Disarming Mental Stress, A Memory Killer



* Emotional stress, when sustained for long periods, will kill brain cells and increase the risk for dementia. The mechanisms are well-known.

* Taking PS made it easier for young volunteers to handle the stress of doing mental arithmetic without a calculator.

* PS can partially rejuvenate the stress coping mechanisms in older people.

* By taking PS and practicing total health management, it is possible to lessen the ravages of stress on the brain and likely lower the risk of dementia.

Mental ("emotional") stress could be the most underrated cause of suffering, lost productivity, and premature death in modern society. Also, solid research has shown it is an awesome destroyer of memory. Stress sustained over a long period causes chronic, abnormal elevation of circulating stress hormones that can kill off brain cells. From this negative effect of emotional stress can come increased risk for dementia.

All living things practice homeostasis--the ability to maintain the constancy of their internal environment. Homeostasis is essential to maintain life, and our brain tissue must maintain homeostasis along with all our other tissues. For our enzymes and other catalytic biomolecules to work at their best, the physical and chemical conditions must be held very close to constant.

Any agent or factor that threatens to disrupt homeostasis is called a stressor. Too much of almost anything can become a stressor. According to the now-classic understanding of stress pioneered by Professor Hans Selye,(n42) a manageable amount of challenge to homeostasis is good "practice" for stress management--this he called eustress. But stressors that are too powerful can push the system far out of balance and threaten to exceed the body's capacity to return to homeostasis. Stress to this extreme degree (distress) can trigger disease or even cause death. Common human stressors include heat, cold, dehydration, starvation, lack of sleep, toxic exposures, infections, radiation, vibration, noise, and emotional challenges of whatever sort.

Along with other higher animals, we humans have what is called The Stress Response. It helps us survive any of these stressors (or combinations of them) that seem to pose an immediate challenge to survival. It was probably very important in keeping our species around for this long. It involves a cascade of physiological adjustments that occur rapidly and on demand. This cascade is normally mediated mainly by the hormone cortisol.

The classic Stress Response develops as the brain's hypothalamus region perceives the threat, then stimulates the pituitary master gland to secrete ACTH (AdrenoCorticoTropic Hormone), which hormone in turn pushes the adrenals to secrete cortisol into the blood. These glands, acting in coordination, are called the Hypothalamic Pituitary Adrenal Axis, or HPAA for short.

The HPAA helps the body successfully handle a stressful incident or situation, but it was designed to be sustained only for a short time, on the order of minutes or hours or possibly days, not for weeks and months or years. Faced with sustained emotional stress, the human body will successfully adapt at first, but as time goes by, this adaptation can run out of energy. As a consequence, long-term stress of any kind is bad for our bodies, but high cortisol over a long period can have an especially bad impact on our brain cells.

Fight or Flight: Good Thing That Can Go Bad
The human Stress Response is a version of the animal Fight-or-Flight Response, a fundamental biological response to a stressful situation. It has the needed effect of activating and coordinating the body's organ systems to cope with a short-term emergency, then to return to the normal way of living as quickly as possible. But in today's chaotic world, the emergencies that confront us are too often long-term rather than immediate. This makes for a problem--when fight or flight has to be sustained, it can deplete the body's resources and move it in a frighteningly negative direction.

The human brain is a gas-guzzling organ. With only 3 percent of the body's mass, the brain at rest consumes more than 20 percent of the body's energy. With intense mental activity the brain can be using as much as 60 percent of the body's energy. The nerve cells are the body's largest cells--motor nerve cells can reach four feet long, for example. They are also our busiest cells--their constant electrical activity demands a lot of energy. This is what makes them so vulnerable to poor circulation or lack of oxygen. High cortisol in the brain from stress has this very effect.

As the body prepares for fight-or-flight, cortisol is released into the circulating blood. Cortisol increases blood flow to the muscles (to fight or flee!), and to come up with this extra blood it reduces the blood going to the brain. However, the brain has such a high demand for blood circulation to supply the nerve cells that maintaining fight-or-flight beyond a mere few minutes can threaten the brain's ability to continue to function.

The nerve cells of the hippocampus and cortex brain regions are our best and brightest cells--they initiate and consolidate experiences into memory. But they are extra vulnerable to high cortisol. Continued high levels of circulating cortisol have been shown to cause the hippocampus to shrink ("atrophy"). As this brain region loses functional circuits, so also does its owner lose the capacity to make new memories.

Emotional stress can act synergistically on the hippocampus with other stressors. The nerve cells are highly vulnerable to "free radicals" and other toxins because they carry high amounts of fats in their outer insulation (myelin). These fats are easily destroyed by mercury, lead, or other heavy metals, by solvents and other organic environmental pollutants, and by any number of other toxic substances.

The brain is equipped with antioxidant defenses to help protect against such stressors, but these can be compromised by poor eating habits, lack of exercise and poor circulation, blood sugar fluctuations, over-consumption of prescription drugs, and many other deleterious factors. All these factors are stressors that compound the damage from emotional stress.

A number of controlled trials and other human studies have been done with PS for stress. Their findings suggest that taking PS can make a real difference in our capacity to manage a stressful challenge while keeping our stress hormones from getting out of control.

PS Helps Students Manage Mental Stress
Dr. David Benton of the University of Wales is a famous researcher on nutrition and mental performance, and has published many groundbreaking studies on children and other youth. In 2001, together with colleagues, he published a double blind trial that indicated PS improved mental performance in some of his male students whom he experimentally subjected to stress.(n43)

Forty-eight male university students, average age 20.8 years, were randomly divided into a PS test group (300 mg/day) and a placebo group. Each student's "baseline" mood--how he felt over the previous week--was assessed by questionnaire, and a mood score developed from it. They also were scored for "neuroticism" and "extroversion." Blood pressure, pulse, and heart rate were recorded, then each subject was sent home with a 30-day supply of PS or placebo at three capsules per day.

After 30 days of supplementation the subjects returned to the laboratory. They reported their mood over the last week of supplementation. They then faced a standard acute stress test: a challenging mental arithmetic calculation to be done within four seconds, and without a calculator! Their heart rates increased during the test and this combined with the students' self-reports to confirm that they did find the test stressful. After the test was completed, their blood pressure was recorded and their mood assessed again.

The results showed that those students with a more "neurotic" personality experienced significantly less stress from the test, if they were on PS. Those who had been receiving only placebo reported a highly significant level of stress from the test and experienced a highly significant worsening of mood (p<0.001). Their counterparts who got PS did not deteriorate in mood.

Individuals who score high on tests for neuroticism are known to respond more poorly to stress, and typically report more distress in daily life. In this trial, the "neurotics" who took PS were not significantly stressed by the test. Their mood remained stable; they scored significantly better on feeling clear-headed, composed, and confident. Through taking PS they were better able to deal with the time-limited challenge of doing mental arithmetic the old-fashioned way.

PS Revitalizes the Stress Response in the Elderly
Other clinical research indicates PS may help revitalize fading HPAA function in the elderly, to help them cope with their perceived mental stress.

The Dexamethasone Suppression Test can be used to test how well the stress response works in an aging person. In young, healthy people 1 mg of dexamethasone (a synthetic glucocorticoid that resembles cortisol) suppresses the production of cortisol and other adrenal steroid hormones linked to the stress response. This suppression usually lasts for more than 24 hours. But many older people do not show this suppression by DEX. Called Early Cortisol Escape, this phenomenon is thought to indicate deterioration of the HPA axis in the elderly.

Dr. Dina Nerozzi and co-researchers at the University of Rome found that by giving PS supplements (at 300 mg per day) to elderly men and women for 60 days, they could restore the youthful capacity for DEX suppression.(n44) They suggested that PS was restoring faded pituitary function, either by stimulating nerve cells to organize into new networks and/or by returning brain chemical transmitter levels toward a more youthful balance.

In their study with depressed elderly patients, Rabboni's group in Milan had some patients who showed poor DEX suppression at the start.(n36) After being on PS at 400 mg per day for 60 days, all nine of these patients had their capacity for DEX suppression restored. These researchers were so impressed with PS that they commented, "Phosphatidylserine could open the way to a new therapeutic conception: the possibility of influencing the complex inter-relations between the neurological, immunological and endocrine systems."(n36)

PS Partially Rejuvenates Aging Brain Rhythms
In addition to revitalizing the aging hypothalamic-pituitary-adrenal axis, PS helps "tune up" the body's 24-hour daily "circadian" rhythms. As we age, these rhythms tend to become less synchronous, resulting in sleep problems and sometimes also hormonal imbalances. This loss of rhythm seems linked to pituitary gland decline, and probably also to decline of the brain's hypothalamus that supervises the pituitary.

Normally the "master" pituitary gland secretes a variety of hormones that coordinate these cycles by stimulating other glands to release other hormones. One important pituitary product is TSH, Thyroid Stimulating Hormone. TSH stimulates the thyroid gland to release thyroxin, which boosts metabolism. Masturzo and collaborators did a randomized, placebo-controlled trial on institutionalized elderly men with abnormally low TSH hormone secretion. (n45)

Going into the trial, these 20 elderly male patients (ages 65 to 85, average age 73.7) were secreting TSH but at lower than youthful levels, and they did not have the youthful circadian rhythm.(n45) The older they were, the more random was their pattern of TSH release. Ten (10) of these older men received PS (at 400 mg per day) for 30 days and 10 received a placebo. Another six men, ages 21-31 (average age 22.3 years), served as youthful controls and received no treatment. After 30 days, the elderly men who received PS showed a circadian rhythm of TSH secretion. Their circadian rhythm was comparable with the young male adult controls (mean age 22.3 years). Those elderly men who received only placebo showed no improvement of their random secretion.

Masturzo and her colleagues suggested that PS was working at the level of cell membranes to cause this rather remarkable benefit. As we recognize the benefits of PS for mental stress, we can recall that being an orthomolecule, PS naturally has a pro-homeostatic, anti-stress influence. Consider that PS works from the cell membrane level throughout the entire cell. Because it is naturally present in all our cells, its beneficial actions on single cells are amplified to benefit the body as a whole.

So PS can be working simultaneously in the hypothalamus, the pituitary, the adrenals, and elsewhere in the organs to keep our life processes within normal limits. Dietary supplementation with PS can help correct functions that are too low and lower them when they are too high. By these means PS can boost a weakened stress response in the elderly person and calm the tendency to exaggerated stress response in the young person.

Why Don't Zebras Get Ulcers? Or Dementia?
Stanford professor Robert Sapolsky has spent much of his career studying animals under stress in the wild. His book Why Zebras Don't Get Ulcers (n30) brilliantly answers its own question.

When the zebra senses a predator, its stress response goes into action. Adrenaline and noradrenaline surge into the bloodstream. Glucose comes surging out of storage tissues into the blood, to provide instant energy. The heart beats faster, the breathing rate increases, to get more oxygen and nutrients to the tissues. Stress hormones divert blood flow away from the brain and into the muscles, to help flee the imminent danger.

For this few minutes that it takes to escape the oncoming lion, the zebra's physiology is controlled by the stress response. Its higher brain functions give way to naked instinctual behavior in order to escape this danger. Then things calm down; having outrun the lion, after just a few minutes the zebra can return to meditating as it grazes.

For humans, the situation is different. The zebra only has stress as a short-term, occasional event, while we modern humans face continual, unrelenting stress. Most of us live in a state of stress almost all the time. Unfortunately, our biological means for coping with stress have remained basically the same as the zebra's. Prof. Sapolsky asks wryly, "How many hippos worry about whether Social Security is going to last, or even what they are going to say on a first date."

The work of Sapolsky, along with that of Lupien on humans,(n29) and many other researchers, joins with Selye's to send a clear message: for humans under sustained stress, the physiological fight-or-flight response becomes pathologic. It drives the individual into disease. We become mental casualties of chronic stress.

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