Benefits
Memory in older adults with memory complaints
In older adults with memory complaints but no dementia, PS at 100 to 300 mg a day has been tested for 12 weeks to 6 months. In the soy PS trial cited here, memory scores rose about as much on placebo as on PS, and a benefit appeared only in people who started with the lowest scores. Effects in these trials are small, and none tested healthy younger adults.
FDA qualified health claim for older adults
The FDA has said it will allow two qualified health claims for PS in older adults, one on the risk of cognitive dysfunction and one on the risk of dementia, but only with required wording: very limited and preliminary research suggests a link, and the FDA concludes there is little scientific evidence supporting the claim. That wording discloses weak evidence; it is not an endorsement.
Cow brain PS versus soy and sunflower PS
The best known PS trial gave 149 older adults with age associated memory impairment 100 mg of cow brain PS three times a day for 12 weeks, with the clearest gains in those who started with the lowest scores. Cow brain PS has been discouraged since the BSE scare. Modern soy and omega-3 bound PS trials show narrower results, so the older findings should not set expectations for current products.
Cortisol response to exercise and stress
In a small trial in 10 healthy men, 600 mg a day of soy PS for 10 days lowered peak cortisol after a short cycling test by about 39% versus placebo; the trial was industry funded. Two trials at 750 mg a day saw no cortisol change after exercise. A PS plus phosphatidic acid complex normalized the cortisol and ACTH response to a lab stress test only in highly stressed men. Cortisol is a hormone marker, not a performance measure.
PS bound to omega-3 fats (PS-DHA)
PS-DHA attaches omega-3 fats to the PS molecule, so any effect cannot be credited to PS alone. In a 15 week double blind trial in 157 older adults with memory complaints and no dementia, immediate verbal recall improved more than on placebo. Wider gains appeared only in a post hoc analysis of people with better starting scores, and the authors called the study exploratory.
Stress and mood
There is limited evidence on how stressed people feel. In a month long study of 300 mg a day in young adults, less stress and better mood during a mental arithmetic task appeared only in those with higher neuroticism scores, and a 6 week trial of a PS plus phosphatidic acid complex found no change in felt stress. No trial cited here tested anxiety.
Soy versus sunflower PS
Both soy and sunflower PS are widely sold. The human trials cited here used soy derived PS or PS bound to omega-3 fats; no sunflower PS trial is cited, so whether it performs the same has not been shown here. Sunflower PS is the practical pick for people avoiding soy for allergy or preference reasons.
Cycling time to exhaustion
In a double-blind trial, 14 active men took 750 mg/day of soy-derived PS or placebo for 10 days. Cycling time to exhaustion at 85% of VO2max rose from about 7:51 to 9:51 minutes on PS and did not change on placebo. This is one small trial. A similar 750 mg trial in soccer players saw only a non-significant trend toward longer running time, and PS did not ease soreness or muscle damage markers after downhill running.
Mechanism of action
Neuronal membrane component
PS is concentrated in the inner layer of nerve cell membranes, where it helps maintain membrane structure and the function of membrane proteins. This is the basic rationale for taking it for memory, not evidence that a supplement changes brain PS.
Neurotransmitter release support
PS has been proposed to help nerve endings release neurotransmitters. Reported increases in acetylcholine, norepinephrine, serotonin and dopamine come mainly from animal experiments and from studies in people already diagnosed with Alzheimer's disease, not from healthy users. This is a proposed explanation for the cognitive research, not something the human trials cited here measured.
HPA axis cortisol modulation
PS has been proposed to blunt the HPA axis (stress hormone) response to physical and psychological stress, possibly through effects on CRH and ACTH release, but how this would work is not established. The human trials cited here are small and disagree: 600 mg a day lowered cortisol after cycling in one, and 750 mg a day did not in two others.
Apoptotic signaling
PS on the outer surface of a cell membrane is the main 'eat me' signal that lets immune cells clear dying cells. This is membrane biology rather than a known effect of taking PS as a supplement.
Form-specific bioavailability
Cow brain PS, used in the older trials, carries different fatty acid chains from the soy or sunflower PS sold today, and PS-DHA products attach omega-3 fats to the PS molecule. Form differences are one proposed explanation for the gap between the older cow brain results and the weaker modern ones, but the materials have not been compared head to head.
Clinical trials
Placebo controlled trial of cow brain derived phosphatidylserine in older adults with age associated memory impairment. It used a material that has since been discouraged over BSE, so it does not test what is in current supplements. (Crook et al. 1991, Neurology)
149 older adults with age-associated memory impairment. 100 mg three times a day (300 mg total) for 12 weeks.
Cow brain PS at 300 mg a day for 12 weeks improved learning and memory measures compared with placebo, with the clearest gains in participants who scored lowest to begin with. Because the source and fatty acid makeup differ, the result does not transfer automatically to soy or sunflower PS.
Randomized, double blind, placebo controlled trial of soy derived PS at 100 or 300 mg a day for 6 months. (Kato-Kataoka et al. 2010, J Clin Biochem Nutr)
78 Japanese adults aged 50 to 69 with memory complaints and mild memory impairment; people with possible dementia were excluded.
Overall memory scores rose about as much in the PS groups as in the placebo group. A benefit appeared only in the subgroup who started with the lowest memory scores, mainly in delayed word recall. No side effects attributed to PS were seen.
Randomized, double blind, placebo controlled 15 week trial of PS with omega-3 fatty acids attached (PS-DHA). (Vakhapova et al. 2010, Dement Geriatr Cogn Disord)
157 older adults with memory complaints and no dementia; 131 completed the study.
Immediate verbal recall improved more on PS-DHA than on placebo. A post hoc analysis found wider gains, in delayed recall, learning and figure copying time, only in people with better starting scores, and the authors described the study as exploratory. Because omega-3 fats are attached, any effect cannot be credited to PS alone.
Double blind, placebo controlled crossover trial of soy derived PS in chewable tablets. Funded by Increnovo LLC, where two co-authors worked, with publication costs paid by Chemi Nutra. (Starks et al. 2008, J Int Soc Sports Nutr)
10 healthy young men (mean age about 26). 600 mg/day soy PS or placebo for 10 days each, then a 15-minute cycling bout rising from 65% to 85% of VO2max.
Compared with placebo, PS lowered peak cortisol by about 39% and the cortisol area under the curve by about 35%, and raised the testosterone to cortisol ratio; lactate and growth hormone did not change. Two other soy PS trials at 750 mg/day found no cortisol change after exercise, and a hormone shift is not evidence of better performance or recovery.
Double-blind, placebo-controlled trial of 750 mg a day of soy-derived PS for 10 days, using a staged cycling test that ended with a bout at 85% of VO2max continued to exhaustion. (Kingsley et al. 2006, Med Sci Sports Exerc)
14 active men.
Time to exhaustion rose from about 7:51 to 9:51 minutes on PS and did not change on placebo (8:09 to 8:02). Oxygen uptake kinetics, serum cortisol, fuel use and feeling states were not affected. A single small trial.