Components of phosphatidylserines:
Blue, green: variable fatty acid groups
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is an important phospholipid membrane component (i.e. component of the cell membrane) which plays a key role in cell cycle signaling, specifically in relationship to apoptosis.
Phosphatidylserine(s) are actively held facing the cytosolic (inner) side of the cell membrane by the enzyme flippase. This is in contrast to normal behavior of phospholipids in the cell membrane which can freely flip their heads between the two faces of the membrane they comprise. However, when a cell undergoes apoptosis phosphatidylserine is no longer restricted to the cytosolic domain by flippase. When the phosphatidylserines naturally flip to the extracellular (outer) surface of the cell, they act as a signal for macrophages to engulf the cells.
Supplementation and health benefits
Memory and cognition
In May, 2003 the Food and Drug Administration gave "qualified health claim" status to phosphatidylserine thus allowing labels to state "consumption of phosphatidylserine may reduce the risk of dementia and cognitive dysfunction in the elderly" along with the disclaimer "very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is little scientific evidence supporting this claim."
The FDA declared that "based on its evaluation of the totality of the publicly available scientific evidence, the agency concludes that there is not significant scientific agreement among qualified experts that a relationship exists between phosphatidylserine and reduced risk of dementia or cognitive dysfunction". The FDA also noted "Of the 10 intervention studies that formed the basis of FDA's evaluation, all were seriously flawed or limited in their reliability in one or more ways", concluding that "most of the evidence does not support a relationship between phosphatidylserine and reduced risk of dementia or cognitive dysfunction, and that the evidence that does support such a relationship is very limited and preliminary".
Early studies of phosphatidylserine on memory and cognition used a supplement which isolated the molecule from the bovine brain. Currently, most commercially available products are made from cabbage or soybeans due to the risk of mad cow disease in bovine brain tissue. These plant-based products have a similar, but not identical chemical structure to the bovine derived supplements; for example, the FDA notes "the phosphatidylserine molecule from soy lecithin contains mainly polyunsaturated acids, while the phosphatidylserine molecule from bovine brain cortex contains mainly saturated and monounsaturated fatty acids and long-chain polyunsaturated fatty acids".
A preliminary study in rats in 1999 indicated that the soy derived phosphatidylserine supplement was as effective as the bovine derived supplement in one of three behavioral tests. However, clinical trials in humans found that "a daily supplement of S-PS [soybean-derived phosphatidylserine] does not affect memory or other cognitive functions in older individuals with memory complaints."
In athletes, phosphatidylserine has been shown to improve performance, endocrine response to exercise stress, and decrease muscle damage in athletes involved in cycling, weight training, golf and endurance running. PS has been reported to be an effective supplement for combating exercise-induced stress by blunting the exercise-induced increase in cortisol levels in a dose dependent manner. PS supplementation promotes a desirable hormonal balance for athletes and might attenuate the physiological deterioration that accompanies overtraining and/or overstretching. In recent studies, PS has been shown to enhance mood in a cohort of young people during mental stress and to improve accuracy during tee-off by increasing the stress resistance of golfers.
Traditionally, PS supplements were derived from bovine cortex (BC-PS). However, due to the risk of potential transfer of infectious diseases, soy-derived PS (S-PS) supplements have been used as an alternative. Soy-derived PS is designated Generally Recognized As Safe by the FDA. A 2002 safety report determined supplementation in elder people at a dosage of 200 mg three times daily to be safe.
Target for tumor treatment
Bavituximab is a monoclonal antibody directed against phosphatidylserine (PS) expressed on tumor endothelium. Various pathophysiologic processes cause the exposure of PS on the external membrane leaflet. Bavituximab, once bound, starts up host effector activities, such as antibody dependent cellular cytotoxicity, causing vessel destruction and enhancing antitumor immunity. Specifically, bavituximab binds PS when recognizing a complex formed by PS and two cross-linked molecules of the PS-binding protein beta 2 glycoprotein-1 (beta 2GP1). Bavituximab is not currently an approved drug, but it has shown promising survival results in previously treated non-small cell lung cancer and other indications.
The average daily phosphatidylserine (PS) intake from diet in Western countries is estimated to be 130 mg. PS may be found in meat and fish. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans and soy lecithin.
Table 1. PS content in different foods.
|Food||PS Content in mg/100 g|
|Soy lecithin||5900 |
|Offal (average value)||305|
|Chicken leg, with skin, without bone||134|
|Chicken breast, with skin||85|
|Turkey leg, without skin or bone||50|
|Turkey breast without skin||45|
|Whole grain barley||20|
|European pilchard (sardine)||16|
|Cow's Milk (whole, 3.5% fat)||1|
Phosphatidylserine is biosynthesized in bacteria by condensing the amino acid serine with CDP (cytidine diphosphate)-activated phosphatidic acid. In mammals, phosphatidylserine is produced by base-exchange reactions with phosphatidylcholine and phosphatidylethanolamine. Conversely, phosphatidylserine can also give rise to phosphatidylethanolamine and phosphatidylcholine, although in animals the pathway to generate phosphatidylcholine from phosphatidylserine only operates in the liver.
- Verhoven, B.; Schlegel, R. A.; Williamson, P (1 November 1995). "Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes" (PDF). Journal of Experimental Medicine 182 (5): 1597–601. doi:10.1084/jem.182.5.1597. PMC 2192221. PMID 7595231. Retrieved 23 August 2014.
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- Monteleone P, Maj M, Beinat L, Natale M, Kemali D; Maj; Beinat; Natale; Kemali (1992). "Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men". European Journal of Clinical Pharmacology 42 (4): 385–8. doi:10.1007/BF00280123 (inactive 2015-02-01). PMID 1325348.
- Fernholz KM, Seifert JG, Bacharach DW, Burke ER, Gazal O (2000). "The Effects of Phosphatidyl Serine on Markers of Muscular Stress in Endurance Runners [abstract]". Medicine and Science in Sports and Exercise 32 (4): S321.
- Benton D, Donohoe RT, Sillance B, Nabb S; Donohoe; Sillance; Nabb (2001). "The Influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor". Nutritional Neuroscience 4 (3): 169–78. PMID 11842886.
- Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ; Brouns; Van Boxtel; Riedel (October 2002). "Safety of soy-derived phosphatidylserine in elderly people". Nutritional Neuroscience 5 (5): 337–43. doi:10.1080/1028415021000033802. PMID 12385596.
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- "bavituximab". National Cancer Institute at the National Institutes of Health. Retrieved 5 January 2015.
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- Souci SW, Fachmann E, Kraut H (2008). Food Composition and Nutrition Tables. Medpharm Scientific Publishers Stuttgart.
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- Christie, William W. (4 April 2013). "Phosphatidylserine and Related Lipids: Structure, Occurrence, Biochemistry and Analysis". The American Oil Chemists’ Society Lipid Library. Retrieved 23 August 2014.
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- DrugBank info page
- FDA Qualified Health Claim Phosphatidylserine and Cognitive Dysfunction and Dementia
- Phosphatidylserines at the US National Library of Medicine Medical Subject Headings (MeSH)