We are happy that phosphatidylserine (PS) is available in capsules, which means it's now easier than ever to keep your brain functioning at a youthful peak. Those of you who have been using Dr. Ward Dean's liquid PS formulation are aware that PS is a type of lecithin known for its positive effect on brain aging. Furthermore, it reverses many of the effects of aging on the brain and restores youthful brain function in a number of ways. For example, in addition to providing vital lipid components of brain cell membranes, it plays a role in:

  • keeping cell membranes flexible and permeable
  • increasing dopamine release
  • restoring youthful synaptic plasticity
  • augmenting brain glucose metabolism
  • increasing the number of neurotransmitter receptor sites
  • spurring the release of the neurotransmitter need acetylcholine (ACh)

All of these benefits associated with PS in liquid form are equally available in the new, convenient PS capsules.

Why Do You Need PS?

Scientists have determined that as we age, nerve cells drop out of the brain's neural network. This occurs because oxidation and other destructive events cause the delicate lipid and protein membrane that surrounds each neuron to become brittle and less permeable and thus to lose its ability to resist stress and damage.

Scientists have found that this type of neuronal deterioration can be slowed or even prevented by replacing phosphatidylserine, one of the important phospholipids that comprise the cell membrane.

Cognitive Improvement

Subtle changes in brain cell membranes are fine, of course, but do these changes translate into changes in behavior and cognition? Yes, they do. Well-controlled trials in laboratory animals and in people with documented memory loss indicate that taking dietary supplements containing PS can help improve cognitive status and may lead to significantly higher mental functioning.

Two of the most important trials of PS were conducted by Dr. T. Crook of the Memory Assessment Clinics in Bethesda, MD. The randomized, double blind, placebo-controlled, multicenter trials included clinicians from Vanderbilt University, Stanford University School of Medicine, Fidia Pharmaceutical Corporation of Italy, and ExPharma of Italy.

Improvement in Cognitive Functioning in People Treated with Phosphatidylserine

In the first trial, 149 people (aged 50-75 years) diagnosed with age associated memory impairment (AAMI) were treated for 12 weeks with either PS, 100 mg three times a day, or placebo. Within 3 weeks, Dr. Crook and his colleagues found the PS-treated subjects were showing significant improvement in three of the five primary variables: learning names and faces, recalling names and faces, and facial recognition.

Closer analysis of the data revealed that those subjects who had the lowest baseline (pretreatment) scores seemed to benefit the most from PS supplements. In addition to the measures noted above, these subgroups also exhibited significant improvement in certain recall abilities - for example; telephone numbers and the location of misplaced objects - and in their ability to concentrate while reading, conversing, and performing tasks. "Blinded" interviewers rated this subgroup as showing significant overall global improvement in cognitive status. Some benefits persisted for 4 weeks or more after the subjects stopped taking PS, suggesting that PS treatment might be contributing to renewal of nerve cell growth and/or restoration of nerve function.

Based on some of the changes recorded, Dr. Crook calculated that the cognitive clock of these participants was turned back 12 years, a magnitude of effect that he and his colleagues concluded "may be considered significant by many subjects and clinicians."1

In the second study by Crook's group, 51 people (aged 55-85 years) with suspected or probable Alzheimer's disease were treated with the same dose of PS or placebo. After 12 weeks, the PS-treated subjects were significantly improved relative to the placebo group on several measures of cognitive function, including memory for names and familiar persons, recall of the location of frequently misplaced objects, recall of details of events from the previous day, and recall of events from within the past week. Among these people, a subgroup of mildly impaired individuals seemed to benefit the most from PS supplementation.2

Double-blind clinical trials of PS and cognitive function in people with various degrees of cognitive impairment have also been conducted in Europe. Although the trials have used different methodologies and different measures of cognitive function, they have all come to the same general conclusion: taking PS dietary supplements can improve learning, memory, cognition, concentration, and other mental functions (see chart).3-8

How Does PS Work?

You would expect that any substance that could alter cognitive function would affect the functioning of neurons in the brain, and with PS, that's exactly what happens. PS enters the bloodstream within 30 minutes of ingestion and is soon found in the liver and shortly thereafter in the brain, where it readily crosses the blood-brain barrier.

PS's site of action in the brain is the nerve cell membrane, which is composed primarily of lipid (fat) and protein molecules. The cell membrane controls the movement of nutrients, waste products, ions, neurotransmitters, and other molecules into and out of the cell. It also influences the shape of the cell and the movement of the cell. PS is one of five types of phospholipid that comprise cell membranes, but PS is the dominant phospholipid in nerve cell membranes. Among other functions, it seems to be important for anchoring proteins in the membrane matrix.

Evidence has demonstrated that PS facilitates a variety of vital cellular activities in brain cells, including:

  • Maintaining the internal cellular environment. Ions moving back and forth across the cell membrane generate constant electrical activity, which requires the participation of ATPase enzymes to regulate the sodium-potassium and calcium-magnesium balance. In animal studies, the breakdown of these functions with age has been reversed when the animals were treated with PS.9PS also seems to act as a kind of "biologic detergent" to help keep fatty substances soluble and cell membranes fluid. It even helps restore youthful synaptic plasticity.
  • Increasing brain receptor density. Cell membranes are covered with various types of receptors that interact with neurotransmitters, hormones, and other substances and enable messages to be transmitted throughout the central nervous system. PS seems to be important for increasing the density of these receptors.10
  • Releasing secretory vesicles. Neurons communicate across synapses by releasing tiny packets of neurotransmitters called secretory vesicles. PS may play an important role in facilitating this release.11
  • Improving cell-to-cell communication. PS is thought to function as a "first messenger" which may speed up pharmacologic activity and increase the release of neurotransmitters such as dopamine and acetylcholine.9
  • Enhancing cell-to-cell recognition. Cells recognize each other by the antigens and receptors on the outer surface of their cell membrane. The results of animal studies suggest that dietary PS may help normalize age related abnormalities in these receptors.12
  • Regulating cell growth. Nerve growth factor (NGF) is a protein that contributes to cell renewal and proliferation. In animal and in vitro studies, PS has been shown to block the age-related decline in NGF receptors and also to stimulate NGF synthesis and release from nerve cells.13 The process of aging is associated with a decrease in the number of neuronal dendrite spines, which act as a kind of receiving antenna for neuronal signals. PS seems to halt this process. When rats were given PS from the age of 3 months to 27 months (over the course of their adult life span), no reduction in their dendritic spines was observed.14
  • Protecting nerve cells from oxidation. PS may have antioxidant properties that help protect nerve cells from attack by oxygen-free radicals, a major cause of brain aging.15

Preservation of Your Faculties

A typical response of many people to the question, "Do you want to live to be 100?" is, "Sure, as long as my mind stays sharp." Nothing is more frightening than the prospect of your mental faculties, which have been sharp all your life, fading away with old age. Until now, there has been no direct way to prevent this loss; however, new findings regarding the value of brain cell membranes and the important role of PS in preserving their integrity offers hope that life extension can mean more than just keeping the bodily machinery working. It means that the mind can continue to function at peak capacity so that you can experience those extra years with all the sharpness that you enjoyed in the ones that preceded them.

1. Crook T, Tinklenberg J, Yesavage J, Petrie W, Nunzi M, Massari D. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41:644-649.
2. Crook T, Petrie W, Wells C, Massari D. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol Bull. 1992;28:61-66.
3. Cenacchi B, et al. Cognitive decline in the elderly: A double-blind, placebo-controlled, multicenter study on efficacy of phosphatidylserine administration. Aging Clin Exp Res. 1993;5:123-133.
4. Amaducci L, SMID Group. Phosphatidylserine in the dosing of Alzheimer's disease: results of a multicenter study. Psychopharmacol Bull. 1988;24:130-134.
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6. Nerozzi D, et al. Fosfatidilserina e disturbi della memoria nell'anziano. La Clinica Terapeutica. 1987;120:399-404.
7. Palmieri G, et al. Double-blind controlled trial of phosphatidylserine in subjects with senile mental deterioration. Clin Trials J. 1987;24:73-83.
8. Villardita C, et al. Muticentre clinical trial of brain phosphatidylserine in elderly subjects with mental deterioration. Clin Trials J. 1987;24:84-93.
9. Toffano G. The therapeutic value of phosphatidylserine effect in the aging brain. In: Hanin I, Ansell G, eds. Lecithin: Technological, Biological, and Therapeutic Aspects. New York: Plenum Press; 1987:137-146.
10. Zanotti A, et al. Pharmacological properties of phosphatidylserine: effects on memory function. In: Essman W, ed. Nutrients and Brain Function. New York: Karger; 1987:95-102.
11. Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science. 1984;225:1365-1370.
12. Cohen S, Mueller W. Age-related alterations in NMDA-receptor properties in the mouse forebrain: partial restoration by chronic phosphatidylserine dosing. Brain Res. 1992;584:174-180.
13. Nunzi M, et al. Therapeutic properties of phosphatidylserine in the aging brain. In: Hanin I, Pepeu G, eds. Phospholipids: Biochemical, Pharmaceutical, and Analytical Considerations. New York: Plenum Press; 1990.
14. Nunzi M, Milan F, Guidolin D, Toffano G. Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration. Neurobiol Aging. 1987;8:501-510.
15. Latorraca S, et al. Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts. J Neural Transmission. 1993;6:73-77.