Phosphatidylserine supplement benefit and side effects - Does a phosphatidylserine pill improve memory?
Are these pills as good as other brain nutrients such as acety l carnitine, DMAE, ginkgo biloba, bacopa monnieri, or a combination formula called Mind Power Rx?
April 1 2018 by Ray Sahelian, M.D.

Phosphatidylserine is a natural nutrient found as part of the cell membrane of cells. It is most notably found in the cell membrane of neurons, comprising about 7 to 10 percent of its lipid content. The average daily intake from the diet in western countries is estimated to be about 130 mg a day. The total amount of phosphatidylserine in the body is about 60 grams, 30 grams of which is in the brain.
   Although lecithin (phosphatidylcholine) has been available as a supplement for many decades, phosphatidylserine became available to the North American market in the mid 1990s. In the past it was obtained from the brain of cows. In fact, if you read some of the research studies, it will identify this nutrient as BC- phosphatidylserine. The BC stands for bovine cortex, or cow brain. The reason BC - phosphatidylserine is not sold is because of the fear of viruses or infectious agents being inadvertently introduced in the product when extracted from the brains of cows. The phosphatidylserine supplements currently available over the counter are derived from soy.

PS or BS?
Does phosphatidylserine really boost memory or are you better off spending your money on a better mind booster? My personal opinion is that PS is not very beneficial as a mind supplement, I prefer a formula called Mind Power Rx.

Research
Several studies in the past in Europe have evaluated the role of oral BC-phosphatidylserine administration in both animals and humans. In general, the results have shown positive benefits in terms of mind and memory enhancement. However, we need to keep a very important point in mind. The studies with phosphatidylserine have used bovine cortex as the source. Can we assume that the results with soy-derived supplement would be similar?
   No, we can't. Phosphatidylserine consists of serine attached to fatty acids. The serine molecule found in cow brain is attached mostly to long chained polyunsaturated fatty acids such as DHA or AA (arachidonic acid). In addition, the cow brain extract is not pure phosphatidylserine. It most likely contains other brain components such as sphingolipids, sphingomyelins, and other brain constituents, which may have led to improvements in brain function. For obvious reasons -- potential viruses present in cow brain -- we should not be using the cow brain extract. The phosphatidylserine in soy is basically serine attached to saturated on monounsaturated fatty acids, along with other fats from soy, which are chemically very different than the fats found in cow brain. Hence we are basically comparing apples to oranges. It is medically and scientifically improper to use the results of studies done with phosphatidylserine from cow brain and thus claim that soy derived phosphatidylserine is also effective.

Summary and review
There are many over the counter natural mind boosters that are supported by scientific research in terms of benefit and effectiveness. Phosphatidylserine, at this time, is low on my list as an effective brain booster particularly since it is also very expensive. However, soy-derived phosphatidylserine does have its supporters who claim that it works for them, and a couple of studies indicate it may have stress modifying effect. As to its relation to memory, I have listed studies below which have come to different conclusions. We have made this product available for those who notice benefits from it. As to overall brain enhancement, most people prefer the results from Mind Power Rx supplement.

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Mind Boosting supplements include
Acetyl-l-carnitine 300 mg taken once daily, lipoic acid at 10 to 50 mg, DMAE at 100 to 300 mg, and SAM-e at only 100 mg a few days a week.

Just wondering why someone would take phosphidylserine instead of cdp choline or vice versa?
   A. There are a number of dietary supplements that enhance brain function and each person has their own favorite or a preferred combination formula. The only way to find out which works for someone is to try each one separately for a couple of weeks.

Review article
Nutrition. 2015. Phosphatidylserine and the human brain. The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes.

Availability over the counter, online and in health food stores
BC-phosphatidylserine is not available in the US but soy-derived is sold in vitamin stores. Each 500 mg gel capsule contains several phospholipids with 100 mg being actual phosphatidylserine . It is an expensive nutrient with each pill costing between 50 cents and one dollar. It is worth emphasizing that the phosphatidylserine currently available is derived from soy products and thus has a different fatty acid composition than the bovine cortex-derived phosphatidylserine used in published studies. There are clinical trials with PS attached to omega-3 fatty acids. This may be a good option but perhaps ingesting PS along with fish oils may also be another option.

Nutr Res. 2012. 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. 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.

Supplement Facts:
Serving Size: 1 Capsule
Servings Per Bottle: 30

Amount Per Softgel:
Phosphatidylserine PS 100 mg
Dosage: One or two capsules a day.

Suggested Usage: Take 1 phosphatidylserine capsule with a meal, or as directed by your qualified health consultant.

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Athletic performance
Although claims have been made that supplementation with phospholipids help improve sports performance, studies have not been consistent in their outcome. Even if PS does help improve sports performance, it is such an expensive supplement that it would not be a cost effective.

Phosphatidylserine supplementation and recovery following downhill running. University of Wales Swansea, Med Sci Sports Exerc. 2006. Kingsley MI, Kilduff LP, Benton D. Singleton Park, Swansea, United Kingdom. M.I.C.
This study investigated the effects of 750 mg of soybean-derived phosphatidylserine, administered daily for 7 days prior to a bout of eccentric exercise and for 2 days following exercise, on delayed onset of muscle soreness and markers of muscle damage, inflammation, and oxidative stress that followed prolonged downhill running. The results suggest that supplementation with 750 mg phosphatidylserine 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.

Effects of phosphatidylserine on exercise capacity during cycling in active males.
Med Sci Sports Exerc. 2006. Kingsley MI, Miller M, Kilduff LP, McEneny JD. Department of Sports Science, University of Wales Swansea, Swansea, Wales, United Kingdom.
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. This is the first study to report improved exercise capacity following phosphatidylserine supplementation. These findings suggest that phosphatidylserine might possess potential ergogenic properties.

Brain enhancement in seniors
BMC Neurol. 2011. Safety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension. Sieratzki Chair of Neurology, Tel-Aviv University Medical School, Ramat Aviv, Israel. Administration of PS extracted from bovine cortex (BC-PS), which contains high levels of omega-3 long chain polyunsaturated fatty acid (LC-PUFA) attached to its backbone, resulted in positive effects on brain functions such as learning and memory. Recently, a novel marine-sourced PS with omega-3 LC-PUFA attached to its backbone was developed (PS-DHA). In the present study, we evaluated the safety profile of the novel PS preparation in non-demented elderly with memory complaints. The efficacy study of this novel formulation indicated that PS-DHA may ameliorate cognitive deficits in non-demented elderly population.

Effect on cortisol
I have ordered 2 bottles of phosphatidylserine 100 mg. I am using these on advice form my doctor to reduce high cortisol. Is it good to reduce high cortisol levels?
    It appears that higher amounts can reduce cortisol levels in those engaged in athletic activity, but it is unlikely that smaller amounts have much of a clinical effect in those who are sedentary.

The effects of phosphatidylserine on endocrine response to moderate intensity exercise.
J Int Soc Sports Nutr. 2008. The University of Mississippi, University, MS, USA. Previous research has indicated that phosphatidylserine (PS) supplementation has the potential to attenuate the serum cortisol response to acute exercise stress. Equivocal findings suggest that this effect might be dose dependent. This study aimed to examine the influence of short-term supplementation with a moderate dose of PS (600 mg per day) on plasma concentrations of cortisol, lactate, growth hormone and testosterone before, during, and following moderate intensity exercise in healthy males. 10 healthy male subjects were assigned to ingest 600 mg PS or placebo per day for 10 days using a double-blind, placebo-controlled, crossover design. Serial venous blood samples were taken at rest, after a 15 minute moderate intensity exercise protocol on a cycle ergometer that consisted of five 3-minute incremental stages beginning at 65% and ending at 85% VO2 max, and during a 65 minute passive recovery. Plasma samples were assessed for cortisol, growth hormone, testosterone, lactate and testosterone to cortisol ratio for treatment (PS or placebo). Mean peak cortisol concentrations and area under the curve (AUC) were lower following PS when compared to placebo. PS increased AUC for testosterone to cortisol ratio when compared to placebo. PS and placebo supplementation had no effect on lactate or growth hormone levels. The findings suggest that PS is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. PS supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels.

Safety, risk, side effects
Safety of soy-derived phosphatidylserine in elderly people.
Nutr Neurosci. 2002.
Earlier studies used brain cortex derived phosphatidylserine, of which the human tolerability of 300mg daily in 130 patients has been shown. The human tolerability of phosphatidylserine derived from soybean has not been reported. We report the results of a study of the safety of two dosages of soy-phosphatidylserine 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-phosphatidylserine 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 phosphatidylserine is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily.

Phosphatidylserine Research studies
Nutr Res. 2013. Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans.

Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress.
Stress. 2004.
Phosphatidylserine , derived from cow brains, has been shown previously to dampen the ACTH and cortisol response to physical stress. Further research investigated the influence of soy lecithin phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. In this study, we investigated the effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) supplementation on pituitary adrenal reactivity (ACTH, cortisol) and on the psychological response (Spielberger State Anxiety Inventory stress subscale) to a mental and emotional stressor. Four groups of 20 subjects were treated for three weeks with daily dosages of either 400 mg PAS, 600 mg PAS, 800 mg PAS, or placebo before exposure to the Trier Social Stress Test (TSST). Treatment with 400 mg PAS resulted in a pronounced blunting of both serum ACTH and cortisol, and salivary cortisol responses to the TSST, but did not affect heart rate. The effect was not seen with larger doses of PAS. With regard to the psychological response, 400 mg PAS seemed to exert a specific positive effect on emotional responses to the TSST. While the placebo group showed the expected increase in distress after the test, the group treated with 400 mg PAS showed decreased distress. These data provide initial evidence for a selective stress dampening effect of PAS on the pituitary-adrenal axis, suggesting the potential of PAS in the treatment of stress related disorders.

The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor.
Benton D. Nutr Neurosci 2001
The present study considered whether phosphatidylserine supplementation influenced subjective feelings of stress and the change in heart rate when a stressful mental arithmetic task was performed. In young adults, with neuroticism scores above rather than below the median, the taking of 300mg phosphatidylserine each day for a month was associated with feeling less stressed and having a better mood. The study for the first time reports an improvement in mood following phosphatidylserine supplementation in a sub-group of young healthy adults.

The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment.
Nutr Neurosci 2001. Experimental Psychopharmacology Unit, Brain & Behaviour Institute, Department of Psychiatry and Neuropsychology, Maastricht, The Netherlands.
We report the results of a clinical trial of soybean-derived PS (S-phosphatidylserine ) in aging subjects with memory complaints. Subjects were 120 elderly (> 57 years) of both sexes who fulfilled the more stringent criteria for age-associated memory impairment (AAMI); some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300mg S-phosphatidylserine daily, or 600mg S-phosphatidylserine daily. Assessments were carried out at baseline, after 6 and 12 weeks of treatment, and after a wash-out period of 3 weeks. Tests of learning and memory, choice reaction time, planning and attentional functions were administered at each assessment. Delayed recall and recognition of a previously learned word list comprised the primary outcome measures. No significant differences were found in any of the outcome variables between the treatment groups. There were also no significant interactions between treatment and 'severity of memory complaints'. In conclusion, a daily supplement of phosphatidylserine does not affect memory or other cognitive functions in older individuals with memory complaints.

An open trial of plant-source derived phosphatidylserine for treatment of age-related cognitive decline.
Isr J Psychiatry Relat Sci. 2000.
We assessed whether the efficacy of plant-source derived phosphatidylserine 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 phosphatidylserine (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).

Expert Opinions
Companies promoting soy-phosphatidylserine make positive claims about this supplement and defend its promotion by citing research studies done on BC-phosphatidylserine. I interviewed many experts on fats, including Drs. Simopoulos, Hibbeln, and Salem, regarding their opinions on phosphatidylserine. All experts were unanimous in their assessment that one can’t automatically use the studies done with BC-phosphatidylserine to claim the same benefits as that of soy-phosphatidylserine. Lloyd Horrocks, Ph. D., Professor Emeritus of Medical Biochemistry at Ohio State University in Columbus, Ohio, and an expert on fatty acids says, “The fatty acids in bovine cortex phosphatidylserine are mostly made of DHA and arachidonic acid while the fatty acids from soy-derived phosphatidylserine are made mostly from oleic, linolenic, and linoleic acids. It’s quite likely the DHA and arachidonic acids in BC-phosphatidylserine could have some cognitive effect. It’s also possible that the clinical effects from taking phosphatidylserine may be due to this nutrient influencing the release of histamine, glucose uptake in the brain, or in other yet unknown ways.”

Michael Schmidt is Professor of Applied Biochemistry and Clinical Nutrition at Northwestern College of Health Sciences. He tells me, “The DHA found in BC-phosphatidylserine could have important effects. However, it’s possible when soy phosphatidylserine is ingested that the body will take its own DHA and attach it to the phosphoserine head group, thus replacing the smaller chained fatty acids. Synthesizing phospholipids requires energy and effort. If phosphatidylserine provides the phosphoserine head, then it will give brain cells a break from having to create it de novo.”

Questions
I'm curious to hear your opinion on soy-based phosphatidylserine versus porcine (pig)-brain based PS. The PS information on your website notes the potentially large differences between soy and (undesirable) bovine-cortex derived PS. Since porcine, I assume, more structurally closer to BC-PS than soy is, do you feel porcine-based PS is an acceptable substitute?
   We have not seen much research on Porcine phosphatidylserine so we don't have a comment on this at this time.

Please note that there is currently available a PS-DHA conjugate, which better resembles the natural (Brain) form of phosphatidylserine and which better emulates the "historical" bovine phosphatidylserine, on which most of clinical evidence is based. Selected studies show greater DHA delivery (twice) than a mix of phosphatidylserine and DHA in animals. I represent the company  Enzymotec.
    I have not tested or tried PS-DHA from Enzymotec but this is an interesting combination. I also wonder whether it offers any benefits over taking a fish oil capsule along with a regular phosphatidylserine pill. It would be interesting to compare the two options in a study.

Mind Power Rx and phosphatidylserine. Are they ok to take with prescription drugs like metoprolol and Lipitor and one aspirin a day? I am anxious to try these products but would like to know if they can be taken with these drugs.
    Your doctor should be aware of your intention to take supplements and if he or she approves one should begin with low dosages and only one supplement at a time. It is difficult to predict supplement / medication interactions in any one individual, much depends on dosage.

I am taking PS 100 Jarrow Formulas Phosphatidylserine almost a month now. After reading Dr. Sahelian analysis between BC and Soy, I thought I agreed with his analysis. The reason I took PS-100 is, during these couple years, I had a recall memory problem, I had a hard time to recall, name, place, or things. I knew the things, but cannot name it, eventually I did, but at that moment completely blank. So making conversation sometime you stop or disturb. My question is, is Mind Power Rx will help this problem?
   It is not possible to predict in any one person what the reaction will be to any supplement or medication. The brain formula could help but it is not possible to know without trying it. One can also, over time, try different dietary supplements such as DMAE, acetyl l carnitine, ginkgo biloba, fish oils and other nutrients and herbs to see which one is most helpful.

I am trying to locate another source of bovine cortex PS.
   As far as I know, the bovine source is not available in the US.

Q. Thank you for such an informative website. I have prostate cancer but am going on nearly 10 years survival since my robotic surgery. My Gleason score after surgery was 7. I am having some cognitive issues based on stress from a spinal cord injury and past surgeries and was wondering if I can take Phosphatidylserine supplements with my past prostate issues?
   A. I have not seen studies regarding the role of this substance in prostate health or cancer, but my best guess is that it does not have a major influence.

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