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Phosphatidylserine, or PS for short, is a member of a class of chemical compounds known as phospholipids. PS is an essential component in all our cells; specifically, it is a major component of the cell membrane. The cell membrane is a kind of "skin" that surrounds living cells. Besides keeping cells intact, this membrane performs vital functions such as moving nutrients into cells and pumping waste products out of them. PS plays an important role in many of these functions.

Good evidence suggests that PS can help declining mental function and depression in the elderly, and it is widely used for this purpose in Italy, Scandinavia, and other parts of Europe. PS has also been marketed as a "brain booster" for people of all ages, said to sharpen memory and increase thinking ability. However, the evidence to support this use is incomplete and inconsistent.

Sources

Your body makes all the PS it needs. However, the only way to get a therapeutic dosage of PS is to take a supplement.

PS was originally manufactured from the brains of cows, and all the studies described here used this form. However, because animal brain cells can harbor viruses, that form is no longer available. Most PS today is made from soybeans or other plant sources.

There are reasons to expect that plant-source PS should function very similarly to PS made from cows' brains, and some animal studies suggest that it is indeed effective. 1-5,43-45 However, in preliminary trials, soy-based PS and cabbage-based PS failed to prove beneficial. 7,47

Therapeutic Dosages

For the purpose of improving mental function, PS is usually taken in dosages of 100 mg two to three times daily. After maximum effect is achieved, the dosage can reportedly be reduced to 100 mg daily without losing benefit. PS can be taken with or without meals.

When taking PS for sports purposes, athletes sometimes take as much as 800 mg daily.

Therapeutic Uses

Meaningful evidence from numerous double-blind studies suggests that animal-source PS is an effective treatment for Alzheimer's disease and other forms of age-related mental decline. 8-17 Vegetable-derived PS has little supporting evidence.

PS is widely marketed as a treatment for ordinary age-related memory loss as well. While there is little direct evidence that it works, in studies of severe mental decline, PS appears to have been equally effective whether the cause was Alzheimer's disease or something entirely unrelated, such as multiple small strokes. This certainly suggests that PS may have a positive impact on the brain that is not specific to any one condition. From this observation, it is not a great leap to suspect that it might be useful for much less severe problems with memory and mental function, such as those that seem to occur in nearly all of us who are older than 40. Indeed, double-blind studies have found that phosphatidylserine could improve mental function in people with age-related memory loss. 18,53 However, two studies failed to find plant-source PS effective for this condition. 7,47 PS has also been proposed for enhancing mental function in young people, but there is no direct evidence at all that any form is effective.

Animal-source PS has also shown a slight bit of promise for depression . 19,20

Recently, PS has become popular among athletes who hope it can help them build muscle more efficiently. This use is based on weak evidence that PS slows the release of cortisol following heavy exercise. 21-23 Cortisol is a hormone that causes muscle tissue to break down. For reasons that are unclear, the body produces increased levels of cortisol after heavy exercise. Strength athletes believe that this natural cortisol release works against their efforts to rapidly build muscle mass and hope that PS will help them advance more quickly. However, only two double-blind placebo-controlled studies of PS as a sports supplement have been reported, and neither one found effects on cortisol levels. 48-49 Of these small trials, one found a possible ergogenic benefit, and the other did not.

Interestingly, PS has also been advocated as an aid to recovery from heavy exercise , according to the theory that use of PS would help reduce muscle soreness. This would seem to contradict the proposed effects on cortisol, as cortisol has anti-inflammatory properties. Nonetheless, researchers performed a double-blind study to evaluate whether 750 mg daily of soy-source PS would reduce muscle soreness following downhill racing; no benefits were seen. 51

One study found preliminary evidence that a combination of soy-based PS and lecithin may moderate the body's reaction to mental stress . 50 Another study evaluated use of phosphatidylserine for reducing stress in golfers, but the benefits seen failed to reach statistical significance . 52 Participants who were given phosphatidylserine did, however, tee-off successfully at a greater rate than those given placebo.

What Is the Scientific Evidence for Phosphatidylserine?
Alzheimer's Disease and Other Forms of Dementia

Overall, the evidence for animal-source PS in dementia is fairly strong. Double-blind studies involving a total of more than 1,000 people suggest that phosphatidylserine is an effective treatment for Alzheimer's disease and other forms of dementia.

The largest of these studies followed 494 elderly subjects in northeastern Italy over a course of 6 months. 24 All suffered from moderate to severe mental decline, as measured by standard tests. Treatment consisted of either 300 mg daily of PS or placebo . The group that took PS did significantly better in both behavior and mental function than the placebo group. Symptoms of depression also improved.

These results agree with those of numerous other smaller double-blind studies involving a total of more than 500 people with Alzheimer's and other types of age-related dementia. 25-32 However, all these studies involved cow-brain PS; studies of plant-source PS for dementia have not been reported.

Ordinary Age-related Memory Loss

There is some evidence that PS can also help people with ordinary age-related memory loss . In one double-blind study that enrolled 149 people with memory loss but not dementia, phosphatidylserine provided significant benefits as compared with placebo. 33 People with the most severe memory loss showed the most improvement. In another study, 131 elderly people with memory problems but no dementia were randomized to receive a combination of PS and omega-3 fatty acids or placebo. 53 Those in the treatment group had improvements in their cognitive abilities compared to the placebo group. It is unclear which of the components produced the beneficial effect if not both of them.

However, a double-blind trial of 120 older people with memory complaints but not dementia failed to find benefits. 47 This discrepancy may have to do with the type of phosphatidylserine used—this trial used the more modern soy-derived form of the supplement (see Therapeutic Dosages). A cabbage-based source of PS has also failed to prove effective for relatively mild memory loss. 7

Athletic Performance

Weak evidence suggests that PS might decrease the release of the hormone cortisol after intense exercise. 34 Among its many effects, cortisol acts to break down muscle tissue—exactly the opposite of the effect desired by a strength athlete or bodybuilder. This double-blind, placebo-controlled study on 11 intensely trained athletes found that 800 mg of PS taken daily reduced the cortisol rise by 20% as compared with placebo. 35 Another small study on 9 nonathletic males found that daily doses of 400 and 800 mg of PS reduced cortisol levels after exercise by 16% and 30%, respectively. 36 Another study found that phosphatidylserine could relieve some overtraining symptoms, including muscle soreness, possibly due to effects on cortisol. 37-39

On the basis of these preliminary trials, PS has been proposed as a sports supplement . However, there is as yet no direct evidence to support the claims that PS actually helps athletes build muscles more quickly and with less training effort. Furthermore, the most recent and best-designed study, using vegetable-source PS, failed to find any effect on cortisol release, muscle soreness, or markers of muscle damage. 48

Safety Issues

Phosphatidylserine is generally regarded as safe when used at recommended dosages. Side effects are rare, and when they do occur they usually consist of nothing much worse than mild gastrointestinal distress. 40 One study found that use of phosphatidylserine did not alter results on standard medical screening tests. 41 However, the maximum safe dosages for young children, pregnant or nursing women, or those with severe liver or kidney disease have not been established.

PS is sometimes taken with ginkgo because they both appear to enhance mental function. However, some caution might be in order: Ginkgo is a "blood thinner," and PS might be one as well. PS is known to enhance the effect of heparin, a very strong prescription blood thinner. 42 It is possible that combined use of PS and any drug or supplement that thins the blood could interfere with normal blood clotting enough to cause problems. Some medications and supplements to consider include warfarin (Coumadin), aspirin, pentoxifylline (Trental), clopidogrel (Plavix), ticlopidine (Ticlid), garlic, ginkgo, and vitamin E.

Keep in mind, too, that Alzheimer's disease and other types of severe age-related mental impairment are too serious to treat on your own with PS or any other supplement. In some cases, the symptoms of these diseases could be confused with symptoms of other serious conditions. If you suspect that you or a loved one may have a severe age-related mental impairment, see your doctor for diagnosis and treatment.

Interactions You Should Know About

If you are taking:

References

1.   Toffano G, Leon A, Benvegnu D. Effect of brain cortex phospholipids on catechol-amine content of mouse brain. Pharmacol Res Commun . 1976;8:581-590.

2.   LaBrake CC, Fung LW. Phospholipid vesicles promote human hemoglobin oxidation. J Biol Chem . 1992;267:16703-16711.

3.   Orlando P, Cerrito F, Zirili P. The fate of doubly-labelled brain phospholipids administered to mice. Farmaco . 1975;30:451-458.

4.   Gindin J, Novikov M, Kedar D, et al. The effect of plant phosphatidylserine on age-associated memory impairment and mood in the functioning elderly. Geriatric Institute for Education and Research and Dept of Geriatrics; Kaplan Hospital; Rehovot, Israel; 1995.

5.   Crook TH III, Adderly BD. The Memory Cure: The Safe, Scientifically Proven Breakthrough That Can Slow, Halt, Or Even Reverse Age-Related Memory Loss . New York, NY: Pocket Books; 1998:71,72.

6.   Gaby AR. Don't believe everything you read. Townsend Letter for Doctors and Patients. May 1997:122-123.

7.   Gindin J, Novikov M, Kedar D, et al. The effect of plant phosphatidylserine on age-associated memory impairment and mood in the functioning elderly. Geriatric Institute for Education and Research and Dept of Geriatrics; Kaplan Hospital; Rehovot, Israel; 1995.

8.   Amaducci L. Phosphatidylserine in the treatment of Alzheimer’s disease: Results of a multicenter study. Psychopharmacol Bull . 1988;24:130-134.

9.   Crook TH, Tinklenberg J, Yesavage J, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology . 1991;41:644-649.

10.   Crook T, Petrie W, Wells C, et al. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull . 1992;28:61-66.

11.   Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, et al. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol Scand . 1986;73:136-140.

12.   Engel RR, Satzger W, Gunther W, et al. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol. 1992;2:149-155.

13.   Funfgeld EW, Baggen M, Nedwidek P, et al. Double-blind study with phosphatidylserine (PS) in Parkinsonian patients with senile dementia of Alzheimer’s type (SDAT). Prog Clin Biol Res . 1989;317:1235-1246.

14.   Nerozzi D, Aceti F, Melia E, et al. Phosphatidylserine and memory disorders in the aged [in Italian; English abstract]. Clin Ther . 1987;120:399-404.

15.   Palmieri G, Palmieri R, Inzoli MR, et al. Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin Trials J . 1987;24:73-83.

16.   Villardita C, Grioli S, Salmeri G, et al. Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin Trials J . 1987;24:84-93.

17.   Cenacchi T, Bertoldin T, Farina C, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging(Milano) . 1993;5:123-133.

18.   Crook TH, Tinklenberg J, Yesavage J, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41:644-649.

19.   Maggioni M, Picotti GB, Bondiolotti GP, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand . 1990;81:265-270.

20.   Brambilla F, Maggioni M, Panerai AE, et al. Beta-endorphin concentration in peripheral blood mononuclear cells of elderly depressed patients—effects of phosphatidylserine therapy. Neuropsychobiology. 1996;34:18-21.

21.   Fahey TD, Pearl M. Hormonal effects of phosphatidylserine during 2 weeks of intense training. Abstract presented at: National Meeting of the American College of Sports Medicine; June, 1998; Orlando, Florida.

22.   Monteleone P, Maj M, Beinat L, 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;42:385-388.

23.   Fahey TD, Pearl M. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport. 1998;15:135-144.

24.   Cenacchi T, Bertoldin T, Farina C, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging(Milano) . 1993;5:123-133.

25.   Amaducci L. Phosphatidylserine in the treatment of Alzheimer’s disease: Results of a multicenter study. Psychopharmacol Bull . 1988;24:130-134.

26.   Crook T, Petrie W, Wells C, et al. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull . 1992;28:61-66.

27.   Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, et al. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol Scand . 1986;73:136-140.

28.   Engel RR, Satzger W, Gunther W, et al. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol. 1992;2:149-155.

29.   Funfgeld EW, Baggen M, Nedwidek P, et al. Double-blind study with phosphatidylserine (PS) in Parkinsonian patients with senile dementia of Alzheimer’s type (SDAT). Prog Clin Biol Res . 1989;317:1235-1246.

30.   Nerozzi D, Aceti F, Melia E, et al. Phosphatidylserine and memory disorders in the aged [in Italian; English abstract]. Clin Ther . 1987;120:399-404.

31.   Palmieri G, Palmieri R, Inzoli MR, et al. Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin Trials J . 1987;24:73-83.

32.   Villardita C, Grioli S, Salmeri G, et al. Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin Trials J . 1987;24:84-93.

33.   Crook TH, Tinklenberg J, Yesavage J, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology . 1991;41:644-649.

34.   Fahey TD, Pearl M. Hormonal effects of phosphatidylserine during 2 weeks of intense training. Abstract presented at: National Meeting of the American College of Sports Medicine; June, 1998; Orlando, FL.

35.   Fahey TD, Pearl M. Hormonal effects of phosphatidylserine during 2 weeks of intense training. Abstract presented at: National Meeting of the American College of Sports Medicine;June, 1998; Orlando, FL.

36.   Monteleone P, Maj M, Beinat L, 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;42:385-388.

37.   Monteleone P, Maj M, Beinat L, 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;42:385-388.

38.   Fahey TD, Pearl M. The hormonal and perceptive effects of phosphatidylserine administration during two weeks of resistive exercise-induced overtraining. Biol Sport. 1998;15:135-144.

39.   Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990;52:243-248.

40.   Cenacchi T, Bertoldin T, Farina C, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging(Milano) . 1993;5:123-133.

41.   Cenacchi B, Baggio C, Palm E. Human tolerability of oral phosphatidylserine assessed through laboratory examinations. Clin Trials J. 1987;24:125-130.

42.   van den Besselaar AM. Phosphatidylethanolamine and phosphatidylserine synergistically promote heparin’s anticoagulant effect. Blood Coagul Fibrinolysis . 1995;6:239-244.

43.   Blokland A, Honig W, Brouns F, et al. Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS. Nutrition . 1999;15:778-783.

44.   Furushiro M, Suzuki S, Shishido Y, et al. Effects of oral administration of soybean lecithin transphosphatidylated phosphatidylserine on impaired learning of passive avoidance in mice. Jpn J Pharmacol . 1997;75:447-450.

45.   Suzuki S, Yamatoya H, Sakai M, et al. Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. J Nutr. 2001;131:2951-2956.

46.   Sakai M, Yamatoya H, Kudo S. Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. J Nutr Sci Vitaminol (Tokyo). 1996;42:47-54.

47.   Jorissen BL, Brouns F, Van Boxtel MP, et al. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutr Neurosci. 2001;4:121-134.

48.   Kingsley MI, Wadsworth D, Kilduff LP et al. Effects of phosphatidylserine on oxidative stress following intermittent running. Med Sci Sports Exerc . 2005;37:1300-1306.

49.   Kingsley MI, Miller M, Kilduff LP, et al. Effects of phosphatidylserine on exercise capacity during cycling in active males. Med Sci Sports Exerc . 2006;38:64-71.

50.   Hellhammer J, Fries E, Buss C, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. 2004;7:119-126.

51.   Kingsley MI, Kilduff LP, McEneny J, et al. Phosphatidylserine supplementation and recovery following downhill running. Med Sci Sports Exerc. 2006;38:1617-1625.

52.   Jager R, Purpura M, Geiss KR, et al. The effect of phosphatidylserine on golf performance. J Int Soc Sports Nutr. 2007 Dec 4.

53.   Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn AD. Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement Geriatr Cogn Disord. 2010;29(5):467-474.



Last reviewed August 2013 by EBSCO CAM Review Board

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

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