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Novel Strategy to Restore Brain Cell Function

May 2006

By Russell Martin

Brain Cells Need DHA and Phosphatidylserine

Phosphatidylserine is the major lipid required to maintain the structural integrity of brain cells. Part of the unique function that DHA plays in protecting the brain involves its role in facilitating the synthesis of structural lipids (such as phosphatidylserine) in nerve cell membranes.16

In the brain, DHA is enzymatically combined with phosphatidylserine (and glyceryl-phosphoryl-choline) to form cell membrane phospholipids needed for nerve cell expansion.17 Substantial laboratory research over the past two decades suggests that phosphatidylserine’s ability to improve cognitive skills is greatly increased in the presence of DHA.

Brain cell membranes are highly enriched with DHA (when DHA is physically available). Dietary DHA deficiency can result in neurological disorders such as depression, memory loss, and dementia.18 Brain cell survival is highly dependent on the availability of DHA to facilitate the incorporation of phosphatidylserine in its membrane.19

Scientists have discovered that DHA attaches itself to phosphatidylserine molecules, and acts as an important ally in the promotion of brain cell energy production. A number of brain researchers, such as Dr. Norman Salem, head of the Laboratory of Membrane Biochemistry and Biophysics at the National Institutes of Health, are convinced that phosphatidylserine with attached DHA is among the most critically important molecules for healthy brain function. Scientists believe that phosphatidylserine supplementation works optimally if DHA levels are kept commensurately high.20

Combining DHA and Phosphatidylserine

In response to an increasing body of research showing the intricate relationship between DHA and phosphatidylserine (PS), scientists have developed a phosphatidylserine (PS)-DHA compound designed to be incorporated directly in the membranes of brain cells. The acronym for this novel compound is PS-DHA.

To evaluate the effects of PS-DHA on memory loss, a study was conducted on middle-aged rats with laboratory-induced accelerated brain aging. Administering traditional sources of DHA did not have an effect on this experimental model, but the group receiving the PS-DHA compound was able to attain a great deal of protection against this neurological challenge. When the brains of these animals were analyzed, there was more DHA incorporated in the cells of the group receiving the PS-DHA than in those receiving other omega-3 agents.3

A randomized, double-blind, placebo-controlled study of humans with attention deficit hyperactivity disorder (ADHD) was conducted using PS-DHA. The aim of the study was to improve behavioral and learning disabilities in patients with ADHD. The psychological evaluation included the Connor’s scoring test and computer-based analysis (T.O.V.A.). At the end of three months, the group receiving the PS-DHA showed a total response of 47% compared to only 19% in the placebo group.3

GPC’s Role in Restoring Cognitive Function

Like phosphatidylserine, glyceryl-phosphoryl-choline, or GPC, is a key structural component of brain cell membranes. GPC is approved as a drug in the European Union, where physicians prescribe it to their patients with dementia and pre-dementia. In the US, however, GPC is available as a dietary supplement.

One of GPC’s cognition-restoring mechanisms is its ability to maintain optimal acetylcholine levels in the brain. The neurotransmitter acetylcholine plays critical roles in memory and other cognitive functions.21

Three double-blind trials have demonstrated GPC’s ability to improve mental acuity in healthy young adults. In studies with middle-aged participants, GPC supplementation led to improvements in several tests of mental performance, including reaction time. Eleven trials to date have focused on the use of GPC in seniors. In studies gauging GPC’s effects on a total of 1,799 participants with minor to severe cognitive deficits, GPC supplementation helped improve memory, attention, and social behavior. Many patients receiving GPC developed renewed interest in relatives and friends, became more capable of self-care, and showed marked improvements in depression, irritability, and emotional function.21

A double-blind, placebo-controlled trial of GPC versus placebo was conducted on Alzheimer’s patients at the National Institute on Aging in Mexico City. Following six months of therapy, participants who took 400 mg of GPC three times daily demonstrated significant improvement on a battery of cognitive tests, including the Alzheimer’s Disease Assessment Scale-Behavioral Subscale. These results suggest that GPC produces marked improvements in Alzheimer’s patients.22

In other promising studies, researchers found that GPC sped recovery and improved quality of life in patients who had undergone surgery. Following bypass and other major invasive procedures, many patients experience problems with cognition, memory, and depression. In four trials with GPC involving a total of 2,804 post-surgical patients, fully 95% showed marked improvement in space-time orientation, degree of consciousness, language, motor capacity, and overall quality of life.22

GPC may be very valuable for patients who have recently suffered head injuries, including subdural hematomas, cerebral contusions, and cerebral concussions. In fact, a 2003 study showed that 96% of the patients with substantial cognitive deficits resulting from their injuries had marked improvement at the end of a three-month period during which they received 800-1000 mg of GPC daily.23

Inhibiting the Acetylcholine-Degrading Enzyme

In recent years, a number of mechanisms of brain aging have been identified, along with potential therapeutic strategies.

As organisms age, an enzyme called acetylcholinesterase increases in the brain. Since this enzyme’s job is to degrade the neurotransmitter acetylcholine, the result of excess acetylcholinesterase can be severe short-term memory-loss problems.

In laboratory experiments in India in 2004, researchers discovered that ashwagandha root extract inhibits acetylcholinesterase, much the same way as Aricept®, a prescription drug currently used in the treatment of Alzheimer’s disease.24 In tests with laboratory mice, ashwagandha demonstrated the ability to promote memory retention in response to experimentally induced amnesia,25 and to protect the brains of laboratory rats against artificially induced stroke.26

Making Old Rat Brains Grow Younger

In groundbreaking studies at Tufts University, laboratory rats (the equivalent of 60- to 65-year-old humans) were fed dried blueberry extract at a dose calibrated to be the human equivalent of one-half cup of blueberries per day. Three other groups of rats received spinach extract, strawberry extract, or a control diet. After eight weeks on the regimen, the investigators evaluated the rats—now equivalent in age to 70- to 75-year-old humans—using various tests of memory function.27

In neuromotor function tests, the blueberry-fed rats significantly outperformed the other groups. These rats were much better able to walk the length of a narrow rod and balance on an accelerating rotating rod compared to the other groups.27

This was indeed a stunning finding within the conventional medical research community, as mainstream scientists have for some time tended to accept as established fact that age-related neuromotor dysfunction is irreversible. These findings appear to flatly contradict this notion. Blueberry extract was clearly capable of reversing this aging process!27

The blueberry-supplemented rats also demonstrated improved learning and memory skills as they navigated mazes and found—and then remembered—the location of an underwater platform on which they could rest from swimming. When scientists examined the brain tissues of these rats, they found that dopamine levels were much higher than in the brains of rats in the other groups. Dopamine is an essential neurotransmitter that enables smooth, controlled movements as well as efficient memory, attention, and problem-solving function. The researchers speculated that blueberry extract might also increase the fluidity of brain cell membranes while reducing levels of inflammatory compounds, thus slowing the brain’s normal aging process.27

These findings have promising implications for aging humans. Older adults tend to fall or stumble—sometimes with catastrophic consequences—because their brains become less adept at monitoring and modulating swaying motion, due to slowing of neural signals in the aging human brain.

Older people likewise tend to suffer memory loss and an inability to learn new behaviors in ways that can starkly limit their ability to lead productive, satisfying lives. By combating the deterioration of memory and neuromotor function that often accompanies aging, blueberries may help support more youthful brain function.