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Phosphatidylserine – The Most Effective Natural Nootropic?

We all consume phosphatidylserine everyday, but unfortunately most of us are still short of it. It’s a phospholipid, and phospholipids are the molecules that form the membranes of cells, so phosphatidylserine is part of the cell membrane of every one of our 20 trillion cells. In the body it makes up around 7-10% of our cell membranes, but the concentration levels of phosphatidylserine rise in the brain where it’s especially important, and where 50% of our total stores of phosphatidylserine lie (1). The Myelin sheath which insulates our brain cells is especially rich in phosphatidylserine. The myelin sheath covers the axon of our neurones, and is vital for the efficient transfer of electrical signals down our brain cells, which allows them to connect together.

Phosphatidylserine In The Brain

When Phosphatidylserine levels are increased in neuronal membranes it makes these brain cells more sensitive to the key neurotransmitters Acetylcholine, Norepinephrine, Serotonin and Dopamine (2-4). This is known scientifically as increased ‘synaptic fidelity’, with a synapse being the gap between 2 brain or nerve cells which allows a transmission or connection of the 2 cells. Synapses allow us to learn, think, remember and move.

Acetylcholine (Ach) is often referred to as the ‘smart’ neurotransmitter, and is vital for learning, memory and increasing our attention span

phosphatidylserine membrane
The Phospholipid Bilayer of Cell Membranes

through ‘Cholinergic’ transmissions (Acetylcholine Synapses). It’s made from acetyl-CoA and choline which is why choline is often included in Nootropic stacks. Norepinephrine (aka Noradrenaline) is associated with mental energy, focus and alertness. Dopamine is associated with motivation and concentration. Serotonin is associated with good mood and improved sleep, a lack of serotonin is strongly associated with depression and poor concentration.

It’s these neurotransmitter effects that mean that many people who take phosphatidylserine notice a very definite difference, where they they feel sharper and clearer. They can more easily remember names and places from the past, as well as form clearer, more fluent sentences.

Another key benefit of phosphatidylserine is the effect is has on the hypothalamus and hippocampus areas of the brain. Both of these areas work together to regulate the release of cortisol, which is the major stress hormone of the body released from the adrenal cortex. Cortisol works on a feedback loop so that when enough is released, the hypothalamus and hippocampus sense it and reduce the amount of CRH (Corticotropin-releasing hormone) released from the hypothalamus, which triggers the pituitary gland to produce less ACTH (Adrenocorticotrophic hormone), which tells the adrenals to produce less cortisol.

However, when cortisol levels are chronically raised, for example if we are chronically stressed, the hypothalamus and hippocampus lose sensitivity to cortisol, so CRH and ACTH release is not turned down, and so cortisol production in the adrenals isn’t switched off. This means we end up with chronically high cortisol levels. Phostidylserine can resensitize the cells of hypothalamus and hippocampus to cortisol so that they ‘hear’ the feedback message again and reduce CRH and ACTH, which reduces cortisol production (5,6,7).


Research Evidence For Phosphatidylserine Effects as a Nootropic?

A study in 2011 tested 18 college age men after 14 days of supplementation with 400mg of phosphatidylserine on a serial subtraction test, (i.e counting backwards from 100 by 7’s or 6’s or 3’s etc). They found that the group who supplemented with phosphatidyl serine reduced the time needed for a correct calculation by 20%, reduced the total amount of errors by 39% and increased the amount of correct calculations by 13% over the placebo group (8).

phosphatidylserine, hypothalamus2 open label trials on older participants suffering from mild cognitive decline, (a loss in memory caused by ageing in people who are otherwise clinically healthy), found that supplementing with 300mg of phosphatidylserine a day improved performance on tests of verbal learning, verbal recall, verbal fluency, visual learning, attention, communication skills, initiative, socialisation and self sufficiency (9,10). A similar study that ran for 90 days found the same results, but also found the study participants improved their ability to recall names and faces (11).

Further studies on memory and phosphatidylserine found that elderly subjects who felt their memory was getting worse had a 42% increase in their ability to recall words (12), as well as achieving a significant improvement in memory recognition, memory recall, executive function, and mental flexibility (13), after supplementing with 300 mg per day.

Phosphatidylserine can also help symptoms associated with ADHD, for example a 2014 study in Japan found that children aged between 4-14 years who supplemented with 200mg a day of phosphatidylserine significantly improved their short term memory, inattention problems and impulsivity (14).

What’s the Best Phosphatidylserine Dosage?

The recommended dosage for phosphatidylserine is 100mg taken 3 times a day with meals. This dosage has been shown to help people suffering from cognitive decline and people looking to improve their cognitive function.

However, with any supplement it’s important to judge supplementation levels based on your own personal requirements, there is no one size fits all. This is especially true for people looking for phosphatidylserine to help reduce high cortisol levels to help with stress. In scientific studies and in clinic we’ve found that people with high cortisol levels may need more than the 300mg a day to make a difference, and may need up to 800mg per day (1,5).

However, once the body builds up phosphatidylserine levels, and cortisol levels return to normal, this high phosphatidylserine dose can be reduced to normal. The key thing is common sense and being aware of any changes in your symptoms. Start at 100mg per day and slowly build up by adding 100mg per day every 4-5 days. If at any time after increasing the dose you find yourself becoming more ‘wired’ or agitated, or if your sleep is affected, it’s a sign you’ve gone past the right dosage level for you, and you should decrease the dose.


(1) Doyle M, Phosphatidyl Serine, Memory and Cortisol: A Primer, May 26, 2014

(2) Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline in the elderly: a double blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging Clin Exp Res 1993;5:123–33.

(3) Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology 1991;41:644–9.

(4) Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 1992;28:61–6.

(5) 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. Eur J Clin Pharmacol. 1992;42(4):385-8.

(6) Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D, Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans, Neuroendocrinology. 1990 Sep;52(3):243-8.

(7) Hellhammer J, Hero T, Franz N, Contreras C, Schubert M. Omega-3 fatty acids administered in phosphatidylserine improved certain aspects of high chronic stress in men. Nutr Res. 2012 Apr;32(4):241-50.

(8) Parker AG1, Gordon J, Thornton A, Byars A, Lubker J, Bartlett M, Byrd M, Oliver J, Simbo S, Rasmussen C, Greenwood M, Kreider RB, The effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exercise, J Int Soc Sports Nutr. 2011 Oct 21;8:16.

(9) Sinforiani E, Agostinis C, Merlo P, Gualtieri S, Mauri M, Mancuso A. Cognitive decline in ageing brain. Therapeutic approach with phosphatidylserine. Clin Trials J 1987;24:115–25.

(10) Caffara P, Santamaria V. The effects of phosphatidylserine in patients with mild cognitive decline. An open trial. Clin Trials J 1987;24:109–14.

(11) ] Schreiber S, Kampf-Sherf O, Gorfine M, Kelly D, Oppenheim Y, Lerer B. An open trial of plant-source derived phosphatidylserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302–7.

(12) Richter Y, Herzog Y, Cohen T, Steinhart Y. The effect of phosphatidylserinecontaining omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study. Clin Interv Aging 2010;5: 313–6.

(13) Richter Y, Herzog Y, Lifshitz Y, Hayun R, Zchut S. The effect of soybeanderived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study. Clin Interv Aging 2013;8: 557–63.

(14) Hirayama S, Terasawa K, Rabeler R, Hirayama T, Inoue T, Tatsumi Y, Purpura M, Jäger R, The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial, J Hum Nutr Diet. 2014 Apr;27 Suppl 2:284-91.

(15) Michael J. Glade Ph.D., Kyl Smith D.C., Phosphatidylserine and the human brain, Nutrition 31 (2015) 781–786