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INDEX OF CONTENTS

1 BRAIN POWER EQUALS NEUROPLASTICITY ....................................................................... 3

1.1 COGNITION AND ITS LIMITATIONS ...................................................................................... 3

1.2 BRAIN AND BRAIN PLASTICITY ........................................................................................... 5

1.3 REWIRE YOUR BRAIN ........................................................................................................... 7

1.4 HOW TO PROMOTE NEUROGENESIS NATURALLY ......................................................... 11

2 MENTAL PREPARATION FOR OPTIMUM BRAIN POWER ................................................... 13

2.1 LEARNING PREPARATION AND GUIDLINES ..................................................................... 18

3 PSYCHOPHYSICAL PREPARATION FOR OPTIMUM BRAIN POWER ................................. 24

3.1 BRAIN FOODS ...................................................................................................................... 24

3.1.1 Brain food guidelines ........................................................................................................ 26

3.2 EXERCISE ............................................................................................................................. 27

3.2.1 Proposed workout system ................................................................................................ 28

3.3 SLEEPING HYGIENE AND NEURAL PLASTICITY .............................................................. 31

4 NOOTROPICS ........................................................................................................................ 33

4.1 NOOPEPT ............................................................................................................................. 34

4.2 HUPERZINE-A ...................................................................................................................... 35

4.3 ALPHA-GPC .......................................................................................................................... 35

4.4 PANAX GINSENG C.A. MEYER ........................................................................................... 36

4.5 RHODIOLA ROSEA .............................................................................................................. 37

4.6 GINKGO BILOBA .................................................................................................................. 38

4.7 L-THEANINE ......................................................................................................................... 39

4.8 PHOSPHATIDYLSERINE ...................................................................................................... 40

4.9 TIMED-RELEASE CAFFEINE ............................................................................................... 40

4.10 MgT (MAGNESIUM-L-THREONATE) .................................................................................. 41

4.11 IRON + vit C ........................................................................................................................ 42

4.12 B-COMPLEX ....................................................................................................................... 43

4.13 ACETYL-L-CARNITINE (ALCAR) ....................................................................................... 44

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1 BRAIN POWER EQUALS NEUROPLASTICITY

1.1 COGNITION AND ITS LIMITATIONS

Cognition is the process of acquiring knowledge and understanding through thought, experience, and the senses. It is highly theoretical »umbrella« term which encompasses practical processes which are used by every individual on day-to-day basis:

a) knowledge

b) attention

c) memory and working memory

d) evaluation and judgement

e) reasoning, decision making, computing and problem solving

f) production of language.

It is obvious our lives wouldn't be half as interesting without those conscious, but as well unconscious cognitive actions – we are constantly using existing knowledge and generating new one. And exactly the process of acquiring new knowledge, to resolve unsolved mysteries of the past, to know and understand more than others have resulted in new intellectual movement, called transhumanism. Transhumanists want to transform the human condition by developing technologies and processes to profoundly enhance person's intellectual, physical and psychological capacities. Transhumanists – but also all people ambitious enough – want to overcome physiological limitations and become better, progress beyond average, not ever being stuck in a mediocratic lifestyle. They have started to exploit the possibilities beyond biological limitation, they are becoming so-called biohackers. Ron Shigeta from Berkely Biolabs adresses biohacking as preferring

»the freedom to sort of dig deep into something, just because you’re interested in it. … The whole idea of biohacking is that people feel entitled, they feel the ability to just follow their curiosity – where it should go –and really get to the bottom of something they want to understand«.

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The building blocks of this new philosophy which is already becoming a lifestyle are also nootropics (also called smart drugs or cognitive enhancers). Every drug, supplement, or other substance that improves cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals, can be considered to have nootropic characteristics. Even coffee, the most used drug in the whole world, contains alkaloid caffeine which increases focus and can therefore be classified as a nootropic, if speaking in everyday (non-professional) terminology. But there is one important additional characteristic that every nootropic should possess (which caffeine alone doesn't) – neuroprotection without adverse effects or toxicity. Romanian psychologist and chemist Corneliu E. Giurgea, the father of nootropics who synthetized Piracetam in 1964, stated that nootropics should have the following characteristics1:

1. They should enhance learning and memory. 2. They should enhance the resistance of learned behaviours/memories to conditions which tend to

disrupt them. 3. They should protect the brain against various physical or chemical injuries. 4. They should increase the efficacy of the tonic cortical/subcortical control mechanisms. 5. They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation) and possess

very few side effects and extremely low toxicity.

But supplementation alone cannot produce the maximum effects to prolong longevity, enhance cognitive functioning, neurogenesis or even long-term neuroprotection. There is a lot we can, and must, do by ourselves with a healthy lifestyle, including diet, sleep patterns and exercising, appropriate work and study techniques and last but not least, relaxation and general (positive) attitude towards life. This guide will help you to understand the basics of brain functioning, present you how to optimize learning efforts and promote neuroplasticity (teaching an old dog new tricks) through simple techniques and life choices. The mission of this handbook is to present you the most realistic and achievable ways of optimizing the usage of nootropics and it is divided into four main sections – intro, mental preparation, psychophysical preparation and nootropics.

1 . http://www.liquisearch.com/corneliu_e_giurgea

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1.2 BRAIN AND BRAIN PLASTICITY

The brain structure is not an immutable machine, but a changeable »muscle« - the phenomenon which is called neuroplasticity or brain plasticity. Brain is changing through the entire life and neuroplasticity can be promoted on a tiniest scale, where individual neurons are changed, but also through general cortical remapping. Nootropics or environmental stimuli can also cause neuroplastic change which we can actually feel as learning or memory enhancement.

Let's talk Brain 101. Neurons are electrically excitable nerve cells – there are around 86 billion of them present in the human brain – which process and transmit information through electro-chemical signals. The small gaps between them are called synapses which pass information from one to another. The interesting fact is that half of the neurons don't survive the passage from adolescence to adulthood – scientists have previously thought that neurons cannot reproduce after the first few years of life, but neurogenesis may continue to occur throughout the whole lifespan. It is an optimistic thought since science may discover an effective way to guide the neuronal growth to repair damaged or diseased areas of the brain.

New findings show us that despite some concrete pathways which are strengthened every time we do a routine thing, brain has an ability to form new pathways, which are also strengthened if we practice new habits. Furthermore, old pathways which are not used in an ordinary fashion anymore, weaken – we can deliberately rewire our brains by directed attention towards a desired change.

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This is sometimes hard because the mesolimbic dopamin system encourages us to seek pleasure and rewards, which leads to meritocratic survival, but not induce any progress. When the reward pathway is activated, the brain is flooded with dopamin – we feel good and we repeat and repeat the activity as the addict's cerebral cortex is trumped by dopamine overload2.

Hippocampus remembers this rapid sense of satisfaction and the circle is connected – prefrontal cortex drives us to seek out the substance or the experience, dopamine is released from nucleus accumbens, hippocampus notes the satisfaction and amygdala remembers further environment cues as people, places, sights or sunds. Not really what we want in long term, since the dosage of habitual pleasures must be eventually increased3.

2 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures sources – whole chapter – George Mortimer) 3 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures sources – whole chapter – George Mortimer)

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1.3 REWIRE YOUR BRAIN

Let us ask ourselves one thing – would we rather stay in the safety of comfort zone, surviving through everyday routine, settling for average, or take some risk in discovering the unknown, what might lead us to getting the most out of lives? Is it possible to deliberately change our mindset to recognize and avoid triggers which cause a downward spiral – social triggers as false friends, emotional triggers as need for attention or unnecessary stressful situations, but even some enviromental ones such as common places?

We have good news. You can rewire your brain to stimulate the process of neuroplasticity (»neuro« = brain, »plastic« = changeable) just by thinking. But you must practice, practice and again, practice! The process of neuroplasticity is quite simple, but you must follow it rigidly every day4:

1. Set (realistic but stil ambitious) goals.

2. Avoid old habits and triggers which cause a downward spiral.

3. Make conscious decisions (it is harder than you think).

4. Seek pleasure and award from »healthy« pursuits.

5. Every time you force to repeat advice from #4, the new pathway gets strentghened.

4 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures sources – whole chapter – George Mortimer)

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6. New healthy habit is formed and not seen as »must do« anymore.

What have we made pursuing this six points? We have avoided being flooded with rapid sense of satisfaction, our dopamine is stable and amygdala has registered the new activity as improved satisfaction. This is how we can find higher goals, such as studying, sport activity or hobby even more gratifying and refreshing as the third snack we want to eat after the dinner.

Sometimes old habits or instant gratifications leads us to old pathways. It is normal that we would often rather watch a movie than learn a new language. »Der«, »die«, »das«, » den«, »die«, »das«, »dem«, »der«, »den« - of course we cannot say this sound as rewarding as two movies in a row, but still, with repetition you can convience our brain that »beta« version of you will produce more comfort in near future. Here we gathered a just a few ad hoc guidelines to avoid that5:

1. Avoid substances, habits or situations that provide you with unhealthy rewards.

2. Learn to combine comfortable and responsible part of life in which your brain is rewarded by further healty pursuits.

3. Exercise, meditate, sleep and eat well.

4. Seek support from your friends, family and peers when you get »too tired«, »too hungry«, »too lonely« or »too angry«.

5 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures sources – whole chapter – George Mortimer)

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The most important part is the actual brain training. The logic behind it is simple – if you don't learn new skills, your brain wouldn't promote the process of neuroplasticity. If you want to keep the brain in good shape, you should engaged in highly focused activities or environmental shifts such as:

If such mental exercise seems baloney to you, read further. Dr. Alvaro Pascual-Leone, professor of Neurology at Harvard Medical school can prove you that »mental training has the power to change the physical structure of the brain« with a simple experiement6:

6 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures sources – whole chapter – George Mortimer)

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As you can see, the power of mind can physically remodel the structure of the brain. Such changes are not happening just in vitro, but in everyday life – since the musicians have typically 130% more grey matter than London cab drivers, they on the other hand has much larger hippocampus which can store a detailed mental map of the city. Brain is a muscle that grows and changes with exercise, which results in faster processing, improved memory, languange skills, enhanced creativity and problem solving ability. We must bear in our mind that not just actual brain »work« increases brain power. We must find our own ways to become calm, we must create mechanisms to become aware of our thoughts and (habitual) decisions by observing our inner experiences as if the were happening to someone else7:

Remodeling structure of brain by forming new brain cells is called neurogenesis. Beside actual mental work this process can be induced by proper food combination – fish and nuts contain omega-3 phospholipids, which upregulates adult neurogenesis8. This is especially beneficial if combined with regular exercise (promoting growth hormone and brain derived neurotrophic factor) and use of “smart” nootropics. Why we said smart? The nootropic trend is going skyhigh and many companies are selling unregulated stimulants as “Adderall”, which works fine during the night (intended for narcolepsy), but might produce neurotoxicity on long-term. At Brainlabs we developed a nootropic formula that is safe and efficient at the same time. We have mentioned omega-3 phospholipids – every ingredient in Examfit is chosen to work sinergistically with other compounds, but also with food we are consuming. Alpha-GPC (200mg) is a superior choline source with omega-3 bonding potential – its precursor is body endogenous phosphatidylcholine, from which our learning neurotransmitter acetylcholinge can be derived9. Alpha-GPC which promotes synthesis of cell’s membranes phospoholipids at increased

rates if combined with DHA- and EPA-containing foods (fatty acids)10. Another ingredient in Examfit which is linked to food we digest is phosphatidylserine (100mg) – it is needed for establishing channels for cell-to-cell communication by building up neuronal membranes (so that neurotransmitters can cooperate). It is a structural component of a cell's bilayer, but it has also a powerful downregulating effect on the enzyme that disintegrates our chief learning neurotransmitter, the process which always correlates with increased levels of acetylcholine11.

Adult neurogenesis is a crucial factor in brain performance, that is why we gathered information and made it simple so everyone can grow new brain cells.

7 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures sources – whole chapter – George Mortimer) 8 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892224/ 9 http://www.ncbi.nlm.nih.gov/pubmed/20492936 10 http://www.ncbi.nlm.nih.gov/pubmed/16366737 11 http://www.jbc.org/content/146/1/35.full.pdf

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1.4 HOW TO PROMOTE NEUROGENESIS NATURALLY

Neurogenesis is the process by which neurons are formed from neural stem cells. The adult neurogenesis differs significantly from that we were going through in our childhood and teenage years – scientists believe that hippocampal adult neurogenesis plays a crucial role in learning and memory formation. The very act of learning is associated with increased rate of neuronal survival12. But what is more important, there are simple ways we can promote neurogenesis – from eating berries to exercising13.

An exercise regimen

A study at the Colombia University has shown that moderately to highly trained individuals were able to grow and maintain new neurons in the dentate gyrus of hippocampus at a 2-3 times rate that those who didn't exercise.

Eating blueberries

In one study, rodents were put on blueberry enriched diet and in the hippocampus region new brain cells were generated. Scientists figured that a so called anthocyanin-dye contains chemicals that can promote the growth of neurons. They believe that anthocyanin dye produces the same effect on the brains of humans.

Taking time for meditation (of any kind)

Researchers at Yale, Harvard, and Massachusetts Institute of Technology revealed that meditation can allow us to “grow bigger brains.” Though this isn’t the same thing as neurogenesis, meditation could very well be an activity that boosts the birth rate of neurons. Meditation also alters the brain structure, enhances brain waves and thickens grey matter.

12 http://www.sciencedirect.com/science/article/pii/S0959438804000339 13 http://4mind4life.com/blog/2008/08/18/7-scientifically-proven-ways-to-stimulate-brain-cell-growth-neurogenesis/

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The very act of learning

Scientists have found the direct relationship between learning and the survival of newly-birthed neurons – the more you learned, the more new cells are able to survive in the hippocampus. Those which would normally die are »rescued« by new experience – so don't forget to always learn something new.

An enriched environment

Studies have shown that memory-related tasks were significantly enhanced when living in a healthy, enriched environment – in rodents they even found larger hippocampus regions. The correlation doesn't end here. The people around us are of equal importance, if not higher.

Restricting caloric intake

This phenomena has not been completely researched – maybe due to the HGH secretion, calorie restriction in middle age is associated with 10-20% increase in longevity, but also enhanced neurogenesis and neuroprotection.

Restricting calorie intake has been associated with an increase in neurogenesis and a better overall neuroprotective effect. Scientists have found that calorie-restricted animals nearly always stay active and healthy up until the end of their lives’. This phenomenon has also been associated with a significantly lowered likelihood of developing a degenerative brain disease and can even produce new nerve cells!

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Usage of nootropics

Some nootropics such as Huperzine-A, Rhodiola rosea, Ginkgo biloba are powerful promoters of neurogenesis in different regions of the brain (most profoundly hippocampus. If you stack those nutraceuticals with some modulated synthetic nootropics (Noopept, acetyl L-carnitine) we can achieve also enhanced secretion of specific growth factors (NGF, BDNF). All this ingredients are found in Examfit, the first 4-level nootropic formula.

2 MENTAL PREPARATION FOR OPTIMUM BRAIN POWER

As we have seen in the previous chapter, we can promote physiological changes that enhance the basic set of cognitive processes purely with the power of mind. Since the pursuit of »healthy habits« – one of them is learning – may not provide you with instant gratification, we will present you just a few methods how you can make it more pleasant while optimizing your cognitive functioning. Michael Roizen, MD from Cleveland clinic suggest you to follow some crucial »must-dos« for a healthy brain before engaging in demanding mental tasks14 15 16:

1.) Establishing fullfilling social connections.

2.) Finding / creating a purpose in life.

3.) Mental game stimulation (not just chess).

4.) Deep breathing.

5.) Meditation and stress management.

6.) A few minutes of very intense exercise, three times a week following by minimum 30 minutes of moderately intense exercise (heart rate greater than 80% of 220 minus your calendar age) – the single most important item in this section which will be discussed thoroughly in Chapter 3.

We won't go step by step. This is in contrary with everything we have learned so far. Let us concentrate on the most awkward one and start with letter d) – deep breathing. It sounds like a »new age« invention, but we can assure you it has its origin in physiology of human brains, since it can promote neuroplasticity and produce new pathways. This mindfulness-based relapse prevention (MBRP) approach tries to increase discriminative awareness which help us to accept uncomfortable states or challenging situation without reaction impulsively. The next simple task may not be so simple after all, and yet we ask you to do just two things simultaneously:

14 https://my.clevelandclinic.org/ccf/media/files/Neurological_Institute/Cleveland-Clinic-Food-for-Brain-Health-Michael-Roizen.pdf 15 http://www.emedexpert.com/tips/brain.shtml 16 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures source – George Mortimer)

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Next example presents diametral oposition of the upper case – the purpose of your existence. How can you do a demanding project or study those boring »Pearson's coefficient« if you don't know what for? Everyone should find their own purpose – we are born to learn whatever is important to us and do this as often as you can. Finding happines in that is sometimes quite difficult. But we must emphasize that we have more control over it than we think. As we are able to unform some »unhealthy« habits, we can also produce patterns for happines. Dr. Richard J. Davidson from University of Winsconsin-Madison is assured that »emotions, moods and states are trainable mental skills«17:

17 http://www.lifehack.org/288159/infographic-tell-you-how-your-brain-works-and-how-train?mid=20150630&ref=mail&uid=499015&feq=daily (pictures source – George Mortimer)

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Happiness can be produced by following some simple methods and life choices. We have mentioned social interactions – from talking on the phone (yes, we know it sounds so 90s) to sharing your most private feelings and concerns. Socializing itself is a form of mental exercise, because dealing with people can be pretty challenging. Researchers from US even made a direct correlation between 10 minutes daily talks and improved memory and test scores – not to mention neuroprotection.

We dont wish to judge anyone for their values and life orientation, but no matter how ambitious you are, you must agree with Coco Chanel's statement that the best things in life are free.

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All listed suggestions go hand in hand with stress management, meditation, and relaxation, no matter how we label it. You must have read a thousand times that chronic stress leads to elevated cortisol levels which may be dangerous to the brain – it can cause hippocampus atrophy or neural death in some other brain regions (mostly in prefrontal cortex) since this areas have many cortisol receptors. Even short-term intensive stress can activate high amount of selective molecules called corticotropin releasing hormones, impairing memory storage and retrieval. That is why you should try to learn to see problems as opportunities, learn relaxation techniques such as meditation, cut down on over-scheduling,

make time for leisure activities and last but not least, laugh as often as you can. Humour promotes secretion of dopamine and improves memory. Everyone should find their own relaxation technique – some of them (playing an instrument or singing) can provide you with additional cognitive benefits (easier language learning).

Additionally, you can use herbal nootropics and adaptogens to battle stress and lower your cortisol levels. You must know that cortisol is not the enemy, it is your friend. Cortisol is like a firefighter which came to rescue your house (body) before it burns (inflammation) to the ground. In Examfit you can find the best natural nootropic herbs which can low-grade inflammation caused by stress – 150mg of Panax ginseng with minimal 10% of ginsenosides and 50mg of 10:1 ratio of Rhodiola rosea (min. 3% rosavins), equivalent to half of gram of usual extract. Those are considered the strongest adaptogens when taken together, successfully reducing brain fatigue. When combined with 200mg of Ginkgo biloba, brain-targeting adaptogen and neuroprotector, 180mg of L-theanine which produce alpha-1 waves and promotes relaxation without sleepiness, and mild psychostimulatory and mood enancing effect of 18mg of Noopept, you should notice the difference the very first day.

We came to the most important section of mental part, mental stimulation. No matter what we do in life, we should always try to be mentally charged and prepared for challenges, or our brain may atrophy – according to the researchers from Albert Einstein College of Medicine the risk of dementia can be lowered as much as 75% with the simplest mental stimulations. Do not ever (ever!) fall into the routine and forget to:

a) Travel as much as you can.

b) Go to museums and events.

c) Read – newspapers, studies, books, fairy tales.

d) Play instruments even if you feel untalented

e) Dance.

f) Do crossword puzzles or play games with your friends.

g) Learn crafts such as painting.

h) Force yourself to calculate (without the calculator).

i) Volunteer, meet different people.

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Furthermore, once in a while you should engage in a so-called mental game, brainy challenges or neurobics. An unique system of brain exercises stimulates both physical and emotional senses in unknown ways that shake up your everyday routine – even tiniest changes in life patterns can induce brain changes. Dr. Lawrence C. Katz, a neurobiology professor at Duke University Medical centre believes that the simplest everyday exercises can activate underused nerve pathways:

a) Dressing while keeping your eyes closed.

b) Using the other hand while brushing your teeth, dialling the phone or operating remote control.

c) Going to school via different road.

d) Doing »multi-sensing« - listen to music while smelling the flower.

e) Buy groceries at a new store.

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2.1 LEARNING PREPARATION AND GUIDLINES

Here we are coming to most demanding but also common mental tasks – learning and studying. Guidance we have presented form a solid mental base for focus, motivation, memory formation and recall and problem solving while studying for exams or upcoming work projects. Because of its central role we sum up some of the best techniques which will help you pass an exam or complete a project before the deadline.

Learning and studying are the fundamental stones of knowledge. We learn from our parents as children, as pupils at school, we study for exams at faculties and later doing work projects. When formalities are over, we are looking for knowledge to live a more fulfilled life. But it is not the same if we just read and listen or if we follow certain guidance that have been used by millions of people before you18 19:

a) Before starting to study, ask yourself why are you studying. Studies have shown that how you approach the whole process matters almost the same as how you do it. You should establish a positive mind-set – we have talked before about pursuing the healthy habits – which will help you to think positively (»It is not too late, I will do even better if I concentrate«), avoid absolute thoughts (»It is always the same«) and comparisons with others. Do not procrastinate – not because of your test scores, but because this will put you in an even more stressful situation.

b) The optimal study environment is major factor for your academic or work performance. You should avoid places with a lot of distraction (TV, computer, a roommate). Computers and smartphones are powerful distractors that usually don't have anything to do with studying – if you can’t control this habit, put it away and turn to old-fashioned paper. But bring anything you need (food and drink included) that you wouldn't waste time with running back and forth. You should:

choose a quiet place for studying,

18 http://psychcentral.com/lib/top-10-most-effective-study-habits/ 19 https://www.intelligent.com/

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set a prearranged time for study sessions (and breaks),

gather all the study materials you will need (textbooks, notes, memory cards) and temporarily block all your social media accounts and games.

c) Look into yourself and your previous achievements. If you didn't achieve well in the past, find a different approach, different atmosphere and different motivation. Changes will boost your confidence and attitude towards life goals. If you are already a good student/learner and have the benefits of firm building block, upgrade them further – you can find ways of saving time or fine-tuning your study techniques. You should know that good planning, down-to-earth organization (including your personal interests, spare time and hobbies) and especially a good study strategy – fine-tuned to your study content – is the only thing that will reflect your academic (working) performance. Let us emphasize again – good strategy counts, not your history.

d) Make a study plan and schedule study time. If you prepare a plan, you will avoid last-minute cramming sessions. The plan isn't about frequency, but about studying on a regular basis. You should also define breaks and rewards which will additionally reinforce your study efforts, making them more sustainable and enjoyable. By setting limits to yourself you are actually teaching

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yourself what we have labelled as »pursuing healthy habits«, which are accompanied by rewards. If this is your first plan, you can check some of the many online »study planner apps« (My Study Planner). A reasonable study plan should be consist of:

Time chart, which elaborates your work, study and spare time activities (general one, then subordinate one, for example one week period).

A schedule. This is not the same as time chart – time chart determinates available days, but a schedule marks them into your calendar day by day and hours (economics Monday to Thursday, epistemology Saturday and Sunday). A schedule is not just about sticking to predefined study hours, but also about prioritizing your assignments – devoting more time to new subjects and organizing a schedule that you will always study harder subjects or making long-lasting projects first20.

Study goals. Dont just think about them – write them down, best at the beginning of each week. Tactics differ significantly if you take a big exam or if you want to raise your average. If you don't have a big test ahead of you, you can read some additional literature in order to grasp the next chapter, but when preparing for upcoming midterms, you should define the time for review of the old midterms and organizing your notes.

Take time for spare-time activities, which will make your mind more receptive while actively studying: exercise, hobbies, socializing. Usually students do not study enough, but you can easily fall into over-study mood. Reserve or at least count in time for »temptations« of any kind – by admitting your weaknesses you wouldn't be discouraged when compromising over fun stuff. Note – reward will come and that thought should give you an extra boost of motivation to accomplish your final goal.

Re-evaluate your study plan and fine-tune it after each exam or term. If it didn't serve you well, something must have been wrong – personalise the strategy and use all your experiences from your previous wins and fails. Maybe you just lack of organization methods that work for you.

20 http://au.reachout.com/how-to-write-a-study-timetable

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e) Use proven and advanced study methods, especially regarding notes and memorizing:

In order to take (and make) effective notes you must first be prepared for class (aka not forgetting your pencils, pre-prepare a binder or folder to organize notes, maybe set a tape recorder if you are not a fast writer). Listening skills and good judgment is fundamental for taking effective notes – focus only on the lecturer, point out the key concepts, note what the professor writes down on the whiteboard etc).

Then you must reinvent the note-taking method that is best adjusted to your learning style (different coloured pens, abbreviations/symbols, notebooks etc). Before that, compare them with other students – you will gain perspective and insight into other (maybe better) »note takers«21.

Outline and review your notes. After class you must make necessary edits (backups if in digital form), since fast-writing makes them messy and disorganized. Yet at this moment you must research any conceptualisation you didn't understand and reference any chapters in textbooks your notes correspond to. Than make a system that suits your learning style to remember pieces of information - connecting similar concepts together (»chunking«) makes them more memorable, but since every student is unique you should do that in your own concepts, words and structure. You must always transform information into terms you understand the most.

f) Start studying. Don't procrastinate! You must start step by step – the sooner you start the lower the pressure will be:

21 http://cw0630.tumblr.com/post/116304730687/how-i-write-outlinestake-notes-for-those-of-you (source of a photo)

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First go through chapters, explore heading and subheading, bold text and important references and last but not least, first go through summary at the end of each chapter. Make a preliminary research that you will understand what you will be reading about and how much time you will spend and point out important questions (that you will answer later while reading).

Study. Read the chapter your professor will be lecturing in advance – you will be more receptive and understand upcoming challenging concepts. After class read again, more profoundly. It is really hard to force yourself to sit down the same day, but it definitely works. Recite the learned info and answer the pre-developed questions – when you gathered a complete grasp of material, put the concept into your own terms and repeat them again. And then, practice as if you are on the real exam using an old exam – again, don't study it, practice (practice makes perfect) it as guide. You can practice in a group of people with similar academic aptitude – going through chapters together or quizzing one another.

Take brakes and rewards. Rewards can be small, but real (»I can spend an extra 30 minutes gaming for every 2 sections of a book chapter I read«). Dreams, on the other hand, must be big. Dream big!

Use advance methods and learning styles. Use anything that helps you. Memory games or mnemonic devices are methods for memorizing using simple associations – if you use the first letter of each word the newly invented phrase you come up with will become more memorable. We all know what ASAP stands for – vice versa, the mnemonic for the lines of the treble EGBDF (musical notes) can be transformed into »Empty Garbage Before Dad Flips«. Other people prefer image-word association – they relate an unfamiliar term to familiar image. Story telling can be also beneficial since what you have visualised in your head will never gone forgotten. Analogy in terms of cause and effect will help you to developed patterns and you will digest course material much easier.

Review everything you have learned – browse your notes to recall, predict important plausible questions, read what you didn't understand completely again and again until you do. Don't forget to review your notes also – they might be insufficient, incomplete, not detailed enough.

g) Play smart through exam day:

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Be mentally and physically ready. Take a good night sleep – brief review will help, night-long study won't. Don't consume excessive caffeine and don't forget to have a healthy meal with enough hydration (bottle of water with you).

Research the format of your test – you can save time for some sections of the test if you know where your weaknesses will be in advance. Rules are also important (restroom, time limit etc).

During an exam read the test directions closely and don't be embarrassed to clarify if something is unclear. If panicking, take several deep breaths. Glance over the entire test (no need to closely inspect them), point out the sections with the highest point value, then read every question closely to see if the professor is just looking for knowledge or if he/she wants to challenge you. Pay attention on key-words in essay questions, address the topic with a direct response (show your reflective thinking but don't show off – this tactic did sometimes work only when I didn't know the actual answer). Don't forget to strategize, especially if there are multiple-choice questions with negative points you must decide where is the space for educated guess and where is not. And never – we repeat – never look toward other students’ answers. If you have time, you should rather double-check your exam for mistakes.

After the exam, do not dwell on how it went. Relax. You have done your best. When you receive the results, you will be able to determine your weaknesses and review your learning strategy. Review/revise your test if possible.

And remember: You can't fail, if you never give up!

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3 PSYCHOPHYSICAL PREPARATION FOR OPTIMUM BRAIN POWER

Before you start to google for »Top 10 study tips« or searching for magical pill, you should bear in mind three golden rules that will enhance your cognitive functioning beyond everything else: Eat well, sleep well and exercise! Why is that trio so important to our brains? Let us start with brain foods.

3.1 BRAIN FOODS

Food was traditionally seen as an energy source and building block of the body, but also as a preventor and protector against diseases. Lately it was recognised by another influential factor – altering the mental function. Omega-3 fatty acids were one of the first nutrition to be known for up-regulating genes, important for maintaining crucial cognitive processes. Progressive research methods have revealed additional benefits – enhancing synaptic plasticity (which we have mentioned in previous chapters), influencing cell metabolism (insulin) and brain health, but also the unconscious processes of emotions, which influences mood and may cause some unwanted psychiatric manifestations. Feeding has – throughout the whole evolution – become an adaptive mechanism for developing cognitive skills. If we stick by DHA, which is the most abundant omega-3 acid in the brain membranes, we can see that solely the access to that nutraceutical during hominid evolution is responsible for increasing the brain/body weight ration.

In a last decade intensive studies have been made, revealing some yet unknown fields which are strongly associated with cognition. Studies have shown that gut indirectly influences the brain plasticity and learning through several gut hormones or peptides. Leptine which sends signals to the brain to supress appetite additionally directly facilitates plasticity in the hippocampal region, promoting long-term potentiation (LTP). Gherlin, on the other hand, is secreted when we feel hungry, but also promotes rapid reorganization of synaptic terminals in the hypothalamus and formation of synapses in dendritic spines, which have been linked with enhanced spatial learning and memory formation. The last but definitely not least, insulin interacts with specific signal-transduction receptors in hippocampus what alters synaptic activity and the whole field of cognitive processing. We know that food gives us energy, but it can also influence the management of energy in neurons and affect synaptic plasticity – BDNF growth factor affects parameters of metabolism such as appetite suppression or lipid transformation, but it carries out also a task of (increased) BDNF-mediated neuroplasticity. Several human studies regarding mutation in BDNF receptors have shown both hyperphagic obesity and learning or memory impairments. It is quite a complex mechanism, since BDNF is acting via insulin-like growth factor 1 (IGF-1) – if enhances not only processes such as diabetes and aging, but also inhibits nerve growth and differentiation, neurotransmitter synthesis and brain plasticity. Here the DHA again plays a crucial role, since stimulating neuronal plasticity through the specific signalling pathway called Akt. If we go further, abnormal

metabolism (diabetes type II) has been strongly linked with severe psychiatric disorders such as schizophrenia and manic depression. In those disorders the low BDNF and diabetes are almost always present simultaneously – that is why both states are treated with drugs and exercise, which influence on mitochondria processes.

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Since DHA is known to be a crucial micronutrient for facilitating brain plasticity and enhancing synaptic membrane fluidity (and reducing oxidative stress, stimulating glucose utilization etc), there is also a pile of epidemiological studies suggesting that food rich in trans and saturated fats negatively affects cognition. One study has shown decline in general cognition and reduced levels of BDNF-related brain plasticity after only 3 weeks of »junk food« administration, regardless of pre-existing insulin resistance or obesity. We can moderately buffer the adverse effect of unhealthy diet with supplementation, but there is a catch. Let’s exemplify that with at quercetin, a major flavonol found in Ginkgo biloba, because it is present also in Examfit (200mg). Its bioflavonid has reduced learning impairment in cerebral icheaemic in rodents, its antioxidant effects are well established in vitro, but still, there is great doubt about reversible in vivo actioning (for any nutraceutical). Most of whole foods – berries are great example for antioxidant food increasing hippocampal plasticity and IGF-1 – probably help to maintain metabolic homeostasis as this protects the membrane from lipid peroxidation (especially in mitochondria). You can use also nootropics such as Noopept, which promotes both IGF-1 and BDNF factors.

Interestingly, the poor dietary supplementation effectiveness can be enhanced by regular exercise – it has been well documented that regular and moderately intensive exercise can reduce the deleterious effect of unhealthy diets since BDNF and BDNF-related molecules are strongly connected with synaptic function. Despite that we suggest a healthy diet (plenty of sleep and regular physical activities) over such supplemented »reparative therapy«.

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3.1.1 Brain food guidelines

Michael Roizen, MD from Cleveland clinic made a brief list of foods, enhancing several aspects of brain functioning and neuroprotection. His suggestions are oriented more around what to avoid over what to eat:

a) Saturated and especially trans-fat – swap burgers with salmon burger or plain turkey, discover the world of »meaty« mushrooms as Portobello (Examfit's commentary: avoid trans-fat and hydrogenated oils completely, but use a moderate amount of butter, coconut oil etc, avoid frying, grilling and other high-temperature cooking methods).

b) Added sugars or syrups – say »No« to soda and sweetened nectars (Examfit's commentary: such syrups are not e.g. maple or syrups in general, but high fructose corn syrups – in Europe that is called glucose-fructose syrup and is present in practically almost every nectar you can buy).

c) Enriched, bleached and refined flour – you should search for whole grains, since those »empty« grains can pass through your intestines spiking your blood sugar metabolism and impair your gut (which we know is interconnected with our brains).

Next step – you should move to food of the choice:

a) Mediterranean diet – people in their 70s in that regions are more than 60% less likely to develop Alzheimer's, eating fish, good fats, legumes, veggies and fruit (Examfit's commentary: pay special attention to blueberries).

b) Omega-3 food and DHA – beside fish, eat lots of walnuts, avocados, flaxseeds, soybeans, canola or olive oil, fortified eggs, chia seeds, walnut and flaxseed oil (Examfit's commentary: long-lived tuna accumulates lot of mercury from the environment, so try not to eat it too often – sardines, mackerel, trout or salmon is a better choice).

c) Leafy greens, especially spinach, tomatoes and onions – according to the studies, carotenoids and flavonoids slows mental decline ad actually makes you and your brain 5 years younger, so eat them every day as carbs subsidiary to proteins. (Examfit's commentary: Add turmeric to every dish that goes by).

d) Quinoa, insoluble fibre and brown rice as carbs of the choice.

e) Drink coffee and tea – studies have shown that 3 coffees a day decrease a chance to develop dementia by 65% while L-theanine activated a part of the brain’s circuitry which promotes attention span. (Examfit's commentary: avoid too much caffeine since it produces rapid spike in human adrenal response, followed by a »crush« - not to mention possible cardiac issues if you are not regularly stress-tested. We suggest stacking caffeine with L-theanine what eases the jitteriness.

Examfit is designed to follow those guidelines multi-target agents. It contains alpha-GPC, which forms a new brain membranes and phosphatidylserine, which promotes inter-neurotransmitter communication, especially if combined with omega-3 food. It contains natural compounds acting against diabetes by reducing blood sugar levels in brains – Rhodiola rosea is known for reducing diabetic toxins and preserving stem cells22, Panax lowers mental fatigue via reducing blood glucose in brain23. Ginkgo biloba is the best example of “greens”, containing various bioflavonoids (quercetin). Combination of slow releasing caffeine and L-theanine, amino acid from green tea in 1:2 ratio promotes speed and accuracy in highly-demanding attention-switching task24. Last but not least, Noopept and Huperzine-A promote neurogenesis by increasing secretion of growth factors such as NGF, BDNF and IGF-12526.

22 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029641 23 http://www.ncbi.nlm.nih.gov/pubmed/15982990 24 http://www.ncbi.nlm.nih.gov/pubmed/18681988 25 http://www.ncbi.nlm.nih.gov/pubmed/19240853 26 http://www.ncbi.nlm.nih.gov/pubmed/23454433

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3.2 EXERCISE

If we look in our evolutionary past we see that our genome – accompanied by active lifestyle which predominated throughout almost 100% of humankind's existence – has been unchanged since our hunter-gatherer-times. But sedentary lifestyle, potentiated by comforts of technological progress is undoubtedly revenging on the health of our brains, with the higher and higher percentage of metabolic disorders. The ability by which exercise influences on the molecular system became especially important for promotion of synaptic plasticity, which enhance learning and memorization – we know that intensive and regular physical activity is modulating energy metabolism, but what is overlooked is that plays a critical role with the brain derived neurotropic factor system (BDNF)27.

Enriched environment is consisted of many fields, such as expanded learning, social interaction, general opportunities and positive mind-set, but concentrating on neuroplasticity and neurogenesis, exercise might be the game-changer. Newer studies have shown that particular high-intensity regular training (such as circular training, HIIT, fartlek or high impact running) simulating hunter-gatherer lifestyle, in contrary of old doctrine of prolonged cardio) produces remarkable changes in peripheral levels of BDNF and catecholamine as dopamine, epinephrine or norepinephrine – one study has demonstrated 20% faster vocabulary after intense exercise with simultaneously better short- and long-term retentions of the novel vocabulary. Furthermore, exercise increases – in some cases almost double – the survival of new-born cells, suggesting that physical activity is one of the best methods to promote neurogenesis28.

How does this happen? Exercise increases neuronal metabolic and mitochondrial functioning and the efficiency of its machinery decreases hippocampal-related oxidative stress. The most obvious is the process of generating new hippocampal neurotrophins – those are a family of growth factors that induce the survival, development, and function of neurons – between which the BDNF is the most prominent.

By up-regulating the levels of BDNF (with help of IGF-1) and supporting hormones (testosterone vs. estrogen), exercise induces both neurogenesis and neuroplasticity. The crucial process regarding learning is called long-term potentiation (LTP). The neurons communicate with each other through axons which end as synapses – when one receives a certain level of excitation, it triggers an action potential which jumps – with help of neurotransmitters – through synapse to another neurone, where producing excitatory or inhibitory response. LTP is simplified the process of enhancing firing from neuron A to neuron B – in reality this is a bit more complicated, since LTP works also by increasing the »input specificity« (one synapse does not spread to other synapses), cooperation between synapses and simultaneous strengthening of several weak signals29.

Studies have shown that combining aerobic and resistance training – if fit enough, simultaneously as circuit training or high intensity interval training – exerts the greatest benefits to cognitive processing. The »richer« the exercise regimen will be, the sharper your mind will become. But how exercise influences the brain differs also from the type of exercise you are engaged in. Resistance and cardio training have showed the greatest results, although they are acting through completely different pathways. Cardio

27 http://www.ncbi.nlm.nih.gov/pubmed/16862541/ 28 http://www.ncbi.nlm.nih.gov/pubmed/17185007/ 29 http://www.freewalkerteam.it/index.php?option=com_content&view=article&id=28&Itemid=298#1-intro-2 (+pictures source throughout the chapter: Freewalkerteam)

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tends to have a greater influence on vascular processes and BDNF, while resistance training influence IGF-1 and other supporting hormones – the highest effect are to be produced by mixed-type regimens30.

There are two more benefits of regular exercise. First, it helps to regulate cortisol levels and stress response, which have been linked multiple times to impaired cognitive functioning, but as well as physical damage to hippocampus. Through activating amygdala enhanced memory-formation since emotionally salient information are stored more efficiently. Secondly, it asserts significant protection against Alzheimer's disease and dementia. Most scientists agree that beta amyloids – the non-pathogenic second level of the protein structure – somehow starts to clump together, interfering and distorting the normal neural network. It is still unknown if the excessive aggregation of its plaques or some other culprit is to blame for (oligomers, dysfunction of cytoskeleton proteins, diabetes)31.

Vigorous training regimen has been found extremely beneficial in an Alzheimer's model by increasing flow of »brain fluid« (CSF) and »cleaning« neuronal structures. Completely different benefits are being asserted in Parkinson's disease, where dopamine-producing cells are lost – but only at first glance. In studies, intensive resistance training has helped to restore impaired motor circles and neuronal differentiation, decreases loss of dopaminergic cells and increase transfer of dopamine-producing cells to damaged regions. It is speculated that exercise in Parkinson's is doing similar thing – while in Alzheimer's cerebrospinal fluid is washing off amyloids beta, in Parkinson's the enhanced cleansing mechanism is diminishing alpha synuclein, another protein that aggregates and – in this case misregulates – dopamine32

3.2.1 Proposed workout system

Following chapter will not give you a workout plan – those are just examplatory guidelines which will help you optimize your workouts for optimal results. You can find plenty of exercises on Youtube, apps, you

30 http://www.freewalkerteam.it/index.php?option=com_content&view=article&id=28&Itemid=298#1-intro-2 31 http://www.freewalkerteam.it/index.php?option=com_content&view=article&id=28&Itemid=298#1-intro-2 32 http://www.freewalkerteam.it/index.php?option=com_content&view=article&id=28&Itemid=298#1-intro-2

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can ask a local personal trainer, a neighbour – but there are certain basic rules you should follow (among others):

a) You should combine many physical activities – martial arts with running or fitness with diving – to achieve the principle of universality. Remember, there is not a single athlete who becomes a champion and has done just one type of workout.

b) Resistance workouts should involve as much complex and bodyweight exercises as you can handle in a limited period of time – including big muscle groups such as back or legs – will challenge your brain chemistry more than isolated ones. The golden standard consists of squat, deadlift, pull-up and bench press (Examfit's team is adding overhead press (or burpee) for advanced, lunges, planking and leg raises).

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c) Never stop at repetition number 12 – do drop-sets and adjust the resistance till you fail to perform another rep safely.

d) You should do both classical resistance training and high intensity metabolic resistance training (circuit training, kettlebells etc). Body weight and free weights should be the core of your workouts, not the exercise machines.

e) You should combine aerobic and anaerobic exercises (during the same session), but not every training. Sometimes you can do training just for an increase in power output etc.

f) Your cardio should not be limited to endurance or high-intensity style – despite trends that are saying HIT, »bootcamp« or tabata is superb, sprints cannot produce trance feeling and a smile at your half marathon run during intensive rain and vice versa. No workout is replaceable.

g) Your cardio should not be the same every session – low intensity mountaineering, medium intensity swimming, high intensity badminton, medium intensity running, 10x1 minute sprint with 10x1 minute walking, medium intensity cycling, variable-intensity climbing, all-day low-intensity skiing etc.

h) Your (moderate and intensive) training shouldn't be longer than 90 minutes – preferable between 45 in 75minutes (look at letter i).

i) Don't forget to take time for longer, low intensity meditation-like workouts (like hiking). j) Adjust your lifestyle to achieve desirable results and to maintain health and wellbeing – healthy

lifestyle with good sleeping hygiene, additional macro nutrients and natural or herbal-based supplementation (hydration, whey or hemp proteins, carbs, nootropics, adaptogens – avoid anabolics, growth factors, strong stimulants etc)

k) Never read articles that begin with »Screw cardio« or any similar »broscience«. l) Fall in love with the process (and results will come).

Additionally, while using Examfit you will notice the difference in your workout routine – will increase your power output and VO2 max33 (but in different way that timed-relased caffeine34), adaptogens such as Panax ginseng and Rhodiola rosea will progressively lower your stress threshold resulting in increased endurance and VO2 max. Ginkgo biloba will enhance your bloodflow, B-complex will give you focus and iron will provide you with oxygen surplus.

33 http://www.ncbi.nlm.nih.gov/pubmed/11120451 34 http://www.ncbi.nlm.nih.gov/pubmed/11053318

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3.3 SLEEPING HYGIENE AND NEURAL PLASTICITY

There is a consensus between scientists that sleeping is connected with the mechanism of neuroplasticity, the process which is probably the most wanted promotor of learning and memory. On the other hand, the mechanism between sleeping and brain plasticity or even neurogenesis is not so clear – but one thing is certain. Sleep loss is linked with deterial effects on plasticity at molecular and electrophysiological level and vice versa. Furthermore, it is known that induction of plastic changes during daytime is linked with changes during sleep time.

Sleep deprivation is the problem we all battle with in 21st century. We often take the 5-6h of sleep for granted, not knowing it induces alteration in LTP (actually promote long-term depression (LTD), the opposite process of LTP), not feeling the excitoxicity in our neurons – maybe, just maybe we feel that »brain fog« feeling when we wanted to learn or work at some demanding task at hand.

Yet in 1971, Allan Rechtschaffen, the pioneer in the field of sleep research stated that »if sleep does not serve an absolute vital function, then it is the biggest mistake the evolutionary process ever made«. He seen sleep a primary and vital need, not differing a lot from drinking – molecular injuries in brain if chronically sleep-deprived can result in death in a matter of weeks. On the other hand, spontaneous wakefulness is associated with molecular changes regarding LTP and increased synaptic density – the thesis states that synaptic potentiation during wakefulness directly correlates

with increase in slow wave activity (SWA) during sleep. SWA is also a measure of sleep need since it increases with the time spent awake. The interesting fact is that SWA and LTP are connected – LTP related molecules are reduced when SWA peak during sleep is »blunted« and higher SWA is associated with stronger synaptic connection. Since we have mentioned it so many times, so far you have probably guessed that increased BDNF leads also to higher SWA during subsequent sleep35 36.

Studies have shown that the richer the experiences during the day are, the higher the sleep need is, but also the greater the synaptic growth is. Current findings support the thesis that experience-based synaptic potentiation during daytime is reflected in the sleep as renormalization or »down phase«, when metabolism decreases and LTD increases. LTP, the unwanted »inhibitory« process during wakefulness is needed during sleep to – ironically – promote neuroplasticity. In sleeping time newly acquired information between different brain-systems are being consolidated by selectively activating the same circuits as during wakefulness (»up phase«). During sleep, brain regions involved in daytime learning are being reactivated. Some newer theories support the thesis that consolidation of knowledge is in fact dual process, involving both SWS and REM sleep – repeated pattern of REM and non-REM sleep37. No matter which theory is correct, sleep deprivation or disturbed sleep is associated with learning difficulties and decrease in memorization, but what is more important, it correlates with neurodegenerative states. In dementias, Alzheimer's and Parkinson's the common pattern of sleep is found – fragmented sleep, decreased SWS and REM phase. Since the increased time awake demand also increased synaptic strength, sleep is the »must do« for homeostatic renormalization of cortical synapses. If you won't get

35 http://www.nature.com/nrn/journal/v3/n9/abs/nrn915.html 36 http://www.hindawi.com/journals/np/2013/103949/ 37 http://www.hindawi.com/journals/np/2013/103949/

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enough sleep, this will have detrimental effect on synaptic plasticity, not to mention over-excitation of neurons38.

To promote neuroplasticity during sleep you should follow a few basic rules39:

a) Try to sleep and get up at the same time every day.

b) Limit your exposure to light prior to sleep (including using smartphones).

c) Get regular exercise.

d) Eat well, eat smart (avoid big meals, caffeine, alcohol).

e) Clear your mind, meditate, and establish a relaxing routine.

f) Keep your room dark, quiet, and cool (below 18 degrees).

g) Use natural sleeping aids and nootropics: alpha-GPC, Huperzine-A, Ginkgo biloba, 5-HTP, Galantamine, L-theanine, Ashwagandha, Asparagus etc. Many of them are found in Examfit, since enhanced daily brain functioning (long-term potentiation) always reflect in enhanced brain activity during nightime (REM, long-term depression, alpha waves).

38 http://www.hindawi.com/journals/np/2013/103949/

39 http://www.helpguide.org/articles/sleep/how-to-sleep-better.htm

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4 NOOTROPICS

Nootropics – also called smart drugs or cognitive enhancers – are substances which improve cognitive functions, particularly executive functions, memory, creativity, or motivation, in healthy individuals. Human beings have always tried to improve their cognition, from the first civilizations they have been using hallucinogens to communicate with the gods, to generalized use of caffeine and more advanced product such as stimulants and glutamate (the chief excitatory neurotransmitter) activators. Currently that is one of most debated topics in neuroscience and its community – since many people are using potentially dangerous prescription drugs such as Ritalin or Adderall, Brainlabs designed a nootropic formula that is both safe and extremely potent40.

Examfit is a unique formula, made of 16 ingredients that not only interact synergistically, but potentiate each other’s effects due to the design of multi-target agents. Nutraceuticals, first seen as single modulators, are being used in defined proportions and amounts to act complementarily on specific aspects of cognition.

Natural extracts are often seen as compounds with unfavourable pharmacological profiles, but binding them together makes it easier to pass the blood-brain barrier or magnify one or more effects. In the following pages you can read about ingredients in details.

40 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462043/

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4.1 NOOPEPT

Noopept is believed to be a nootropic to »end« all nootropics – as a dipeptid piracetam matching partner it kept its protection against beta-amyloid build-up (Alzheimer’s), but introduced a novel dual-functioning mechanism. By affecting both AMPA and NMDA receptors Noopept simultaneously increases the speed of synaptic transmission, memory formation and neuroplasticity41. To put it simply, boosted piracetam, multiplied by tenth of its maintenance dose, minus side effects42.

Piracetam, one of the first nootropics, has probably had the most remarkable effect on treatment of Alzheimer's disease, with decades of clinical studies. Noopept is actually not a racetam, but it shares the common modulation of the acetylcholine system and AMPA receptors43, with simultaneous secretion of specific growth factors (NGF, BDNF). In brief, this promising peptide has preserved the neuroprotective role44 of its predecessor while amplifying beta2 wave activity spreading through the whole brain45, which results in general cognitive enhancement, decreased irritability, apathy and fatigue reduction and last, but not least, mood and sleeping pattern stabilization46.

Why is Noopept so special? It produces the unique effect on the brain – the molecule rapidly, within 25 minutes after oral ingestion; convert into something similar to cyclopropyl glycine that is almost identical to the endogenous peptide that triggers the enhanced nootropic activity47. The differentiation between metabolized molecules and that of cyclopropyl glycine to the human brain is so minor, that they choose pathways that they know best.

We have to mention another important attribute of Noopept. In a comparative study of cognitive injuries 20mg of Noopept produced 1.8-fold less adverse effects than treatment associated with as much as 1200 mg of Piracetam48. And with 1.8-fold fewer side effects exerts a great level of neuroprotection. Some preliminary in vitro studies are suggesting the Noopept's ability to reduce that cytotoxic formation through acceleration of fibrilization rates of alpha-synuclein (brain protein that interacts with phospholipids and other proteins) and production of new beta sheets. It is highly unorthodox way of actioning, implicating that exactly by producing (longer) beta sheets – usually considered as the cause of Alzheimer's disease – instead of flexible oligomers asserts a notable protective role. That might confirm the alternative hypothesis from in vitro studies that oligomers rather than plaques lead to amyloid diseases.

41 http://www.ncbi.nlm.nih.gov/pubmed/21414388 42

https://www.researchgate.net/publication/24032577_Comparative_studies_of_Noopept_and_piracetam_in_the_treatment_of_patients_with_mild_cognitive_disorders_in_organic_brain_diseases_of_vascular_and_traumatic_origin 43 http://www.ncbi.nlm.nih.gov/pubmed/9358206 44 http://www.ncbi.nlm.nih.gov/pubmed/19240853 45 http://www.ncbi.nlm.nih.gov/pubmed/21414388 46

https://www.researchgate.net/publication/24032577_Comparative_studies_of_Noopept_and_piracetam_in_the_treatment_of_patients_with_mild_cognitive_disorders_in_organic_brain_diseases_of_vascular_and_traumatic_origin 47 http://www.ncbi.nlm.nih.gov/pubmed/10977920 48

https://www.researchgate.net/publication/24032577_Comparative_studies_of_Noopept_and_piracetam_in_the_treatment_of_patients_with_mild_cognitive_disorders_in_organic_brain_diseases_of_vascular_and_traumatic_origin

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4.2 HUPERZINE-A

Huperzine-A is the only natural alkaloid that suppresses the major culprit for memory-related issues such as forgetfulness. This Traditional Chinese medicine is able to suppress the enzyme that disintegrates our lead learning neurotransmiter, acetylcholine. But little did the ancient Chinese know, Huperizine-A may promote neurogenesis as much as 4 weeks after completing the initial cycle49.

Huperzine-A was extracted from Chinese club moss (Huperzia serrata) in late ‘80s and used primarily for the treatment of Alzheimer's

disease50. Years later the scientists realised the rare pharmacological characteristic of this alkaloid – Huperzine-A produces a rapid initial spike, but long-lasting half-life51 and can be therefore used for enhancing study efforts also by healthy individuals. Studies indicate completely different approaches to nootropic activity, suggesting various transmission-dependent and neurogenesis-related mechanisms.

The most obvious one is related to acetylcholinesterase inhibition. It inhibits G4 isomer of enzyme that in excessive amounts diminishes individual learning efforts. By indirectly increasing acetyholine levels it enhances the magnitude of neurotransmissions to the cerebral cortex, which plays a key role in memory formation, attention, perceptual awareness, thought, language, and consciousness in general52. But »Hup-A« is also a powerful promoter of neurogenesis – in the study, conducted by a Beijing Laboratory of Biomembrane and Membrane Biotechnology in 2013, Huperzine-A promoted the significant cell growth of cultured neural stem cells (NSCs) in adult mice, as well as increased formation of new-born cells in the subgranular zone. Furthermore, it suppresses glutamate that makes cortical circuits more responsive to sensory stimulation – in that way not only improves memory recall, but also protects against H2O2-induced toxicity53.

4.3 ALPHA-GPC

A superior choline source with chemical name »l-alpha glycerylphosphorylcholin«, is actually quite similar to many other cholinergics. GPC enhances memory and learning54, but with one major difference – it actually builds new brain membranes. And later, when the mission is finished, it promotes further synthesis of phospholipids simply by adding omega-355. Who doesn't like fish?

Multiple clinical studies show that this highly bioavailable cholinergic agent is capable of crossing the blood-brain barrier and increasing acetylcholine, raising up growth hormone levels, but most importantly, it is able to form new nerve cells due to its omega-3 bonding potential56.

Since Alzheimer's disease is linked with phospholipid degradation and body catabolises them back

49 http://www.ncbi.nlm.nih.gov/pubmed/23454433 50 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781107/ 51 http://pubs.acs.org/doi/abs/10.1021/ar9800892 52 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097009/ 53 http://www.ncbi.nlm.nih.gov/pubmed/23454433 54 https://books.google.si/books?id=iKOl4cAbh08C&printsec=frontcover&dq=GPC+(ClyceroPhosphoCholine)+Mind-

Body+Power+for+Active+Living+and+Healthy+Aging.&hl=en&sa=X&ei=0r5KUueCKJSh4APg7IDgBg&redir_esc=y#v=onepage&q&f=false 55 http://www.ncbi.nlm.nih.gov/pubmed/16366737 56 http://www.ncbi.nlm.nih.gov/pubmed/16366737

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from phospholipides, GPC can be beneficial to this process thanks to the fact that acetylcholine can be derived also from phosphatidylcholine, the known precursor of GPC57.

Let's find out why alpha-GPC is so far ahead of the game as an acetylcholine promoter. This water-soluble precursor of phosphatidylcholine actually isn't the classical precursor as we often oversimplify. Another process takes place after the phosphatidylcholine metabolization – fatty acids are peeled off and gylcerol remains bounded to phosphocholine58. Since phosphatidylcholine is metabolised from lecithin precursors, some of the same enzymes for metabolism and absorption are being used, which brings GPC much closer to the natural body process than other cholinergics59.

But note: You can substantially potentiate its effects by eating fish like raw Norwegian salmon or enjoying krill oil.

4.4 PANAX GINSENG C.A. MEYER

Known as the only »true ginseng«, this fleshy root is probably the most convincing single plant when we think of adaptogens. It was discovered 5000 years ago in the Manchurian mountains and used as a medicine from the early Xia to the modern Han dynasty. Nowadays, various clinical trials are supporting the early records of that herbal remedy. Enhanced energy and well-being, calmness, immunity, cognition, sexual and athletic performance – one billion Chinese can't be mistaken!

Today we know a lot more – ginseng supports normal adrenal functions and lowers stress response, regulates blood sugar, protects against cancer, but what is the most appealing, it enhances cognition through yet unknown and complex mechanisms. Ginseng owns its healing properties to steroidal saponins, called ginsenosides (Rx). Even though there are more than 100 of them out there, the very special attention was given to Rg3 and Rh2. Those two ginsenosides have been found to assert complex neuroprotection against cerebral ischemia injuries and inhibition of cancer’s proliferation – enjoying Panax on a daily basis may reduce overall cancer risk by an unbelievable 50%60 61.

Ginseng also affects cognition in dose-dependent manner. While 200mg showed mood stabilization properties, 400mg improved working memory and mental arithmetic62. Others studies have showed notable cognitive effects at lower doses – the significant improvement in the Serial sevens contraction test in healthy young adults may be related to reduced subjective mental fatigue, reduction of blood glucose63 and increased alertness. Some attributes can be applied also to notable changes in EEG readings. P300 waves, elicited in decision-making process, are associated with different forms of cognitive impairment – longer waves are more likely to be found in patients with dementias64. Such cerebrovascular mechanisms are most likely responsible for the interesting fact – Ginseng does not increase memory formation as much as it improves abstract thinking65.

57 http://www.ncbi.nlm.nih.gov/pubmed/20492936 58 http://www.llamp.net/?q=Cho%20Phosphatidylcholine%20metabolism 59 http://www.ncbi.nlm.nih.gov/pubmed/6764726 60 http://www.ncbi.nlm.nih.gov/pubmed/7655337 61 http://www.ncbi.nlm.nih.gov/pubmed/20521975 62 http://www.ncbi.nlm.nih.gov/pubmed/20737519 63 http://www.ncbi.nlm.nih.gov/pubmed/15982990 64 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766544/ 65 http://www.currenttherapeuticres.com/article/S0011-393X(96)80114-7/abstract

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4.5 RHODIOLA ROSEA

What did Vikings, Soviet cosmonauts and Chinese emperors have in common? With completely different therapeutic traditions, they all relied on one bushy yellow rose. Subarctic »Roseroot« is a high-altitude adaptogen with far-reaching effects on body and mind – it is like a steady 6h coffee infusion66 alongside anti-fatigue67 and antidepressant pills68, falling from the Altai mountains.

Do you still remember that shinny moving »star« called MIR? It is not a joke – Russian cosmonauts were indeed using Rhodiola for their lengthy stay at that accident-prone space station – dr. Valeri Polyakov, specialist in astronautics medicine, and his team did not experience any prolonged cognitive or performance impairments spending 437 days aboard. Pharmacologist dr. Nikolai Lazarev defined

adaptogens as substances that help the body to adapt to environmental stress while normalizing pathological changes. Rhodiola has been linked to decreased physical fatigue with simultaneously improved cognitive abilities by repairing deviant hormonal perturbations, but also through its mild, but linear and long-lasting psycho-stimulatory and serotonergic effect69.

The most interesting characteristic of Rhodiola – beside its powerful performance enhancing effects – is its influence on bioelectrical activity in the brain, regarding both cerebral cortex-related cognitive functions (such as calculating or analysing) and prefrontal-related cognitive functions (such as memory). Rhodiola reverses acetylcholine blockers and increases levels of acetylcholine, our primary learning neurotransmitter. Additionally, the salidrosides found in R. rosea assert neuroprotection via hypoglycemia-related starvation and reduce the stress from beta amyloid proteins, associated with Alzheimer's disease70.

Nowadays, those effects are widely recognized in the academic milieu, particularly in high-stress situations (MDs doing rounds71 and student in during exams72). Strong evidence of short-termed improvement in processing errors reduction, reaction time and cognitive fatigue has been established73 – nevertheless, Rhodiola also enhanced some basic perceptive and cognitive cerebral functions74.

66 http://www.ncbi.nlm.nih.gov/pubmed/16261511 67 http://www.ncbi.nlm.nih.gov/pubmed/10839209 68 http://www.ncbi.nlm.nih.gov/pubmed/17990195 69 http://www.ncbi.nlm.nih.gov/pubmed/22921986 70 http://www.ncbi.nlm.nih.gov/pubmed/20615444 71 http://www.ncbi.nlm.nih.gov/pubmed/11081987 72 http://www.ncbi.nlm.nih.gov/pubmed/10839209 73 http://www.ncbi.nlm.nih.gov/pubmed/10839209 74 http://www.ncbi.nlm.nih.gov/pubmed/11081987

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4.6 GINKGO BILOBA

There has been a great fuss about efficiency of this fossil tree. But a few things are certain. It dates back in time before dinosaurs. It improves acute processing speed75 and memory recall at high demanding tasks76. The effects build up if combined with phosphatidylserine77. Paired with ginseng it enhances long-term memory and accuracy of tasks in young adults78, stress reduction79, better sleep80, increased brain flow81 - those are the reasons why they use it as prescription drug in Germany.

Nowadays, the most commonly used standardization of terpenoid and flavonoid composition of Ginkgo is called EGb

761. It is actually a 50:1 extract, equivalent to 15 g of Ginkgo leaves – in various trails it showed notable protection by scavenging free radicals82 (workers who have been exposed to the Chernobyl accident were administrated with 120mg of Ginkgo, which significantly repaired their clastogenic and free-radical induced DNA damage83). Besides repairing and remodelling broken chromosomes, Ginkgo promotes apoptosis by decreasing PBR (peripheral benzodiazepine receptor) and inhibits proliferation of many metastatic forms of cancer84 – in one study the effective rate of tumour reduction was astonishing 73.4%85.

Ginkgo is acknowledged mostly by its success in treating different forms of cerebral insufficiency, which may cause memory impairment, mood swings and hearing disorders. The mechanism of neuroprotection is multidimensional. Its anti-thrombotic effect lies in reducing platelet activating factor (PAF), which leads to improved circulation86. This inhibition of PAF signalling also protects against hypoxic injuries like stroke and improves both executive functioning as well as attention span. Furthermore, it appears to inhibit both apoptosis and the acetylcholine leaking from beta amyloids suggesting better signalling function87.

There is also substantial in-vitro evidence of Ginkgo's potential to induce neurogenesis and synaptogenesis. Bilobalide itself induces neuronal regenesis after injuries as well as proliferation of neurons and dendrites in a healthy brain. Ginkgo restores beta-amyloid oligomers-induced synaptic loss by responding to the common signalling. That is why in Germany many general practitioners are using Ginkgo over donepezil and other cholinesterases at treating consequences of dementia88.

75 http://www.ncbi.nlm.nih.gov/pubmed/108903304 76 http://www.ncbi.nlm.nih.gov/pubmed/21802920 77 http://www.ncbi.nlm.nih.gov/pubmed/17457961 78 http://www.ncbi.nlm.nih.gov/pubmed/12020739 79 http://www.ncbi.nlm.nih.gov/pubmed/12369732 80 http://www.ncbi.nlm.nih.gov/pubmed/11302564 81 http://www.ncbi.nlm.nih.gov/pubmed/22840457 82 http://www.ncbi.nlm.nih.gov/pubmed/10635450 83 http://www.ncbi.nlm.nih.gov/pubmed/7480646 84 http://www.ncbi.nlm.nih.gov/pubmed/16475673 85 http://www.ncbi.nlm.nih.gov/pubmed/14606069 86 http://www.ncbi.nlm.nih.gov/pubmed/15693702 87 http://www.ncbi.nlm.nih.gov/pubmed/23828103 88 http://www.ncbi.nlm.nih.gov/pubmed/16930364

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4.7 L-THEANINE

We have all heard of EGCG and caffeine in green tea. However, there is another crucial substance found in this elixir of youth. Theanine is an amino acid with the ability to increase alpha-1 waves which gives green tea its calming effect without sedation89. Cognitive benefits – memory, attention span, flexible learning, decreased anxiety and even creativity – are best observed under conditions of chronic stress9091.

Relaxation of green tea comes from the fact that theanine is a compound with a structural similarity to glutamine-derived neurotransmitters glutamate and GABA and it is able to

penetrate to occipital and parietal regions of the brain's surface. And relaxation itself is more important to maintain cognitive performance than we might have thought.

How exactly does stress cloud your mind? The answer lies in hormones, neurotransmitters and the synaptic response. Increased levels of corticosterone always suppress working memory and long term potentiation in the hippocampus by jamming hippocampal synaptic transmission92. This may happen due to stress-related overexcited neurons and the NMDA and AMPA receptors are over-activated by glutamatergic storm. Furthermore, the over-excitation may result even in beta-amyloid protein aggregation, present in the brain of patients with Alzheimer's dementia93.

Here comes the L-theanine. After the ingestion it crosses a blood-brain barrier and generates brain waves called alpha-1. They signify relaxation without sleepiness, some state of waking relaxation, which stay elevated up to 5h – this can be noticed potentially during »close eye rest«94 or during visio-spatial tasks95. These 8-12Hz waves are associated also with selective attention mechanism96 – anxiolitic properties of theanine are particularly interesting because they don't weaken if they are combined with caffeine. Since this combination increases mental alertness97 and information retention – with simultaneous increase in hexobarbital-induced sleeping time – it has become the most popular aid for students and project workers98 99.

89 http://espace.library.uq.edu.au/view/UQ:284103 90 http://www.ncbi.nlm.nih.gov/pubmed/17272967 91 http://www.ncbi.nlm.nih.gov/pubmed/23458739 92 http://www.ncbi.nlm.nih.gov/pubmed/11304755 93 http://www.northwestern.edu/newscenter/stories/2007/12/morimoto.html 94 http://www.ncbi.nlm.nih.gov/pubmed/15378679 95 http://www.ncbi.nlm.nih.gov/pubmed/18841456 96 http://www.ncbi.nlm.nih.gov/pubmed/9572588 97 http://www.ncbi.nlm.nih.gov/pubmed/9572588 98 http://www.sciencedirect.com/science/article/pii/S0924224499000448 99 http://www.ncbi.nlm.nih.gov/pubmed/4397636

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4.8 PHOSPHATIDYLSERINE

This phospholipid forms up to 10% of cell's lipids, where it acts as a neurotransmitter in the fundamental learning and decision making processes. By a down-regulating enzyme that breaks apart acetylcholine it stimulates formation of memories and promotes neuroplasticity100. Moreover, it can improve processing speed and accuracy in young adults by more than a fifth101.

Phosphatidylserine (PS) is fat-soluble builder of the cellular structure and therefore present in up to 10% of cell's lipids – being modified phospholipid it is concentrated mainly in the brain. Thus, PS is required for establishing channels for cell-to-cell communication by building up

neuronal membranes – especially during intense mental activity on intensified workload when circulatory acetylcholine levels are being reduced102. PS indirectly promotes intercellular cooperation by supporting acetylcholine-, serotonine-, dopamine- and noradrenaline–based neurotransmission.

The biological importance of PS lies in its physiological role – as mentioned above, it is structural component of a cell's bilayer, involved in increasing cell fluidity and up-regulating ATPase (enzyme that releases energy)103. It also has a down-regulating effect on acetylcholinesterase, the process which always leads to increased levels of acetylcholine104 – that way PS influences profoundly on memory retrieval, particularly by improving episodic memory. In one study subjects with subjective memory complaints have been observed for six weeks. When administrated PS combined with omega-3, this compound was able to store, hold and recall words in delayed condition 42% successfully than a placebo105. Other studies have cited the PS's ability to prolong attention in youth with attention-deficit hyperactivity disorder (ADHD), improving both short-term auditory memory and decreasing impulsivity106. It has been repeatedly pointed out that PS must be bound with EPA and DHA for producing the best results.

So, rewire your brain by eating fish!

4.9 TIMED-RELEASE CAFFEINE

Imagine receiving a coffee infusion with a drop rate 2 drops/min? This most widely consumed psychoactive drug on the planet can be extracted from coffee beans or synthetically produced in a lab. Being an alkaloid relates him closely to adenine107 – and by antagonizing adenosine receptors, caffeine becomes a powerful nootropic, especially when stacked with L-theanine108. But with the pleasant rush, when body (too) rapidly produces adrenaline and dopamine, comes also the crush. Encapsulated slow release granules of caffeine sort that problem out.

100 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981104/ 101 http://www.ncbi.nlm.nih.gov/pubmed/22017963 102 http://jissn.biomedcentral.com/articles/10.1186/1550-2783-4-5 103 http://enzyme.expasy.org/EC/3.6.1.3 104 http://www.jbc.org/content/146/1/35.full.pdf 105 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981104/ 106 http://www.ncbi.nlm.nih.gov/pubmed/23495677 107 http://www.drugbank.ca/drugs/DB00201#pharmacology 108 http://www.ncbi.nlm.nih.gov/pubmed/18681988

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Caffeine is a central nervous system stimulant with a bitter taste and both positive and negative effects on human health. We all have met them and here is neither the time nor the space to talk about it – we are eager to know one thing. How does it affect learning, does it enhance brain power?

Let's talk science. Caffeine competes with adenosine for its receptor, but it does not exclude it completely. Specific subset which induces sedation is called adenosine receptors and by preventing adenosine to fit into its receptor caffeine also inhibits adenosine's drowsiness effect and promotes brain activation and excitation109. With increased serotonine levels combined with analgesic effect, caffeine may be the quickest temporary memory enhancer available.

What about memory and brain? Some studies have showed that caffeine's antagonistic blockage of A1 and A2a receptors can increase acetylcholine – our major learning neurotransmitter – in the medial pre-frontal cortex110. The others have focused on mental alertness in different personality types by measuring IQ scale – caffeine may boost cognitive performance by promoting alertness in »afternoon-aroused« extraverts and vice versa111. More memory enhancement can be expected from its influence on neurotransmitters, stimulation of CNS and vasodilation – the psycho-stimulation through the process of phosphorylation also leads to better dopaminergic signalling112.

Those are the pros. What about the aftermath? There are ways to bypass negative effects of it. One way is by drinking one cup of coffee for hours. Others are more realistic. Encapsulated caffeine is ordinary caffeine, but intentionally timed to prolong its release, what almost completely eliminates excessive cortisol secretion, impulsivity and spikes in anxiety.

Some synergistic ingredients or herbal extracts can also be beneficial. Stacking caffeine with relaxation-promoting agent such as L-theanine improves speed, but also the accuracy in highly-demanding attention-switching task113. Jittering effects of caffeine can be also buffered if adding some adaptogens (as ginseng or Rhodiola) – not only that lowers the cortisol level, but also boosts focus.

4.10 MgT (MAGNESIUM-L-THREONATE)

Magnesium is a highly efficient mineral, but it just doesn't seem to be able to get into the bloodstream. Consequently, a large proportion of adults don't meet the required daily intake (RDA) of magnesium, which makes them tired, wired and cognitively impaired114. Low supplement's absorption is what led scientists from MIT to design MgT. L-threonate which is a vitamin C metabolite, used as a magnesium chelating agent for raising its bioavailability. High levels of brain's magnesium results in increased synaptic density and plasticity115 – a process which is associated closely with memory recall.

Magnesium is an essential mineral, used also as a cofactor for hundreds of enzymes – without it, our body would suffer from generalized fatigue, neural excitation, glucose intolerance, high blood pressure and arrhythmias, not to mention muscle spasm, eye twitches or even sudden death116.

Magnesium deficiency – quite common state – is affecting the brain by mental fatigue, anxiety or different forms of cognitive impairment. Magnesium ions down-regulate the calcium at NMDA

109 http://www.ncbi.nlm.nih.gov/pubmed/21970461 110 http://www.ncbi.nlm.nih.gov/pubmed/12093592 111 http://psycnet.apa.org/psycinfo/1991-14780-001 112 http://www.ncbi.nlm.nih.gov/pubmed/12181566 113 http://www.ncbi.nlm.nih.gov/pubmed/18681988 114 http://www.ars.usda.gov/Services/docs.htm?docid=15672 115 http://www.drperlmutter.com/wp-content/uploads/2015/01/MagT-Nureon-article-2010.pdf 116 http://www.ncbi.nlm.nih.gov/pubmed/1636608

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receptors by occupying calcium ion channels and supporting long-term potentiation (LTP) and alertness. If levels of magnesium are too low, neurons slip into hyper-excited synaptic mode and start with random neuron firing117 (inducing neurotoxicity and anxiety118). When neurons are not in »firing mode«, function of magnesium is preserving its resting potential, but when needed, they are activated immediately. MgT acts in a way to achieve activation of NMDA receptors at its weakest possible input119.

A well-designed animal study that compared different forms of magnesium has shown some extraordinary improvements – NORT scores, associated with short-term memory were elevated by 15%, while those measuring long-term memory showed 54% advantage compared to magnesium citrate. Results, suggesting the increased brain plasticity, were the consequences of the elevated number of functioning neurotransmitter release sites, as well as its greater density. Furthermore, after just 24 days of supplementation, short-term spatial memory was improved by more than 17% and by the day 30, spatial working memory of older animals became comparable to their younger counterparts.

MgT supplementation is associated with the ability to change the number of neurons, called neuroplasticity (chapter 1.2), but also with the density of presynaptic »boutons«. A greater density of boutons releases the neurotransmitters to transmit the stimulus to the next neuron – the more amplified that signal is, the more sustained the memory stays120.

4.11 IRON + vit C

Iron, found primarily in hemoglobin and myoglobin, helps erythrocytes deliver oxygen throughout the body. While iron deficiency has been traditionally associated with fatigue-related changes, newer studies suggest the unthinkable. Iron status is closely connected with executive functioning skills and disorders – working memory, cognitive flexibility, planning and logical reasoning121.

The absorption topic has been stress out as »leitmotiv« of iron-based studies – the amount, ingested orally, ranges only from 5% to 35%122. Why is that level so low – putting different medical states aside? The problem with absorption is that physiological pH rapidly oxidizes iron into an insoluble form – enzymes called ferric reductases are here to enhance the solubility and to promote uptake of ferric iron.

Another issue are dietary factors. It is commonly known that ascorbic acid optimizes its bioavailability by “chelating” iron. Industrial processing, as well as cooking and storing, impairs that enhancing effect.123 Some of the purely plant-based diets contain high amounts of phytate which is main inhibitor of absorption124. Furthermore, it has been showed that several other metals compete against each other through the same absorption pathways.

The problem with iron deficiency (ID) is that it can exist with or without anemia. ID often impairs cognition and causes long-term behavioural changes – mostly seen cognitive disturbances and 117 http://www.ncbi.nlm.nih.gov/pubmed/6320006 118 http://www.ncbi.nlm.nih.gov/pubmed/15466958 119 http://www.ncbi.nlm.nih.gov/pubmed/20152124 120 http://www.ncbi.nlm.nih.gov/books/NBK5275/ 121 http://www.ncbi.nlm.nih.gov/pubmed/26661838 122 http://www.ncbi.nlm.nih.gov/pubmed/9023471 123 http://www.ncbi.nlm.nih.gov/pubmed/5663503 124 http://www.ncbi.nlm.nih.gov/pubmed/20200263

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visuomotor impairment. ID impairs executive functioning, shows slower reaction times, less accuracy, but also some EEG changes such as delayed latency of P300 wave. Tests revealed lower test scores in general cognition, fine motor, lower scores on language, sound perception and motor measures, but also disturbances in social and emotional areas125.

What about improving cognition with iron supplementation if not having ID? In one study anemic and non-anemic group were compared while one was supplemented with iron – both adult and older children irrespective of baseline iron status were found to have improved attention and concentration. Furthermore, in anaemic group IQ was improved by 2.5 points126. A similar study was published recently analysing executive functioning among 127 women of reproductive age. Women with better iron status were associated with faster reaction time, better inhibitory control and faster planning time – but paradoxically, there was also a weak negative association with working memory in women with iron surplus127.

Cognitive ramification of simple and low-cost iron supplementation might profoundly change an individual’s well-being and learning performance. But it should be emphasized that an iron overload holds equal if not more danger, so people should regularly check their iron status.

4.12 B-COMPLEX

Even though vitamins B5 (pantothenic acid), B6 (pyridoxal phosphate) and B12 (methylcobalamin) are chemically quite distinct, they are involved in common biochemical processes such as cellular conversion of food energy into ATP or neurological functioning. For some vitamins – methylcobalamin is one of them – it is crucial to maintain a high plasma concentration in order to improve memory, emotional functions and communication skills, but also to reduce stress and fatigue128.

Did you ever wonder why energy drinks produce greater alertness than coffee?

B vitamins actually aren’t one complex, but a group of eight vitamins, sharing common characteristics and similar pathways. They are regarded as essential micronutrients,

helping the body convert food into glucose and providing fast energy, boosting the immune system, help with the production of hormones and neurotransmitters. B vitamins are required to maintain and modulate optimal neurological functioning, mainly through promotion of some vital hormones and neurotransmitters in memory consolidation, but also in executive functioning.

Pantothenic acid (B5) helps to break down carbohydrates and fats into energy. It plays a major role in manufacturing red blood cells, but also promotes the production of sex and adrenal hormones (called also the anti-stress vitamin). Furthermore, vitamin B5 is needed in synthesis of cholesterol. It enhances both memory and concentration by neutralizing excess levels of toxic homocysteine, associated with “auto-degeneration and ischemic heart disease”129 130.

125 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235202/ 126 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235202/ 127 http://www.ncbi.nlm.nih.gov/pubmed/26661838 128 http://www.ncbi.nlm.nih.gov/pubmed/?term=intravenous+mecobalamin+ikeda 129 http://www.med-health.net/B-Complex-Benefits.html 130 http://umm.edu/health/medical/altmed/supplement/vitamin-b5-pantothenic-acid

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Pyridoxal phosphate (B6) promotes interneural communication by helping to produce several neurotransmitters. It is involved in dopaminergic mechanism – by increasing enzyme PLP (pyridoxine-5’-phospate) it converts L-DOPA into active dopamine131 – and serotonergic neurotransmission. B6 is especially beneficial in respect to long-term memory storage132.

Methylcobalamin, the superior form of vitamin B12 also plays an important role in maintaining healthy nerve cells, but through different pathways – it promotes the production of its genetic material (DNA and RNA) by acting as a carbon donor to a DNA base-pairs. Notable cognitive effect can be achieved also through supplementation – when levels in cerebrospinal fluid are high, methylcobalamin can improve memory, emotional functions and verbal fluency.133 134.

The answer, regarding the difference between coffee and energy drink is simple. B vitamins are constitutive agents, builders and promoters of central nervous system. They help with the production of hormone, genetic material, nervous tissues, while stimulants only temporarily induce improvement by blocking this or that receptor.

4.13 ACETYL-L-CARNITINE (ALCAR)

No magic here. Old-fashioned l-carnitine, bonded with an acetyl group

to pass the blood-brain barrier. Even though ALCAR showed notable

results in neuroprotection from alcohol boozing in Freshman year135,

most people use it as a home remedy for mood swings or ADHD

disorders. ALCAR exhibits increased attention span in short- and long-

term administration136.

Acetyl-L-carnitine (ALCAR) is a naturally occurring amino acid – a

derivate of lysine and methionine – bonded to an acetyl group to

provide a more bioavailable version of supplementation. But ALCAR is

not just a product of lab synthesis – it is naturally present in

mitochondria, where together with L-carnitine and acetyl-CoA it

controls mitochondrial activity. Acetyl-L-Carnitine (ALCAR), present in

Examfit, is a bit different. With the acetyl group it represents the »neurological version« of L-carnitine –

its interactional ability can modulate various cognitive or related mechanisms, for example improved

mental fatigue levels (other forms of carnitine influence just physical aspect of it)137. But first of all, it acts

as a powerful longevity promotor. According to the fact that aging goes hand in hand with decreased

mitochondrial membranes functionality, and that ALCAR can attenuate the decline in a membrane

constituent cardiolipin, it is believed that ALCAR supplementation can reverse the age-associated decline

by restoring mitochondrial and ambulatory activity138.

However, the real potential of ALCAR remains in its ability to enhance memory and particularly in its

neuroprotective effects. Well-established animal and human based studies support the theory that it can

alleviate the cognitive decline, especially when related to older individual or neurodegenerative diseases.

A study on 40 older subjects showed significant improvements of the main mental parameters – it has to

131 http://www.ncbi.nlm.nih.gov/pubmed/2374548 132 http://www.ncbi.nlm.nih.gov/pubmed/1365868 133 http://www.med-health.net/B-Complex-Benefits.html 134 http://umm.edu/health/medical/altmed/supplement/vitamin-b12-cobalamin 135 http://www.ncbi.nlm.nih.gov/pubmed/20708681 136 http://www.ncbi.nlm.nih.gov/pubmed/12213433 137 http://www.ncbi.nlm.nih.gov/pubmed/15039515 138 http://www.ncbi.nlm.nih.gov/pubmed/9689120

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be emphasized that current results noticed in short-term, intensive ALCAR administration have produced

no significant side effects139.

Simultaneously, it may mediate its protective effect by buffering both oxydative stress and maintaining

ATP levels. The decline in ATP usually happens when neurons are near to the beta-amyloid pigmentation

(Alzheimer's dementia)140.

Summa summarum, it is not short-term memory enhancement that people should seek in ALCAR

supplementation. Since being »mitochondria thing«, ALCAR functions more in ATP-related manner – it

reduces mental fatigue, stabilizes and prolongs attention span and promotes long-term neuroprotection.

ADHD (attention-deficit/hyperactivity disorder) trials have been made primarily on young people and

children, suggesting supplement can be used as attention promoting agent at all ages141.

But again: Tune up your brain as one by sleeping enough, exercising and eating fish once a weak!

139 http://www.ncbi.nlm.nih.gov/pubmed/3781687 140 http://www.ncbi.nlm.nih.gov/pubmed/12199155 141 http://www.ncbi.nlm.nih.gov/pubmed/12213433

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DID YOU KNOW THAT OUR IQ HAS DROPPED OVER 13 POINTS SINCE THE VICTORIAN ERA? TIME FOR EXAMFIT :)