the hind paw of the mice. CFA-challenged mice were intravenously treated with nanoliposomal formulations at the dose of 250 µmol/kg 16 h after CFA challenge that is coincided with peak serum CRP level. After 2 h, the blood was collected and serum level of CRP was measured using a quantitative sandwich enzyme-linked immunosorbent assay. All nanoliposomal formulations showed a size range from 100 to 150 nm in diameter and a polydispersity index of < 0.1. Results showed that all nanoliposomal formulations including DOPC/DOPS, HSPC and HSPC/DSPG could significantly decrease serum levels of CRP by 82.76% (74.44-86.92%, p = 0.0001), 44.41% (35.79-50.21%, p = 0.0001) and 38.47% (17.21-43.52%, p=0.0002) [Median (interquartile range)], respectively, when compared with the control group. Dexamethasone as a standard could decrease serum CRP level by 27.47% (16.32-31.63%, p = 0.0025) which was a smaller effect compared with the nanoliposomal preparations. In conclusion, negatively charged nanoliposomes could efficiently reduce the elevated serum levels of CRP in CFA-challenged mice.

A Phosphatidylserine Source of Docosahexanoic Acid Improves Neurodevelopment and Survival of Preterm Pigs.

The amount, composition, and sources of nutrition support provided to preterm infants is critical for normal growth and development, and particularly for structural and functional neurodevelopment. Although omega-3 long chain polyunsaturated fatty acids (LC-PUFA), and particularly docosahexanoic acid (DHA), are considered of particular importance, results from clinical trials with preterm infants have been inconclusive because of ethical limitations and confounding variables. A translational large animal model is needed to understand the structural and functional responses to DHA. Neurodevelopment of preterm pigs was evaluated in response to feeding formulas to term-equivalent age supplemented with DHA attached to phosphatidylserine (PS-DHA) or sunflower oil as the placebo. Newborn term pigs were used as a control for normal in utero neurodevelopment. Supplementing formula with PS-DHA increased weight of the brain, and particularly the cerebellum, at term-equivalent age compared with placebo preterm pigs (P's < 0.10 and 0.05 respectively), with a higher degree of myelination in all regions of the brain examined (all p < 0.06). Brains of pigs provided PS-DHA were similar in weight to newborn term pigs. Event-related brain potentials and performance in a novel object recognition test indicated the PS-DHA supplement accelerated development of sensory pathways and recognition memory compared with placebo preterm pigs. The PS-DHA did not increase weight gain, but was associated with higher survival. The benefits of PS-DHA include improving neurodevelopment and possibly improvement of survival, and justify further studies to define dose-response relations, compare benefits associated with other sources of DHA, and understand the mechanisms underlying the benefits and influences on the development of other tissues and organ systems.

Enhanced aerobic exercise performance in women by a combination of three mineral Chelates plus two conditionally essential nutrients.

BACKGROUND: Certain essential and conditionally essential nutrients (CENs) perform functions involved in aerobic exercise performance. However, increased intake of such nutrient combinations has not actually been shown to improve such performance. METHODS: For 1 mo, aerobically fit, young adult women took either a combination of 3 mineral glycinate complexes (daily dose: 36 mg iron, 15 mg zinc, and 2 mg copper) + 2 CENs (daily dose: 2 g carnitine and 400 mg phosphatidylserine), or the same combination with generic mineral complexes, or placebo (n = 14/group). In Trial 1, before and after 1 mo, subjects were tested for 3 mile run time (primary outcome), followed by distance covered in 25 min on a stationary bike (secondary outcome), followed by a 90 s step test (secondary outcome). To test reproducibility of the run results, and to examine a lower dose of carnitine, a second trial was done. New subjects took either mineral glycinates + CENs (1 g carnitine) or placebo (n = 17/group); subjects were tested for pre- and post-treatment 3 mile run time (primary outcome). RESULTS: In Trial 1, the mineral glycinates + CENs decreased 3 mile run time (25.6 ± 2.4 vs 26.5 ± 2.3 min, p < 0.05, paired t-test) increased stationary bike distance after 25 min (6.5 ± 0.6 vs 6.0 ± 0.8 miles, p < 0.05, paired t-test), and increased steps in the step test (43.8 ± 4.8 vs 40.3 ± 6.4 steps, p < 0.05, paired t-test). The placebo significantly affected only the biking distance, but it was less than for the glycinates-CENs treatment (0.2 ± 0.4. vs 0.5 ± 0.1 miles, p < 0.05, ANOVA + Tukey). The generic minerals + CENs only significantly affected the step test (44.1 ± 5.2 vs 41.0 ± 5.9 steps, p < 0.05, paired t-test) In Trial 2, 3 mile run time was decreased for the mineral glycinates + CENs (23.9 ± 3.1 vs 24.7 ± 2.5, p < 0.005, paired t-test), but not by the placebo. All changes for Test Formula II or III were high compared to placebo (1.9 to 4.9, Cohen's D), and high for Test Formula II vs I for running and biking (3.2 & 3.5, Cohen's D). CONCLUSION: In summary, a combination of certain mineral complexes plus two CENs improved aerobic exercise performance in fit young adult women.

Effect of pegylated phosphatidylserine-containing liposomes in experimental chronic arthritis.

BACKGROUND: Phosphatidylserine-containing liposomes (PSL) have been shown to reduce inflammation in experimental models of acute arthritis, by mimicking the apoptotic process. The aim of this study was to evaluate the effect of pegylated PSL (PEG-PSL) on chronic inflammation of collagen induced arthritis (CIA) in DBA/1J mice. METHODS: CIA was induced in 24 DBA/1J mice (n = 6/group), which were divided into control (0.9 % saline) or treated with PEG-PSL (5, 10 and 15 mg/kg/day, subcutaneously for 20 days). Clinical score, limb histology and measurement of cytokines in knee joints of animals by ELISA and cytometric bead array (CBA) were evaluated. The in vitro study employed macrophage cultures stimulated with 100 ng/ml of LPS plus 10 ng/ml of PMA and treated with 100 µM PEG-PSL. RESULTS: Resolution of the disease in vivo and the inflammatory process in vitro were not observed. PEG-PSL, in doses of 10 and 15 mg/kg, were not shown to reduce the score of the disease in animals, whereas with the dose of 5 mg/kg, the animals did not show the advanced stage of the disease when compared to the controls. The PEG- PSL 5, 10 and 15 mg/kg treatment groups did not show significant reduction of TNF-α, IL-1ß, IL-6, IL-2 and IFN-γ when compared to the controls. Disease incidence and animal weights were not affected by treatment. Regarding the paw histology, PEG-PSL did not yield any reductions in the infiltrating mononuclear, synovial hyperplasia, extension of pannus formation, synovial fibrosis, erosion of cartilage, bone erosion or cartilage degradation. The concentration of 100 µM of PEG-PSL has not been shown to reduce inflammation induced by LPS/PMA in the in vitro study. Treated groups did not show any reduction in inflammatory cytokines in the knee joints of animals affected by the disease compared to the control, although there were higher concentrations of TGF-ß1 in all experimental groups. CONCLUSION: The experimental model showed an expression of severe arthritis after the booster. TGF-ß1 as well other pro inflammatory cytokines were presented in high concentrations in all groups. PEG-PSL had no impact on the clinical score, the histopathology from tibial-tarsal joints or the production of cytokines in the knee joints. Other alternatives such as dosage, route of administration, and as an adjunct to a drug already on the market, should be evaluated to support the use of PEG-PSL as a new therapeutic tool in inflammatory diseases.

The effects of acute and chronic administration of phosphatidylserine on cell proliferation and survival in the dentate gyrus of adult and middle-aged rats.

Phosphatidylserine (PS) is an acidic phospholipid that is widely used as an alternative and/or complementary treatment of cognitive impairments. We hypothesize that these changes may be attributable, at least in part, to alterations in hippocampal neurogenesis. The aim of the present study was to investigate the effects of acute and chronic PS administration on hippocampal cell proliferation and survival in adult (5 months old) and middle-aged (12 months old) male Wistar rats. PS was injected daily (50mg/kg, i.p.) during 7 days (acute experiment) or 21 days (chronic experiment). To label newly generated cells, rats received a single BrdU injection (200mg/kg, i.p.) one day before PS treatment. The object recognition test was performed, and the rats were perfused. The brains were removed and processed with immunohistochemistry techniques for Ki-67 (cell proliferation) and BrdU (cell survival). The acute and chronic regimens were unable to promote cognitive improvement in either age group in the object recognition test. The analysis of cell proliferation showed a significant increase in the number of Ki-67-positive cells after acute and chronic PS administration in both age groups. The analysis of cell survival showed that acute and chronic PS administration increased the number of BrdU-positive cells only in adult animals.

Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer's disease and dementia.

INTRODUCTION: We report previously unpublished, early pilot studies performed with a brain-health food supplement containing a proprietary blend of 100 mg phosphatidylserine (PS) and 80 mg phosphatidic acid (PA) produced from soy lecithin. METHODS: Serum analysis after single PS+PA ingestion was performed in healthy volunteers. A 3-month double-blind, placebo-controlled study assessed the influence of three PS+PA capsules/day, (300 mg PS + 240 mg PA/day) or placebo on memory and mood in functioning, non-depressive elderly people with memory problems, using the Wechsler Memory Scale and the List of Depressive Symptoms. Furthermore, a 2-month randomized, double-blind, placebo-controlled trial assessed the effect of three PS+PA capsules/day (300 mg PS + 240 mg PA/day) or placebo on daily functioning, mental health, emotional state, and self-reported general condition in patients with Alzheimer's disease (AD). RESULTS: Serum PS peaked 90 min after ingestion, returning to baseline after 180 min. In the elderly, PS+PA [per protocol (PP) n = 31], unlike placebo (PP n = 26), significantly improved memory and prevented "winter blues" in a pre-post comparison. In the patients with AD, daily functioning (i.e., 7 activities of daily living) under PS+PA (PP n = 53) remained unchanged, but declined from 5.62 to 4.90 under placebo (PP n = 39; P = 0.035), with significant group difference (P = 0.021). The PS+PA group had 3.8% deterioration and 90.6% stability in daily functioning, compared to 17.9% and 79.5% under placebo, respectively (P = 0.066). Forty-nine percent of the PS+PA patients reported an improved general condition, compared to 26.3% under placebo (P = 0.084). Approximately, 43% of the PS+PA patients, but none under placebo, continued post-trial supplementation (while double-blinded). No negative side effects were observed. CONCLUSION: PS is efficiently absorbed after oral consumption. A positive influence of PS+PA on memory, mood, and cognition was demonstrated among elderly test subjects. Short-term supplementation with PS+PA in patients with AD showed a stabilizing effect on daily functioning, emotional state and self-reported general condition. The data encourage long-term studies with PS+PA in AD patients and other elderly with memory or cognition problems.

A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study.

BACKGROUND: Supplementation with a phosphatidylserine and phosphatidylserine/ phosphatidic acid complex (PAS) has been observed to normalize stress induced dysregulations of the hypothalamus-pituitary-adrenal axis (HPAA). Prolonged stress first induces a hyper-activation of the HPAA, which then can be followed by a state of hypo-activation.The aim of this study was to examine effects of an oral supplementation with 400 mg PS & 400 mg PA (PAS 400) per day on the endocrine stress response (ACTH, saliva and serum cortisol) to a psychosocial stressor. A special focus was to analyze subgroups of low versus high chronically stressed subjects as well as to test efficacy of 200 mg PS & 200 mg PA (PAS 200). METHODS: 75 healthy male volunteers were enrolled for this double-blind, placebo-controlled study, stratified by chronic stress level, and randomly allocated to one of three study arms (placebo, PAS 200 and PAS 400 per day, respectively). Study supplementation was administered for 42 days for each participant. Chronic stress was measured with the Trier Inventory for Chronic Stress (TICS), and subgroups of high and low chronic stress were differentiated by median values as provided by the TICS authors. A six week period of supplementation was followed by an acute stress test (Trier Social Stress Test - TSST). RESULTS: Chronic stress levels and other baseline measures did not differ between treatment groups (all p>0.05). Acute stress was successfully induced by the TSST and resulted in a hyper-responsivity of the HPAA in chronically stressed subjects. Compared to placebo, a supplementation with a daily dose of PAS 400 was effective in normalizing the ACTH (p=0.010), salivary (p=0.043) and serum cortisol responses (p=0.035) to the TSST in chronically high but not in low stressed subjects (all p>0.05). Compared to placebo, supplementation with PAS 200 did not result in any significant differences in these variables (all p>0.05). There were no significant effects of supplementation with PAS on heart rate, pulse transit time, or psychological stress response (all p>0.05). CONCLUSION: In chronically stressed subjects, a supplementation with PAS 400 (MemreePlus™) can normalize the hyper-responsivity of the HPAA to an acute stressor. TRIAL REGISTRATION: DRKS-ID: DRKS00005125.

In vivo optical imaging of brain tumors and arthritis using fluorescent SapC-DOPS nanovesicles.

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent marker. Mouse models (brain tumor and arthritis) were used to evaluate the usefulness of this method. Saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles tagged with CellVue Maroon (CVM) fluorophore were administered intravenously. Animals were then placed in the rotational holder (MARS) of the in vivo imaging system. Images were acquired in 10° steps over 380°. A rectangular region of interest (ROI) was placed across the full image width at the model disease site. Within the ROI, and for every image, mean fluorescence intensity was computed after background subtraction. In the mouse models studied, the labeled nanovesicles were taken up in both the orthotopic and transgenic brain tumors, and in the arthritic sites (toes and ankles). Curve analysis of the multi angle image ROIs determined the angle with the highest signal. Thus, the optimal angle for imaging each disease site was characterized. The MAROI method applied to imaging of fluorescent compounds is a noninvasive, economical, and precise tool for in vivo quantitative analysis of the disease states in the described mouse models.

Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study.

BACKGROUND: The present study is an open-label extension (OLE) aimed at evaluating the effect of 100 mg/day of phosphatidylserine enriched with docosahexaenoic acid (PS-DHA) on cognitive performance in nondemented elderly individuals with memory complaints. METHODS: From the participants who completed the core study, 122 continued with a 15-week OLE. Efficacy was assessed using a computerized tool and the Clinical Global Impression of Change (CGI-C) rating scale. RESULTS: A significant improvement in sustained attention and memory recognition was observed in the PS-DHA naïve group, while the PS-DHA continuers maintained their cognitive status. Additionally, a significant improvement in CGI-C was observed in the naïve group. CONCLUSIONS: The results demonstrate that consumption of 100 mg/day of PS-DHA might be associated with improving or maintaining cognitive status in elderly subjects with memory complaints.

The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. METHODS: Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day(-1) PS (n = 19) for 2 months in a randomised, double-blind manner. Main outcome measures included: (i) ADHD symptoms based on DSM-IV-TR; (ii) short-term auditory memory and working memory using the Digit Span Test of the Wechsler Intelligence Scale for Children; and (iii) mental performance to visual stimuli (GO/NO GO task). RESULTS: PS supplementation resulted in significant improvements in: (i) ADHD (P < 0.01), AD (P < 0.01) and HD (P < 0.01); (ii) short-term auditory memory (P < 0.05); and (iii) inattention (differentiation and reverse differentiation, P < 0.05) and inattention and impulsivity (P < 0.05). No significant differences were observed in other measurements and in the placebo group. PS was well-tolerated and showed no adverse effects. CONCLUSIONS: PS significantly improved ADHD symptoms and short-term auditory memory in children. PS supplementation might be a safe and natural nutritional strategy for improving mental performance in young children suffering from ADHD.

Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans.

Phosphatidylserine (PS) may attenuate the adverse effects of physical fatigue. Therefore, we investigated the effects of a multi-ingredient supplement containing 400 mg/d PS and 100 mg/d caffeine (supplement [SUP]) for 2 weeks on measures of cognitive function (CF), reaction time (RT), and mood (MD) following an acute exercise stress. It is hypothesized that PS will maintain preexercise CF and RT scores, while attenuating postexercise fatigue. Participants completed 2 acute bouts of resistance exercise (T1 and T2) separated by 2-week ingestion of SUP or control (CON). Outcome measures were assessed pre- and postexercise. When collapsed across groups, a significant decrease in RT performance was seen in the 60-second reaction drill from pre- to postexercise at T1. All other RT tests were similar from pre- to postexercise at T1. Reaction time was not significantly changed by PS. When collapsed across groups, a significant increase in performance of the serial subtraction test was seen. A significant increase (8.9% and 7.1%) in the number of correct answers and a significant decrease (8.0% and 7.5%) in time to answer were seen from pre- to postworkout at T1 and T2, respectively. A significant increase in total MD score from pre- to postworkout was observed for CON but not for PS at T2. Phosphatidylserine significantly attenuated pre- to postexercise perception of fatigue compared to CON. Ingestion of SUP for 14 days appears to attenuate postexercise MD scores and perception of fatigue, but does not affect CF or RT, in recreationally trained individuals.

Exposure to factor VIII protein in the presence of phosphatidylserine induces hypo-responsiveness toward factor VIII challenge in hemophilia A mice.

Administration of recombinant factor VIII (FVIII), an important co-factor in blood clotting cascade, elicits unwanted anti-FVIII antibodies in hemophilia A (HA) patients. Previously, FVIII associated with phosphatidylserine (PS) showed significant reduction in the anti-FVIII antibody response in HA mice. The reduction in the immune response to FVIII-PS could be due either to a failure of the immune system to recognize the antigen (i.e. immunological ignorance) or to an active induction of an antigen-specific nonresponsiveness (i.e. immunological tolerance). If it were a result of tolerance, one would predict that pre-exposure to FVIII-PS would render the mice hypo-responsive to a subsequent FVIII challenge. Here, we have demonstrated that naive HA mice that were pretreated with FVIII-PS showed a significantly reduced FVIII immune response to further challenge with native FVIII and that this decreased responsiveness could be adoptively transferred to other mice. An increase in number of FoxP3-expressing CD4(+) regulatory T-cells (Treg) was observed for the FVIII-PS-immunized group as compared with animals that received FVIII alone, suggesting the involvement of Treg in PS-mediated hypo-responsiveness. The PS-mediated reduction in antibody response was reversed by the co-administration of function-blocking anti-TGF-ß antibody with FVIII-PS. The decreased response to FVIII induced by FVIII-PS was determined to be antigen-specific because the immune response to another non-cross-reactive antigen (ovalbumin) was not altered. These results are consistent with the notion that FVIII-PS is tolerogenic and suggest that immunization with this tolerogenic form of the protein could be a useful treatment option to minimize immunogenicity of FVIII and other protein-based therapeutics.

Dietary phosphatidylinositol protects C57BL/6 mice from concanavalin A-induced liver injury by modulating immune cell functions.

SCOPE: Several recent studies have demonstrated that phospholipids (PLs) supplementation can modulate the function of cultured-immune cells. Furthermore, dietary PLs have been shown to ameliorate inflammatory processes and immune responses in arthritic and diabetic murine models, respectively. Thus, the aim of this study was to examine the immune-modulating activities of dietary soybean PLs in mice, with particular emphasis on the immune cell functions. METHODS AND RESULTS: Mice were fed semisynthetic diets for 6 weeks, which contained either 7% soybean oil or 5% soybean oil plus 2% of either PL: phosphatidylcholine (PC), phosphatidylinositol (PI), or phosphatidylserine (PS). Production of concanavalin A (Con A)-induced proinflammatory cytokines was significantly decreased in the splenocytes isolated from mice fed PI compared to other lipids. Supplementation of the diet with PI, but not with the other lipids, significantly suppressed the proinflammatory cytokine serum levels and the development of Con A-induced liver damages. CONCLUSION: These observations suggest that dietary PI influenced immune functions, resulting in the prevention of pathogenesis and development of the liver injury in mice.

Docosahexaenoic acid and phosphatidylserine improves the antioxidant activities in vitro and in vivo and cognitive functions of the developing brain.

Fish oil during early postnatal period may modulate the impact of oxidative stress in the developing brain and thus improve memory and cognitive behaviour. This study investigated the impacts of docosahexaenoic acid (DHA, C22:6, n-3) and/or phosphatidylserine (PS) on antioxidant activities in vitro, and the beneficial effects of feeding with DHA and/or PS on antioxidant activities in brain and liver tissues and on the cognitive functions of the developing brain. Results indicated that DHA and/or PS significantly enhanced antioxidant activities and increased cell viabilities in vitro. Feeding with DHA and/or PS supplementation not only significantly improved escape latency of animals, but it also improved the oxidative parameters in the brain, enhanced glutathione peroxidase activity as well as reduced nitric mono-oxide levels in the liver. DHA and PS may serve to protect cells from oxidative stress and further improve learning and memory ability in vivo.

Omega-3 fatty acids administered in phosphatidylserine improved certain aspects of high chronic stress in men.

Nutrients such as omega-3 oils and phosphatidylserine have been considered to exert stress-buffering effects. In this randomized, double-blind, placebo-controlled trial, we investigated effects of omega-3 phosphatidylserine (PS) on perceived chronic stress, assessed by the Trier Inventory for Chronic Stress (Schulz P, Schlotz W, Becker P. TICS: Trierer Inventar zum chronischen Stress. Göttingen, Germany: Hogrefe, 2004.), and on psychobiological stress responses to an acute laboratory stress protocol, the Trier Social Stress Test (Neuropsychobiology.1993;28:76-81), at baseline and after the treatment period. We hypothesized that omega-3 PS supplementation lowers chronic and acute stress. Sixty healthy nonsmoking men aged 30 to 60 years either received omega-3 PS or a matching placebo for 12 weeks. Results revealed no significant main effect of omega-3 PS supplementation on stress measures. However, by accounting for chronic stress level of study participants, stress-reducing effects of omega-3 PS were found exclusively for high chronically stressed subjects. As expected, these individuals also showed a blunted cortisol response to the Trier Social Stress Test. Treatment with omega-3 PS seemed to restore the cortisol response in this particular subgroup of low responders. These results are in line with previous findings. We conclude that subgroups characterized by high chronic stress and/or a dysfunctional response of the hypothalamus-pituitary-adrenal axis may profit from omega-3 PS supplementation.

The effect of phosphatidylserine-containing omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study.

OBJECTIVE: To evaluate for the first time the efficacy of safe-sourced phosphatidylserine-containing omega-3 long chain polyunsaturated fatty acid (PS-omega-3) in improving memory abilities. METHODS: PS-omega-3 was administered daily for 6 weeks to eight elderly volunteers with subjective memory complaints. The Cognitive Drug Research test battery was used to assess the effect on their cognitive abilities. RESULTS: PS-omega-3 supplementation resulted in 42% increase in the ability to recall words in the delayed condition. CONCLUSION: PS-omega-3 may have a favorable effect on memory in subjects with subjective memory complaints. PS-omega-3 may serve as a safe alternative to phosphatidylserine extracted from bovine cortex.

Phosphatidylserine-containing liposomes inhibit the differentiation of osteoclasts and trabecular bone loss.

Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-beta1 and PGE(2), which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-kappaB ligand, receptor activator of NF-kappaB, ICAM-1, and CD44. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-beta1 and PGE(2) and decreased the expression of receptor activator for NF-kappaB ligand, receptor activator of NF-kappaB, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-beta1 together with PGE(2) significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-beta1 and PGE(2) release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.

Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress.

The aim of this study was to investigate the effect of phosphatidylserine (PS) on cognition and cortical activity after mental stress. After familiarization, 16 healthy subjects completed cognitive tasks after induced stress in a test-re-test design (T1 and T2). Directly after T1, subjects were assigned double-blind to either PS or placebo groups followed by T2 after 42 days. At T1 and T2, cortical activity was measured at baseline and immediately after stress with cognitive tasks using electro-encephalography (EEG). EEG was recorded at 17 electrode positions and fast Fourier transforms (FFT) determined power at Theta, Alpha-1, Alpha-2, Beta-1 and Beta-2. Statistics were calculated using ANOVA (group x trial x time). The main finding of the study was that chronic supplementation of phosphatidylserine significantly decreases Beta-1 power in right hemispheric frontal brain regions (F8; P < 0.05) before and after induced stress. The results for Beta-1 power in the PS group were connected to a more relaxed state compared to the controls.