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Phosphatidylserine (PS) - The Essential Brain Nutrient

September 2002

Mood and stress

Image with Caption
Evidence has been emerging for
several years now, indicating that
phosphatidylserine derived from
plant sources, such as soybean
lecithin, may be equally effective
and safer than that derived from
animal brain sources.

With regards to mood and stress, studies have also shown favorable results with phosphatidylserine supplementation. For example, studies in both men and women, old and young, have found that phosphatidylserine can alleviate depressive and stress-induced symptoms. Researchers at the University of Milan conducted a small study of 10 elderly women with depression, aged 70 to 81 years, treated with phosphatidylserine (300 milligrams per day) for 30 days, following a 15-day course of placebo. Results showed that phosphatidylserine increased brain turnover of noradrenaline, dopamine, acetylcholine and glucose reserves. Using the Hamilton Rating Scale for Depression (HRSD) and clinical observation, the researchers also found that, compared with pre-treatment baseline scores and controls, treatment with phosphatidylserine caused anxiety levels to decrease significantly and interests and socialization to increase, while long-term memory and learning also improved.12

In another study conducted at the University of Naples, Italy, researchers showed that high-doses of phosphatidylserine administered over a short period of time could elicit neuroendocrine responses to physical stress in men that suggest a positive effect on mood. The experimentation consisted of nine young, healthy men taking phosphatidylserine (at 800 milligrams per day) for 10 days. Results from blood samples revealed that phosphatidylserine significantly blunted the responses of stress hormones, such as adrenocorticotropin (ACTH) and cortisol, to physical exercise without affecting the rise in plasma growth hormone and prolactin. The authors concluded that "chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man." Otherwise known as the HPAA, this working trio of hypothalamus, pituitary gland and adrenal glands is what's responsible for how we respond to various kinds of stress, be it emotional, mental or physical in nature. With advancing age, however, the HPAA suffers decline and dysfunction, which can affect mood.13

An earlier study by the same research team, which examined physical stress response more specifically, illustrated that phosphatidylserine could offset the body's response to physical stress as shown by a marked decrease in stress hormones. The study involved eight healthy men being subjected to a series of three experiments with a bicycle ergometer. Ten minutes before starting the exercise, each subject received 50 or 75 milligrams of intravenously administered PS or a placebo. Blood samples were taken before and after the exercise for plasma epinephrine, norepinephrine, dopamine, adrenocorticotropin, cortisol, growth hormone, prolactin and glucose levels. Blood pressure and heart rate were also recorded. Physical stress increased plasma epinephrine, norepinephrine, adrenocorticotropin, cortisol, growth hormone and prolactin, but not dopamine or glucose. Results showed that phosphatidylserine administration prior to exertion decreased the physical stress response, as indicated by a significant decrease in cortisol and adrenocorticotropin, which secretes cortisol.14

At the University of Wales, psychology experts decided to extend such findings on cortisol response and mood by measuring self-reported feelings of stress and the change in heart rate in regards to phosphatidylserine supplementation. A group of young, healthy adults who had higher than average neuroticism scores were required to take 300 milligrams of phosphatidylserine each day for a month, then they were asked to perform a stressful mental arithmetic task. Despite the frustrating task, they reported feeling less stressed and having a better mood.15

Cows vs. soybean debate


One issue of debate among researchers is whether phosphatidylserine from soybean lecithin can match the abilities of bovine cortex derived phosphatidylserine, since many of the earlier, telling studies have involved the use of the latter. Bovine source phosphatidylserine, however, is not available in North America, given a concern about risk of infectious agents entering the product when extracted from cows' brains. But evidence has been emerging for several years now, indicating that phosphatidylserine derived from plant sources, such as soybean lecithin, may be equally effective and safer than that derived from animal brain sources.

In 1990, a two-month treatment study using plant-derived soybean phosphatidylserine showed positive effects on daily functioning, emotional state and self-reported general condition of Alzheimer's disease patients.16

A team of Tokyo scientists compared both the composition and pharmacological properties of phosphatidylserine prepared from soybean lecithin with those of bovine cortex source phosphatidylserine to improve cognitive disorders of senile dementia patients. They found a difference in their fatty acid composition. The plant derived phosphatidylserine was rich in linoleic and palmitic acids, whereas the animal source phosphatidylserine was mainly comprised of stearic and oleic acids. Despite their different makeup, both forms of phosphatidylserine, orally administered at a dose of 300 milligrams per day, were able to significantly increase brain glucose concentrations in mice, and restore memory function experimentally impeded by pharmacologically-induced amnesia in rats.17

In another study, Israeli researchers found that treating 15 healthy elderly volunteers with age related memory impairment with 300 milligrams per day plant-source derived phosphatidylserine for 12 weeks improved memory. The authors conclude that, if born out by large, controlled trials, "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."18

A more recent Japanese study looked at how phosphatidylserine from soybean lecithin might improve memory impairment in aged rats. These researchers found that phosphatidylserine significantly improved performance in a water maze escape test compared to control aged rats, much like bovine brain cortex derived phosphatidylserine. Additionally, it also increased acetylcholine release and synaptic activity (which helps to build communication links between working brain cells).19

Safe and sound findings

Image with Caption
A younger population may take
advantage of phosphatidylserine's
ability to fight stress, improve
mood and sharpen mental
faculties, while resting assured
that this vital brain nutrient also
plays a hand in preventing the
damage done by passing years.

The fact that there have been no reported toxicity issues or adverse effects with phosphatidylserine supplementation speaks to its high safety profile. A follow-up survey of Alzheimer's patients in a two-month treatment study found that phosphatidylserine is very tolerable for patients, since nearly half of the participants of the treatment group decided to continue treatment at their own expense, in contrast to none in the placebo group.16 Likewise, in a large, multicenter study of nearly 500 geriatric patients over a six-month period, the administration of phosphatidylserine together with other drugs that they were taking failed to show any pharmacological interactions, as no clinical signs and symptoms were evident.5 The only contraindications with other drugs to date are blood thinners, such as Coumadin and heparin-phosphatidylserine may enhance their effects.20 This means if you are taking Coumadin and phosphatidylserine, your doctor may be able to lower the dose of Coumadin if your coagulation blood tests (Prothrombin and INR) indicate that phosphatidylserine is helping Coumadin work better.

Given the emergence of the safer soybean lecithin-derived phosphat-idylserine and the evidence building to support its role in brain health, we can consider this phospholipid a dutiful soldier in the battle against age-related cognitive decline. Moreover, a younger population may take advantage of phosphatidylserine's ability to fight stress, improve mood and sharpen mental faculties, while resting assured that this vital brain nutrient also plays a hand in preventing the damage done by passing years.


  1. Kidd PM. A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern Med Rev 1999 Jun;4(3):144-61.
  2. Palmieri, G., et al., Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin. Trials J. 1987;24:73-83.
  3. Delwaide PJ, et al. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol Scand 1986 Feb;73(2):136-40.
  4. Crook TH, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology 1991 May;41(5):644-649.
  5. Cenacchi T, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano) 1993 Apr;5(2):123-33.
  6. Funfgeld EW, et al. Double-blind study with phosphatidylserine (PS) in parkinsonian patients with senile dementia of Alzheimer's type (SDAT). Prog Clin Biol Res 1989;317:1235-46.
  7. (no authors listed) Phosphatidylserine in the treatment of clinically diagnosed Alzheimer's disease. The SMID Group. J Neural Transm Suppl 1987;24:287-92.
  8. Amenta F, et al. Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches? Mech Ageing Dev 2001 Nov;122(16):2025-40.
  9. Heiss WD, et al. Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's disease. Ann N Y Acad Sci 1993 Sep 24;695:327-31.
  10. Crook T, et al. Effects of Phosphatidylserine in Alzheimer's Disease. Psychopharmacol Bull 1992;28(1):61-66.
  11. Engel RR, Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol 1992 Jun;2(2):149-55.
  12. Maggioni M, et al. Effects of Phosphatidylserine Therapy in Geriatric Patients With Depressive Disorders. Acta Psychiatr Scand 1990;81:265-270.
  13. Monteleone P, et al. 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):385-388.
  14. Monteleone P, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 1990 Sep;52(3):243-8.
  15. Benton D, et al. The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci 2001;4(3):169-78.
  16. Gindin, J., et al. 1990, Effect of Soy Lecithin Phosphatidylserine (PS) Treatment on Daily Functioning and Self-Reported General Condition in Patients with Alzheimer's Disease, The Geriatric Institute of Education and Research Kaplan Medical Centre, Rehovot, and Hadassah Medical School, Hebrew University of Jerusalem, Israel.
  17. Sakai M, et al. Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. J Nutr Sci Vitaminol (Tokyo) 1996 Feb;42(1):47-54.
  18. Schreiber S, et al. An open trial of plant-source derived phosphatidylserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37(4):302-7.
  19. Suzuki S, et al. Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. J Nutr 2001 Nov;131(11):2951-6.
  20. Van den Besselaar AM. Phosphatidylethanolamine and phosphatidylserine synergistically promote heparin's anticoagulant effect. Blood Coagul Fibrinolysis 1995;6:239-244.