Phosphatidylserine
Various

INTRODUZIONE

Phosphatidylserine, or 1,2-diacyl-sn-glycero-3-phospho-L-serine or PS for short, is a member of a class of chemical compounds known as phospholipids, usually kept on the inner-leaflet (the cytosolic side) of cell membranes by an enzyme called flippase. When a cell undergoes apoptosis, phosphatidylserine is no longer restricted to the cytosolic part of the membrane, but becomes exposed on the surface of the cell.

In humans, PS is most concentrated in the brain where it comprises 15% of the total phospholipid pool.
In other human tissue the ratio of PS in the Phospholipid pool varies:
• lungs (7.4%)
• testes (6.4%)
• kidneys (5.7%)
• liver (3.8%)
• skeletal muscle (3.3%)
• heart (3.2%)
• blood plasma (0.2%).

Phosphatidylcholine, structure, occurrence, biochemistry and analysis

The total body PS pool is estimated to be approximately 60 grams, with 30 grams in the brain and 30 grams in the rest of the body. The average daily PS intake from the diet in western countries is estimated to be 130 mg.

As a generality, the concentration of phosphatidylserine is highest in plasma membranes and endosomes, but is very low in mitochondria. As it is located entirely on the inner monolayer surface of the plasma membrane (and of other cellular membranes) and it is the most abundant anionic phospholipid, it may make the largest contribution to interfacial effects in membranes involving non-specific electrostatic interactions. Indeed, PS plays an important role in many functions of cell membrane.
In addition to its function as a component of cellular membranes or like a promoter of the blood coagulation process in platelet, good evidence suggests that PS can help declining mental function and depression in the elderly. PS has also been marketed as a "brain booster" for people of all ages and it is widely used to improve sharpen memory and increase thinking ability.

Biosynthesis of phosphatidylserine
L-Serine is a non-essential amino acid that is actively synthesised by most organisms. In animals, it is produced in nearly all cell types, although in brain it is synthesised by astrocytes but not by neurons.
1. In bacteria and in other prokaryotic organism phosphatidylserine is biosynthesized by condensing the amino acid serine with CDP (cytidine diphosphate)-activated phosphatidic acid.

CDP-diacylglycerol + L-serine → phosphatidylserine + CMP

2. In contrast in animal tissues, there are two routes to phosphatidylserine involving distinct enzymes (PS synthase I and II) with 30% homology and several membrane-spanning domains but utilizing different substrates.
Phosphatidylserine synthase-I is expressed in all mouse tissues, but especially the kidney, liver and brain, while phosphatidylserine synthase-II is most active in the brain and testis and much less so in other tissues. Elimination of both enzymes is embryonically lethal in knock-out mice, but each of them can be knocked out separately and the mice survive, even though they have substantially reduced levels of phosphatidylserine and phosphatidylethanolamine. This shows the importance of either enzymes in the byosinthesis.
The reaction, that starts in the endoplasmic reticulum of the cell, involves exchange of L-serine with phosphatidylcholine, catalysed by PS synthase I, or with phosphatidylethanolamine, catalysed by PS synthase II. It is strictly dependent on calcium ions and requires no further source of energy. The new lipid is then transported to the mitochondria, probably by transient membrane contact, where it is decarboxylated to phosphatidylethanolamine by a specific decarboxylase. The latter can return to the endoplasmic reticulum where it may be converted back to phosphatidylserine by the action of PS synthase II.

phosphatidylcholine + L-serine → phosphatylserine + choline

phosphatylethanolamine + L-serine → phosphatidylserine + ethanolamine

phosphatidylserine → phosphatidylethanolamine + anidride carbonica

Natural sources of PS and diet
PS can be found in meat, but is most abundant in the brain and in innards such as liver and kidney. Only small amounts of PS can be found in dairy products or in vegetables, with the exception of white beans. The average daily PS intake from the diet in Western countries is estimated to be 130 mg.
Sources of Food and Nutrient Data

Food	PS Content in mg/100 g
Soy lecithin	59000
Bovine brain	713
Atlantic mackerel	480
Chicken heart	414
Atlantic herring	360
Eel	335
Offal (average value)	305
Pig's spleen	239
Pig's kidney	218
Tuna	194
Chicken leg, with skin	134
Chicken liver	123
White beans	107

What Is the Scientific Evidence for Phosphatidylserine?

Sport

The participation in physical activity often challenges a variety of physiological systems; consequently, the ability to maintain normal cellular function during activity can determine sporting performance. PS has been established as a safe oral supplement capable of attenuating the serum cortisol and creatine kinase responses to acute exercise stress. As a consequence, supplementation tended to increase running time to exhaustion, to decrease muscle and to improve well-being following exercise.
Several double-blind, placebo-controlled clinical trials have been performed to investigate whether phosphatidylserine supplementation (BC-PS and S-PS) prior to exercise can prevent the exercise-induced increase in cortisol levels and improve other markers related to hard training.
Effects of phosphatidylserine on exercise capacity during cycling in active males
The effects of phosphatidylserine on endocrine response to moderate intensity exercise
Show them.

• Ciclyng
Eight non-physically trained healthy male volunteers (aged 24–42 years) underwent two exercise trials, composed of three distinct stages of cycle ergometry. The subjects received intravenously either placebo or BC-PS 10 minutes before exercise. As expected, physical exercise resulted in a significant increase in ACTH and cortisol levels after administration of a placebo. Bovine cortex-PS supplementation significantly suppressed ACTH and cortisol responses to exercise.
Phospholipids and sports performance

Compared to placebo, cortisol levels were 30% lower (800 mg S-PS), demonstrating that PS supplementation can lessen the severity of stress responses to exercise. Figure 1.

• Wheight-training
A 1998 study conducted at California State University investigated the effect of PS on hormone levels . The results were that athletes had less muscle soreness when they were taking S-PS compared to the placebo. Figure 2. In addiction, PS supplementation significantly improves well-being. Figure 3.

• Running
A recent double-blind, randomised, placebo-controlled, crossover study investigated the effects of S-PS supplementation on markers of muscle damage, inflammation and oxidative stress following eccentric exercise-induced muscle damage (figura ). This study shows that S-PS supplementation significantly lowered creatine kinase (CK) activities in the circulation, an index of oxidative stress of muscolar fiber. Figure 4
Phosphatidylserine supplementation and recovery following downhill running
Effects of phosphatidylserine on oxidative stress following intermittent running

• Golf
The golf swing requires the interaction of the central nervous system and skeletal muscles as well as the correct combination of power, velocity and endurance. Under the stress and fatigue, salivary cortisol levels have been reported to increase in male golfers. So This might result in negative effects on performance due to an inaccuracy in striking the ball. It has been showed that phosphatidylserine supplementation significantly increased ball flight accuracy, whereas placebo intake had no effect on performance. Figure 5
The effect of phosphatidylserine on golf performance
Furthermore, perceived stress levels are diminished in people who takes PS, rather than placebo.
Figure 5

Conclusion and discussion

Figure 6 _On the basis of these trials, PS has been proposed as a sports supplement. Indeed, PS administration promotes a desirable hormonal balance for athletes and might attenuate the physiological deterioration that accompanies overtraining and/or overstretching. We can see in the figure the effect of phosphatydyl serine on endocrine system.
However, it is important to underline 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._

NEUROLOGY

COGNITIVE FUNCTION AND DEMENTIA

Declines in cognitive functions, such as memory, are characteristic of normal aging. Several age-related neurochemical changes have been associated with biochemical, structural, and functional neuronal membrane alterations, such as changes in the composition and/or content of lipids, leading to a loss in membrane fluidity.PS has been shown to play a key role in the functioning of neuron membranes, such as signal transduction, secretory vesicle release, cell-to-cell communication, and cell growth regulation.Observations associated the administration of PS extracted from bovine cortex (BC-PS) with positive effect on brain function. Supplementation of BC-PS (300 mg PS/d) to subjects with age-associated memory impairment (AAMI) resulted in improved performance in tests related to attention, learning, and memory tasks of daily life. This rewiew report a pilot study tested the effect of PS-omega-3 consumption on the memory abilities of subjects with subjective memory complaints. The key finding of this exploratory study indicates that PS-omega-3 may have a favorable effect on memory recall in subjects with subjective memory complaints, specifically on the ability to store, hold, and retrieve information of an episodic nature. PS-omega-3 supplementation resulted in a significant increase of 42% in the ability to recall words in the delayed condition. As immediate word recall for the group remained unchanged over the period, the increase in delayed recall would reflect a decline in the decay of information held in epis memory.
The effect of phosphatidylserine-containing omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study
See Table

Table 1
Effect of PS-omega-3 on individual task outcome measures and cognitive factor scores from the CDR battery. Mean baseline and study termination scores are presented (with standard errors of the mean)

CDR measure	Baseline	Six weeks	P
Individual task
Immediate word	36.67 ± 4.36	36.67 ± 6.42	0.854
Simple reaction	338.80 ± 23.82	346.20 ± 8.16	0.889
Digit vigilance targets detected	98.33 ± 0.91	97.22 ± 1.17	0.414
Digit vigilance false alarms	2.00 ± 0.57	1.50 ± 0.42	0.518
Digit vigilance reaction time	467.40 ± 17.56	491.50 ± 18.65	0.036
Choice reaction time accuracy	97.00 ± 1.13	96.75 ± 1.19	0.783
Choice reaction time	554.30 ± 18.68	544.60 ± 16.07	0.484
Spatial working memory sensitivity index	0.97 ± 0.01	0.96 ± 0.02	0.786
Spatial working memory reaction time	1199.00 ± 107.00	1084.00 ± 61.08	0.161
Numeric working memory sensitivity index	0.96 ± 0.02	0.94 ± 0.04	0.588
Numeric working memory reaction time	932.20 ± 56.28U	979.20 ± 74.50	0.401
Delayed word recall	20.00 ± 4.36	28.33 ± 7.43	0.041
Decay immediate to	16.67 ± 3.09	8.335 ± 3.51	0.027
Word recognition	0.66 ± 0.06	0.76 ± 0.05	0.141
Picture recognition	0.76 ± 0.05	0.74 ± 0.06	0.484
Cognitive factor
Power of attention	1360.5 ± 51.9	1382.3 ± 36.2	0.484
Continuity attention	90.8 ± 1.0	90.6 ± 0.8	0.916
Quality of working memory	1.93 ± 0.03	1.90 ± 0.04	0.612
Quality of episodic secondary memory	189.8 ± 13.1	205.6 ± 21.5	0.208
Speed of memory	4397.3 ± 270.0	4425.1 ± 198.6	0.889

Researchs have noted that prolonged supplementation of phosphatidylserine to rats during the aging process can reduce the rate of cognitive decline or otherwise show trends to reverse it in the range of 15-50mg/kg daily.

However, there are various clinical and non-clinical studies that have indicated that phosphatidylserine (PS) treatment can improve cognitive functions in humans and other animals. But treatment with PS derived from bovine cortex is not desirable for possible transfer of infectious diseases. So, researchers had led various studies in which they search to known if Soybean-derived phosphatidylserine (Soy-PS) can hahe the same effects.

Soybean-Derived Phosphatidylserine Improves Memory Function of the Elderly Japanese Subjects with Memory Complaints

MEMORY AND ADHD

Different studies had shown that two months of supplementation of 200mg Phosphatidylserine (PS) appears to improve symptoms of global and subscale attention deficit and hyperactivity disorders in children with ADHD, and secondary to improving symptoms of ADHD an improvement in short-term auditory memory and impulsivity was noted.In otherwise healthy young adults given 400mg PS for 2 weeks, a significant improvement in processing speed (20%) and accuracy (13% more correct responses, 39% less wrong responses) is noted relative to placebo and independent of mood state.

The effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exercise

Other studies led by researchers show different uses of phosphatydylserine, for example in the treatment of Alzheimer’s disease or like a protector against stress.
For all reasons we have shown in this rewiew, we can consider phosphatydylserine like an important drug, despite important effects of PS must be still explained.

ANGELELLI ALESSIA canale A