Phosphatidylserine Introduction

Phosphatidylserine is a phospholipid that is classified as a polar ionic compound. Like phosphatidylcholine, it too is made of an alcohol and a diacylglycerol, or sphingosine, linked by a phosphodiester bridge. [1] Phosphatidylserine is synthesized in the body primarily via exchange of ethanolamine, from phosphatidylethanolamine, for serine. [2] Biosynthesis also requires adequate levels of folic acid, vitamin B12, and essential fatty acids.

Phosphatidylserine is a vital component of cell membranes and is the major acidic phospholipid in the brain. [2] Its fluid nature, which is necessary for cell to cell communication and cellular metabolism, underscores the importance of this compound in cell membrane function and integrity.

This phospholipid has broad effects in the central nervous system. Administering preparations of phosphatidylserine to aged rats has increased dopamine release in the striatum, stimulated acetylcholine secretion, and has prevented age-related atrophy of cholinergic cells in the basal forebrain. [3] Phosphatidylserine supplementation has demonstrated changes in EEG activity in humans. [4] As well, taking PS over a period of 30 days has restored the circadian rhythmicity of thyroid-stimulating hormone (TSH) secretion in hospitalized patients. [5]

Phosphatidylserine Food Sources

Soybean oil is the primary dietary source of phosphatidylserine. Synthesis of this compound within the body requires an adequate supply of serine, which can be found in meats, soy, dairy products, wheat gluten, and peanuts. In order to obtain therapeutic levels of phosphatidylserine, supplements are required. Preparations are derived either from bovine brain cortex or soybeans. [6]

Phosphatidylserine Uses

The main applications of phosphatidylserine include the treatment of cognitive impairments, stress and depression.

Cognitive Conditions:

Phosphatidylserine supplementation has demonstrated positive effects on cognitive decline in elderly patients, A double-blind randomized, placebo-controlled study was conducted involving 42 hospitalized patients with dementia. [7] Half the subjects were given 100 milligrams of brain-cortex phosphatidylserine three times per day for six weeks. The other half received placebo. The results showed that cognitive ability was significantly improved in the PS group, as assessed by the Peri Scale, when compared to the placebo group.

Similarly, an open trial of elderly volunteers meeting the criteria for Age-Associated Memory Impairment was conducted to determine the effect of plant-derived phophatidylserine. [8] Subjects were given 100 milligrams of the supplement, three times per day for 12 weeks. Except for two outcome measures, the rest of the control group demonstrated significant improvements from phosphatidylserine over time, as measured at 6 and 12 weeks of treatment. Other placebo-controlled trials also support these findings. [9, 10] However, there are also some studies that discount these findings, including a 2001 trial using soybean derived phosphatidylserine to treat age-related memory impairment. [11]

A review published in 2003 summarized that most of the studies demonstrate a modest benefit of phosphatidylserine on, specifically, word recall in elderly patients with cognitive decline; but only one study showed improvement in a variety of memory tests. [12]

Alzheimer's disease has also received interest in the phosphatidylserine research community, as memory is also impacted in this condition. An initial study of patients with probable Alzheimer’s disease examined the effect of bovine cortex phosphatidylserine versus placebo. [13] The supplement was administered at a dosage level of 100 milligrams three times daily for 12 weeks. Results showed improvement on several measures of cognitive ability, and was most pronounced in patients with less severe impairment. The authors concluded that this treatment would be most beneficial for patients with early stage Alzheimer’s disease.


An interesting application of phosphatidylserine is in addressing stress. In a double- blind study of healthy men, phosphatidylserine was administered to half of the participants10 minutes before starting exercise (physically induced stress). [14] The treatment standard was set at administering 50 or 75 milligrams of bovine-cortex phosphatidylserine (BC-PS) intravenously, or oral placebo. The results showed that pretreatment with both 50 and 75mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.

Another study examined the effect of an oral supplementation of BC-PS on physically induced stress. [15] Healthy subjects took 800mg per day for 10 days. Again, BC-PS significantly blunted the ACTH and cortisol responses to physical exercise without affecting the rise in plasma growth hormone and prolactin.

Plant derived phosphatidylserine has also demonstrated positive effects on stress in humans. In 2004, a placebo controlled study was conducted to determine the effect of a soy derived preparation of phosphatidic acid and phosphatidylserine complex (PAS) on acute stress. [16] Four groups of 20 subjects were treated daily for three weeks with either 400mg PAS, 600mg PAS, 800mg PAS, or placebo, before exposure to the Trier Social Stress Test (TSST). The results showed that in the group taking 400mg PAS, a pronounced blunting of serum ACTH, cortisol, and salivary cortisol responses to the TSST was observed. Additionally, heart rate was not affected, nor was it affected at any of the higher doses. 400mg PAS appeared to exert a specific positive effect on emotional responses to the stress test.


In patients with depressive disorders, supplementation with 300 milligrams daily of bovine-cortex phophatidylserine for 30 days resulted in consistent improvement of depressive symptoms, memory and behavior.[17]

Phosphatidylserine Dosages

Most studies show effective oral dosage levels of 100 milligrams three times daily. Occasionally, 400 milligram daily doses are recommended for specific disease conditions. Some studies employ intravenous doses which have also demonstrated efficacy.

Phosphatidylserine Toxicities and Deficiencies

Phosphatidylserine Deficiency

Low levels of phosphatidylserine are more common in the elderly. In order to synthesize this compound, an adequate supply of folic acid, vitamin B12, and essential fatty acids are necessary. [18] If any of these levels are low, the brain may not be able to manufacture sufficient levels of phospahtidylserine. Impaired mental function and depression are also associated with low phosphatidylserine levels.

Phosphatidylserine Toxicities

Phosphatidylserine is generally considered a safe therapeutic agent. Bovine brain-cortex phosphatidylserine supplements have been consistently tolerated in humans at levels exceeding 300 milligrams daily. Phosphatidylserine derived from soybeans has demonstrated tolerability in elderly subjects at dosages of both 300 milligrams and 600 milligrams daily as well. [19] Moreover, standard biochemical and hematological safety parameters, blood pressure, heart rate, and adverse events were not affected as compared with placebo after 6 and 12 weeks of treatment.

Nausea may occur as an adverse effect in some patients. No teratogenicity or mutation has been observed in animal studies. [20]


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