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1、Phosphatidylserine(PS)-The brain nutrient for all ages,Dr.Ralf JgerDirector of R&D Degussa BioActivesApril 2002,LECI-PS-The importance of brain functions,Hi,I am Bob.Its a pleasure to meet you.Oh,we met before,and can even save lives.,Of course I remember Sarahs phone number:Its 217-352-58.5843.or 5
2、843 or.,Our anniversary is TODAY?,But I thought you loved seafood.,Good memory and cognition are important for todays business and private life.,No Teresa,I gave you back your stapler.I think.,LECI-PS-The brain nutrient for all ages,INTRODUCTION AGE-RELATED COGNITIVE DECLINE improving brain function
3、s that tend to decline with age ATTENTION DEFICIT HYPERACTIVITY DISORDER improving attention span,concentration,academic performance and hyperactivity SPORTS NUTRITION natural cortisol control,train hard-train smart MENTAL STRESS improves stress resistance in healthy young students,Definition,Defini
4、tion of Lecithin and PhospholipidsLecithin(scientific)Phosphatidylcholine(1,2-diacyl-sn-glycero-3-phosphocholine),Lecithin(commercial)Complex mixture of polar lipids(phospho-and glycolipids),traces of carbohydrates and triglycerides derived from animal or plant source,PhospholipidsPhosphorus contain
5、ing lipid(substances that dissolve in non-polar solvents(“fat-soluble”),functional ingredients of Lecithin,Phospholipid Structure,Hundreds of different phospholipid(PL)molecules have been described,but the major types are the phosphatidyl-phospholipids,Head:Chemical subgroup(R)and Phosphate,H,2,C,C,
6、H,C,H,2,O,O,O,P,O,O,O,R,F,a,t,t,y,A,c,y,l,F,a,t,t,y,A,c,y,l,Unique property:Head:Carries a charge,mixes with waterhydrophilic,Basic structure,Backbone:Glycerol,Two Tails:Fatty acid chains,Tail:No charge,does not mix with waterhydrophobic,What determines the Phospholipid Physiology?,Type of head grou
7、p(type of phospholipid)cholinephosphatidylcholine(PC)inositolphosphatidylinositol(PI)serinephosphatidylserine(PS)Type and compositions of fatty acids(source)Soya-PL:essential fatty acids(linoleic,linolenic)Egg-PL:long chain polyunsaturated fatty acids(ARA,DHA)Dosage(quantity)Type and form of adminis
8、tration,Cell exterior,PS,PS,PS,PS,PS,PS,PS,PS,PS,PS,PS,PS,PS,PS,PS,Cell interior,Protein,Glycolipid,Glycoprotein,Key cell membrane building block(PS is predominantly found in brain and nerve cells)membrane fluidity enzyme activity enhances transmitters(release,receptor actions)nerve cell homeostasis
9、 regulation(e.g.enzymes),Functions of PS,Functions of PS,Impulse Transport across the Synaptic Gap,INTRODUCTION AGE-RELATED COGNITIVE DECLINE improving brain functions that tend to decline with age ATTENTION DEFICIT HYPERACTIVITY DISORDER improving attention span,concentration,academic performance a
10、nd hyperactivity SPORTS NUTRITION natural cortisol control,train hard-train smart MENTAL STRESS improves stress resistance in healthy young students,LECI-PS APPLICATIONS,What is Age Related Cognitive Decline?,diagnostic term for memory loss in elderly people who are clinically healthy,physiological
11、process,occurs during middle age and later life,Results in:impaired capacity to recall names,faces and numbers,Age Related Cognitive Decline(1),1.American University Sampling2.Crook,T.H.&West,R.L.(1990),British Journal of Psychology,81,335-349.,Memory decline from age 25Remembering Names Immediately
12、 After Introduction 1,2,Age Related Cognitive Decline(2),THREE THEORIES OF AGINGBiochemical and structural changes during the aging process:,Age Related Cognitive Decline(3),MEMBRANE HYPOTHESIS OF AGING Changes in lipid composition and content in the cell membranes(increase of Cholesterol content in
13、 cell membrane)decrease in membrane fluidity results in reduced enzyme activity,reduced receptor function,etc.,CHOLINERGIC HYPOTHESIS OF AGING reduced synthesis and release of neurotransmitters,MORPHOLOGICAL HYPOTHESIS OF AGING decrease in synaptic density,death of nerve cells,Age Related Cognitive
14、Decline(4),Examples of cell culture and animal trails on how PS benefits all three hypotheses of aging(mechanistic investigation on how PS benefits age-related cognitive decline)MEMBRANE HYPOTHESIS OF AGINGCHOLINERGIC HYPOTHESIS OF AGINGMORPHOLOGICAL HYPOTHESIS OF AGING,Age Related Cognitive Decline
15、(5),MEMBRANE HYPOTHESIS OF AGINGIncreased Cholesterol to Phospholipid ratio results in alteration of fluidity/viscosity(enzymatic activities,receptor functions,membrane carriers,neuronal electrical properties)has a negative influence on neurotransmisson negative impact on cerebral functions(behavior
16、,learning,memory)PS normalizes Cholesterol/PL ratio(restoration of membrane fluidity and composition),MORPHOLOGICAL HYPOTHESIS OF AGING Dendritic spine loss studied in rats:death of nerve cells decreased density of nerve cell interconnections(loss of dendrites),Source:Neurol.Aging 8,501-510,1987,Age
17、 Related Cognitive Decline(6),The effect on PS on dendrites Chronic treatment with PS prevents the age-related reduction in dendritic spine density in rat hippocampus,Age Related Cognitive Decline(7),Age Related Cognitive Decline(8),CHOLINERGIC HYPOTHESIS OF AGINGNeurotransmitter deficit Multiple ne
18、urotransmitter deficits have been implicated in memory and attention loss,in particular in aged people.PS supplementation restores neurotransmitter release,ChAT-positive cells,*,*p 0.05vs.young,Examples of animal and human clinical trails on the effect of PS on Age-Related Cognitive DeclineProof tha
19、t observed effects in animal and cell culture trials have a beneficial effect in humans,Age Related Cognitive Decline(9),*,*,Animal trials(an example)Effect of chronic treatment with PS on Morris Water Maze,Age Related Cognitive Decline(10),Age Related Cognitive Decline(11),Human trials:how to test
20、brain functions?A self-test.Are you in need of Leci-PS?NAME-FACE ASSOCIATION TEST FIRST-LAST NAMES TEST,NAME-FACE ASSOCIATION TEST,Norman Janice Christine,Phyllis Henry James,Look at the following faces and names.Take a few seconds to study each one.Than turn to next page.,NAME-FACE ASSOCIATION TEST
21、,1._ 2._ 3._,Please write the name corresponding to each face.,4._ 5._ 6._,NAME-FACE ASSOCIATION TEST,1.Christine 2.Henry 3.Phyllis,Please check if your answer was correct.The correct names:,4.Norman 5.James 6.Janice,FIRST-LAST NAMES TEST,Please read the first and last names.Than turn to next page.D
22、enise JacksonGary RobinsMargaret TaylorPeter Johnson,FIRST-LAST NAMES TEST,Please write the first name that corresponds to each last name:_ Taylor_ Jackson_ Johnson_ Robins,FIRST-LAST NAMES TEST,The correct first names associated with each last name are listed below.Please check if your answer is co
23、rrect.Margaret TaylorDenise JacksonPeter JohnsonGary Robins,HOW DID YOU DO?NAME-FACE ASSOCIATION TEST AGE Average Score 18-29 6 30-39 5 40-49 4 50-59 3 60-69 2-3 70+1-2FIRST-LAST NAMES TEST AGE Average Score 18-29 3 30-49 2 50-69 1 70+0-1,NAME-FACE ASSOCIATION TEST,Delwaide et al.(1986):Senile demen
24、tiaRansmayr et al.(1987):Mild to moderate age-dependent cognitive dysfunction with evidence of arteriosclerotic encephalopathyPalmieri et al.(1987):Senile mental deteriorationVillardita et al.(1987):Moderate senile deterioration of cognitive functionAmaducci et al.(1988):Alzheimers disease and relat
25、ed cognitive disorders Herrmann and Dietrich(1988):Age associated memory impairment(AAMI)Hippius et(1990):Mild primary degenerative dementiaCrook et al.(1991):Age associated memory impairment(AAMI)Engel et al.(1992):Early dementia of Alzheimer typeCenacchi et al.(1993):Cognitive impairmentHeiss et a
26、l.(1994):Neuropsychological,EEG and PET investigationGindin et al.(1995):Age associated memory impairment(AAMI)Crook et al.(1998):Age related cognitive disorder(ARCD),Double-Blind Human Clinical trials(examples),Age Related Cognitive Decline(12),Double-Blind Human Clinical trials(examples),Age Relat
27、ed Cognitive Decline(13),Double-Blind trial for Memory with PSMagnitude of effects beyond those of Placebo,Source:Anti-Aging Therapeutics Vol.II,pp.20-29,1998,300 mg LECI-PS for 12 weeks 50 patients(mean age 60.5 years),Age Related Cognitive Decline(14),Effects of PS on brain metabolism,PET imaging
28、of the brain of a 59-year-old female shows intensity of glucose metabolism in different regions of the brain,Top:before PSBottom:after 500 mg PS daily for three weeks,Source:Dementia 1,197-201,1990,Age Related Cognitive Decline(15),PET imaging of brain,How does PS work?-a summary on the mechanisms h
29、ow PS improves brain functions that tend to decline with age(from cell culture experiments,animal and human clinical trials)Improves brain glucose metabolism CHOLINERGIC HYPOTHESIS OF AGING stimulates acetylcholine synthesis in the brain cascading effects on signal transductionMEMBRANE HYPOTHESIS OF
30、 AGING normalizes Cholesterol to Phospholipid ratio in membranes improves receptor functions stimulates activity of ion pumpsMORPHOLOGICAL HYPOTHESIS OF AGING reverses age associated nerve cell dendrite loss,Age Related Cognitive Decline(16),Quotation Thomas H.Crook,Ph.D.,“For several multinational
31、pharmaceutical companies I have tested 17 substances which have shown promising results in animals-but not a single one was successful in humans-except Phosphatidylserine.”(Psychologist,Head of two US memory assessment clinics,Director National Institute of Mental Health),Age Related Cognitive Decli
32、ne(17),LECI-PS APPLICATIONS,INTRODUCTION AGE-RELATED COGNITIVE DECLINE improving brain functions that tend to decline with age ATTENTION DEFICIT HYPERACTIVITY DISORDER improving attention span,concentration,academic performance and hyperactivity SPORTS NUTRITION natural cortisol control,train hard-t
33、rain smart MENTAL STRESS improves stress resistance in healthy young students,ATTENTION DECIFIT HYPERACTIVITY DISORDER,WHAT IS ADHD?Attention Deficit Hyperactivity Disorder(ADHD)is a syndrome which is usually characterized by serious and persistent difficulties resulting in:-poor attention span(inat
34、tention)-weak impulse control(impulsivity)-hyperactivity complex disorder which affects approximately 3 to 6 percent of the population Boys with ADHD tend to outnumber girls by 3 to 1 It had been identified in medical literature more than 100 years agoA popular German tale(Hoffmanns Struwwelpeter)wr
35、itten in rhyme for children,portrays a child with ADHD,ATTENTION DECIFIT HYPERACTIVITY DISORDER,DIAGNOSTIC CRITERIA FOR ADHD:INATTENTION six or more of the following symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level
36、 a)often fails to give close attention to details or makes careless mistakes in schoolwork,work,or other activities.b)often has difficulty sustaining attention in tasks or play activities.c)often does not seem to listen when spoken to directly.d)often does not follow through on instructions and fail
37、s to finish schoolwork,chores,or duties in the workplace(not due to oppositional behavior or failure to understand instructions).e)often has difficulty organizing tasks and activities.f)often avoids,dislikes,or is reluctant to engage in tasks that require sustained mental effort(such as schoolwork o
38、r homework)g)often loses things necessary for tasks or activities(e.g.,toys school assignments,pencils,books,or tools)h)is often easily distracted by extraneous stimuli.i)is often forgetful in daily activities.,ATTENTION DECIFIT HYPERACTIVITY DISORDER,DIAGNOSTIC CRITERIA FOR ADHD:HYPERACTIVITY-IMPUL
39、SIVITY six or more of the following symptoms of hyperactivity-impulsivity have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental levelHYPERACTIVITY a)often fidgets with hands or feet or squirms in seat.b)often leaves seat in classroom or in other sit
40、uation in which remaining seated is expected.c)often runs about or climbs excessively in situations in which it is inappropriate(in adolescents or adults,may be limited to subjective feelings of restlessness)d)often has difficulty playing or engaging in leisure activities quietlye)is often on the go
41、 or often acts as if driven by a motorf)often talks excessively.IMPULSIVITY g)often blurts out answers before questions have been completed.h)often has difficulty awaiting turn.i)often interrupts or intrudes on others(e.g.,at school or work and at home).,ATTENTION DECIFIT HYPERACTIVITY DISORDER,DIAG
42、NOSTIC CRITERIA FOR ADHD(continued):Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 years.Some impairment from the symptoms is present in two or more settings(e.g.,at school or work and at home).There must be clear evidence of clinically significan
43、t impairment in social,academic,or occupational functioning.The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder,Schizophrenia,or other Psychotic Disorder and are not better accounted for by another mental disorder(e.g.,Mood Disorder,Anxiety Disorder,Dissocia
44、tive Disorder,or a Personality Disorder).,ATTENTION DECIFIT HYPERACTIVITY DISORDER,WHAT CAUSES ADHD?A single cause has not been conclusively proven.Some possibilities are:Genetic/Hereditary(strongest correlation)Brain damage(head trauma)before,after or during birth(twice as likely to have had labor
45、13 hrs)Brain damage by toxins(internal:bacterial and viral,external:fetal alcohol syndrome,metal intoxication,e.g.lead)ACCOMPANYING CNS PROBLEMS(examples)Learning Disabilities TIC disorders(such as Tourettes)in 20%of ADHD children.Whereas 40 to 60%of TIC children have ADHD Gross and Fine Motor contr
46、ol delays(coordination)50%of ADHD children developmental delays(such as speech)Autism,Asbergers,WHAT IS THE LONG-TERM PROGNOSIS?Evidence appears to indicate that ADHD is a permanent condition.Some children may outgrow the hyperactive portion.Unidentified and untreated,the disorder will increase the
47、risk for:Impaired educational performance Decreased self esteem Social problems Family difficulties Potential long term effects SOME STATISTICS 75%people with ADHD get divorced 50%stay behind a grade 46%have been suspended 11%have been expelled 3-5%(going on 15-20%)school aged population have it 2.5
48、-3 million school aged children have it,ATTENTION DECIFIT HYPERACTIVITY DISORDER,POTENTIAL TREATMENTS FOR ADHDThere is no simple treatment.Usually multi-modal approach is used:Medication Training of parents Counseling/training of child including behavior modeling,self-verbalization and self-reinforc
49、ement.Special education environment Dietary investigations DRUGS Psychostimulants(e.g.Ritalin)Antidepressants Neuroleptics Tranquilizers Impulsive/Tantrums Mood stabilizers,ATTENTION DECIFIT HYPERACTIVITY DISORDER,ATTENTION DECIFIT HYPERACTIVITY DISORDER,PILOT STUDY(OPEN DESIGN)ON THE USE OF LECI-PS
50、 IN ADHDDr.Carol Ann Ryser,Kansas City,MI,USA Design:Open clinical trial on 27 children aged 3-19 placed children on individual regime which combined nutrients,drugs as indicated(e.g.Ritalin),treatment for gastrointestinal imbalances,counseling,and other interventions ADHD children received 200 to 3
