Phosphatidylserine (PS)

Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints.
Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano T, Miyamori T.
J Clin Biochem Nutr. 2010 Nov;47(3):246-55

 Soybean-derived phosphatidylserine (Soy-PS) is a phosphatidylserine made from soybean lecithin by enzymatic reaction with L-serine. A double-blind, randomized controlled study was conducted to investigate the effects of Soy-PS on the cognitive functions of the elderly Japanese subjects with memory complaints. Seventy-eight elderly people with mild cognitive impairment (50-69 years old) were randomly allocated to take Soy-PS (100 mg, 300 mg/day) or placebo for 6 months. As a result, there was no difference in blood markers and vital signs during Soy-PS treatment and any side effect caused by Soy-PS treatment was not observed. Neuropsychological test scores were similarly increased in all groups including placebo group. However, in the subjects with relatively low score at baseline, the memory scores in PS treated groups were significantly increased against the baseline, while those of placebo group remained unchanged. And the memory improvements in Soy-PS-treated groups were mostly attributed to the increase in delayed verbal recall, a memory ability attenuated in the earliest stage of dementia. In conclusion, Soy-PS used in this study is considered as safety food ingredient and 6 months of Soy-PS supplementation could improve the memory functions of the elderly with memory complaints. PMID: 21103034

  Effects of phosphatidylserine supplementation on exercising humans.
Kingsley M.
Sports Med. 2006;36(8):657-69.

 Phosphatidylserine (PtdSer) is a ubiquitous phospholipid species that is normally located within the inner leaflet of the cell membrane. PtdSer has been implicated in a myriad of membrane-related functions. As a cofactor for a variety of enzymes, PtdSer is thought to be important in cell excitability and communication. PtdSer has also been shown to regulate a variety of neuroendocrine responses that include the release of acetylcholine, dopamine and noradrenaline. Additionally, PtdSer has been extensively demonstrated to influence tissue responses to inflammation. Finally, PtdSer has the potential to act as an effective antioxidant, especially in response to iron-mediated oxidation. The majority of the available research that has investigated the effects of PtdSer supplementation on humans has concentrated on memory and cognitive function; patients experiencing some degree of cognitive decline have traditionally been the main focus of investigation. Although investigators have administered PtdSer through intravenous and oral routes, oral supplementation has wider appeal. Indeed, PtdSer is commercially available as an oral supplement intended to improve cognitive function, with recommended doses usually ranging from 100 to 500 mg/day. The main sources that have been used to derive PtdSer for supplements are bovine-cortex (BC-PtdSer) and soy (S-PtdSer); however, due to the possibility of transferring infection through the consumption of prion contaminated brain, S-PtdSer is the preferred supplement for use in humans. Although the pharmacokinetics of PtdSer have not been fully elucidated, it is likely that oral supplementation leads to small but quantifiable increases in the PtdSer content within the cell membrane.A small number of peer-reviewed full articles exist that investigate the effects of PtdSer supplementation in the exercising human. Early research indicated that oral supplementation with BC-PtdSer 800 mg/day moderated exercise-induced changes to the hypothalamo-pituitary-adrenal axis in untrained participants. Subsequently, this finding was extended to suggest that S-PtdSer 800 mg/day reduced the cortisol response to overtraining during weight training while improving feeling of well-being and decreasing perceived muscle soreness. However, equivocal findings from our laboratory might suggest that the dose required to undertake this neuroendocrine action may vary between participants. Interestingly, recent findings demonstrating that short-term supplementation with S-PtdSer 750 mg/day improved exercise capacity during high-intensity cycling and tended to increase performance during intermittent running might suggest an innovative application for this supplement. With the findings from the existing body of literature in mind, this article focuses on the potential effects of PtdSer supplementation in humans during and following exercise. PMID: 16869708

  Phosphatidylserine supplementation and recovery following downhill running.
Kingsley MI, Kilduff LP, McEneny J, Dietzig RE, Benton D.
Med Sci Sports Exerc. 2006 Sep;38(9):1617-25.

 This study investigated the effects of 750 mg of soybean-derived phosphatidylserine (S-PtdSer), administered daily for 7 d prior to a bout of eccentric exercise and for 2d following exercise, on delayed onset of muscle soreness and markers of muscle damage, inflammation, and oxidative stress that followed prolonged downhill running. Following preliminary testing and a familiarization session, eight recreationally active males repeated an individualized downhill run at -16.5% for 51.0 +/- 1.5 min at 8.7 +/- 0.3 km x h(-1) on four occasions (trials 1-4). Trials 1 and 37 were presupplementation control trials. After trials 1 and 3 the subjects received, in a double-blind and crossover fashion, either S-PtdSer or a glucose polymer placebo. Trials 2 and 3 were separated by a 4-wk washout period. Venous blood, perceived soreness ratings, and feeling states were assessed prior to exercise, after exercise, and at 24 and 48 h after exercise during each trial. Downhill running led to elevations in perceived soreness (P < 0.05), creatine kinase activities (P < 0.001), myoglobin concentrations (P < 0.001), interleukin-6 (IL-6) concentrations (P < 0.001), and lipid hydroperoxide concentrations (P < 0.01). However, supplementation did not significantly attenuate these responses. These results suggest that supplementation with 750 mg x d(-1) S-PtdSer for 10 d does not afford additional protection against delayed onset of muscle soreness and markers of muscle damage, inflammation, and oxidative stress that follow prolonged downhill running.
PMID: 16960523

  Phospholipids and sports performance.
Jäger R, Purpura M, Kingsley M.
J Int Soc Sports Nutr. 2007 Jul 25;4:5.

 Phospholipids are essential components of all biological membranes. Phosphatidylcholine (PC) and Phosphatidylserine (PS) are Phosphatidyl-phospholipids that are required for normal cellular structure and function. The participation in physical activity often challenges a variety of physiological systems; consequently, the ability to maintain normal cellular function during activity can determine sporting performance. The participation in prolonged intense exercise has been shown to reduce circulatory choline concentrations in some individuals. As choline is a pre-cursor to the neurotransmitter Acetylcholine, this finding has encouraged researchers to investigate the hypothesis that supplementation with PC (or choline salts) could enhance sporting performance. Although the available data that evaluates the effects of PC supplementation on performance are equivocal, acute oral supplementation with PC (~0.2 g PC per kg body mass) has been demonstrated to improve performance in a variety of sporting activities where exercise has depleted circulatory choline concentrations. Short term oral supplementation with soy-derived PS (S-PS) has been reported to attenuate circulating cortisol concentrations, improve perceived well-being, and reduce perceived muscle soreness after exercise. More recently, short term oral supplementation (750 mg per day of S-PS for 10 days) has been demonstrated to improve exercise capacity during high intensity cycling and tended to increase performance during intermittent running. Although more research is warranted to determine minimum dietary Phospholipid requirements for optimal sporting performance, these findings suggest that some participants might benefit from dietary interventions that increase the intakes of PC and PS. PMID: 17908342

 Effects of phosphatidylserine on exercise capacity during cycling in active males.
Kingsley MI, Miller M, Kilduff LP, McEneny J, Benton D.
Med Sci Sports Exerc. 2006 Jan;38(1):64-71.

 The purpose of the study was to investigate the effects of 750 mg of soybean-derived phosphatidylserine, administered daily for 10 d, on exercise capacity, oxygen uptake kinetic response, neuroendocrine function, and feeling states during exhaustive intermittent exercise. Following preliminary testing, fourteen active males completed a staged intermittent exercise protocol on two further occasions (T1 and T2) separated by 16 +/- 1 d. The protocol consisted of three 10-min stages of cycling at 45, 55, and 65% VO2max, followed by a final bout at 85% VO2max that was continued until exhaustion. Approximately 5 d after T1 the subjects were assigned, in a double-blind manner, to either phosphatidylserine (PS) or placebo (P). Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol, and blood samples were obtained at rest, during the rest periods within the protocol (Post-55, Post-65), at the end of exercise (Post-85), 20 min after the completion of exercise (postexercise), and the day following exercise (Post-24 h). The main finding of this study was that supplementation had a significant effect on exercise time to exhaustion at 85% VO2max (P = 0.005). The exercise time to exhaustion in PS increased following supplementation (7:51 +/- 1:36 to 9:51 +/- 1:42 min:s, P = 0.001), whereas P remained unchanged (8:09 +/- 0:54 to 8:02 +/- 0:54 min:s, P = 0.670). Supplementation did not significantly affect oxygen kinetic mean response times (MRT(on) and MRT(off)), serum cortisol concentrations, substrate oxidation, and feeling states during the trial. This is the first study to report improved exercise capacity following phosphatidylserine supplementation. These findings suggest that phosphatidylserine might possess potential ergogenic properties. PMID: 16394955

 Safety of soy-derived phosphatidylserine in elderly people.
Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ.
Nutr Neurosci. 2002 Oct;5(5):337-43.

 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. PMID: 12385596

 Phosphatidylserine reverses reserpine-induced amnesia.
Alves CS, Andreatini R, da Cunha C, Tufik S, Vital MA.
Eur J Pharmacol. 2000 Sep 15;404(1-2):161-7.

 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

  Attention deficit/hyperactivity disorder (ADHD) in children: rationale for its integrative management.
Kidd PM.
Altern Med Rev. 2000 Oct;5(5):402-28.

 Attention Deficit/Hyperactivity Disorder (ADHD) is the most common behavioral disorder in children. ADHD is characterized by attention deficit, impulsivity, and sometimes overactivity (“hyperactivity”). The diagnosis is empirical, with no objective confirmation available to date from laboratory measures. ADHD begins in childhood and often persists into adulthood. The exact etiology is unknown; genetics plays a role, but major etiologic contributors also include adverse responses to food additives, intolerances to foods, sensitivities to environmental chemicals, molds, and fungi, and exposures to neurodevelopmental toxins such as heavy metals and organohalide pollutants. Thyroid hypofunction may be a common denominator linking toxic insults with ADHD symptomatologies. Abnormalities in the frontostriatal brain circuitry and possible hypofunctioning of dopaminergic pathways are apparent in ADHD, and are consistent with the benefits obtained in some instances by the use of methylphenidate (Ritalin) and other potent psychostimulants. Mounting controversy over the widespread use of methylphenidate and possible life-threatening effects from its long-term use make it imperative that alternative modalities be implemented for ADHD management. Nutrient deficiencies are common in ADHD; supplementation with minerals, the B vitamins (added in singly), omega-3 and omega-6 essential fatty acids, flavonoids, and the essential phospholipid phosphatidylserine (PS) can ameliorate ADHD symptoms. When individually managed with supplementation, dietary modification, detoxification, correction of intestinal dysbiosis, and other features of a wholistic/integrative program of management, the ADHD subject can lead a normal and productive life. PMID: 11056411

 Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
Kidd PM.
Altern Med Rev. 2007 Sep;12(3):207-27.

 The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications. PMID: 18072818

  Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids.
Vaisman N, Kaysar N, Zaruk-Adasha Y, Pelled D, Brichon G, Zwingelstein G, Bodennec J.
Am J Clin Nutr. 2008 May;87(5):1170-80.

 Increasing evidence supports n-3 fatty acid (FA) supplementation for patients with psychiatric disorders, such as attention deficit hyperactivity disorder. However, the exact metabolic fate of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on different glyceride carriers remains unclear. We investigated whether conjugation of EPA and DHA to phospholipid (PL-n-3) or to triacylglycerol (fish oil; FO) affects their incorporation in blood compartments and influences executive functioning. Children aged 8-13 y with impaired visual sustained attention performance received placebo, 250 mg/d EPA + DHA esterified to PL-n-3 (300 mg/d phosphatidylserine), or FO for 3 mo in a randomized double-blind manner. Main outcome measures included plasma and erythrocyte FA profile and continuous performance test results (Test of Variables of Attention; TOVA). Sixty of the 83 children enrolled completed the interventions (n = 18-21 per group). There was an enrichment of EPA (1.5-2.2-fold), docosapentaenoic acid (DPA; 1.2-fold), and DHA (1.3-fold) in the PL fraction in the plasma of FO- and PL-n-3-fed children. In erythrocytes, only PL-n-3 resulted in a significant reduction (approximately 30%) of very-long-chain saturated FAs (C20-24) and in an increase (1.2- and 2.2-fold, respectively) in linoleic acid and DPA. Total TOVA scores increased in the PL-n-3 (mean +/- SD: 3.35 +/- 1.86) and FO (1.72 +/- 1.67) groups but not in the placebo group (-0.42 +/- 2.51) (PL-n-3 > FO > placebo; P < 0.001). A significant correlation between the alterations in FAs and increased TOVA scores mainly occurred in the PL-n-3 group. Consumption of EPA+DHA esterified to different carriers had different effects on the incorporation of these FAs in blood fractions and on the visual sustained attention performance in children. PMID: 18469236