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What is Phosphatidylserine?

Written by Andy Mobbs
Reviewed by Lamia A Kader, MD
phosphatidylserine improves short term memory, inattention problems and impulsivity

What is phosphatidylserine? Well, we all consume phosphatidylserine every day, but unfortunately, most of us are still short of it. Phosphatidylserine is available in a number of foods, including soy (which is the main source), white beans, egg yolks, chicken liver, and beef liver. Unfortunately, it’s difficult for our bodies to absorb sufficient amounts from dietary sources. It this article we are going to explain what is phosphatidylserine and to find out is the really the most effective natural nootropic?

What Is Phosphatidylserine?

Phosphatidylserine is a cell membrane phospholipid, it is a component of the cell membrane of every one of our 20 trillion cells. In the body, it makes up around 2-15% of our cell membranes, but the highest concentration levels of phosphatidylserine are found in the brain where it’s especially nerve cellimportant, and where it comprises 10–20% of the total phospholipid pool (1).

The basic units of the brain and nervous systems are called neurons (nerve cells). The output part of the neuron is called axon (nerve fiber); when a neuron wants to talk to another neuron, it sends an electrical message through the axon. Axons are covered by a layer called myelin sheath. This myelin sheath protects and insulates the axon, allowing electrical signals to transmit quickly and efficiently between neurons.

Myelin sheath is especially rich in phosphatidylserine. Lately, it has been found that phosphatidylserine improves neuronal function, and helps in functional regeneration and restoring normal function to injured neurons (2).

Phosphatidylserine In the Brain

The recent discovery of the critical role of Phosphatidylserine in activating important signal transmission and modulating key neurotransmitters release (Acetylcholine, Norepinephrine, Serotonin and Dopamine) and receptor function, have renewed the interest in phosphatidylserine in relation to brain function (3-5).

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 neurotransmitters effects that make people who take phosphatidylserine notice a very definite difference, where they feel their brains are sharper and clearer. They can more easily focus, concentrate, remember names and places from the past, form clearer and more fluent sentences, in addition to, good mood and improved sleep.

Phosphatidylserine Benefits

Recent studies showed that oral administration of phosphatidylserine improves memory impairment that occurs during normal aging (6).

Cholinergic SynapseAnother key benefit of phosphatidylserine is the effect is having 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 (Adrenocorticotropic 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. Phosphatidylserine can re-sensitize the cells of the 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).

The level of phosphatidylserine in the body decreases with aging and reduced phosphatidylserine is associated with cognitive impairment and pathogenesis of Alzheimer’s disease (AD) (10,11).

take phosphatidylserine and enjoy the sunshine

Research Evidence For Phosphatidylserine Effects as a Nootropic

The latest study in 2020, found that dietary supplementation with phosphatidylserine significantly increased resistance to oxidative stress, diminished the aging response and may have a preventive effect on age-related diseases in addition to extending lifespan expectancy (12).

Oxidative stress plays a key role in the development of age-related diseases including arthritis, diabetes, dementia, cancer, atherosclerosis, vascular diseases, obesity, osteoporosis, and metabolic syndromes, which has been proven by several studies (13,14).

Another recent study to assess the roles and importance of phosphatidylserine found that supplementing with (300-800 mg per day) safely slows or reverses alterations and deterioration in nerve cells and supports 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 (15).

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 backward from 100 by 7’s or 6’s or 3’s etc). They found that the group who was supplemented with phosphatidylserine reduced the time needed for a correct calculation by 20%, reduced the total amount of errors by 39% and increased the number of correct calculations by 13% over the placebo group (16).

phosphatidylserine, hypothalamus2 open-label trials on older participants suffering from mild cognitive decline, (a loss in memory caused by aging 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, socialization and self-sufficiency (17,18). 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 (19).

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 (20), as well as achieving a significant improvement in memory recognition, memory recall, executive function, and mental flexibility (21), after supplementing with 300 mg per day.

In 2015, supplementation with phosphatidylserine was found to reduce major depression symptoms in elderly individuals by reducing cortisol basal concentrations  (22).

In 2016, a study showed associations between dietary supplements, cortisol regulation, sleep and possible implications for the risk of Alzheimer’s disease, and that phosphatidylserine supplementation help restoring cortisol concentrations, thus may ease sleep disorders and regulate sleep quality which facilitates brain clearance and positively preserve or increase brain functions and consequently reduce the risk of cognitive impairment and dementia (23).

Additionally, phosphatidylserine supplementation was associated with feeling less stressed and having a better mood in young adults, when taking of 300mg each day for a month (24).

Findings also suggested that phosphatidylserine is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. Phosphatidylserine supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels (25,26).

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 (27).

improve your cognitive function with phosphatidylserine

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 (28).

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, we’ve found that people with high cortisol levels may need more than 300mg a day to make a difference, and may need up to 800mg per day (15).

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.

References:

(1) Zanotti, A., Rubini, R., Calderini, G., and Toffano, G., 1987, Pharmacological properties of phosphatidylserine: effects on memory function, in: “Nutrients and Brain Function,” W.B. Essman, ed., Karger, Basel, pp. 95–102.

(2) Abay ZC, Wong MY, Teoh JS, Vijayaraghavan T, Hilliard MA,Neumann B (2017) Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 114, E10196–E10205. 13.

(3) Kim, H. Y., Huang, B. X., & Spector, A. A. (2014). Phosphatidylserine in the brain: metabolism and function. Progress in lipid research, 56, 1–18.

(4) 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.

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

(6) Lee B, Sur BJ, Han JJ, Shim I, Her S, Lee YS, Lee HJ, Hahm DH(2015) Oral administration of squid lecithin-transphos-phatidylatedphosphatidylserineimprovesmemoryimpairment in aged rats. Prog Neuropsychopharmacol BiolPsychiatry 56:1–10.

(7) 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.

(8) 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.

(9) 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.

(10) Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J,Fortier M, Bennett DA, Morris MC (2012) Plasma and brain fatty acid profiles in mild cognitive impairment andAlzheimer’s disease. J Alzheimers Dis 29:691–697.

(11) Suleimanova RR, Hudz EA, Melnychuk DO, Kalachniuk LH(2017) Age-related changes phospholipids of sterlet in liver and dorsal muscles. Ukr Biochem J 89:71–75.

(12) Kim, B., Park, S. Phosphatidylserine modulates response to oxidative stress through hormesis and increases lifespan via DAF-16 in Caenorhabditis elegans. Biogerontology (2020).

(13) Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical interventions in aging, 13, 757–772.

(14) H Van Remmen, Oxidative Stress And Age-related Diseases, Innovation In Aging, Volume 2, Issue Suppl_1, 1 November 2018, Page 347.

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

(16) 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 IQ PLUS Focus on cognitive function, mood and endocrine response before and following acute exercise, J Int Soc Sports Nutr. 2011 Oct 21;8:16.

(17) Kidd, Parris. (1996). Phosphatidylserine; Membrane Nutrient for Memory. A Clinical and Mechanistic Assessment. Altern. Med. Rev..1

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

(19) ] 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.

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

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

(22) Komori T. The Effects of Phosphatidylserine and Omega-3 Fatty Acid-Containing Supplement on Late Life Depression. Ment Illn 2015;7:5647.

(23) Pistollato, F., Sumalla Cano, S., Elio, I., Masias Vergara, M., Giampieri, F., & Battino, M. (2016). Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease. Advances in nutrition (Bethesda, Md.), 7(4), 679–689.

(24) Benton D, Donohoe RT, Sillance B, Nabb S: The Influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci. 2001, 4 (3): 169-178.

(25) Starks, M.A., Starks, S.L., Kingsley, M. et al. The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr 5, 11 (2008).

(26) Hellhammer, J., Vogt, D., Franz, N., Freitas, U., & Rutenberg, D. (2014). 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. Lipids in health and disease, 13, 121.

(27) 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.

(28) “Phosphatidylserine,” Examine.com, published on 10 April 2013, last updated on 14 June 2018.