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PHOSPHATIDYLSERINE



"Time bears away all things, even our minds"


(Virgil, ca. 70 B.C.)



Contemporary humans face a major dilema: while we may enjoy longer life-spans than our ancestors, we are also confronted with the unique prospect of physically outlasting our capacities to think and reason. Currently, there are more than 30 million U.S. citizens over the age of 65, and it has been estimated that up to 50% will experience a noticeable decline in their mental abilities when faced with such common daily tasks as manipulating words, recalling names, and maintaining concentration and mental focus. A gradual loss of higher-level cognitive functions can appear in otherwise healthy individuals as young as fifty years of age, and can have a devastating impact on self-esteem, productivity, and general well-being.

Much of the current research being conducted in the field of human memory is aimed at slowing down this gradual loss of cognitive capacity and devising protocols for conserving one's mental abilities. Over the last decade investigators have become particularly interested in Phosphatidylserine (PS), a naturally-occurring phospholipid nutrient with a unique ability to improve cognitive functions and enhance mental ability.

Until recently, Phosphatidylserine was only found in trace amounts (1-3%) in commercial lecithins, in combination with other phospho-lipids such as Phosphatidylcholine, Phosphatidylethanolamine and Phosphatidylinositol. Now Phosphatidylserine is available in 20% (100 mg) doses in 500 mg gel capsules. Phosphatidylserine has been shown to exhibit excellent bioavailability when taken orally, with elevated blood serum levels appearing after about 30 minutes, with subsequent uptake by the liver, and later, the brain.

Extensive human and animal studies have found no danger from long-term supplemental intake of Phosphatidylserine (one study tested dogs fed up to 70 grams of PS per day and found no serious side effects). Phosphatidylserine increases dopamine release which may cause nausea in some individuals if taken on an empty stomach. This can be avoided by taking Phosphatidylserine with meals. It is also advisable to avoid taking PS before going to bed as it may delay the onset of sleep.


Double-Blind Studies

While Phosphatidylserine is essential to the healthy functioning of virtually all cells in our bodies, its highest concentrations are found in the human brain. In this organ it acts upon an assortment of nerve cell functions including: the conduction of nerve impulses; the accumulation, storage and release of neurotransmitters; the activity and number of receptors involved in synaptic discharge; and the maintainence of cellular "housekeeping" functions.

Recent double-blind controlled trials conducted in Europe and the U.S. indicate that dietary supplementation with Phosphatidylserine can play a vital role in supporting human cognitive functions as we age. Among the numerous studies conducted with PS, most were concerned with subjects already experiencing noticeable declines in judgement, abstract thought, memory, behavior, and personality.

In one study conducted by Thomas Crook, in association with Vanderbilt University, Stanford University, and the Fidia Pharmaceutical Corporation of Italy, researchers gave 149 subjects (age 50-75) 100 mg. of Phosphatidylserine three times per day. At the end of the 12-week study, investigators discovered that a cluster of subjects who were the most memory-impaired benefitted the most dramatically from Phosphatidylserine, showing significant improvement in cognitive function. Researchers also noted that some subjects experienced improved mental function up to four weeks after discontinuing intake of Phosphatidylserine.

The investigators noted that, in terms of overall cognitive status, those taking the Phosphatidylserine had "rolled back the clock" by roughly 12 years. In other words, those subjects with a "cognitive age" equivalent to age 64 were restored, on average, to a cognitive age of 52. In the researchers' own words, "The magnitude of effect may be considered significant by many subjects and clinicians" (Crook, et al, Neuro. 41:644-649).

A second study conducted by Dr. Crook's Memory Assessment Clinic, in association with Vanderbilt University and ExPharma of Italy, studied fifty-one subjects aver-aging 71 years of age. At the end of the 12-week study, researchers found that the Phosphatidylserine-treated subjects showed improvements in their abilities to:

  1. Recall names of familiar persons.
  2. Recall the location of misplaced objects.
  3. Recall details from the previous day.
  4. Recall details from the past week.
  5. Maintain mental concentration.
Phosphatidylserine has also been the focus of numerous studies conducted in Europe since 1985. A six week study conducted in 1986 at the University of Liege, Belgium, involved 35 hospitalized subjects (ages 65-91) suffering from mild to moderate memory and cognitive impairment. The authors reported that the group given 300 mg. of Phosphatidylserine per day showed significant improvement in overall cognitive performance. In their report, the investigators commented that, "...the changes observed in the present study reflect an improvement in behavior which can be useful for subjects and their families" (Delwaid, et al., Acta Neurol. Scand, 73: 136-140).

In a trial conducted at three Italian clinics, 87 subjects (ages 55-80 years) suffering from moderate cognitive deterioration were given either Phosphatidylserine (at a dose of 3 x 100 mg per day) or a placebo. Once again the researchers reported that the group receiving the PS benefitted on tests that measured short-term memory, concentration, and attention. Researchers also linked intake of Phosphatidylserine to marked improvements in general life-style, and more specifically, to a lessening of apathy and withdrawal. The authors state, "phosphatidylserine appears to exert an action in two distinct contexts: one relating to the cognitive effects of vigilance, attention, and short-term memory, and the other relating to behavioral aspects such as apathy, withdrawal and daily living...".

A surprising finding from many studies was that Phosphatidylserine at levels as low as 200 mg. per day could still provide beneficial effects as long as three months after the subjects stopped taking it. When all trials are evaluated the results are clear: in mature adults PS may help maintain cognition, concentration, and related mental functions. Any supplemental program utilizing Phosphatidylserine to enhance mental fitness will be still more effective when combined with moderate exercise and a good diet.



Research Summaries: Phosphatidylserine And Brain Function

A 1991 study utilizing EEG's (electro encephalolgraphs) to study the effects of Phosphatidylserine on eight healthy male volunteers ranging from 21 to 28 years of age found that those receiving PS responded with a 15-20 percent elevation in alpha rhythms, indicating elevated acetylcholine/ cholinergic activity in the brain.

In a double-blind trial conducted on elderly women, Phosphatidylserine brought about consistent improvement of memory and behavior (Maggioni et al., 1990).

Mastuno et al. (1990) did an open, placebo-controlled trial on elderly men with disturbances to their daily "clock" (the 24-hour circadian rhythm). Phosphatidyl-serine restored the daily rhythm of thyrotropin (TSH) hormone secretion.

An open, placebo-controlled trial of young, healthy men subjected to exercise-induced stress found that pretreatment with Phosphatidylserine can lower stress hormone production (Monteleone et al., 1992). This confirmed findings from an earlier study (Monteleone et al., 1990).

In 1994, researchers investigating PS in combination with the nerve transmitter GABA (gamma-amino-butyric acid) concluded that human epilepsy may require chronic administration of Phosphatidylserine.



Bibliography

Allegro, L., V. Favaretto, and G. Ziliotto, 1987. "Oral phosphatidylserine in elderly subjects with cognitive deterioration-an open study." Clin. Trials J. 24: 104-108.
Amaducci, L., and the SMID Group, 1988. "Phosphatidylserine in the dosing of Alzheimer's disease" Psychopharmacol. Bull. 24: 130-134.
Bruni, A., and G. Toffano, 1982. "Lysophosphatidylserine, a short-lived intermediate with plasma membrane regulatory properties." Pharmacological Res. Comms. 14: 469-484.
Caffarra, P., and V. Santamaria, 1987. "The effects of phosphatidylserine in subjects with mild cognitive decline." Clin. Trials J. 24: 109-114.
Cenacchi, B., et al., 1993." Aging Clin. Exp. Res. 5: 123-133.
Cocito, L., et al., 1994. "GABA and phosphatidylserine in human photosensitivity: a pilot study." Epilepsy Research 17: 49-53.
Crook, T.H., et al., 1991. "Effects of phosphatidylserine in age-associated memory mpairment." Neurol. 4 1: 644-649.
Crook, T.H., et al., 1992. "Effects of phosphatidylserine in Alzheimer's disease." Psychopharmacol. Bull. 28: 61-66.
Delwaide, P.J., et al., 1986. "Double-blind randomized controlled study of phosphatidylserine in demented subjects." Acta Neurol. Scand. 73: 136-140.
Engel, R.R., et al., 1992. "Double-blind cross-over study of phosphatidylserine vs. placebo in subjects with early cognitive deterioration of the Alhzeimer type." :Neuropsychophamacol. 2: 149-55.
Funfgeld, E.W., and P. Nedwidek, 1987. "Neurohomologous phosphatidylserine in Parkin-sonian subjects with associated disorders of cerebral metabolism." Clin. Trials J. 24: 42-6 1 .
Heiss, W.D., et al., 1994. "Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's Disease." Cognitive Deterioration 5: 88-98.
Toffano, G., et al., 1978. "Modification of noradrenergic hypothalamic system in rat injected with phosphatidylserine liposomes." Life Sciences 23: 1093.
Villardita, C., et al., 1987. "Multicentre clinical trial of brain phosphatidylserine in elderly subjects with mental deterioration." Clin. Trials J. 24: 84-93.
Zannoti, A., et al., 1987. "Pharmacological properties of phosphatidylserine: effects on memory function." In, Nutrients and Brain Function (ed. W.B. Essman), pp. 95-102.

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