Phosphatidylserine appears to help some people with cognitive impairment, but effects are not consistent.
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Description
- Phosphatidylserine is an endogenous, acidic phospholipid that composes 10% to 15% of the lipid bilayer of cell membranes; it is particularly abundant in neuronal cell membranes (1).
- It can be endogenously formed from serine, glycerophosphate, and two fatty acid molecules; some phosphatidylserine comes from dietary sources (2). However, orally ingested phospholipids are partially digested in the small intestine, losing fatty acids, and are unlikely to be absorbed intact (Linder, personal communication, 2001).
- Most currently available supplements are derived from soy; some are combined with other phospholipids.
Food Sources
Phosphatidylserine is found in small quantities in food plants and animal products but is not very bioavailable.
Main Functions/Pharmacokinetics
- Phosphatidylserine is involved in cell-to-cell communication and protein regulation (including enzymes that mediate signal transduction); activates different protein kinase C isoforms; and affects levels of acetylcholine, dopamine, and norepinephrine (2). Cell membrane experiments have demonstrated an increase in the activity of Na+-K+-dependent ATPase, activation of tyrosine hydroxylase, and regulation of calcium uptake. Intravenous injection in mice increases brain glucose and blood glucose and decreases adrenal catecholamines (1).
- Most orally ingested phosphatidylserine is degraded in the gastrointestinal tract; the amount that reaches the central nervous system after oral administration is extremely small, and chronic or repeated administration is necessary to see effects in animal studies (1).
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Clinical Trials
Numerous trials have been conducted of phosphatidylserine and dementia, but consistent effects have not been demonstrated. Most experiments have used phosphatidylserine derived from bovine cortex, which is no longer available (see question and answer section).
- Alzheimer’s disease
- A 6-month study of 70 patients with probable Alzheimer’s disease randomized patients to one of four groups: 17 received social support, 18 cognitive training (twice weekly), 17 cognitive training and pyritinol, and 18 cognitive training and phosphatidylserine (200 mg b.i.d.) (3). Outcome measures included neuropsychologic testing and positron emission tomography scanning for activated glucose pattern in regions typically affected in Alzheimer’s disease. At 6 months there were no significant differences between groups in activated glucose pattern or neuropsychologic testing. Scores in the orientation questionnaire were significantly higher at 8 weeks in both the phosphatidylserine and pyritinol groups compared with the other two groups; in addition, the rate of responders (defined as an improvement of 3 or more in the Mini-Mental State Examination score) was significantly higher in both the phosphatidylserine and pyritinol groups compared with the other two groups.
- A double-blind randomized controlled trial in 42 hospitalized Alzheimer’s patients (35 completed) tested 100 mg phosphatidylserine t.i.d. against placebo for 6 weeks (4). There was not a significant difference in the Crichton Rating Scale or circle crossing test but there was a significant difference in the Peri test.
- A double-blind crossover study (300 mg/day phosphatidylserine × 8 weeks) in 33 patients with early Alzheimer’s found that clinical global improvement was better in treated patients but there was no difference in the Gottfries, Brane and Steen (GBS) dementia scale, psychometric tests, or electroencephalographic mapping (5).
- Age-related cognitive impairment and decline
- A placebo-controlled study of 149 patients 50 to 75 years with age-related cognitive impairment found a significant benefit of 100 mg phosphatidylserine at 3, 6, and 12 weeks in several recall tests, facial recognition, and ability to concentrate (6); patients with initially poor performance were said to benefit the most.
- Another study by the same researcher tested 100 mg phosphatidylserine t.i.d. × 12 weeks against placebo in 51 elderly patients with "probable Alzheimer’s disease." The treated group significantly improved several recall tests (the less impaired did better) (7).
- A double-blind, placebo-controlled study in 494 elderly patients (425 completed) age 65 to 93 with moderate to severe cognitive decline found that 6 months treatment with 300 mg/day phosphatidylserine significantly improved behavior (including motivation, initiative, and socialization) but not behavioral impairment for activities of daily living (self-sufficiency, self care) (8).
- A study of phosphatidylserine 200 mg/day versus placebo in 142 patients with gradual progressive intellectual decline over at least 6 months found no differences in moderately impaired patients. In the subgroup of patients with severe cognitive impairment, significant improvements (p < 0.05) in the Blessed dementia scale and the Set test but not the Clifton Assessment scale were demonstrated in the treated group; however this was only a small subgroup of 18 patients that included only 8 treated patients (9).
Animal/in Vitro Evidence
Phosphatidylserine may decrease severity of several neurochemical and behavioral aging-related changes in rats (1).
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Adverse Reactions
Stomach upset.
Doses greater than 600 mg near bedtime can cause insomnia.
Doses greater than 300 mg/day lower serum uric acid and alanine aminotransferase (2).
Animal Toxicity
In rats, the LD50 is greater than 5 g/kg body weight (2).
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Deficiency Signs and Symptoms
None identified
Factors Decreasing Availability/Absorption
None identified
Factors Increasing Availability/Absorption
None identified
Laboratory Tests
None identified
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Q: What is the difference between phosphatidylserine from bovine sources and from soy?
A: There is not much difference; docosahexaenoic acid, an omega-3 fatty acid, is found in the 2 position of bovine but not soy phosphatidylserine. Most clinical trials used phosphatidylserine derived from bovine cortex, no longer considered a safe source. Soybean-derived phosphatidylserine is often sold in a complex containing phosphatidylcholine and phosphatidylethanolamine; no clinical trials have been done on soy preparations.