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Phosphatidylserine: Protecting Brain Health

Brain scan

Multiple clinical trials have demonstrated that phosphatidylserine (PS) supplements improve memory and other aspects of thinking in elderly people with mild to severe memory complaints. Some individuals in these trials were in mid-life, but the overall results reflect the population which averaged in their 70’s. Does PS improve memory in younger adults?  

The Effects of Phosphatidylserine in Young Adults

Does PS improve memory in healthy younger adults? It is one thing to restore an impaired memory and another to supercharge a normal memory. It is possible, but the data is not yet in to answer that question. PS might however protect and preserve brain health and decrease the risk of later dementia. 

It is now recognized that damage starts to accumulate in the brain decades before memory loss becomes obvious. Behavioral changes in mid-life – such as improved diet, adequate exercise decrease the risk of dementia 20+ years later. Similar studies have not yet been done with PS, but animal models and clinical studies suggest PS could be protective.  

Basic Science Studies

PS modulates several key signaling pathways, including P13K/Akt, PKC and Raf/Ras, which increase neuronal survival, growth and formation of contacts called synapses. It improves communication by increasing release of key chemicals, like acetylcholine, a messenger in memory circuits. 

In an animal model of Alzheimer disease, brain content of PS and other phospholipids was observed to decrease prior to observable memory decline. The authors concluded that the abnormal neuronal cell membranes altered interaction with the Alzheimer A-beta amyloid protein leading to eventual Alzheimer disease. This would suggest a potential protective role for PS. 

PS has been shown to positively effect a number of processes which injure the brain and contribute to development of dementia. These effects include:

  • Decreased neuroinflammation;
  • Improved anti-oxidant protection;
  • Decreased neuronal injury and death in the hippocampus, a key part of memory circuits. 

    Together these observations suggest that PS might interrupt the cascade of damage which eventually produces Alzheimer’s disease.

    PS Decreases Stress Response in Young Adults

    Chronic stress in mid-life increases the risk of later dementia. Stress increases serum and brain cortisol levels. Cortisol can damage or kill neurons in the hippocampus. Clinical studies in young adults, typically in their 20s, showed that PS supplements prevented cortisol spikes caused by a variety of acute stressors, including intense physical exercise, mental arithmetic, social stressors or premenstrual hormonal changes. Interestingly the cortisol responses to PS tended to be greatest in people who probably had underlying chronic stress. These people had abnormal cortisol responses, either hyperactive or blunted, which is seen after repeated adrenal stimulation. After several weeks of PS treatment, EEGs showed normalization of the chronic stress related pattern of asymmetrically increased right frontal Beta-1. Decreasing exposure of the brain to elevated cortisol would be expected to improve memory. Only one study examined cognition, and it did report improved performance of mental arithmetic. Over time, lowering exposure to harmful cortisol would be predicted to help preserve memory circuits.

    In some studies, people reported subjectively lower stress and improvement in their sense of overall well-being. Improved mood was noted in some of the stress studies, as it has been in some memory studies in elderly adults. Perhaps in athletes this may have been related to improved performance in those taking PS.

    Together the observations that PS decreases cortisol responses in people with the observations with its brain protective effects in animal models suggest that it may slow the gradually accumulated brain damage that over the years leads to dementia. And more immediately younger adults might experience benefits of increased stress tolerance and an improved sense of well-being.  


    By Patricia Walicke MD, PhD