Phosphatidylserine
Phosphatidylserine is a phospholipid present in cell membranes particularly in the brain. It is present in many foods but can also be made by the body. Its high concentrations in nervous tissue led to it being investigated as a potential cognitive enhancer. It is commonly used for this purpose among many others.
The research demonstrates that at least in the right circumstances it can improve cognition and in particular certain types of memory. Most studies showing improvement were in the elderly or people with cognitive problems. Thus it may be preferential to the optimal brain functioning as opposed to enhancement. However no studies on healthy subjects have been reported so this is not known. One small study shows that phosphatidylserine can reverse the cognitive deficits caused by stress.
Most beneficial for - Produces the most improvement in those suffering greater cognitive difficulties. No data regarding completely healthy subjects
Effective dose - 300mg daily
Length of action - Beneficial effect reported after 15 days of use
Safety - Up to 600mg daily has been demonstrated to be safe
Type cognition effected - Improvements to verbal memory, visual memory and memorizing information and numbers reported
Enhancers - May be effective in combination with ginkgo biloba or omega 3 fatty acids
Supporting Human Studies
Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration (Cenacchi et al, 1993)
Four hundred and ninety four elderly patients with mild to severe cognitive impairments received 300mg/day of phosphatidylserine or a placebo for 6 months. Statistically significant improvements in both behavioural and cognitive parameters were observed in the group taking the phosphatidylserine compared to controls. The study also demonstrated that phosphatidylserine was well tolerated and safe.
Soybean-Derived Phosphatidylserine Improves Memory Function of the Elderly Japanese Subjects with Memory Complaints (Kato-Kataoka et al, 2010)
In this double blind placebo controlled trial 78 elderly patients with mild cognitive impairment were allocated 300mg/day of phosphatidylserine or a placebo for 6 months. Those with low initial scores showed the most benefit from phosphatidylserine. They showed significant improvements in memory scores particularly delayed verbal recall compared to the placebo group.
Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress (Baumeister et al, 2008)
Sixteen healthy subjects completed cognitive tasks after being stressed. They were then randomly assigned phosphatidylserine or a placebo daily for 42 days. The tests were then repeated and EEG of brain waves analyzed. The main results showed that those receiving the phosphatidylserine showed an increase in brain wave patterns associated with relaxation.
Effects of phosphatidylserine in age‐associated memory impairment (Crook et al, 1991)
One hundred and forty nine elderly patients with associated memory impairments recieved 100mg/day of phosphatidylserine or a placebo for 12 weeks. The group receiving the phosphatidylserine improved on learning and memory tasks relative to the placebo group. Also noted was those that had the worst initial test scores before the trial showed the most improvement from phosphatidylserine supplementation.
Effects of phosphatidylserine therapy in geriatric patients with depressive disorders (Maggioni et al, 2007)
Ten elderly women with depressive disorders received a placebo for 15 days followed by 300mg/day of phosphatidylserine for 30 days. The phosphatidylserine was able to consistently improve depressive symptoms, memory and behavior compared to the placebo.
The Effect of Plant Phosphatidylserine on Age-Associated Memory Impairment and Mood in the Functioning elderly (Gindin et al)
In this double blind study 72 functioning elderly subjects received either 300mg of phosphatidylserine or a placebo daily for three months. At the end of the three months tests showed significant improvements in both cognitive and mood measures. The cognitive aspects most improved were memorizing information and numbers and visual memory.
Supporting Animal Studies
Enhanced Learning of Normal Adult Rodents by Repeated Oral Administration of Soybean Transphosphatidylated Phosphatidylserine (Kataoka Kato et al, 2005)
Normal Rats received 50mg/kg/day for 34 days of transphosphatidylated phosphatidylserine before undergoing cognitive testing. The Phosphatidylserine was shown to improve both conditioned avoidance and brightness discrimination test. These tests are linked to learning ability.
Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS (Blokland et al, 1999)
Phosphatidyserine from different sources (bovine, egg, soy) was given to rats (15mg/kg) daily. Bovine and soy derived phosphatidylserine were shown to enhance results in a two way avoidance task compared to control groups but had no effect on psychomotor or spacial discrimination tasks. Egg derived phospatidylserine did not have cognitive enhancing effects.
Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats (Zanotti et al, 1989)
Aged rats received 50mg/kg/day for up to 12 weeks of phosphatidylserine. They were then tested for spatial memory and for passive avoidance. In both these test the rats performed better than a group of control rats who did not receive the phosphatidylserine supplement.
Oral Administration of Soybean Lecithin Transphosphatidylated Phosphatidylserine Improves Memory Impairment in Aged Rats (Suzuki et al, 2001)
Adult male rats received 60mg/kg daily of a lecithin-phosphatidylserine complex for 60 days. This significantly improved water maze escape times compared to control rats. Brain analysis later showed that the lecithin-phosphatidylserine complex could restore acetylcholine and sodium/potassium-ATPase activity to the levle seen in young rats.
Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats (Lee et al, 2010)
Aged rats were administered 20 or 50mg/kg of krill derived phosphatidaylserine daily for 7 days. The rats times for escaping a water maze was significantly improved by the phosphatidylserine. Analysis of brain chemicals involved in learning and memory showed that the phosphatidylserine prevented changes associated with aging.
Effect of exogenous phosphatidylserine on cognitive function and hippocampus phospholipid turnover in old rats (Babenko et al, 2009)
Old rats were fed phosphatidylserine. The levels of phosphatidylserine increased to that of young rats for those taking the phosphatidylserine. The production of phosphatidylcholine in the hippocampus of these rats also increased. The phosphatidylserine also improved results in active avoidance tests.Contradictory Studies
The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment (Jorissen et al, 2001)
One hundred and twenty elderly adults with cognitive impairment received 300mg phosphatidylserine, 600mg phosphatidylserine or placebo daily for 12 weeks. No significant differences were observed between the groups when tests for learning, memory, attention and planning administered.
Phosphatidylserine: an antidepressive or a cognitive enhancer? (Castilho et al, 2004)
Rats were given varying doses of phosphatidylserine or a placebo one hour before commencing forced swimming and water maze tests. Results demonstrated that the phosphatidylserine could improve results of the forced swimming test for depression but showed no enhancement in water maze abilities.
Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: Amelioration of passive avoidance deficits without changes in psychomotor task performance (Corwin et al, 1985)
Aged rats received a dose of phosphatidylserine before undergoing passive avoidance tests. The phosphatidylserine showed a significant enhanced effect of passive avoidance retention tests. No changes were observed in psychomotor tasks.
Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aging rats (Vannucchi et al, 1987)
Rats were pretreated with phosphatidylserine for 7 days and the levels of acetylcholine in their brains compared to rats who did not receive phosphatidylserine. No difference was observed in young rats however in older rats those taking the phosphatidylserine had acetylcholine levels 44% higher than rats without. These levels were similar to the young rats indicating that phosphatidylserine restores normal acetylcholine levels.
Combinational Studies
Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine (Kennedy et al, 2007)
In this double blind placebo controlled crossover study 28 healthy adults received either 120mg Ginkgo extract, 120mg ginkgo extract complexed with phosphatidylserine, 120mg ginkgo extract complexed with phosphatidylcholine or a placebo. The dose occurred once with testing 1, 2.5, 4 and 6 hours after ingestion. The ginkgo extract alone showed no cognitive improvements. The ginkgo complexed with phosphatidylserine significantly improved secondary memory and speed of memory. The ginkgo phosphatidylcholine complex resulted in a mild improvement of secondary memory.
Phosphatidylserine Containing ω–3 Fatty Acids May Improve Memory Abilities in Non-Demented Elderly with Memory Complaints: A Double-Blind Placebo-Controlled Trial (Vakhapova et al, 2010)
One hundred elderly with minor memory complaints received either a phosphatidylserine-omega 3 complex or a placebo for 15 weeks. Results showed that those receiving the phosphatidylserine-omega 3 complex showed significantly better verbal immediate recall than the placebo group. Those taking the supplement also showed improvements in delayed verbal recall, learning abilities and time to copy a complex figure.
Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine (Araujo et al, 2008)
Nine aged dogs were given a supplement containing phosphatidylserine, ginkgo biloba, vitamin E and pyridoxine or a placebo and then visuospatial memory tested. Significant improvements were seen in the dogs taking the supplement compare to the control group and these effects were long lasting.
Safety Studies
Safety of Soy-derived Phosphatidylserine in Elderly People (Jorissen et al, 2002)
Elderly participants received up to 600mg daily of soy derived phosphatidylserine supplement. Safety and side effects were assessed and it was found that phosphatidylserine is safe in elderly adults up to a dose of 600mg.
Safety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension (Vakhapova et el, 2011)
One Hundred and fifty seven non-demented elderly patients received a phosphatidylserine-omega 3 supplement containing 300mg of phosphatidylserine daily for 15 weeks. No significant adverse effects were reported. Tests revealed a slight decrease in blood pressure and some weight gain in those taking the supplement. Other parameters tested showed no changes.
The research demonstrates that at least in the right circumstances it can improve cognition and in particular certain types of memory. Most studies showing improvement were in the elderly or people with cognitive problems. Thus it may be preferential to the optimal brain functioning as opposed to enhancement. However no studies on healthy subjects have been reported so this is not known. One small study shows that phosphatidylserine can reverse the cognitive deficits caused by stress.
Most beneficial for - Produces the most improvement in those suffering greater cognitive difficulties. No data regarding completely healthy subjects
Effective dose - 300mg daily
Length of action - Beneficial effect reported after 15 days of use
Safety - Up to 600mg daily has been demonstrated to be safe
Type cognition effected - Improvements to verbal memory, visual memory and memorizing information and numbers reported
Enhancers - May be effective in combination with ginkgo biloba or omega 3 fatty acids
Supporting Human Studies
Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration (Cenacchi et al, 1993)
Four hundred and ninety four elderly patients with mild to severe cognitive impairments received 300mg/day of phosphatidylserine or a placebo for 6 months. Statistically significant improvements in both behavioural and cognitive parameters were observed in the group taking the phosphatidylserine compared to controls. The study also demonstrated that phosphatidylserine was well tolerated and safe.
Soybean-Derived Phosphatidylserine Improves Memory Function of the Elderly Japanese Subjects with Memory Complaints (Kato-Kataoka et al, 2010)
In this double blind placebo controlled trial 78 elderly patients with mild cognitive impairment were allocated 300mg/day of phosphatidylserine or a placebo for 6 months. Those with low initial scores showed the most benefit from phosphatidylserine. They showed significant improvements in memory scores particularly delayed verbal recall compared to the placebo group.
Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress (Baumeister et al, 2008)
Sixteen healthy subjects completed cognitive tasks after being stressed. They were then randomly assigned phosphatidylserine or a placebo daily for 42 days. The tests were then repeated and EEG of brain waves analyzed. The main results showed that those receiving the phosphatidylserine showed an increase in brain wave patterns associated with relaxation.
Effects of phosphatidylserine in age‐associated memory impairment (Crook et al, 1991)
One hundred and forty nine elderly patients with associated memory impairments recieved 100mg/day of phosphatidylserine or a placebo for 12 weeks. The group receiving the phosphatidylserine improved on learning and memory tasks relative to the placebo group. Also noted was those that had the worst initial test scores before the trial showed the most improvement from phosphatidylserine supplementation.
Effects of phosphatidylserine therapy in geriatric patients with depressive disorders (Maggioni et al, 2007)
Ten elderly women with depressive disorders received a placebo for 15 days followed by 300mg/day of phosphatidylserine for 30 days. The phosphatidylserine was able to consistently improve depressive symptoms, memory and behavior compared to the placebo.
The Effect of Plant Phosphatidylserine on Age-Associated Memory Impairment and Mood in the Functioning elderly (Gindin et al)
In this double blind study 72 functioning elderly subjects received either 300mg of phosphatidylserine or a placebo daily for three months. At the end of the three months tests showed significant improvements in both cognitive and mood measures. The cognitive aspects most improved were memorizing information and numbers and visual memory.
Supporting Animal Studies
Enhanced Learning of Normal Adult Rodents by Repeated Oral Administration of Soybean Transphosphatidylated Phosphatidylserine (Kataoka Kato et al, 2005)
Normal Rats received 50mg/kg/day for 34 days of transphosphatidylated phosphatidylserine before undergoing cognitive testing. The Phosphatidylserine was shown to improve both conditioned avoidance and brightness discrimination test. These tests are linked to learning ability.
Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS (Blokland et al, 1999)
Phosphatidyserine from different sources (bovine, egg, soy) was given to rats (15mg/kg) daily. Bovine and soy derived phosphatidylserine were shown to enhance results in a two way avoidance task compared to control groups but had no effect on psychomotor or spacial discrimination tasks. Egg derived phospatidylserine did not have cognitive enhancing effects.
Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats (Zanotti et al, 1989)
Aged rats received 50mg/kg/day for up to 12 weeks of phosphatidylserine. They were then tested for spatial memory and for passive avoidance. In both these test the rats performed better than a group of control rats who did not receive the phosphatidylserine supplement.
Oral Administration of Soybean Lecithin Transphosphatidylated Phosphatidylserine Improves Memory Impairment in Aged Rats (Suzuki et al, 2001)
Adult male rats received 60mg/kg daily of a lecithin-phosphatidylserine complex for 60 days. This significantly improved water maze escape times compared to control rats. Brain analysis later showed that the lecithin-phosphatidylserine complex could restore acetylcholine and sodium/potassium-ATPase activity to the levle seen in young rats.
Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats (Lee et al, 2010)
Aged rats were administered 20 or 50mg/kg of krill derived phosphatidaylserine daily for 7 days. The rats times for escaping a water maze was significantly improved by the phosphatidylserine. Analysis of brain chemicals involved in learning and memory showed that the phosphatidylserine prevented changes associated with aging.
Effect of exogenous phosphatidylserine on cognitive function and hippocampus phospholipid turnover in old rats (Babenko et al, 2009)
Old rats were fed phosphatidylserine. The levels of phosphatidylserine increased to that of young rats for those taking the phosphatidylserine. The production of phosphatidylcholine in the hippocampus of these rats also increased. The phosphatidylserine also improved results in active avoidance tests.Contradictory Studies
The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment (Jorissen et al, 2001)
One hundred and twenty elderly adults with cognitive impairment received 300mg phosphatidylserine, 600mg phosphatidylserine or placebo daily for 12 weeks. No significant differences were observed between the groups when tests for learning, memory, attention and planning administered.
Phosphatidylserine: an antidepressive or a cognitive enhancer? (Castilho et al, 2004)
Rats were given varying doses of phosphatidylserine or a placebo one hour before commencing forced swimming and water maze tests. Results demonstrated that the phosphatidylserine could improve results of the forced swimming test for depression but showed no enhancement in water maze abilities.
Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: Amelioration of passive avoidance deficits without changes in psychomotor task performance (Corwin et al, 1985)
Aged rats received a dose of phosphatidylserine before undergoing passive avoidance tests. The phosphatidylserine showed a significant enhanced effect of passive avoidance retention tests. No changes were observed in psychomotor tasks.
Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aging rats (Vannucchi et al, 1987)
Rats were pretreated with phosphatidylserine for 7 days and the levels of acetylcholine in their brains compared to rats who did not receive phosphatidylserine. No difference was observed in young rats however in older rats those taking the phosphatidylserine had acetylcholine levels 44% higher than rats without. These levels were similar to the young rats indicating that phosphatidylserine restores normal acetylcholine levels.
Combinational Studies
Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserine (Kennedy et al, 2007)
In this double blind placebo controlled crossover study 28 healthy adults received either 120mg Ginkgo extract, 120mg ginkgo extract complexed with phosphatidylserine, 120mg ginkgo extract complexed with phosphatidylcholine or a placebo. The dose occurred once with testing 1, 2.5, 4 and 6 hours after ingestion. The ginkgo extract alone showed no cognitive improvements. The ginkgo complexed with phosphatidylserine significantly improved secondary memory and speed of memory. The ginkgo phosphatidylcholine complex resulted in a mild improvement of secondary memory.
Phosphatidylserine Containing ω–3 Fatty Acids May Improve Memory Abilities in Non-Demented Elderly with Memory Complaints: A Double-Blind Placebo-Controlled Trial (Vakhapova et al, 2010)
One hundred elderly with minor memory complaints received either a phosphatidylserine-omega 3 complex or a placebo for 15 weeks. Results showed that those receiving the phosphatidylserine-omega 3 complex showed significantly better verbal immediate recall than the placebo group. Those taking the supplement also showed improvements in delayed verbal recall, learning abilities and time to copy a complex figure.
Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine (Araujo et al, 2008)
Nine aged dogs were given a supplement containing phosphatidylserine, ginkgo biloba, vitamin E and pyridoxine or a placebo and then visuospatial memory tested. Significant improvements were seen in the dogs taking the supplement compare to the control group and these effects were long lasting.
Safety Studies
Safety of Soy-derived Phosphatidylserine in Elderly People (Jorissen et al, 2002)
Elderly participants received up to 600mg daily of soy derived phosphatidylserine supplement. Safety and side effects were assessed and it was found that phosphatidylserine is safe in elderly adults up to a dose of 600mg.
Safety of phosphatidylserine containing omega-3 fatty acids in non-demented elderly: a double-blind placebo-controlled trial followed by an open-label extension (Vakhapova et el, 2011)
One Hundred and fifty seven non-demented elderly patients received a phosphatidylserine-omega 3 supplement containing 300mg of phosphatidylserine daily for 15 weeks. No significant adverse effects were reported. Tests revealed a slight decrease in blood pressure and some weight gain in those taking the supplement. Other parameters tested showed no changes.