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'BRAINBOW'
CLINICALLY PROVEN:
THE DATA
1 THE EFFECT OF SOY LECITHIN PHOSPHATIDIC ACID AND PHOSPHATIDYLSERINE COMPLEX (PAS) ON STRESS
Hellhammer, J., E. Fries, C. Buss, et al.,
Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS)
on the endocrine and psychological responses to mental stress.
The International Journal on the Biology of Stress, 2004. 7(2): p. 119-26.
German researchers have demonstrated that soy lecithin phosphatidic acid and phosphatidylserine are capable of reducing the effects of emotional and physical stress. This discovery is important because many modern syndromes such as, among other things, burnout, alcoholism, certain forms of obesity and premature senility can be associated with stress management.
PHOSPHOLIPIDS
Phospholipids appear in soy beans and other seeds, as well as in eggs, for example. The various phospholipids are phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidic acid (PA) and phosphatidylserine (PS). Phospholipids are made up of one glycerol unit which is bonded with two fatty acids and one or more phosphate groups.
Phospholipids are important for every cell membrane in the human body. They are the essential building blocks for all cells and are made up of a head-shaped water-soluble part and a tail-shaped fat-soluble part.
Phospholipids are arranged in a bilayer because of the fact that the hydrophilic ëphosphate headsí face outwards and the hydrophobic fatty acid tails face inwards. These phospholipids are continually in motion and thus do not form a rigid structure, and the membrane contains large protein molecules, which serve a function in allowing nutrients to pass through.
PHOSPHATIDIC ACID
Phosphatidic acid is a member of the phospholipids group. Phospholipids are for the most part somewhat more complex in structure because extra bases and possibly other groups are connected with them. According to German researchers, phosphatidic acid is the basic phospholipid, and it has received a great deal of attention from researchers during the last couple of years. It may fulfil an active roll in cell membrane processes. Phosphatidic acid also appears to be involved as a neuronal signal carrier [1].
HOW DO THE PHOSPHOLIPIDS WORK AT THE CELLULAR LEVEL?
The three most important phospholipids in the human body are phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidic acid (PA).
Phosphatidylcholine is to be found in the liver in particular, while phosphatidylserine and phosphatidic acid are much more clearly concentrated in the brain.
Phosphatidylserine and phosphatidic acid are important for memory and for the ability to concentrate. Both these phospholipids have the effect of reducing stress and improving mood [2]. Phosphatidylserine and phosphatidic acid are essential for healthy and optimum brain activity.
Phosphatidylserine (PS) and phosphatidic acid (PA) are concentrated in brain tissue cell membranes. Both phospholipids secure glycoproteins and multiple unsaturated fatty acids in the cell membranes and ensure that they remain flexible and permeable, so that the exchange of cell nutrients and waste products is safeguarded. Along with this, phosphatidylserine and phosphatidic acid support the transfer of neural stimuli.
They regulate the storage, issue and activity of neurotransmitters and their receptors, and they influence cell growth, intercellular communication and the activity of signal molecules, ion channels and enzymes.
Phosphatidylserine is not an essential nutrient. The body produces phosphatidylserine from other phospholipids such as phosphatidylcholine and phosphatidylethanolamine. Previously the greater part of the phosphadylserine present in the body came from the food we ate, and organically produced tripe and uncontaminated fatty fish were especially good sources for this. During the last decade the natural availability of phosphatidylserine via our diet has obviously declined. This has to do with the quality of our modern diet and most peopleís preference for ready-made meals which are lacking in an entire series of important nutrients.
Add to this increasing work and environmental stress, and it becomes clear why contemporary ëhealth foodí can no longer guarantee the sufficient provision of vital cellular nutrients.
One of the consequences of this is an extremely high cortisol value in an increasing number of older as well as young people.
STRESS AND THE CONSEQUENCES OF EXCESSIVELY HIGH CORTISOL VALUES
Cortisol is a hormone which is produced in the body in the adrenal cortex (small glands adjacent to the kidneys). Cortisol plays a role in many processes in the body, including in the digestion of food, the immune system and the sleeping-waking rhythm. The secretion of cortisol by the adrenal cortex is increased, for example, also as a reaction to various forms of stress. This can be physical stress, such as illness, injury or extreme temperatures, but it can also be psychological stress (for example, stress at work or verbal violence), which increases the concentration of cortisol.
The secretion of cortisol is regulated by glands in the brain. The hypothalamus sends the chemical CRF (Corticotropic Releasing Factor) to the pituitary gland. As a reaction to this, ACTH (the Adreno-Cortico-Tropic-Hormone) is released in the pituitary gland, which in turn stimulates the secretion of cortisol in the adrenal cortex.
Due to the presence of cortisol in the body, proteins are broken down in the muscles, by which action energy (in the form of glucose) is created. The body can then use this energy in order to deal with physical or mental stress. If there is too much cortisol in the body, in normal circumstances the brain receives a signal about it, and less CRF and ACTH, and thus less cortisol, are produced.
Long-lasting high cortisol levels lead to brain damage, due to which permanent memory and concentration problems and mood disorders can appear. Researchers already knew that people produce more cortisol if their life circumstances are poor and if they think they do not have any control over their lives. Consequently they are ill more often, have a higher blood pressure and have a greater chance of cardiovascular disease and cancer [3].
What is damaging about chronic stress is that the energy-consuming adrenaline system is chronically slowed down due to a permanently heightened cortisol level. This could cause great damage to the body. In particular the hippocampusóthe part of the brain which plays an important role in stressóis sensitive to cortisol. The hippocampus is part of the limbic system and plays a role in remembering situations of stress. In addition, the hippocampus ensures that just the right amount of cortisol hormone is produced in the body. This occurs via the so-called feedback mechanism. As soon as cortisol reaches the hippocampus, a signal goes to the adrenal glands that production can be ceased. If this feedback mechanism must continually come into action, it becomes insensitive to the signals. Consequently the cortisol content of the blood will become too high or, on the contrary, too low. From that moment onwards, temporary or permanent health problems can appear due to stress and the excessive cortisol values associated with it.
THE HELLHAMMER STUDY
This German study [4] clearly demonstrates that specific phospholipids, in the correct dosage, ensure lower cortisol values, a result of which is that people suffer less from stress.
The new research is not the first demonstration that phosphatidylserine has a positive, calming effect upon stress. Benton et al. [2] already showed in 2001 that 300 milligrams of phosphatidylserine had a calming effect on people who were confronted with carrying out mathematical tasks under severe mental pressure. This study allowed the conjecture that phosphatidylserine exerted a beneficial effect on the hypothalamus-pituitary gland-adrenal cortex system (HPA). The German researchers wanted to check whether a patented complex of phosphatidylserine, phosphatidic acid and other phospholipids (PAS) was able to shield eighty healthy people in the age category of 20 ñ 45 years against increased cortisol values during the demanding TSST test. ëTSSTí stands for Trier Social Stress Test.
The entire study lasted four weeks. First eighty volunteer test subjects had the condition of their health thoroughly tested. None of the participants were to be on medication, smoke or be particularly sensitive to stress.
The test subjects were subsequently subdivided into four groups. The first group wouldówithout knowing itótake placebos, a second group received 400 milligrams of phosphatidic acid and phosphatidylserine complex (PAS) per day, a third group took 600 milligrams of PAS per 24-hour period and a fourth group used 800 milligrams of PAS.
PATENTED COMPOSITION OF A PAS CAPSULE
Each PAS capsule was made up of 100 milligrams of phosphatidylserine, 125 milligrams of phosphatidic acid and 270 milligrams of other phospholipids (PC, PI, PE and lyso-phospholipids). This composition was patented in 2002.
Three weeks before the TSST test, all participants received the assignment of taking the PAS capsules or placebo daily. On the testing day, all test subjects first had to rest in the laboratory building for 90 minutes. During this time a catheter was inserted in the forearm in order to be able to take blood samples regularly before and after the stress test. The first rest period of ninety minutes was necessary also in order to exclude any possible activation of the hypothalamus-pituitary gland-adrenal cortex system (HPA). At the end of this rest period the first blood and saliva samples were taken. After this the actual stress test followed, which lasted 15 minutes.
The stress test itself was as follows: Each participant had to take a seat behind a microphone. Before him/her was an examining board of behavioural psychologists who gave the task of giving a speech which was to last five minutes. The participants were to act as if they were applying for an available position. Everyone received only three minutes to prepare his/her text. The participants were also informed of the fact that the conversation would be recorded on video and audiotape. After the speech there immediately followed a second task of five minutes, which involved counting backwards from 2083 to 0 as fast as possible. Each time the number 17 had to be subtracted from the new amount.
Afterwards the participants were required to rest for one hour in the building. Blood and saliva samples were taken at one minute, ten minutes, twenty minutes, thirty minutes, forty-five minutes and one hour following the stress test.
From the results it appeared that the test subjects who had taken 400 milligrams of PAS demonstrated a distinct reduction in the HPA reaction vis-ý-vis the psychological stress caused. The 400 milligram group saw their ACTH rise from 0 to 20 pg per millilitre of blood. The 600 and 800 milligram group displayed an ACTH increase up to 30 pg per millilitre of blood, and the placebo group recorded an ACTH increase up to 50 pg per millilitre of blood.
The cortisol values rose up to a maximum of 40 ng/ml in the 400 milligram group, and up to 70 ng/ml in the 600 and 800 milligram group. The same values were recorded in the people who had used a placebo. Barely 45 minutes after the test, the cortisol value in the 400 milligram group had dropped to 0. The other three groups still displayed cortisol values which fluctuated between 35 and 40 ng/ml.
These research data demonstrate for the first time that 400 milligrams of PAS per 24-hour period can have a cortisol-inhibiting effect on the HPA. The higher PAS doses had insufficient effect. The researchers emphasise that PAS does not eliminate the stress but merely tones it down. PAS also does not appear to interfere with the proper functioning of the hypothalamus-pituitary gland-adrenal cortex system (HPA). According to the results of this study, the test subjects who took 400 milligrams of PAS every 24 hours appear to adapt more quickly, and in a healthier way, to a new stress factor. The lower ACTH and cortisol values may be attributable to this.
These results are promising. They can give occasion for clinical applications in the treatment of stress-related syndromes. Not one of the participants suffered from any side effect during the entire duration of this study [4].
POSTSCRIPT
* Phosphatidic acid was described by Munnik in 2001 as an important signal molecule in plants and animals. In plants, phosphatidic acid is involved in various conditions signalling stress such as dryness, injuries and in the appearance of pathogenic infections. It is formed as a reaction to the stress hormone ethylene and the plant hormone ABA (abscisic acid). In plants, phosphatidic acid is produced ten minutes after a stress reaction which is caused by osmotic, oxidative, pathogenic or hormonal stress.
REFERENCES:
(1). Lee, Y.N., H.Y. Lee, H.K. Kang, et al., Phosphatidic acid positively regulates LPS-induced differentiation of RAW264.7 murine macrophage cell line into dendritic-like cells. Biochem Biophys Res Commun, 2004. 318(4): p. 839-45.
(2). Benton, D., R.T. Donohoe, B. Sillance, et al., The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor. Nutr Neurosci, 2001. 4(3): p. 169-78.
(3). Talbot, P.S., The molecular neuroimaging of anxiety disorders. Curr Psychiatry Rep, 2004. 6(4): p. 274-9.
(4). Hellhammer, J., E. Fries, C. Buss, et al., Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress, 2004. 7(2): p. 119-26.
© Nutrience, an initiative of Springfield Nutraceuticals
2 PHOSPHATIDYLSERINE: SPECIAL NUTRITION FOR BRAIN CELLS
DETERIORATION OF BRAIN FUNCTIONS DUE TO AGEING
Memory and learning processes allow us to store new information for later retrieval. Current theory is that information is stored as a pattern in neurons the brain cells that make up the brain. As from the age of 30, our memory functions deteriorate. Such deterioration can be as high as 50% at a senior age (80-90). This memory loss is probably caused by changes in some brain functions and the Œnormal¹ decrease of cellular metabolism.
PHOSPHATIDYLSERINE AND ITS ROLE IN THE BRAIN
One of the most conspicuous substances which decreases as the body gets older is phosphatidylserine, one of the major phospholipids in the brain cells. Phospholipids have a vital biological function: they form the basis of all biological cell membranes. Although phosphatidylserine is especially concentrated in the brain and in nerve tissue, it is indispensable for all cells of the body. Phosphatidylserine is a negatively charged phospholipid. It is located on the inside of cell membranes and keeps these liquid and stable. Generally speaking, the consumption of phospholipids appears to fall short of the recommended daily allowance. It is therefore advisable to add these substances as a food supplement.
MAIN EFFECTS OF PHOSPHATIDYLSERINE
Activates protein-kinase C, an important enzyme that has been proven to decrease in the ageing brain.
Increases acetylcholin receptors in the brain. Acetylcholin is a neurotransmitter and plays a large role in the autonomous nervous system.
Increases dopamine release. Dopamine controls the activity in the brain and has an inhibitive effect, so that one does not get too many impressions to process.
Produces better stimulus transmission. This is also related to the production of such neurotransmitters as acetylcholin and dopamine in the synapses between nerve cells and dendrites (branched protrusions of the nerve cells which guide the stimuli towards a cell body.)
Possibly provides a signal function for the immune system, allowing it to determine which cells are old or unhealthy and therefore need to be replaced by new ones. Although this has not been extensively tested in clinical practice, it is known by researchers.
Increases glucose metabolism. Approx. 30% of all glucose in the body is used as nutrition for the brain.
The brain continuously uses large quantities of energy. Any organ which uses so much energy is sensitive to damage by free radicals. It seems that also phosphatidylserine has an antioxidant, free-radical suppressing effect on the receptors of brain cells. The effects of phosphatidylserine can help to prevent the age-related decrease of cognitive functions. Phosphatidylserine also has a local antioxidant effect at receptor level. It prevents these receptors from being restricted in their function and allows an increase in the synthesis and release of growth factors.
BACKGROUND AND AVAILABILITY OF PHOSPHATIDYLSERINE
Since the 1970s, worldwide scientific research has been carried out into the effect of phosphatidylserine. Human studies, which were started only in the 1980s, have been made in renowned institutions (mostly in Italy) among healthy senior citizens and those suffering from senile dementia and Alzheimerís.
Without exception, all studies (totalling several dozen) demonstrated phosphatidylserineís positive effect. There were improvements in such abilities as recalling names and faces, concentration, orientation, memory for
numbers and other cognitive functions. All studies used memory tests generally recognized by the scientific community.
Whereas previously phosphatidylserine could only be obtained from animal sources, an Israeli research team in cooperation with the Weizman Institute of Science managed to use an enzyme reaction to obtain concentrated phosphatidylserine from soy lecithin. Usually, soy contains such a small quantity of phosphatidylserine that it has hardly any effect. The enzymes from Savoy cabbage produce an effective quantity in an entirely natural process. Phosphatidylserine taken orally provides excellent bioavailability.
AGE-RELATED MEMORY REDUCTION
Memory reduction is associated with ageing. The phenomenon can be unpleasant for both the individual and his/her family, and can adversely affect the self-confidence and self-respect of the person concerned. The age-related decrease of such mental functions as memory, learning ability and alertness parallels the decrease of phosphatidylserine. The effects of phosphatidylserine on cognitive functions is surprisingly positive. Recent double-blind studies in Europe and the US have proved that phosphatidylserine suppletion can play a vital role in supporting cognitive functions during ageing.
A double-blind clinical study by Dr Jacob Gindin (head of the Geriatric Institute of Education and Research at Kaplan Hospital, Rehovot, Israel) compared a group of 72 healthy individuals aged between 60 and 80 years over a period of three months. Half received a placebo and the rest were given the phosphatidylserine preparation developed in Israel (100 mg of phosphatidylserine). Two of the parameters used were the Wechsler memory test and the List of Depressive Symptoms. The results indicated a strong and important positive effect of the treatment on both memory and attitude. The powers of memory and observation most enhanced by the treatment were the recall of information, visual memory (faces, situations, etc.) and the recollection of numbers. Also the subjectsí attitude improved. So-called autumn depression developed in the placebo group, but not in the group treated with phosphatidylserine.
One of the most striking improvements during this study occurred in a 70-year-old kibbutz telephone operator. Over the years, he had had to make increasing use of the telephone directory in order to connect incoming calls; just before the study started, he could not work at all without the directory. During the study, however, he managed to connect all calls without using the directory.
The positive effect of phosphatidylserine on healthy senior individuals has been confirmed by several earlier studies, such as that by Crook et al. (1991). This study, which was carried out in cooperation with Vanderbilt University and Stanford University, involved 149 individuals aged between 50 and 75, and
lasted 12 weeks. Subjects received a daily dose of 3 x 100 mg of phosphatidylserine, or a placebo. The researchers found that a cluster of individuals who suffered the most from memory loss derived the most benefit from phosphatidylserine. It was remarked that in terms of cognitive status, those who had taken phosphatidylserine had had ìîtheir clock turned back 12 yearsî.
ALZHEIMERíS AND DEMENTIA
Senile dementia and Alzheimerís are progressive degenerative diseases, for which there is no cure. Current treatments are almost exclusively based on alleviating those symptoms that can improve the quality of life. The following is from the literature on Alzheimerís.
Transmitter replacement therapy could also reduce the extended pathology in the various stages of Alzheimerís disease by encouraging the production of neurotransmitters. This therapy could be used to
influence neurons which release various neurotransmitters, such as acetylcholin, norepinephrin, serotin,
somatostatin and glucamat (Selkoe 1992). These findings have been confirmed scientific studies as carried out by Dr J. Gindin at Kaplan Hospital, Rehovot, Israel (1996).
In this study, Alzheimerís patients were given a daily dose of 300 mg of phosphatidylserine. The study lasted two months and involved 94 subjects. The group treated with phosphatidylserine showed clear mental and physical improvement, whereas most individuals in the placebo group deteriorated, as is normal for those suffering from the disease. The difference between the two groups was more pronounced in patients in the early phase of the disease. However, other scientific studies have produced the opposite results, i.e. in a later phase of Alzheimerís, suppletion with phosphatidylserine was seen to provide more benefits. The parameters used were based on medical aspects and comprised a study of both mental and physical health and wellbeing. The improvements were especially expressed in the recognition of faces and persons, restoration of the day and night rhythm, sanitary needs, etc.
Case story: A man suffering from Alzheimerís was deteriorating rapidly to the point of becoming aggressive. After six months of 3 x phosphatidylserine per day, his wife stated that he had become calmer, his responses were more alert and the deterioration had stopped.
The study in Israel was carried out using vegetable phosphatidylserine. Previous studies had been carried out using the animal version of phospatidylserin. T.H. Cookís Memory Assessment Clinic in cooperation with Vanderbilt University studied 51 Alzheimerís patients for 12 weeks. The group treated with phosphatidylserine showed an improvement in some cognitive functions.
P.J. Delwaide of the University of Luik (Belgium) also studied the effect of phosphatidylserine on 35 clinical patients (aged 65-91), all of whom were suffering from mild to fair deterioration of memory and perception. The group treated with 300 mg of phosphatidylserine a day showed a considerable enhancement of cognitive functions.
It is clear that a great deal of study into dementia and Alzheimerís still needs to be done. In the case of brain cells dying, it seems important to supply especially healthy brain cells with additional nutrition in the form of phosphatidylserine supplements.
Thanks to the high production of acetylcholin, phosphatidylserine can in some cases help improve cognitive functions. A daily dose of 3 x 100 mg in combination with 395 mg of other phospholipids and glycerids seems to have the best effect. Researchers consider it pointless to increase the dose.
OTHER APPLICATIONS
Researchers have discovered another positive effect of phosphatidylserine, one partly related to stress hormones. As yet no direct link has been made, but there are indications that phosphatidylserine will allow for a better response to physical stress and for better control and balance of stress hormones. In a study involving top athletes (especially weight-lifters), cortisol levels dropped by up to 35% after taking 400-800 mg of phosphatidylserine an hour before engaging in heavy physical effort. In addition to its preventive use, phosphatidylserine is prescribed by some doctors for patients suffering from a wide range
of conditions, for example, brain infarction, consequences of coma, whiplash, learning problems, dyslexia, and brain damage due to accidents.
CONTENT/USE/SIDE EFFECTS
Each capsule contains 100 mg of phosphatidylserine and 395 mg of other phospholipids (e.g. cholin, lecithin, ethanolamin and phosphatidic acid). Phosphatidylserine can successfully pass the blood-brain barrier. Under normal conditions, it is advisable to start with 3 x one capsule a day taken with meals for 6-8 weeks. Healthy senior individuals can then reduce the dose to 2 capsules a day, and later possibly to
1 capsule a day for maintenance purposes. In other situations, it is advisable to continue to take 100 mg of phosphatidylserine 3 x a day.
Researchers consider it pointless to increase the dose of phosphatidylserine beyond 300 mg a day. For those aged up to approximately 50 years, it is advisable to take 2 x one capsule a day for 4-6 weeks, and thereafter 1 x one capsule a day. A very gradual change occurs after starting to take phosphatidylserine. Possibly, the change will be hardly noticeable because slight improvement occurs each day. However, after 6 months, the difference will be much more clear. Raised blood serum levels occur approximately 30 minutes after intake,
with consecutive absorption by the liver and later by the brain. It is advisable to take phosphatidylserine continually. If stopped, the effect will gradually disappear.
No side effects were established during the studies. Phosphatidylserine and the other phospholipids are entirely vegetable-based. A study carried out on rats which were given a considerably larger daily dose of phosphatidylserine than that given to humans did not show any side effects. It was remarkable that in human studies, those using phosphatidylserine supplements did not suffer from depression (especially so-called autumn depression). This applied only to individuals suffering from slightly depressed feelings.
Since phosphatidylserine causes the release of acetylcholin and dopamine, some users may develop slight stomach problems if they take phosphatidylserine between meals. It is therefore advisable to take it during or immediately after meals. Preparations with phosphatidylserine are food supplements, since they are completely composed of vegetable matter.
PREVENTION
Phosphatidylserine possibly has an important role to play in providing long-time suppletion in order to help prevent long-term degeneration, as discussed above. Recent double-blind studies in Europe and the US were based on the theory that phosphatidylserine suppletion can play a vital role in supporting cognitive functions during the ageing process. Loss of nerve tissue leaves us with fewer paths along which to transmit nerve signals. Such loss means less clarity, poor memory or information retrieval, less mental activity, etc. Generally speaking, in all these areas phosphatidylserine helped to combat both age-related memory loss and age-related depression. A wide range of age-related cognitive reductions (memory, posture, attitude, etc.) seemed to be improved by phosphatidylserine.
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