Phosphatidylserine is an important phospholipid membrane component which
plays a key role in cell cycle signaling, specifically in relationship
to apoptosis. Cell signaling
Phosphatidylserine(s) are actively held facing the cytosolic 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
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." = Sports nutrition=
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.
Safety Traditionally, PS supplements were
derived from bovine cortex. However, due to the risk of potential transfer of
infectious diseases, soy-derived 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 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. 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.
Dietary sources The average daily phosphatidylserine
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. Metabolism
Phosphatidylserine is biosynthesized in bacteria by condensing the amino acid
serine with CDP-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.
References External links
DrugBank info page FDA Qualified Health Claim
Phosphatidylserine and Cognitive Dysfunction and Dementia
Phosphatidylserines at the US National Library of Medicine Medical Subject
Headings