Phosphatidylserine Expert Guide

phosphatidyl serinePhosphatidylserine Background / Overview

Phosphatidylserine (abbreviated PS) is an amino acid-derived dietary fat present in all animal species. It is especially prevalent in neural tissue, where it is an vital component in the formation of neural cellular membranes (the outer “skin” of cells), and is therefore essential for proper cognitive function at large.

PS can be synthesized endogenously (in the body), and is most typically acquired from one’s diet, especially from fish. PS also comes in a variety of synthetic forms, derived from among multiple sources including bovine cortex, krill oil, soy, lecithin (a phospholipid protein found in marine life), and sunflower oil.

The recommended daily intake for an average adult is about 130mg, although PS can also be supplemented beyond this amount for a variety of beneficial effects, which has led to its adoption as a nootropic compound.

Namely, PS appears to have a variety of positive effects when used as a nootropic, including improvements in memory and general cognitive capacity, as well as improving attentional focus. It also appears to alleviate the effects of stress as well as protects against age-related cognitive decline. Additionally, PS has also become popular for enhancing athletic performance, as it prevents fatigue and aids in the body’s recovery from the stresses associated with intense physical activity.

Although the precise mechanisms involved remain largely unknown, evidence currently suggests that one of PS’s main biological effects is to increase acetylcholine levels in the brain, which would fit well with its role as a memory enhancer.

In any case, the wide variety of cognitive, motor, and memory-related benefits of PS make it a highly promising candidate as a nootropic compound.


Primary Effects of Phosphatidylserine

Memory enhancement

One of PS’s primary effects are its ability to enhance the acquisition, encoding, and retrieval of memories in the brain.

A substantial amount of what is currently known about PS’s role in memory enhancement has come from a variety of animal studies. For example, an early study of PS was shown to improve the performance of rats in a spatial memory task. A related (and more recent) study found that PS improved learning in healthy adult rats when administered at an equivalent human dose of ~550mg per day.

These studies are ultimately only a few examples of a much wider body of research work on PS:

  • A study from 2013 showed that oral supplementation with PS in rats improved their performance on a water-maze task. The authors also found that the PS treatment increased the level of brain-derived neurotrophic factor (BDNF) – a chemical related to neural growth, thereby indicating that some of PS’s beneficial effects may come from its ability to promote the growth of new neurons.
  • A related study from 2015 showed similar memory improvements in older rats after only one week of treatment. Notably, these improvements were dose-dependent – in other words, the beneficial effects became larger and more pronounced at progressively higher dosage levels. Because this study was performed in older rats, the authors concluded that PS may be a promising treatment for fighting the effects of normal age-related cognitive decline.
  • The anti-aging and memory-promoting effects of PS reported in the above studies have also been replicated in other animal species, including chicks and mice, which lend further support for the nootropic use of PS in human populations.

Studies of PS’s role in memory enhancement is not limited only to animal studies, but has also been extensively tested in human populations. For example, several studies have furnished evidence for its efficacy in managing and treating the memory-related impairments that typically occur in a variety of neurodegenerative disorders associated with advanced age, such as Alzheimer’s and dementia:

  • A double-blind study provided 78 elderly subjects with either PS or a placebo for six months, and found that the PS group showed improvements in memory, especially in verbal recall abilities.
  • A 2013 study investigated the effects of short-term PS supplementation on memory and cognitive performance in elderly subjects reporting sub-clinical difficulties with memory. The researchers reported that only 12 weeks of PS supplementation was sufficient to bring about increases in learning rates, along with improvements in tests of recognition, memory recall, mental flexibility, and executive functioning. PS supplementation also appeared to have beneficial side-effects on subjects’ blood pressure, without causing any other adverse side-effects.
  • In 2014, a three-month study of elderly patients with either Alzheimer’s disease or mild memory impairments revealed that daily supplementation with 300mg of PS brought about improvements in memory, and also had positive effects on mood and daily functioning.
  • Most recently, a 2015 study showed that 300mg / day of PS supplementation in Alzheimer’s disease patients improved their performance on a variety of memory, cognitive, and vocabulary recall tests.

Importantly, the ability of PS to improve multiple aspects of memory and overall cognitive functioning is not limited only to clinical patients, but has also been extensively documented in healthy populations:

  • A 2010 study with 157 healthy volunteers showed that treatment with PS produced significant improvements in immediate- and delayed verbal recall, spatial pattern memory, and general learning ability after only 15 weeks of supplementation.
  • In 2014, a similar study in 122 non-demented elderly patients with mild, age-related memory impairments demonstrated marked improvements in attentional focus and recognition memory after 15 weeks of treatment with 100mg/day of an enriched PS compound.
  • A recent study from 2016, with a sample group of healthy, post-menopausal women, showed that PS supplementation brought about improvements in a variety of cognitive and motor processes, as indicated by increases in verbal recall abilities, enhanced reaction times, and improvements in mobility. The authors concluded that PS may be a potent compound for protecting against age-related impairments in cognition and physical movement.

Overall, a large body of evidence from animal, clinical, and non-clinical human research provides strong support for the potency of PS supplementation in improving a broad variety of cognitive, memory-related, and motor processes.


Enhancing attentional focus

Several studies of children with ADHD has provided evidence that PS supplementation may improve attentional abilities. For example, a 2008 study showed that children with ADHD who were treated with 300mg / day exhibited significant improvements in their attentional symptoms, as indicated by enhanced performance on the TOVA test – a task that measures how well attentional focus is maintained over time. A later follow-up study was performed to verify the safety of PS treatment in these populations, and found no adverse side-effects. Thus, while this line of research is still in its relative infancy, there are promising signs that PS supplementation may enhance attentional and executive functioning, and that it may have potential as an alternative treatment of ADHD and other syndromes involving attentional symptoms.


Stress relief

There is some suggestive evidence that PS may also act to make users more resilient against stress. For example, a study with 16 healthy subjects tested brain responses to induced stress following 42 days of PS supplementation, and found that the PS-treated group were more resistant to the effects of stress compared to a control (placebo) group, as indicated by lower overall levels of brain activity in frequency bands commonly associated with stress-evoked responses. While the precise neurobiological mechanisms for this effect remain unknown, some researchers have hypothesized that PS’s anti-stress capabilities may come from its ability to reduce cortisol levels – a brain hormone frequently implicated in the body’s stress response.


Fatigue reduction and enhancement of physical / athletic performance

PS’s anti-stress effects also appear to generalize to the stresses associated with physical activity, and therefore shows potential as a compound for improving various aspects of athletic performance. For example, supplementation with PS after periods of high-intensity physical activity has been shown to decrease exercise-induced muscle soreness and reduces cortisol levels. Additionally, even relatively short-term oral supplementation (750mg/day for 10 days) improves total exercise capacity, by allowing athletes to perform at high intensities for up to 30% longer.


Anti-aging and protection against cognitive decline

Importantly, the body’s natural PS levels tend to decline with advancing age. Given the importance of this compound for proper neural functioning, this gradual decline in PS may account for some of the common symptoms of cognitive decline associated with aging. For this reason, a number of large-scale studies have specifically focused on the potential for PS to be used as a preventative treatment in forestalling the progression of age-related cognitive decline. These studies have not only shown that PS supplementation is effective in improving mental functioning in older adults, but have also provided extensive evidence that such treatment is exceptionally safe and well-tolerated.


Phosphatidylserine Safety information

Given the rich body of scientific research on the effects of PS, its safety as a therapeutic and nootropic compound has been extremely well-established. Few (if any) studies report adverse side-effects; and studies with sample groups of a hundred or more subjects have repeatedly found that as many as 99% of PS users report no negative side-effects.

PS supplements have traditionally been synthesized from a variety of animal products – including bovine tissue – although such animal sources are generally falling out of favor due to concerns regarding the risk of the transmission of prion-borne diseases such as Creutzfeldt-Jakob disease. Although no such cases have ever been reported from supplement users, manufacturers of synthetic PS have largely switched to alternative sources as a precautionary safety measure. Consequentially, most commercially-available PS supplements today are synthesized from plant products – most often soy, which is believed to be both structurally and functionally identical to bovine-derived PS. Additionally, like previous synthetic PS compounds, these newer, plant-derived PS supplements have been repeatedly shown to be exceptionally safe.

In summary, PS has been extensively studied – and the overwhelming weight of empirical evidence suggests that it is a highly safe compound to use as a nootropic supplement.


Phosphatidylserine Usage information

Among the body of currently-available studies, the various nootropic benefits discussed above have been observed with doses commonly ranging from as little as 100mg up to 400mg per day. When taken as a nutritional supplement, one’s PS dose can be taken all at once, or split into multiple smaller doses throughout the day. However, it should be noted that PS is highly fat-soluble, and so should be taken with full meals – ideally those which are high in fatty acids, such as fish.

However, it remains unclear to what extent PS’s effects are dose-dependent (i.e. getting stronger with progressively higher doses) – so it is best to start with a relatively low dose while keeping careful track of its psychological effects, and increasing the dose only as much as needed to experience a beneficial effect.


Summary / Conclusions

Current evidence suggests that phosphatidylserine confers a variety of beneficial cognitive effects, including enhancements in memory, learning, and attentional focus. Additionally, it also reduces fatigue and helps the body recover from intense bouts of stress – both physical and mental. Finally – like many other nootropics – it also appears to protect against age-related cognitive decline, therefore making it a potent anti-aging compound.

The sheer range of these benefits, together with phosphatidylserine’s excellent safety profile, makes it an exceptionally attractive candidate for inclusion in any nootropic user’s “stack.”

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