aor vol 4 cognitive health singles

8/13/2019 Aor Vol 4 Cognitive Health Singles

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VOLUME 4 ISSUE 4

Cognitive Health Use Your Mind, Dont Lose It

vances

I N O R T H O M O L E C U L A R R E S E A R C H

RESEARCH-DRIVEN BOTANICAL INTEGRATIVE ORTHOMOLECULAR


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Supports the Hippocampus

1.800.387.0177

www.ovos.ca

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Advances 3

Advances in Orthomolecular Researchis published and distributed through integrativephysicians, health care practitioners, and progressivehealth food retailers.

Te content of this magazine is provided forinformational purposes only, and is not intendedas medical advice for individuals, which can onlybe provided by a healthcare professional. Contentsand design 2013 AOR. Any reproduction in whole

or part and in print or electronic form withoutexpress permission is strictly forbidden. Permissionto reproduce selected material may be granted bycontacting the publisher.

Published in Canada by Advanced Orthomolecular Research Inc.

Publisher/Editor-in-Chief Jaime Tomas, BSc

Research & Writing Dr. raj Nibber, PHD Dr. Colin OBrien, ND Dr. Chantal Ann Dumas, ND (Qc)

Dr. Paul Hrkal, ND Adesh Nibber

Graphic Design/Art Production Neil Bromley

Alvin Cha email: [email protected] Volume 4 Issue 4

Digital versions o this magazine and back issues areavailable online at www.AOR.ca

ADVANCEDORTHOMOLECULAR RESEARCH

Memory and CognitivePerformanceCognitive per ormanceencompasses severalabilities includingmemory, language,reaction time, ocus,mood and in ormationprocessing. How muchcognitive decline isconsidered normal?

Ayurveda and CognitionBacopa and curcuminenhance cognitive healthand have extensiveresearch to supporttheir efficacy. A new andhighly bioavailable ormo curcumin has gainedworldwide attention.

Exciting NewIngredients forImproving CognitionEnhance energyproduction in the brainwith PyrroloquinolineQuinone. Vivimind, asupplement containinghomotaurine, improves

memory, learning abilityand slows cognitive decline.

New Perspectives andNatural Compounds forTraumatic Brain InjuryLearn about new insightsinto the pathophysiologybehind traumatic braininjuries ( BI) and how

to help heal them withnatural substances.

Common Supplementsto Improve Memory andCognitive Function Explore natural options tohelp protect and improve

cognitive unction.

Stress-InducedCognitive DysfunctionTe body maintainsa delicate balanceo hormonal andneurotransmitter activityin order or the brain tounction well and produce a

healthy emotional response.

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Te human brain is like no other interms o its ability to simultaneouslysynthesize in ormation and carry outcomplex tasks on a regular basis. Whileit would be naive to say that we ullyunderstand its interrelationship with therest o the body and our environment,modern research has made great stridesto elucidate its various structures andunctions. Here is a brie look at ourcurrent understanding o cognitiveunction and the risk actors thatthreaten its well-being. While a ocuson memory is highlighted, all aspectso cognitive per ormance includinglanguage, reaction time, ocus, mood andin ormation processing must be assessedtogether, due to the minds highlyintegrative nature.What is Normal?

It is widely accepted that memory andother cognitive unctions decline withage, but how do we know i someone has anormal amount o decline? A literaturereview published in 2004, concluded thatno cognitive decline is normally seenbe ore the age o 60. 1 Yet, there are manythat question this statement and contendthat signs o deterioration can be seenat an even earlier age. Challenging thisschool o thought, a more recent study in

2012 showed that cognitive decline mightnormally be seen as early as age 45! 2

Be ore going any urther, it isimportant to note that not all o ourcognitive abilities peak at the same age.Te ability to process in ormation in arapid manner peaks around the relativelyyoung age o 25.1 In other words, afer age25, the rate at which people understandand utilize new in ormation generallystarts to slow down. In contrast, verbalmemory, inductive reasoning and spatialreasoning all peak around the age o 53.Finally, verbal abilities actually peak aferage 60!1 Considering all o these acts, it isnot air to simply say that ageing leads tocognitive decline.

Researchers have also shown thatnot all cognitive unctions wane in thesame manner or to the same degree.

For example, it is now well known thatthe ability to encode new memoriesand process in ormation at a rapid paceboth steadily decline with age. 1 Workingmemory also steadily declines; that is, theskill o utilizing short-term memory tomanipulate and use relevant in ormation.

However, it is interesting that short-term memory on its own does not showthis downhill pattern throughout li e.Short-term memory is ound to have

very slight declines throughout adultli e until nally hitting a turning pointsomewhere afer the age o 70, whereit starts a sharper decline. 1 Similarly,autobiographical memory, semanticknowledge, emotional processes and vocabulary remain airly stable untila dip late in li e. 1 O course, there are variations among individuals or all othese abilities, but the general trendsremain the same.

Cognitive deterioration can alsotell us a lot about our overall health.Interestingly enough, an accelerationo cognitive decline is ofen seen 3-6years be ore an individuals death. 3,4 Ina sense, cognitive unction is a relativemeasurement to ones own baselinestatus and can be a strong predictor o

mortality i interventions are not applied.Overall, its important to know thatthere is a wide range o cognitive decline,some o which may be considerednormal and others that may requiremedical attention. See Key erms or abrie understanding o the various levelso cognitive deterioration and memoryloss.Measuring Cognitive Decline: TeMini-Mental State Exam (MMSE)

In order to provide a solution toany problem, it is rst imperative tounderstand the problem and its severity.I you misplace your wallet and youare unable to remember its location,does it mean that youre a candidateor dementia? O course noti it onlyhappens once or twice. But i yourehaving difficulty, on a daily basis, withsimple tasks like remembering thelocation o basic items, bathing, handlingnances, or maintaining hobbies thenit may be o concern. Dementia is a seto signs and symptoms in which brain

unction, such as memory, language,problem solving and attention areaffected. Alzheimers Disease is just oneo several different orms o dementia.

So how can we determine i anindividual is simply ageing in a healthymanner or i they are on their way towardAlzheimers Disease (AD)? As muchas we can rely on our amily, riends oreven physicians to notice changes inour mental health, an objective measure

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must be implemented in order to betterdetermine what areas o cognitiveunction may be impaired and to whatextent.

With this in mind, many assessmentsare available to determine the global levelo cognitive decline, but perhaps the mostcommonly used tool by practitioners isthe Mini-Mental State Exam (MMSE). 7 Te MMSE contains 19 items designedto measure a variety o unctions, andultimately gives a score between 0-30indicating whether a cognitive decitor dementia may be present. Exampleso typical questions used on the MMSEcan be ound on page 6. Te cognitiveunctions that are measured include theollowing7: Orientation: knowing details about

the current time and location Attention: the ability to, or example,spell a common word backwards

Registration: measured by repeatingnamed prompts (immediate memory)

Recall: measures short-term verbalmemory

Language: the ability to write, speakand understand language

Praxis: the ability to put thoughts andideas into actionTe MMSE is a popular test because

o its relatively simple design andimplementation, along with its ability tomeasure cognitive change over time. 7 Ithas also been shown to correlate quitewell with the abilities o individuals tocarry out unctional everyday tasks,thereby giving a good indication ohow cognitive decline may be affectingday-to-day living.8 For example, when aperson exhibits that they are oriented andattentive through MMSE testing, thesendings correlate well with the ability tocommunicate by telephone, recognize

driving rules and road signs, balance acheckbook, and carry out shopping tasksrom memory. 8

On the other hand, the MMSE doeshave its limitations. It is consideredunreliable or measuring subtle changesin ability and is perhaps more indicatedor repeated use to determine over alonger period o time whether cognitivedecline or improvement has occurred. 7 Tere are well-known ceiling and

oor effects o the MMSE, meaning

that it cannot detect cognitive changesin those individuals on extreme ends othe spectrum ( or example in a 90-yearold with severe dementia or a highlyeducated 40 year old). 9 Nevertheless,the MMSE should be considered agreat preliminary screening tool usedin the assessment o cognitive decline.Depending on the circumstances, morespecic and integrated testing may benecessary.

Does Memory Loss Always Lead to

Alzheimers Disease?As described in the Key erms textbox, age-associated memory impairment(AAMI) appears to be independentand unrelated to the progression oAlzheimers Disease (AD). 5 However,there is no consensus as to whetherAAMI bears an increased risk or AD.One researcher has concluded that thereis zero additional risk but others claim athree- old increased risk. 5

Te Nun Study

Te Nun Study is one o the best examples o how healthy diet and li estylechoices can preserve cognitive unction in ageing individuals. Te NunStudy involves the ongoing unctional assessment o women at the CatholicOrder School Sisters o Notre Dame, with additional permission to assess thebrains o deceased sisters or autopsy. Findings have shown that the relativenon-occurrence o Alzheimers Disease (AD) in the nuns correlate with theircognitive capacity, li estyle, and diet. In other words, some combination otheir unspoiled li estyles (including diet, spirituality, community li e, mentalexercise, etc.) all seem to have contributed to a much lower incidence o ADthan the general population. 5,11

Key erms

Age-Associated Memory Impairment (AAMI): not considered a pathologi-cal condition. While AAMI may be annoying or the individual, the memory

loss is considered a part o normal ageing similar to ading eyesight.5

Mild Cognitive Impairment (MCI): cognitive deterioration that is measur-able based on clinical assessments and noticeable by others. However, it isnot severe enough to consistently impair daily productivity in other words,the efficiency o per orming daily activities may be decreased but not somuch that the tasks must be discontinued. 5

Dementia: a group o disorders that cause cognitive decline as a result odeath or damage to brain cells. Cognitive decline must be present in two oour essential cognitive unctions (1. Memory; 2. Language/speech; 3. Visualprocessing; 4. Planning capacity/ability to carry out complex tasks). 5

Alzheimers Disease (AD): a orm o dementia carrying similar criteria. Temain differentiating eature is the deposition o abnormal protein plaquesin the central nervous system (known as beta-amyloid and neurobrillarytangles).5

Note: there is signicant overlap between these denitions and even re-searchers have ound it difficult to denitively differentiate between theseterms. 6 Tese are given as general guidelines only in order to better under-stand the varying degrees o memory/cognitive decline.


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According to the most currentevidence, it seems as though individualswith mild cognitive impairment (MCI)tend to progress toward dementia, yetnot necessarily AD. 5 In act, certainstudies have shown that up to 25 percento those with MCI can actually revertto normal cognitive capacity. 10 o addto the perplexity, a subgroup o MCIindividuals with quite severe memory

loss, termed amnestic MCI (aMCI),do conclusively show an increased riskor the development o AD. In patientswith aMCI, more than hal progressto AD.5 In this sense, severe memoryimpairment in combination withother cognitive decits does warrantmore investigation and treatmentinterventions to, perhaps, decrease thelikelihood o progression to AD.

Much o the difficulty in determining

an accurate risk assessment lies in theact that there are many characteristicsoverlapping between the categories ocognitive unction. For example, onestudy showed that 67% o individualsdiagnosed with AAMI could also beidentied as MCI subjects. 6 For these67%, their risk assessment varies quitea bit depending which category they areplaced in. Te reason or this variation,

o course, comes down to differencesin subjective measures and differencesbetween objective tests (such as usingthe MMSE versus utilizing anothercognitive test). 6

Given the complexity o categorizingcognitive decit, as well as the multipleand interconnecting risk actorsassociated with decline, it appearsprudent to take a multi- actorialapproach to mitigate and offset any

risk actors that may be present orthe development o MCI, AD or anyorm o dementia. 5,11 Essentially, giventhat there may be an increased risk ordementia and AD with any memoryloss, isnt it worth taking all possiblemeasures to offset this risk, just in case?Preserving Memory and CognitiveFunction

A list o actors that appear to impaircognitive per ormance includingmemory unction, 12-21 can be seen inable 1. I you look closely at this listo risk actors, you will see that many,i not all, are caused by poor li estyleand dietary health. It is clear thatnutrition and li estyle improvementsmust be primary interventions orthe prevention o memory and

cognitive impairments. A diet highin polyunsaturated ats (such as thoseound in sh), monounsaturatedats (such as those ound in oliveoil), vitamin E, polyphenols andantioxidants (in oods such as citrusruits and vegetables) has been shown topossibly slow down the rate o cognitivedecline and prevent progression toAD.1 Un ortunately, with the manychallenges acing optimal nutrition,supplemental nutrients are ofenindicated as well. Certain supplementshave been proven as effective treatmentsor cognitive decline and should beconsidered adjunctive measures withdietary and li estyle improvements(see articles Supplements Known toImprove Memory and Ayurveda andCognition).

Aside rom mitigating risk actorsthrough dietary measures, perhaps themost important preventative measureand disease intervention is mentalexercise. Research has shown that the

old adage, Use it or lose it, holds truein the context o cognitive health. 1,5 Animal studies have shown that mentalexercise increases neurogenesis (growtho the nervous system), while clinicalobservations support this idea that thehuman brain is capable o rebuildingailed circuits. 5

A randomized control trial per ormedin 2006 showed that a cognitive trainingprogram or 10 weeks led to signicant

Examples of Mini-Mental State Exam Questions

1. What day o the week is it today?2. Repeat these words: apple, penny and table. ry to remember them, as

you will be asked to recall them at a later point in the exam.3. Can you tell me the name o the city that were in?4. Please spell the word world. Now, spell the same word backwards.5. Can you per orm this action?: CLOSE YOUR EYES.6. List the three words that you were asked to try to remember.7. Write a complete sentence anything that comes to mind (it should have a

verb and a subject).

*Please Note: Tese questions are only provided as examples. Tis is not a ullMMSE, nor does it quali y or diagnosis or proper assessment o cognitiveunction. For a ull examination, be sure to see your healthcare practitioner.

Medical Conditions

Elevated homocysteine levels

Hypertension Cardiovascular disease Impaired glucose tolerance (conditions such as pre-

diabetes) and type 2 diabetes mellitus Obesity

Lifestyle Factors

Dehydration Chronic alcohol abuse Skipping breakfast High stress and elevated cortisol levels Poor diet (speci cally high intake of total fat,

saturated at and cholesterol) Multiple mineral and vitamin de ciencies

Table 1:Factors That Impair Cognitive Performance


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cognitive improvement over thoseindividuals that did not participate inthe training program. 22 Tis positiveeffect was seen 5 years afer the trainingwas per ormed! It should be notedthat a random sample o the treatmentgroup received additional trainingsessions at 11 and 35 months that ledto even better outcomes. 22 Intuitively,this means that the more ofen we areexercising our brains, the better theyunction over time.

Physical exercise has also shownpromise in the prevention and treatmento cognitive deterioration. Certainstudies have ound that physical exercise

aids executive unction and overallcognitive unction, while also reducingthe amount o brain density loss withage (specically in areas used orexecutive processes). 1 On the contrary,a review released in 2011 stated thatalthough there are numerous positivestudies supporting the notion thatexercise reduces the risk o cognitivedecline, there is insufficient evidenceto ully prove this. 23 At the very least, weknow that exercise decreases the risk odeveloping other chronic diseases andthere ore may be viewed as a primaryintervention or reducing the risk ocognitive deterioration.

As with all traits, there is a natural variation among the population in termso cognitive unction. Not everyone hasthe same ability to store, process andutilize in ormation, but this does notmean that everyone cannot maximizethe potential that they do have. Amixture o li estyle, environmental,dietary and genetic actors all play a partin the maintenance, or deterioration, oour cognitive health. Without a doubt,healthy dietary habits, consistentmental exercise and the preventiono chronic disease must be the primarytreatment or the preservation ocognitive unction.

References1. Hedden and Gabrieli JDE. Insights in the ageing mind: a view rom cognitive neuroscience. Nature Reviews (Neuroscience) 2004; 5: 87-97

2. Singh-Manoux A, Kivimaki M, Glymour M, et al. iming o onset o cognitive decline: results rom Whitehall II prospective cohort study. BMJ2012;344:d7622 doi: 10.1136/bmj.d7622

3. Small BJ, Fratiglioni L, von Strauss E, et al. erminal decline and cognitive per ormance in very old age: does cause o death matter? Psychol. Aging 2003; 18:193202

4. Wilson RS, Beckett LA, Bienias JL, et al. erminal decline in cognitive unction. Neurology 2003; 60:17821787 5. Kidd, Parris M. Alzheimers disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and

progress toward integrative prevention. Alt Med Review 2008; 13(2): 85-1156. Bartrs-Faz D, Junqu C, Lpez-Alomar A, et al. Neuropsychological and Genetic Differences Between Age-Associated Memory Impairment

and Mild Cognitive Impairment Entities. Journal o the American Geriatrics Society 2001; 49:985-9907. Marioni RE, Chateld M, Brayne C, et al. Te Reliability o assigning individuals to cognitive states using the mini mental-state examination:

a population-based prospective cohort study. BMC Medical Research Methodology 2011; 11:127-1328. Razani J, Wong J , Da aeeboini N, et al. Predicting everyday unctional abilities o dementia with the mini mental state examination. J Geriatr

Psychiatry Neurol 2009; 22(1):62-70

9. ombaugh N and McIntyre NJ: Te mini-mental state examination: a comprehensive review. J Am Geriatr Soc 1992, 40(9):922-935.10. Rosenberg PB, Johnston D, Lyketsos CG. A clinical approach to mild cognitive impairment. Am J Psychiatry 2006;163:1884-1890.11. yas SL, Snowdon DA, Desrosiers MF, et al. Healthy ageing in the Nun Study: denition and neuropathologic Correlates. Age Ageing. 2007

November ; 36(6): 650655.12. Grandjean AC and Grandjean NR. Dehydration and cognitive per ormance. J Am Coll Nutr. 2007; 26(5):549S-554S.13. Adan A. Cognitive per ormance and dehydration. J Am Coll Nutr. 2012; 31(2):71-8.14. Ceballos NA. obacco use, alcohol dependence, and cognitive per ormance. J Gen Psychol. 2006; 133(4):375-88.15. eunissen CE, van Boxtel MP, Jolles J, et al. Homocysteine in relation to cognitive per ormance in pathological and non-pathological conditions.

Clin Chem Lab Med. 2005; 43(10):1089-95.16. Greenwood CE. Dietary carbohydrate, glucose regulation, and cognitive per ormance in elderly persons. Nutr Rev. 2003; 61(5-2):S68-74.17. Grima NA, Pase MP, Macpherson H, et al. Te effects o multivitamins on cognitive per ormance: a systematic review and meta-analysis. J

Alzheimers Dis. 2012;29(3):561-9.18. Crichton GE, Elias MF, Buckley JD, et al. Metabolic syndrome, cognitive per ormance, and dementia. J Alzheimers Dis. 2012; 30(S2):S77-87.

19. Hoyland A, Dye L, Lawton CL. A systematic review o the effect o break ast on the cognitive per ormance o children and adolescents. Nutr ResRev. 2009; 22(2):220-43.

20. Eilander A, Gera , Sachdev HS, et al. Multiple micronutrient supplementation or improving cognitive per ormance in children: systematicreview o randomized controlled trials. Am J Clin Nutr. 2010; 91(1):115-30.

21. Leininger S and Skeel R. Cortisol and sel -report measures o anxiety as predictors o neuropsychological per ormance. Arch Clin Neuropsychol.2012 May;27(3):318-28

22. Willis SL, ennstedt SL, Marsiske M, et al. Long-term effects o cognitive training on everyday unctional outcomes in older adults. JAMA 2006;296(23):2805-14.

23. Snowden M, Steinman L, Mochan K, et al. Effect o exercise on cognitive per ormance in community-dwelling older adults: review o interventiontrials and recommendations or public health practice and research. J Am Geriatr Soc. 2011 Apr;59(4):704-16


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Pyrroloquinoline Quinone (PQQ)PQQ is a relatively large molecule

that was rst discovered in bacteria, byscientists in 1979. Te signicance othis molecule wasnt ully realized untila ew years later when researchers oundthat the PQQ molecule could take partin redox reactions. Tese reactions are vital to the body or energy generation.Energy is the key, since it is required incarrying out virtually all the unctionsin a cell including: growth, repair,reproduction, synthesis, breakdown,waste removal and others. I energyisnt produced rapidly and efficientlythen cells die.How PQQ Functions in the Body

PQQ research was taken up by theJapanese; the mechanism o action

was painstakingly worked out andattributed to these redox reactions.Redox reactions are a two way streetwhere both oxidation (gain o oxygenor loss o electrons) and reduction(loss o oxygen or gain o electrons)occur simultaneously. In other words,while one molecule is being oxidized,the second is being reduced. Redoxreactions allow cells to do two thingsat once, while saving considerable

amounts o energy rather thanper orming these reactions separately.Redox reactions are an essential part ocells existence, and tens o thousandso these reactions occur at any onetime. In this regard, PQQ is detected in various tissues and in bodily uids suchas saliva and tears and breast milk.

PQQ acts as a catalyst by speedingup reactions, thus saving cells evenmore energy. Some researchers haveclassied this as a co-enzyme and a vitalingredient or cell survival, and thushave pushed or PQQ to be classied asa B vitamin; the jury is still out on thelatter request. Nonetheless, researchersand clinicians have come to realizeand appreciate the importance o PQQin various diseases but especially in

cognitive health.PQQs Role in Cognitive HealthResearchers realized early on that

people who consumed quantities ooods rich in PQQ such as to u, celery,bell peppers and various ermentedoods, had better brain unction thanpeople consuming lower quantities.Tis led scientists to look at the effect oPQQ on memory, learning, and otherrelated cognitive unctions. At rst

they looked at PQQs mode o action inanimals and then in humans.Te Research on PQQ

Animal studies have shown thatPQQ protects nerve cells rom damagecaused by various toxins, it preventsoxidation o nerve tissue by quenchingree radicals that otherwise cause muchdestruction, it increases the productiono nerve growth actor which protectsnerve cells and was shown to improvethe memory tasks that the animalsper ormed. In addition, it wasdiscovered that PQQs effectiveness wasenhanced when used in combinationwith another important molecule calledCoenzyme Q10.

Recently, two human studieshave looked at the PQQ+CoQ10

combination and the effects on memory.Te rst study o 12 weeks durationand which was a double-blind placebocontrolled randomised study in healthypatients, looked at three differentsupplement groups: (i) 22 patientsreceived 20mg o PQQ, (ii) 24 patientsreceived 20mg o PQQ plus 300mgCoQ10 and, (iii) 23 patients receiveda placebo. Patients per ormed various verbal and identication memorytests or the study. Both the PQQ andPQQ+CoQ10 groups per ormed muchbetter than the placebo group in termso improved memory scores. However,the PQQ+CoQ10 group was evenbetter than the PQQ group on its own;thus indicating the synergy betweenthe two molecules.

A second study published in 2012showed that when 20mg o PQQalone was administered or 8 weeks,it signicantly improved sleep qualityand duration, reduced anxiety andatigue, and improved overall quality

o li e.PQQ+CoQ10 presents a novel and asa e approach to maintaining healthybrain unction in terms o memory andlearning.Vivimind

In the pharmaceutical world, alldrugs have to go through extensivetesting and studies rom preclinical(test tube and animal), phase I (usuallyto determine pharmacokinetic prole,

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Advances 9

Researchers at Queens University inKingston, Ontario discovered a uniquemolecule that was ound in certainseaweeds and which had remarkableproperties in improving memory,learning, and slowed the normal agingprocess o the brain. Te molecule wasidentied as homotaurine, a close relativeo the amino acid taurine, but withunique and distinctive properties thattaurine does not possess. A Canadiandrug discovery company decided to test

this molecule and conduct all the studiesrequired, rom pre-clinical all the wayto phase III studies. Te company spentover two hundred million dollars andtook feen years to conduct testing inover two thousand patients across sixty-seven centres in Canada, US and Europeto complete sixteen studies in total (seeable 1). Un ortunately, homotaurine

just missed the relevant statisticalsignicance value in conclusively

absorption, distribution o the drugin various tissues, and its excretion),Phase II (which determines the sa etyand establishes the dose required), andnally phase III which is the last, mostexpensive part, and involves hundredsto thousands o patients to determine aclinical end point (such as a reductionin pain or inammation or animprovement o memory or any otherpositive/negative outcome). It is rare tond a natural health product that has

a completed phase III study. Te costsare just too high. At best, most naturalhealth products stop at phase I and theodd one proceeds to a phase II study.Vivimind is one o the very ew naturalhealth products that has success ullycompleted all the phases that arenormally required or a drug approval,and has thus generated unprecedentedsa ety and efficacy data unlike anyother natural health product.

demonstrating the efficacy using thestandard psychometric tests. HealthCanada required additional studies tobe conducted be ore any Alzheimersdisease claim would be granted. Tecompany decided to abandon the drugapplication as this would cost a lot moremoney and time.

Subsequent analysis o the datahowever, showed a clear statisticallysignicant evidence o effectiveness inseveral cognitive unctions including:

memory preservation, maintenance o verbal skills and execution o varioustasks, all o which are severely affectedin Alzheimers disease (see Figure 1). Inaddition, homotaurine demonstrated ahighly signicant effect in a high-riskgroup o Alzheimers disease patients,those carrying the ApoE4 gene (seeFigure 2). Approximately, a quartero the AD population carry thisaggressive gene.


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10 Advances

Te company decided to markethomotaurine as a natural health productunder the trade name Vivimind, or

maintaining optimal cognitive health.Health Canada allowed the ollowingclaim or Vivimind, May help supportthe specic area o the brain known asthe hippocampus.

Te hippocampus is the part o thebrain that is responsible or learningand memory. As we age, this area othe brain starts to shrink due to aloss o brain tissue and nerve cells.Tis is a normal part o ageing, butin Alzheimers disease this processis greatly accelerated. MagneticResonance Imaging (MRI) o the brainshows that Vivimind greatly reducesthe loss o brain tissues by an incredible

68% (see Figure 3) as compared withplacebo group.

What is the mechanism o action

o Vivimind? Studies have shownthat Vivimind acts via two distinctpathways: It reduces and helps clear the glue-

like deposits o the highly toxic beta-amyloid peptide that orms plaquesin the brain.

It inhibits the ormation o theamyloid tendrils which can literallychoke the nerve cells (see Figure 4)Not only does Vivimind reduce the

ormation o these toxic plaques andbril-like projections, but Vivimindmay also help clear any such depositsrom the brain.

One o the key requirements o

any product that can help improvecognition and/or prevent acceleratedageing o the brain, is or that molecule

to be able to get into the brain by by-passing the super astidious gatekeeperknown as the blood brain barrier.Vivimind actually gets into the braineasily and thus is able to per orm itsunction.

Finally, Vivimind does not inter erewith important liver detoxicationenzymes such as CytochromeP450, or even interact with bloodthinning drugs like war arin, unlikesupplements such as Ginkgo biloba and vitamin E. Vivimind has extensive datashowing both sa ety and effectivenessin improving various cognitiveparameters (see able 2 on page 9).

References1. Aisen PS, Gauthier S, Ferris S et al ramiprosate in mild-to-moderate Alzheimers disease- a randomised, double blind, placebo-controlled,

multi-centre study Arch Med Sci. 2011; 1: 102-1112. Caltagirone C, Ferrannini L, Marchionni N et al Te potential protective effect o ramiprosate (homotaurine) against Alzheimer disease: a

review Aging Clin. Exp. Res. Sept 5 20123. Greenberg S M, Rosand J, Schneider A et al A phase 2 study o tramiprosate or cerebral amyloid angiopathy Alzheimer Dis. Assoc. Discord.

2006; 20: 269-2744. Koikeda , NereNo M, and Masuda K et al Pyrroloquinoline quinone disodium salt improves higher brain unction. Med Consult New

Remedies, 2011; 48: 519-527 5. Nakano M, Yamamoto , Okamura H et al Effect o pyrroloquinoline quinone(PQQ) on mental status o middle-aged and elderly persons.

FOOD style, 2008; 21 13: 50-53 (Japanese)6. Nakano M, akeda H, Yamazaki M et-al Effects o oral supplementation with pyrroloquinoline quinone on stress, atigue, and sleep. Functional

oods in health and disease, 2012; 2: 307-3247. Ohwada K, akeda H, Yamazaki M et al Pyrroloquinoline quinone(PQQ) prevents cognitive decit caused by oxidative stress in rats. J Clin

Biochem Nutri, 2008; 42: 29-34.8. Saumier D, Duong A, Haine D et al Domain-specic cognitive effects o tramiprosate in patients with mild to moderate Alzheimers disease:

ADSS-cog subscale results rom the Alphase study J Nutr Health Aging, 2009; 13: 808-8129. Zhang Y, Feustel PJ, Kimelberg HK et al Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in

the adult rat. Brain Res, 2009; 1094: 200-206.


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12 Advances

PhosphatidylserinePhosphatidylserine (PS) is one o

the major phospholipids ound in thebrain. 10 Among other phospholipids,it is structurally responsible ormaking up the cell membrane andunctionally responsible or triggeringcell-to-cell communication by trans ero biochemical in ormation into thecell.10 Overall, PS plays a crucial rolein cellular unction and the overallunction o the central nervous system!

Animal research has suggestedthat PS supports the growth o thebrain by increasing the densityo nerve growth actor receptors,normally ound to decrease as weage.10 PS has also shown to positivelyaffect specic neurotransmitters inthe brain including: acetylcholine,norepinephrine, serotonin anddopamine. 11 With these mechanisms inmind, it comes as no surprise that PS

has shown positive clinical research inits application or improved cognitiveunction. In act, more than a dozenstudies have exhibited signicantimprovements in learning, memory,concentration, and recall. 12

In one o the largest studiesexamining the possible role in treatingAge-Associated Memory Impairment(AAMI), signicant improvementswere recorded. 494 elderly patients

(aged 65-93) with moderate to severecognitive decline (as measured by validated assessment tools, includingthe MMSE) were shown to benetin areas o behavioral and cognitiveper ormance with 300 mg per day oPS.13 Te placebo group did not exhibitthe benets in learning and memorythat the PS treatment group did afer 6months. 13

A double-blinded, placebo-controlled trial utilizing 300 mg perday o PS also showed signicantenhancements in memory tests withAAMI afer only three weeks otreatment. 14 Specically, improvementswere seen in the treatment subjectsabilities to remember names andaces, recall telephone numbers andremember the placement location okeys and glasses. Afer three months,PS improved memory by 30 percentcompared to placebo. 14 It should be

noted that the greatest improvements intest scores were shown in those with thelowest cognitive unction at baseline.In these individuals, three months oPS supplementation led to an averagecognitive age score o 52 in those withan original average score o 64. 14

As one would expect, PS has alsoshown promise in treating AD.Signicant improvements in globalcognitive unction have been shown

across the board, including activitieso daily living, personal and non-personal memory, learning, motivation,socialization and in ormationprocessing.15, 16, 17 Certain studies haveshown that the greatest improvementsare ound in those AD patients with lesssevere cognitive decline. 15, 16, 17

Te most effective method osupplementation is oral ingestion, as PSreadily passes through the blood-brainbarrier, a trait necessary or therapeuticeffects on the nervous system. 10 Also,there has been some controversy overthe source o PS and the correspondingeffectiveness o supplementation. PScan be sourced rom either bovinecortex (BC-PS) or soybean (SB-PS)and some research has questioned the

effectiveness o the vegetarian source.18

However, a recent study conrmedthat SB-PS is effective or memoryand cognition, while also avoiding thetheoretical risk or bovine spongi ormencephalopathy rom BS-PS andmaintaining a sustainable source oPS.18

As a nal note, PS has proven to alsobe benecial or cognitive measures incases o depression, ADHD and chronicstress 10, 19 and has demonstrated anextremely high sa ety prole. 20 Mostclinical studies examining the effectso PS on cognition and memory havedosed the nutrient at 200-400mg perday. Tere ore, given current evidence,300mg per day appears to be the bestdosage or supporting memory relatedconditions. 10Citicoline

Citicoline is a known neuroprotectiveagent and an extremely importantmolecule necessary or the biosynthesiso phosphatidylcholine, a cell membrane

phospholipid in the nervous system.21

Levels o this crucial phospholipidcan be depleted when the body needsto make more neurotransmitters(specically acetylcholine), there orecompromising the integrity o the nervecell membrane and overall nervoussystem.21 Te good news is that citicolinecan be taken as an oral supplementwith antastic bioavailability (almostall o the citicoline gets absorbed


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Advances 13

into the bloodstream and passesthe blood-brain barrier). 21 Like PS,citicoline improves the structure andunctionality o nervous system cellmembranes, yielding improvements inmemory and other cognitive measures.

Specically, much o the clinicalresearch on citicoline has been appliedto stroke victims. Phosphatidylcholinesynthesis appears to be impairedafer brain ischemia, 22 indicating thatsupplementation o citicoline maybe necessary to drive this pathway.Afer suffering a stroke, patients are attwice the risk or developing dementiaand can ofen be lef with decits incognitive abilities.23 With this in mind,preventative measures to reduce thisrisk are extremely valuable.

Alvarez-Sabin et al. ound that1000mg per day improved cognitive

unction at 6 and 12 months post-stroke (specically in areas o attention,executive unction and temporalorientation). 23 Another analysis statedthat initiating citicoline within 24hours afer the occurrence o a strokeincreases the probability o completerecovery at three months. 24 Mostrecently, researchers in Italy examinedthe effects o citicoline in those withmild vascular cognitive impairment

and no diagnosis o AD. Afer 9 monthso taking 500mg per day, the treatmentgroup (mean age o 79) did not showdeterioration in mental unction basedon MMSE scores, whereas the controlgroup showed signicant declines. 25

Tese ndings are quite signicantbecause much o the researchexamining citicoline has not looked atits effects or such a long duration otime. Researchers in the Italian studyconcluded that the most pronouncedbenets o citicoline on vascularcognitive impairment might be seenover an even greater duration o use. 25

Citicoline has also shown applicationas a memory aid without vascular causes,most likely through the enhancemento neurotransmitter synthesis in thesecircumstances. Animal studies in agingrats and young dogs have clearly shown

its use ulness in enhancing memory andlearning, 26, 27, 28 while human clinicaltrials have supported these ndings.A double-blind, randomized controltrial ound that 1000-2000mg ociticoline or up to 5 months durationled to improved verbal memory inindividuals with poorer-than-averagememory. 29 Tis study built on theprevious research showing that taking1 gram per day o citicoline or 6

weeks enhanced global memory and,specically, acquisition efficiency (theability to acquire new memories) inthose with mild-to-moderate memoryloss.21

Finally, citicoline has also shownpromising application in treating otherconditions including Parkinsons (dueto its dopaminergic action), 21 amnesticmild cognitive impairment, 30 early-onset AD, 31,32 spinal cord or braininjury 33 and glaucoma. 21 Please see thearticle titled raumatic Brain Injuryor more in ormation on citicolinesuse in preserving cognitive unctionafer physical trauma to the head.

Overall, citicoline shows promise intreating memory decits and cognitivedecline due to a variety o causativeactors, and also through a variety omechanisms. A 2005 Cochrane Review

looked at all o the data rom published,double-blind, randomized humantrials on citicoline and cognitiveimpairment at the time. It concludedthat there was clear evidence o thebenets o citicoline on memoryunction and behavior. 34 It is clear thatanyone looking to support their brainand nervous system unction shouldconsider the benets o citicolinesupplementation quite seriously.

AOR Cognitive Health ProductsDosage Recommendations According to Research Studies

Mechanism of Action Acetyl-L-Carnitine(amino acid)2-4g/day

Phosphatidylserine(phospholipid)

300mg/day

Citicoline(phospholipid)

1000mg/day

Supports protein synthesis

Increases density of nerve growthreceptors

Supports cell membrane andphospholipid synthesis

Increases synapticneurotransmission

Neuroprotective agent

Supports neurotransmitterfunction

Enhances memory and providessupport for cognitive disorders


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14 Advances

References1. Acetyl-L-Carnitine Monograph. Alternative Medicine Review 2010; 15(1):76-832. Michael E Hasselmo. Te role o acetylcholine in learning and memory. Curr Opin Neurobiol. 2006 December; 16(6): 710715.3. Gavrilova SI, Kalyn IaB, Kolykhalov IV et al. Acetyl-L-carnitine (carnicetine) in the treatment o early stages o Alzheimers disease and

vascular dementia. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(9):16-22.4. Montgomery SA, Tal LJ, Amreim R. Meta-analysis o double blind randomized controlled clinical trials o acteyl-l-carnitine versus placebo in

the treatment o mild cognitive impairment and mild Alzheimers disease. Int Clin Psychopharmacol 2003; 18:61-715. Rai G, Wright G, Scott L, et al. Double-blind, placebo controlled study o acetyl-L-carnitine in patients with Alzheimers dementia. Curr Med

Res Opin 1990; 11:638-647 6. Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimers disease. Neurology. 1991; 41:1726-17327. Malaguarnera M, Gargante MP, Cristaldi E, et al. Acetyl-L-Carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci 2008; 53:3018-

30258. Kobayashi S, Iwamoto M, Kon K, et al. Acetyl-L-carnitine improves aged brain unction. Geriatr Gerontol Int. 2010 Jul;10 Suppl 1:S99-106 9. Scadi S, Racz J, Hazelton J, et al. Neuroprotection by acetyl-L-carnitine afer traumatic injury to the immature rat brain. Dev Neurosci.

2010;32(5-6):480-7.10. Phosphatidylserine Monograph. Alt Med Review 2008; 13(3):245-247 11. Richter Y, Herzog Y, Cohen , et al. Te effect o phosphatidylserine-containing omega-3 atty acids on memory abilities in subjects with

subjective memory complaints: a pilot study. Clinical Interventions in Aging 2010; 5:313-316 12. Kidd PM. Phosphatidylserine; membrane nutrient or memory. A clinical and mechanistic assessment. Altern Med Rev 1996;1:70-84.13. Cenacchi , Bertoldin , Farina C, et al. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy o

phosphatidylserine administration. Aging (Milano) 1993;5:123-13314. Crook H, inklenberg J, Yesavage J, et al. Effects o phosphatidylserine in age-associated memory impairment. Neurology 1991;41:644-64915. Crook , Petrie W, Wells C, et al. Effects o phosphatidylserine in Alzheimers disease. Psychopharmacol Bull 1992;28:61-66.16. Amaducci L. Phosphatidylserine in the treatment o Alzheimers disease: results o a multicenter study. Psychopharmacol Bull 1988;24:130-134.17. Klinkhammer P, Szelies B, Heiss WD. Effect o phosphatidylserine on cerebral glucose metabolism in Alzheimers disease. Dementia 1990;1:197-

201.18. Kato-Kataoka A, Sakai M, Ebina R, et al. Soybean Derived Phosphatidylserine Improves Memory Function o the Elderly Japanese Subjects

with Memory Complaints. J. Clin. Biochem. Nutr. 2010; 47:24625519. Baumeister J, Barthel , Geiss KR, et al. Inuence o phosphatidylserine on cognitive per ormance and cortical activity afer induced stress.

Nutritional Neuroscience. 2008; 11(3):103-11020. Vakhapova V, Richter Y, Cohen , et al. Sa ety o phosphatidylserine containing omega-3 atty acids in non-demented elderly: a doubleblind

placebo-controlled trial ollowed by an open-label extension. BMC Neurology 2011, 11:79-8021. Citicoline Monograph. Alt Med Review 2008; 13(1):50-57

22. Adibhatla RM, Hatcher JF, Dempsey RJ. Cytidine-5-disphosphocholine affects C P-phosphocholine cytidylyltrans erase and lyso- phosphatidylcholine afer transient brain ischemia. J Neurosci Res 2004;76:390-396 23. Alvarez-Sabn J, Ortega G, Jacas C, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment.

Cerebrovasc Dis. 2013;35(2):146-54.24. Davalos A, Castillo J, Alvarez-Sabin J, et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis o clinical trials.

Stroke 2002;33:2850-2857.25. Cotroneo AM, Catsagna A, Putignano S, et al. Effectiveness and sa ety o citicoline in mild vascular cognitive impairment: the IDEALE study.

Clinical Investigation in Aging 2013; 8:131-137 26. Bruhwyler J, Liegeois JF, Geczy J. Facilitatory effects o chronically administered citicoline on learning and memory processes in the dog. Prog

Neuropsychopharmacol Biol Psychiatry 1998;22:115-128.27. Drago F, Mauceri F, Nardo L, et al. Effects o cytidine-diphosphocholine on acetylcholine-mediated behaviors in the rat. Brain Res Bull

1993;31:485-489.28. Petkov VD, Kehayov RA, Mosharro AH, et al. Effects o cytidine diphosphate choline on rats with memory decits. Arzneimittel orschung

1993;43:822- 828.

29. Spiers PA, Myers M, Hochanadel GS, et al. Citicoline improves verbal memory in aging. Arch Neurol 1996; 53:441-44830. Gavrilova SI, Fedorova IaB, Gantman, Kalyn IaB et al. [Ceraxon (citicoline) in the treatment o the mild cognitive impairment syndrome].[Article in Russian] Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111 (12):16-20.

31. Caamano J and Gomez MJ. Effects o CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimers disease. Methods FindExp Clin Pharmacol 1994;16:211-218.

32. Alvarez XA, Sampedro C, Lozano R, et al.Citicoline protects hippocampal neurons against apoptosis induced by brain beta-amyloid deposits plus cerebral hypoper usion in rats. Methods Find Exp Clin Pharmacol 1999;21:535-540.

33. Leon-Carrion J, Dominguez-Roldan JM, Murillo-Cabezas F, et al. Te role o citicoline in neuropsychological training afer traumatic braininjury. NeuroRehabilitation 2000;14:33-40

34. Fioravanti M and Yanagi M. Cytidinediphosphocholine (CDP-choline) or cognitive and behavioural disturbances associated with chroniccerebral disorders in the elderly. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000269


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Advances 15

Ayurveda or the science o li e, is awidely popular system o healing andis considered the oldest as describedin ancient Indian texts dating backto 3500 BCE. Classically, Ayurveda isa holistic method o treating healthby addressing the physical, mentaland spiritual aspects in unison. Diet,exercise and meditation play a key rolein this traditional but highly effectivesystem. Naturally, Ayurveda uses awide variety o herbs and mineralsin various combinations that stillcontinue to be used today and that have

been described in detail in numeroustexts. Ayurveda and homeopathy areconsidered on par with the westernbased pharmacological medical systemand are recognised by the governmento India as legitimate medical systems.

Tis brie review o Ayurveda andcognition will not cover the time-honored principles o Ayurveda,rather it will ocus on the experimentaland clinical evidence on the use o the

herbs. Tere are many herbs thatare highly regarded in Ayurvedicmedicine including: Mucuna pruriens,Centella asiatica, Withania somine eraand many others. Un ortunately, manyo the published studies reporting theuse o such herbs are o poor qualityin terms o design, quality, sample size,statistical analysis (or a lack o ), notblinded and there ore allowing bias,and would not be accepted by manyresearchers as meaning ul. However,two herbs that have good scienticdata behind their use are turmeric and

Bacopa.Epidemiologists, or scientists whostudy health in populations, ofenobserve that the incidence o variousneurological diseases in countries likeIndia are ofen at the lower end o thespectrum. Tis indicates that li estyle,diet, and the use o herbs and spicesseem to be offering protection to theIndian population when compared tothe western countries. India has some

o the lowest rates o Alzheimers andParkinsons diseases, other orms odementia and depression. Te regularuse o various herbs and spices in thediet, such as turmeric in curries andBacopa in tea, has been implicated intheir protective effects.Bacopa

Bacopa is an herb that growsthroughout the Indian sub-continentand is so highly revered that it is calledbrahmi afer one o the major Hindudeities, Bhrama the God o Creation.Bacopa is a popular and widely used

herb throughout the whole o India,due to its remarkable and positiveeffects on cognition in persons o allages.

ypically the whole o the plant isused, especially the leaves and stem.Tere are various active componentsincluding alkaloids and saponins,but the main active compounds orcognitive effects are thought to bebacosides A and B.

Ayurveda and Cognition


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16 Advances

Bacopa has been subject toextensive research in both animals andhumans and produces a multitude ophysiological effects. First, Bacopa isregarded as an important adaptogen.An adaptogen is any compound thathelps the body maintain normalstatus-quo during any orm o stress.Stress may be described as the sumtotal o all the reactions o the bodythat disturbs its normal equilibriumand homeostasis. In Ayurvedic texts,Bacopa is considered a tonic or boththe brain and the body and this mayreect Bacopas ability to help thebody cope with stress. As an example,animals given aspirin to cause stomachulcers were largely protected when

given Bacopa at the same time. Second,Bacopa has been used in patients totreat epilepsy, anxiety, insomnia, aswell as or providing a mild analgesiceffect.

Perhaps the most importanttherapeutic effect o Bacopa is inthe eld o cognition. Bacopa hasbeen studied or enhancing memoryin children as well as in seniors.Behavioural animal studies conrm

that Bacopa improves motor learning;in other words, animals seem toremember tasks better or are able toescape a maze much quicker thanuntreated animals. Other studies haveshown that Bacopa protects against various toxins that act on the nerve cellsas well as reversing amnesia induced bysuch toxins.Human Studies on Bacopa

One human study involved childrenwho were given Bacopa syrup. It wasgiven to twenty children under the ageo eight, while another group o childreno same age were given syrup withoutany Bacopa in it. Improvements werenoticed in word association, patternrecognition and other reasoning tests

in the Bacopa group compared to theplacebo group; these improvementswere statistically signicant.

A second study in nineteen childrendiagnosed with attention decithyperactivity disorder (ADHD) wascarried out or sixteen weeks. Likethe previous study, positive resultswere noticed in various tests relatedto sentence repetition, memory, andother learning tasks.

Researchers in Australia investigatedthe effects o Bacopa and tested thecompound in eighteen normal healthyadults at a daily dose o 300mg. Testudy participants were evaluated twohours afer intake with a battery ocognitive tests involving actors suchas verbal recall o numbers, symbolrecognition, speed o comprehension,reaction times and others. However,no difference was ound in the Bacopagroup when compared to the placebogroup. Next, the researchers evaluatedthe same group afer chronic use oBacopa at a 300mg dose or twelveweeks; this time they ound signicantimprovements in cognitive unction.Other research groups in India have

also ound similar benets or chronicuse o Bacopa. Tus it seems thatBacopa works very well when taken ona regular basis.

Te mechanism o action o Bacopaseems to be that Bacopa increases levelso acetylcholine (Ach), an importantchemical messenger in the brain.Lower levels o Ach have been linked tocognitive decline including Alzheimersdisease. Bacopas ayurvedic reputation

P l a s m a C u r c u m i n ( n g / m L )

95% Curcuminoids(650 mg dose group)

24

20

16

12

8

4

0

0.0 1 2 3 4 6 8

95% Curcuminoids(650 mg dose group)

Figure 1. Mean plasma concentration of Longvida curcumin was 65 times more bioavailable than unformulated curcumin based on Cmax, antimes more bioavailable based on Area Under the Curve (AUC). One signicant nding over the course of several bioavailability studies usithat Longvida curcumin dosages lead to therapeutic levels of free curcumin in the bloodstream and target tissues.


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Advances 17

as a brain tonic or children andadults (especially seniors) has beenconrmed by researchers.Curcumin

Te brightly coloured spice turmericis a widely used condiment in SouthEast Asia and beyond. Besides oodapplication, the spice is used as acolouring agent, ood preservativeand or health benets. Ayurvedalauds the diverse application oturmeric; its uses range rom treatingintestinal problems, ever, cataracts,inammation and heart disease. It isalso used as an antimicrobial, a topicaltreatment, to help prevent cancer, ando course or cognitive health.

Te active ingredients o the turmericroot are the three curcuminoids, o

which by ar the largest componentis curcumin. Much o the researchsupports the use o curcumin inhealthly brain unction.

Many research groups are activelylooking at curcumins brain protectiveeffects, especially against Alzheimersdisease. One o the key requirementsor any compound (natural orpharmaceutical) is the ability to cross

the blood-brain-barrier (BBB). TeBBB offers a de ence against unwantedentry to many compounds both riendand oe. Te brain is afer all thecommand centre and thus must beprotected at all costs. Te BBB acts asa gatekeeper, allowing access to keynutrients such as glucose and certainminerals, but also preventing access toothers and there ore posing a challengeto the ormulators o natural healthproducts.Longvida- Te Best CurcuminSupplement Available

Afer studying the curcumin moleculeor many years, scientists at theamed University o Cali ornia at LosAngeles (UCLA) nally came up witha ormulation that could get across the

BBB and thus provide cognitive effects.Tey called this product Longvida (see www.longvida.com) and patentedit. While a number o animal studiesshowed the positive effects o thismolecule, the scientists wanted to seei the benets could be translated tohumans. Late last year, researchers led byDr Di Silvestro at Ohio State Universitylooked at 30 healthy adults and gave

them the Longvida ormulation. Teyound that not only did Longvida deliver high quantities o ree curcumindue to its very high bioavailability, thehighest in any ormulation (see gure1), but it also reduced the levels o oneo the markers o Alzheimers diseasecalled beta amyloid peptide. Tis smallprotein like structure is thought to beone o the culprits in the causation othis dreaded disease. Acting like Velcro,this glue-like protein sticks to the nervecells causing their death. Te act thatLongvida reduced its circulating levelswas a signicant nding.Te Ohio State University Studyis Important for the FollowingReasons:

A very low dose was used (only 80

mg which is the exact dose in AORsCurcuViva). Te study was or only30 days and it was remarkable that asignicant effect was seen in such ashort duration!

Te act that signicant results wereseen in healthy adults may mean that inpeople with higher levels o this toxicpeptide such as in Alzheimers patients,the results ought to be better.

References1. Sharma R, Chaturvedi C, ewari PV, et al. Bacopa monnieri in revitalizing intellectual unctions in children. J Res Education. Indian Med, 1987

June 1-12.2. Negi KS, Singh YD, Kushwaha KP, et al. Clinical evaluation o memory Plus in children with ADHD. Ind J Physciatry, 2000; 42: Suppl.3. Bhattacharya SK and Ghosal S. Anxiolytic activity o a standardized extract o Bacopa monniera in an experimental study. Phytomedicine,

1998; 5: 77-82.4. Nathan P J, anner S, Lloyd J, et al. Effects o a combined extract o Gingko biloba and Bacopa monniera on cognitive unction in healthy

humans. Human Psypharmacology Clin Exp, 2004;19: 91-96.5. Stough C, Lloyd J, Clarke J, et al. Te chronic effects o an extract o Bacopa monniera (Brahmi) on cognitive unction in healthy human subjects.

Pshychopharmacology, 2001;156:481-484.6. Nathan PJ, Clarke J, Lloyd J, et al. Te acute effects o an extract o Bacopa monniera (Brahmi) on cognitive unction in healthy normal subjects.

Human Psychopharmacology Clin. Exp. 2001; 16: 345-351.7. Rai D, Bhatia G, Sen , et al. Adaptogenic effect o Bacopa monniera (Brahmi). Pharmacolology, Biochemistry and Behaviour, 2003;75:823-

830.8. Singh H K and Dhawan, B.N. Brain enhancing ingredients rom ayurvedic medicine: quintessential example o Bacopa monniera, a narrative

review. Nutrients, 2013;5:478-497.9. Ma Q, Xiaohong Z, Fusheng Y, et al. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic and behavioral decits

in aged human tau transgenic mice. J Biological Chemistry on line, published Dec 2012.10. Disilvestro R, Joseph E, Zhao S, et al. Diverse effects o a low dose supplement o lipidated curcumin in healthy middle aged people. Nutrition

Journal 2012, 11:79-87.11. Gota V S, Maru GB, Soni G, et al. Sa ety and Pharmacokinetics o a Solid Lipid Curcumin Particle Formulation in Osteosarcoma Patients and

Healthy Volunteers. J. Agric. Food Chem. 2010, 58, 20952099 2095.12. Begum A N, Hillman Z, Duran E, et al. Curcumin structure- unction, bioavailability, and efficacy in models o neuroinammation and

Alzheimers disease. Journal o Pharmacology and Experimental Terapeutics. 2008 Jul; 326:196-208.


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18 Advances18 Advances

raumatic brain injuries ( BI) andconcussions are generating greatermedical and research interest as publicawareness grows, especially in termso their impact on younger and more vulnerable populations. A recent studyound there are approximately 30,000concussions or head related injuriesreported annually among the 12 to 19year old age group, with over 80% beingsports related. 1 While these numbersare increasing every year, the majorityo concussions are still not beingreported so the true numbers are mostlikely underestimated. 1

An explosion o recent researchhas uncovered some o thepathophysiological pathways involvedin BI. While one unied theory

has yet to be conrmed, there isemerging evidence that brain traumacauses neurotransmitter and calciumrelease which initiates a cascade oneuroinammation, excitotoxinproduction, mitochondrial dys unctionand immune activation. 2 People thatsustain a BI undergo a very brieperiod o increased metabolism asbrain cells try to restore balance anddeal with the trauma. Following

the brie hypermetabolic period,brain tissue rapidly progresses into ahypometabolic state as mitochondriaunction is impaired. Tis state canlast 7 days or longer (30 days in severecases) depending on the severity o theBI. A very prevalent problem is thatmany athletes underplay or hide theirsymptoms in order to return to activityearlier. Te risk o a concussion appearsto increase when the brain has suffereda prior concussive injury.

Until recently, little has been knownabout the long-term effects o BIs andsub-concussive injuries. Te symptomso most concussions (mild to moderateseverity) resolve spontaneously afer1-2 weeks, but a small proportion (lessthan 10%) progress to more advanced

stages with persistent symptoms andcognitive impairment. 3 Te spectrumo post-concussive conditions includesacute BI symptoms, post-concussionsyndrome (PCS), prolonged post-concussion syndrome (PPCS), mildcognitive impairment (MCI), chronictraumatic encephalopathy (C E), anddementia pugilistica (DP). 3 Incompleterecovery, early return to activity andmultiple injuries may contribute to the

prolonged duration o symptoms andgreatly increase the chance and severityo uture concussions. 3

BI is a common orm o injury,which ofen goes un-reported and iscommonly mismanaged. Researchersare just now beginning to understandthe complex pathophysiological cascadeafer a brain injury. Te current treatmentand management o BI and PCS isrest, reduction o sensory inputs, andsymptomatic treatment ( or conditionssuch as depression). 2 Conventionaland pharmaceutical approaches haveshown limited benets due to theirsingular mechanisms. Currently, noneuroprotective treatment options existthat improve symptoms afer a BI. 4Now many researchers are starting to

study a wide range o natural compoundsand vitamins that have promising broad-spectrum, neuroprotective and anti-inammatory activity.Natural Compounds forNeuroprotection and Recovery

While the evidence is ar romconclusive, some simple conclusionscan be drawn and applied to clinicalpractice. Some o the most promisingnatural compounds in active treatmento BI are CDP-choline, omega-3 attyacids, curcumin, green tea extract, vitamin E and resveratrol. From apreventative perspective, a diet high inpolyphenols ound in colour ul ruitsand vegetables, and omega-3 atty acids,along with supplementation o vitaminE, may improve recovery afer a BI.Te one denitive point is that very ew(i any) side effects and negative resultshave been ound in trials with naturalsubstances, making their use sa e.We can remain cautiously optimisticthat more evidence will emerge to

support natural therapies or BI.Tis article will explore a number othe most promising natural treatmentoptions to address the symptoms andpathophysiological pathways ound inBI. CDP-choline and omega-3 attyacids have the most evidence, while vitamin E, curcumin, green tea andresveratrol are some o the compoundswhich also offer potential therapeuticbenet in the treatment o BI.

New Perspectives and NaturalCompounds for Traumatic Brain Injury


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20 Advances

Te impact o oxidative stress onneuronal unction and plasticityafer ( BI) is becoming increasinglyrecognized. Animal studies haveevaluated the capacity o this power ulantioxidant ound in curry spiceand ound it is able to counteract the

oxidative damage encountered in theinjured brain as well as interact withmolecular mechanisms that maintainsynaptic plasticity and cognition.Other animal data suggests thatclinically achievable concentrations ocurcumin reduce glial activation and

cerebral edema ollowing neurotrauma.Supplementation o curcumin in the dietdramatically reduced oxidative damageand normalized levels o Brain DerivedNeurotrophic Factor, synapsin I, andcellular transcription actors that hadbeen altered afer BI. Furthermore,curcumin supplementation counteractedthe cognitive impairment caused by BI.Further, another animal study revealedthe potential o a curcumin derivativeto promote membrane homeostasisollowing BI, which may oster anew line o non-invasive therapeutictreatments or BI patients by up-regulation o molecules important orneural repair and plasticity. For morein ormation on Curcumin, please see thearticle titled Ayurveda and Cognition.

Green ea, Resveratrol and OtherPolyphenolsEGCG-rich green tea extract has

been shown to have antioxidant andanti-inammatory effects in animalmodels o brain injury. 19,20 Tere havealso been a number o animal trialsusing polyphenols such as resveratrol,demonstrating anti-inammatory andneuroprotective effects in BI, but likegreen tea there have been no humantrials to date. 21,22Endocrine Dysfunction and BI

Tere may be other actors toinvestigate in cases involving traumaticbrain injuries. One study investigatedthe prevalence o anterior pituitarydys unction in a multi-centre screeningprogram across ve German endocrinecentres in patients rehabilitating romBI. A total o 246 patients underwent aseries o endocrine tests. In 21% o theseBI patients, some degree o impairedanterior pituitary unction was observed.Tese ndings strongly suggest that

patients who suffer head trauma shouldroutinely undergo endocrine evaluationand may benet rom supplements thathelp to balance the endocrine system suchas adaptogenic botanicals and nutrientsto support the adrenals, thyroid and otherglands. Please see the article titled Stress-Induced Cognitive Dys untion: TeHormone-Neurotransmitter Connectionor urther in ormation on the endocrinesystems effects on cognitive health.

Metabolic disarray

Excitotoxic effects

Glutamate

NMDA-receptor

Reactive oxygen species

Nitric oxide species

Oxidative stress

Macrophages

Energy failure

Cell swelling

Microglia

Leucocyte inltration

Neutrophils

CytokinesChemokinesNeurotrophins

Capillary

Cell swelling and blood-brain barrier dysfunctionBrain oedema ICP Ischemia

I n a m m a t i o n Axonal laments

Axonal cytoskeleton disruptionImpaired axonal transport

Lactate

Glutamine

Neuronal Death

Neuronal Death

Axonal damage

Brain oedema

Figure 1. Pathophysiology of traumatic brain injury.(1) In traumatic brain injury, excitotoxic effects (which occur when nerve cells die from being overstimulated), are mediated by an increased concentration of extracellular glutamate resulting fromneuronal death and overproduction. Normally glutamate is taken up by astrocytes (cells in the brain),which convert it into glutamine and deliver it back to neurons as an alternative energy source. Ifglutamate is excessively produced, the astrocytes cannot remove it from the extracellular space.(2) Glutamate binding to neuronal receptors, such as NMDA, causes the inux of Ca2+ and Na+ andthe efflux of K+. This ion imbalance causes depolarisation of the cell membrane and an overload ofintracellular Ca2+.(3a) Compromised mitochondrial integrity is followed by release of reactive oxygen species and nitricoxide species, which together cause the oxidative stress that damages membrane lipids, proteins, and

DNA, eventually leading to death of the nerve cell.(3b) Free Ca2+ also activates several enzymes, such as caspases, which contribute to DNA fragmentationand cell apoptosis. Other calcium-activated enzymes such as calpains impair axonal transport andfunction.(4) Ischaemia (low oxygen) causes a shift to anaerobic metabolism by astrocytes, producing lactate,which provides an alternative energy source to neurons in a process called coupled lactate metabolism.(5) Neuroinammation consists of activation of glial cells (line the exterior of the neuron), theastrocytes, and microglia, which undergo several morphological and molecular changes. Glial cellssecrete inammatory cytokines, chemokines (which stimulate the transmigration of activated bloodleucocytes into the brain), and reparative factors such as neurotrophins. Together with broblasts,these cells form the glial scar, which impairs axonal regrowth.(6) Microglia accumulate in the injured brain region and phagocytose the debris that originate fromdying cells.(7) Inltrated neutrophils and monocytes sustain the immune response to injury, thus impairing theintegrity of the bloodbrain barrier, which leads to increased extracellular uid that, combined withcell swelling, leads to brain oedema and increased intracranial pressure.


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References1. Gordon KE, Dooley JM, Wood EP. Descriptive epidemiology o concussion. Pediatr Neurol. 2006 May;34(5):376-8.2. Maroon JC, Lepere DB, Blaylock RL, et al. Postconcussion syndrome: a review o pathophysiology and potential nonpharmacological approaches

to treatment. Phys Sportsmed. 2012 Nov;40(4):73-87.3. Giza CC and Diori JP. Pathophysiology o sports-related concussion: an update on basic science and translational research. Sports Health.

2011 Jan;3(1):46-514. McConeghy KW, Hatton J, Hughes L, et al. A review o neuroprotection pharmacology and therapies in patients with acute traumatic brain

injury. CNS Drugs. 2012 Jul 1;26(7):613-36.5. Blaylock R and Maroon J. Natural plant products and extracts that reduce immunoexcitotoxicity-associated neurodegeneration and promote

repair within the central nervous system. Surg Neurol Int. 2012; 3: 19.6. Levin HS. reatment o postconcussional symptoms with CDP-choline. J Neurol Sci. 1991 Jul;103 Suppl:S39-42.7. Calatayud Maldonado V, Calatayud Prez JB, Aso Escario J.J Neurol Sci. Effects o CDP-choline on the recovery o patients with head injury.

1991 Jul;103 Suppl:S15-8.8. Dyall SC and Michael- itus A. Neurological benets o omega-3 atty acids. Neuromolecular Med. 2008; 10(4):219-35.9. Mania, Wojciechowska-Mazurek M, Starska K, et al. Fish and sea ood as a source o human exposure to methylmercury. Rocz Panstw Zakl Hig.

2012;63(3):257-64.10. Mills JD, Bailes JE, Sedney CL, et al. Omega-3 atty acid supplementation and reduction o traumatic axonal injury in a rodent head injury

model. J Neurosurg. 2011 Jan; 114(1):77-84.11. Wu A, Ying Z, Gomez-Pinilla F. Omega-3 atty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain

injury. J Neurotrauma. 2007 Oct; 24(10) :1587-95

12. Wu A, Zhe Y and Gomez-Pinilla F. Vitamin E protects against oxidative damage and learning disability afer mild traumatic brain injury inrats. Neurorehabil Neural Repair. 2010;24:2908.13. Conte V, Uryu K, Fujimoto S, et al. Vitamin E reduces amyloidosis and improves cognitive unction in g2576 mice ollowing repetitive

concussive brain injury. J Neurochem. 2004;90:75864.14. Usoro OB and Mousa SA. Vitamin E orms in Alzheimers disease: A review o controversial and clinical experiences. Crit Rev Food Sci

Nutr. 2010;50:414915. Sen CK, Khanna S, Roy S. ocotrienols: Vitamin E beyond tocopherols. Li e Sci. 2006 Mar 27;78(18):2088-98. Epub 2006 Feb 3.16. Wu A, Ying Z, Gomez-Pinilla F. Dietary curcumin counteracts the outcome o traumatic brain injury on oxidative stress, synaptic plasticity, and

cognition. Exp Neurol. 2006 Feb;197(2):309-17. Epub 2005 Dec 20.17. Laird MD, Sukumari-Ramesh S, Swif AE, et al. Curcumin attenuates cerebral edema ollowing traumatic brain injury in mice: a possible role

or aquaporin-4? J Neurochem. 2010 May;113(3):637-48.18. Sharma S, Ying Z, Gomez-Pinilla F. A pyrazole curcumin derivative restores membrane homeostasis disrupted afer brain trauma.Exp Neurol.

2010 Nov;226(1):191-9.19. Wei IH, u HC, Huang CC, et al. (-)-Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons o rats ollowing

peripheral nerve injury BMC Neurosci. 2011 Jun 1; 12():52.20. Itoh , Imano M, Nishida S, et al. Neuroprotective effect o (-)-epigallocatechin-3-gallate in rats when administered pre- or post-traumatic braininjury. J Neural ransm. 2012 Nov 21.

21. Ates O, Cayli S, Altinoz E, et al. Neuroprotection by resveratrol against traumatic brain injury in rats. Mol Cell Biochem. 2007 Jan; 294(1-2):137-44.

22. Gatson JW, Liu MM, Abdel attah K, et al. Resveratrol decreases inammation in the brain o mice with mild traumatic brain injury. J rauma Acute Care Surg. 2013 Feb;74(2):470-4.

Additional Re erencesPetraglia AL, Winkler EA, Bailes JE. Stuck at the bench: Potential natural neuroprotective compounds or concussion. Surg Neurol Int. 2011;2:146.doi: 10.4103/2152-7806.85987. Epub 2011 Oct 12Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthaseinhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006 Jan-Feb; 30(1):45-51.Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial o curcumin in patients with Alzheimer disease. J Clin Psychopharmacol. 2008 Feb; 28(1):110-3.

Wu A, Ying Z, Schubert D, et al. Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive decits aferbrain trauma. Neurorehabil Neural Repair. 2011 May;25(4):332-42.Park SK, Jung IC, Lee WK, et al. A combination o green tea extract and l-theanine improves memory and attention in subjects with mild cognitiveimpairment: a double-blind placebo-controlled study. J Med Food. 2011 Apr; 14(4):334-43.Begum AN, Jones MR, Lim GP, et al .Curcumin structure- unction, bioavailability, and efficacy in models o neuroinammation and Alzheimersdisease. J Pharmacol Exp Ter. 2008 Jul; 326(1):196-208.DiSilvestro RA, Joseph E, Zhao S, et al. Diverse effects o a low dose supplement o lipidated curcumin in healthy middle aged people. Nutrition Journal 2012, 11:79Petraglia AL, Winkler EA, Bailes JE. Stuck at the bench: Potential natural neuroprotective compounds or concussion. Surg Neurol Int. 2011;2:146.doi: 10.4103/2152-7806.85987. Epub 2011 Oct 12.Kakuda . Neuroprotective effects o theanine and its preventive effects on cognitive dys unction. Pharmacol Res. 2011 Aug;64(2):162-8.


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Several studies have examined the

inuence o emotions on cognition,but common everyday situationsalso testi y to the prevalence o thisphenomenon. Indeed, who has neverorgotten something importantunder the effect o acute stress,or hasnt witnessed a menopausalrelative complaining about becomingorget ul? Te mechanisms andneural circuits involved in emotionsand cognition are inextricably

linked, and the maintenance o this

delicate neurochemical balance iseasily disrupted rom exposure tostress. Stress triggers a cascade ohormone and neurotransmitter releasethroughout the brain, affecting ourthoughts, decision-making processand behavior.Understanding the Impact of Stress

Hans Selye (1907-1982), a Hungarianendocrinologist who conducted hisresearch in Montreal (Qubec), was

the rst to give a scientic explanationor biological stress. Selye explainedthat in response to a stressor, thehypothalamic-pituitary-adrenal (HPA)system is activated, leading to a three-stage bodily response. 1 Te HPA systemtriggers the production and release osteroid hormones (glucocorticoids),including cortisol. Cortisol isconsidered the primary stress hormonedue to its importance in mobilizingsystems throughout the body against astressor. Te HPA system also releasescertain neurotransmitters (chemicalmessengers) called catecholamines,particularly dopamine, norepinephrine,and epinephrine. Catecholaminesactivate the amygdala, an area insidethe brain which triggers an emotional

response to the stress ul event. Tebrain also releases neuropeptide S, asmall protein that modulates stress byincreasing alertness, decreasing sleepand generating a sense o urgency andanxiety in the individual acing thestressor.Effects of Stress on CognitiveFunctions

Te pre rontal cortex (PFC) is theanterior part o the rontal lobes othe brain that governs higher-levelcognitive processes and executiveunction. Te basic activity o the PFCis considered to be orchestration othoughts and actions in accordancewith internal goals. 2 Under optimal,stress- ree conditions, microcircuitswithin the PFC work in concertto allow nuanced decision-making and inhibit inappropriateresponses. 3 During exposure to stresshowever, catecholamines (mainlynorepinephrine and dopamine) andglucocorticoids (mainly cortisol)

suppress activity in areas at the ront othe brain concerned with short-termmemory, concentration, inhibition,and rational thought. Glucocorticoidsactivate glucocorticoid receptors (GRs)in the hippocampus in order to storethe emotionally loaded experience inlong-term memory. 4 Cortisol may alsoindirectly exacerbate working memoryimpairments through interactionswith the catecholamine systems. 5 Tis

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Stress-Induced CognitiveDysfunction: The Hormone-Neurotransmitter Connection


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Advances 23

sequence o mental events encounteredduring stress allows a person to reactquickly in the ace o a perceived danger,but it also inter eres with the ability tohandle difficult social or intellectualtasks and behaviors during that time.

In primitive times, this brain actionwould have been essential or survival(long-lasting memories o dangerousstimuli would be critical or avoidingsuch threats in the uture) but intodays world, the almost chronicactivation o these same circuitsby non-li e-threatening stressors isproving detrimental to daily li e. Inaddition to the alteration o cognitiveand emotional processes throughout

the brain markedly impairing workingmemory, 6 the activation o the HPAaxis impacts almost every systemin our body. Research shows thatuntreated chronic stress can result inserious health conditions includinganxiety, depression, insomnia, musclepain, high blood pressure, weakenedimmune system and obesity. 7

Te question that begs to beasked is just how prevalent stress

really is. According to the AmericanPsychological Associations Stress inAmerica survey, 40 percent o all adultsadmit to lying awake at night becauseo stress. And whats worse, 33 percentreveal never having discussed ways tomanage stress with their healthcareprovider. 8

Sex Differences and Estrogen EffectsSex differences in basal and stress

HPA unction and neuropathologiesassociated with HPA dys unctionsuggest that the HPA axis is subjectto gonadal inuence. 9 For example,stress-related mental illnesses such asmajor depressive disorder and post-traumatic stress disorder (P SD) are

twice as prevalent in women.10

Toughthe exact mechanisms are not yetully understood (the vast majority obehavioral neuroscience research isconducted in male animals), a growingbody o literature points to the role oestrogen in modulating the action oneurotransmitters and glucocorticoidsdescribed above.

Several mechanisms could explainhow estrogens may sensitize the PFC to

the detrimental effects o stress. First,high estrogen levels may exacerbate theeffects o stress-induced glucocorticoidrelease. 11 Another means by whichestrogens may exert their inuenceis through the dopaminergic system.In this scenario, both high and low-estrogen emales present an increasedsensitivity to stress (see gure 1). 12

Minimizing the Impact of Stress andHormonal Imbalance

Te key to managing stress isrecognizing and changing thebehaviors that cause it. 13 However,modi ying behavior, li estyle, oreven eating habits can be challengingespecially while undergoing stress ul

events! For example, physical activityis known to increase the bodysproduction o endorphins ( eel-goodneurotransmitters in the brain) and canhelp treat mild orms o depression andanxiety. 14 Un ortunately, prioritizingexercising during intense periods ostress is not something easily achievedby most people. And when it comesdown to achieving hormonal balance,the challenge is even greater! But

No Stress

D1 signaling

optimal

poor

P F C

f u n c t i o n

Low estrogen High estrogen

Stress-induced enhancement of D1 signalling

Figure 1:Estrogen ahead of the curve hypothesis. Estrogens may amplify the stress response in females by raising baseline dopamine D1 sigmaking small shifts more apparent in behavioral measures. In this model, high and low estrogen females perform equally well at working meno-stress conditions, but mild stress shifts high estrogen animals down into the far end of the D1 inverted U, while only pushing low-estrogenacross the middle. (adapted from Selye, H., 1976)


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anxiety, 24 lifing depressed mood, 25 and maintaining blood sugar withinan optimal range. 26

Ashwagandha Ashwagandha ( Withania somni era)

is one o the best known medicinalherbs originating rom the Ayurvedictradition. In traditional Indianmedicine, ashwagandha is considereda panacea and it is used as a treatmentor an array o ailments such as: stress,atigue, pain, diabetes, gastro-intestinaland rheumatologic disorders. 27 Clinicalstudies conrm the neuroprotectivepotential o this adaptogenic herb. Ithas been shown to prevent damage toneurons and improves neurologicalunction in the presence o stress. 28,29,30 In a double blind, randomized,

placebo-controlled clinical trialassessing the effects o ashwagandhain 130 chronically stressed subjectsover a 60-day period (125-500 mg/day), a signicant improvement oscores on a standardized measuremento stress intensity, and biomarkersassociated with cardiovascular healthwas reported. Moreover, the subjectsthat received 500 mg o ashwagandhadaily had cortisol levels nearly 30%lower than those in the placebo group,and their DHEA levels were alsosignicantly higher. 31Siberian ginseng

Siberian ginseng ( Eleutherococcussenticosus), constitutes anotherexample o a widely known and well-documented adaptogen. While it is nottechnically a true ginseng botanical,E. senticosus shares similar benecialproperties with its close relativesrom the Panax amily o plants. 32 TeEuropean Medicines Agency classiesthis herb as a tonic or invigoration in

atigue and impairment, in decreasingcapability and power o concentrationas well as in reconvalescence. 33

Modulating EstrogensAs we have seen, balancing estrogen

levels is important in modulating thestress response. Supporting estrogenmetabolism by increasing sul oraphaneconsumption and modulatingtheir activity with phytoestrogenconsumption (plant-based estrogen-

like substances) can help achieve thatgoal. Since phytoestrogens resembleestradiol in their chemical structureand unction, they can help substituteor a womans declining levels oestrogens. 34 In the case o high estrogenlevels, phytoestrogens may offer someprotection by blocking the action oendogenous estrogens by interactingwith some members o the estrogenreceptor amily. 35Sulforaphane

Broccoli is a plenti ul source oglucosinolates, which are convertedenzymatically into isothiocyanates.One o the primary isothiocyanatesin broccoli is sul oraphane. Tisplant chemical has been shown toincrease the production o glutathioneS-trans erase and other phase IIdetoxication enzymes, enhance

antioxidant status, and protectanimals against chemically inducedcancer. 36 Tese power ul enzymes areresponsible or metabolizing estrogensand eliminating other harm ul toxinsand carcinogens rom the body.Hops

Although the hops plant ( Humulushupus) owes most o its ame to itsrole in brewing beer, it has a longtradition o use as a sedative and

hypnotic herb. 37 More recently,an extract o the hops cone hasbeen ound to contain a previouslyunknown class o nonsteroidalphytoestrogens (prenylavonoids)o which 8-prenylnaringenin (8-PN)is the most potent. Clinical studiesdemonstrate that 8-PN is signicantlymore potent than the isoavonesdaidzein and genistein, but marketedlyless estrogenic than estradiol. 38 Hopsextract provides the ideal balancebetween potency and sa ety when itcomes to modulating estrogens levels.

Stress ul events can lead toimmediate and marked impairmentsin working memory and othercognitive unctions which dependon a balanced neurochemicalstate. Research has shown that thisimpairment is driven by increased

catecholamines signaling, which maybe urther modulated or exacerbatedby changes in steroid hormone levels.A sa e and natural strategy to supportthe bodys capacity to cope with stressthrough the use o science-basedadaptogenic herbs, standardized ortheir content in active ingredientsand combined with the modulationo estrogen level, may help improvecognitive unctions.


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References1. Selye H. Te Stress o Li e (rev. edn.) 1976. New York: McGraw-Hill 2. Miller EK, Freedman DJ, Wallis JD. Te pre rontal cortex: categories, concepts and cognition. Philos. rans. R. Soc. Lond., B, Biol. Sci. 2002;

357 (1424): 112336.3. Goldman-Rakic PS. Cellular basis o working memory. Neuron. 1995; 14: 477485.4. De Kloet ER, Jols M, Holsboer F. Stress and the brain: rom adaptation to disease. Nat. Rev. Neurosci. 2005; 6: 463475.5. Shansky RM and Lipps J. Stress-induced cognitive dys unction: hormone-neurotransmitter interactions in the pre rontal cortex. Front Hum

Neurosci. 2013; 7: 123.6. Arnsten AF . Stress signalling pathways that impair pre rontal cortex structure and unction. Nat. Rev. Neurosci. 2009; 10: 410422.7. Baum A and Polsusnzy D. Health Psychology: Mapping Biobehavioral Contributions to Health and Illness. Annual Review o Psychology.

1999; 50: 137-163.8. American Psychological Association. Stress in America: Missing the Health Care Connection. Accessed May 2012, http://www.apa.org/news/

press/releases/stress/index.aspx 9. Viau V. Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes. J Neuroendocrinol. 2002;14(6):506-13.10. Becker JB, Monteggia LM, Perrot-Sinal S, et al. Stress and disease: is being emale a predisposing actor? J. Neurosci. 2007; 27: 1185111855.11. Arnsten AF . Stress signalling pathways that impair pre rontal cortex structure and unction. Nat. Rev. Neurosci. 2009; 10: 410422.12. Idem13. Idem14. American Psychological Association http://www.apa.org/helpcenter/understanding-chronic-stress.aspx 15. Fox KR. Te inuence o physical activity on mental well-being. Public Health Nutrition. 1999; 2: 411-418.16. Samuelsson G and Bohlin L. Drugs o Natural Origin: A reatise o Pharmacognosy, 6 ed., Swedish Academy o Phramaceutical Sciences,

Stockholm, Sweden. 2009; 226-228.17. Panossian A, Wikman G, Wagner H. Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode o action. Phytomedicine.

1999; 6 (4): 287300.18. Brown R, Gerbarg P, and Ramazanov Z. Rhodiola rosea: A Phytomedicinal Overview. Herbalgram. 2002; 56:40-52.19. Khanum F, Bawa AS, Singh B. Rhodiola rosea: a versatile adaptogen. Comp. Rev. Food Sci. Food Sa . 2005: 4; 5562.20. Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced atiguea double blind cross-over study o a standardized extract

SHR-5 with a repeated low-dose regimen on the mental per ormance o healthy physicians during night duty. Phytomedicine. 2000; 7(5):365-71.

21. Brown R, Gerbarg P, and Ramazanov Z. Rhodiola rosea: A Phytomedicinal Overview. Herbalgram. 2002; 56:40-52.22. Idem23. Zhang L, Yu H, Sun Y, et al. Protective effects o salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells.

Eur J Pharmacol. 2007; 564(1-3):18-25.

24. Li , Xu G, Wu L, Sun C. Pharmacological studies on the sedative and hypnotic effect o salidroside rom the Chinese medicinal plant Rhodiolasachalinensis. Phytomedicine. 2007; 14(9):601-4.25. Per umi M. and Mattioli L. Adaptogenic and central nervous system effects o single doses o 3% rosavin and 1% salidroside Rhodiola rosea L.

extract in mice. Phytother Res. 2007; 21(1):37-43.26. Idem27. Kim SH, Hyun SH and Choung SY. Antioxidative effects o Cinnamomi cassiae and Rhodiola rosea extracts in liver o diabetic mice. Bio ac

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