Pramiracetam vs Noopept

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noopept vs. pramiracetamBoth Noopept and Pramiracetam are considered to be among a classification of supplements known as cognitive enhancers or memory supplements. They are both also among the more potent Nootropics and have surprisingly similar benefits and effects. So, which one is better? What are these effects, benefits, and mechanisms of action?

Noopept Effects and Benefits

This supplement is reported to be over 1,000 times stronger than Piracetam, the original member of the Nootropic family. Developed in Russia, this supplement helps to enhance memory, recall, and learning. There is also evidence to suggest that it may act as a neuroprotectant, helping to shield the brain from damage (in some cases, research suggests, it may even help to repair certain types of damage). Noopept also improves nerve growth factor (NGF) and acts like a powerful anti-oxidant, ridding the brain of toxins and poisons. Additional research suggests that Noopept may even be able to improve communication between both hemispheres of the brain.

Pramiracetam Powder Effects and Benefits

Since this supplement is also very potent, the effective Pramiracetam dosage is much lower than Piracetam. Most of the benefits are actually quite similar to those produced by Noopept and include improved memory and learning and better overall cognitive functions. It does seem to have a slight edge in terms of improving focus and motivation. Just as is the case with Noopept, this supplement has evidence to suggest that it is also a neuroprotective.

Pramiracetam vs Noopept

The major difference between these supplements is simply their method of action. Noopept focuses more on the AMPA receptors within the brain, modulating them and also binding to these receptors. This allows the powerful brain neurotransmitter Glutamate to move between brain cells more easily, increasing synaptic plasticity and helping to produce a number of cognitive benefits.

Pramiracetam, on the other hand, works by increasing the uptake of Choline within the brain. This helps to speed up the rate at which Choline is used to synthesize the neurotransmitter Acetylcholine (Choline is a precursor and eventually turns into this powerful brain chemical). As new Acetylcholine is produced, many scientists and researchers believe that the brain is able to form new neurons and connections which help to improve working memory.

Final Verdict?

Ultimately which one to take is a personal decision. You may wish to try both, separately, and see which one works best for your particular body. Then, make an informed decision based on how you feel and the benefits conferred.

Noopept Dosage: The Megadose

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There is no question that Noopept is one of the most effective, and powerful, Nootropics on the market today. It has been estimated to be more than 1,000 times stronger than Piracetam, the original Nootropic. So this is definitely one of those brain boosters or memory supplements to be careful with. The recommended dose for this supplement is in the range of 20-50mg per day. Recently, there has been some experimentation with a mega dose. So, exactly what can be classified as a Noopept mega dose? What have been the results of these experiments? Finally, were there—or can there be—any side effects?

Noopept Effects

where to buy noopeptAt the recommended dosage levels, Noopept is among the most effective and powerful cognitive enhancers on the market today. It has the ability to increase memory and recall, improve learning ability and may even be effective at long-term memory improvement. Studies also indicate that it may act to protect the neurons and potentially even reverse some types of damage. It also increases nerve growth factor and improve connections and communications between the hemispheres of the brain. Additionally, this supplement acts as a powerful anti-oxidant, cleansing the brain from excess calcium and other toxins.

Research continues into additional medical uses for Noopept. This may include potential help with symptoms of age-related memory loss and possibly even neuro degenerative disorders.

What Constitutes A Mega Dose?

noopept megadoseA mega dose of Noopept, considering its recommendations, would be anything over 100mg. Once again, this is not something to ‘try at home.’ There can be some rather strong side effects, despite the supplement being generally regarded as safe.

Mega Dosing Experiences

Several reports and studies have used mega doses of Noopept under controlled conditions. There seem to be several possible types of results and it is impossible to predict how anyone will react. The first experiment involved a 100mg mega dose one time only. The end result of this was the feeling of extreme nervousness, anxiety and irritation all over the body. This was described as being pricked with thousands of little pins or needles. Not very pleasant.

On the other hand, someone who has been using Noopept and other Nootropics for quite some time conducted the next mega dosing experiment. Perhaps this will account for the different results. This was much more pleasant and involved 100-200 mg doses over a period of several days. They noticed an incredible increase in perception and all senses along with tremendous mental energy, clarity of thought and focus. Basically, what one would expect from Noopept only more.

Nootropics Guide for Beginners

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Perhaps you have heard the buzz surrounding a class of supplements known as nootropics and are eager to try them. Maybe you are wondering if these would be right for you? This guide is aimed at beginners, those who have just started taking nootropics or are thinking about it. There are a number of positive benefits which can result, but it is also certainly helpful to have a handy reference as to how to get started.

Racetams

Probably the best place for a beginner to start is with a category of nootropics known as racetams. These were among the first to be discovered and released for general use. The most popular of these supplements are:

  • Piracetam
  • Aniracetam
  • Oxiracetam
  • Pramiracetam

These are all generally considered to be risk free and are unregulated by the FDA. They are also fairly easy to find although you will probably not see them at your local GNC (the internet is your best source). They all essentially work by disabling an enzyme which deactivates a key neurotransmitter known as acetlycholine. The main differences are whether they are fat or water soluble and the exact mechanism and speed with which they cross the blood brain barrier. They are all excellent supplements to start with.

Choline Supplements

This supplement is an interesting memory enhancer and it is already present in a number of different foods such as eggs, fish, and chicken. It is a precursor to the already discussed neurotransmitter acetlycholine. Some research suggests that it may even make the action of racetams more effective, producing a synergistic effect. It is also possible that existing racetam users may experience headaches, which are usually relieved through the use of Choline.

While Choline is not harmful, you will want to make sure not to overdo this. Too much can produce an interesting and surprisingly bad odor. It is akin to the smell of decomposing fish.

Sulbutiamine Supplements

This one is a chemical variant of B1, except it is capable of readily and effectively crossing the blood brain barrier. It is also known as a powerful and effective memory enhancer. Sulbutiamine is a stimulant and may produce some side effects in certain people. Generally speaking, the more sensitive you are to other stimulants like caffeine, the more effected you will be by this supplement. If this is combined with exercise you will probably feel a bit more energetic.

A beginner is well advised to start out with choosing a quality racetam formulation. After determining their initial effects, it might be a wise idea to add Choline to the mix, especially if you are experiencing any headaches (and if not, it still can have a synergistic effect). Feel free to mix and match any of these, since most nootropics are generally very well tolerated, and pay attention to the effects on your cognition, memory and concentration.

Aniracetam Benefits: Pros and Cons

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Aniracetam has been shown to increase one’s creative output.

Aniracetam is a cognitive enhancer that is increadibly popular. Most people use it to enhance their creativity and holistic thinking abilities, which can be useful for problem-solving in just about anything: Work, school, social life, gaming, you name it.

This effect is subtle for some users and more powerful for others. Admittedly, it’s subtle for me, but where else can I find a creativity booster? I’m not just talking supplements, I mean anywhere and everywhere. The only other creativity enhancer I’m aware of is getting enough sleep, but that’s something I already do (okay, try to do) for a host of other reasons.

So hey, I’ll take it. The effect is certainly noticeable: I find myself making more connections than I used to when I’m brainstorming about something, instead of just staring at the wall. I’ve also gotten compliments on my creativity, which is cool. This means that aniracetam is a regular part of my stack now, and I recommend giving it a try to anyone and everyone.

So what about those pros and cons?

First the pros: both scientific research and experience reports point to other potential benefits: enhanced memory and learning ability, improved mood, and reductions in anxiety and depression. Some people experience these benefits (some strongly) and some don’t, but the potential for these additional positive effects definitely increase this supplement’s desirability. I notice the improved learning ability myself, and I love it.

Aniracetam is well-researched and safe to use, it’s not expensive, and it’s ten times stronger than piracetam, the basic supplement in the racetam class. If you’ve already tried piracetam and its effects were too subtle for you, then giving aniracetam a go is your obvious next step, or you’ve never tried a racetam before, think about starting with aniracetam to start strong.

I also recommend combining aniracetam with the other racetams, like piracetam, oxiracetam and pramiracetam, since evidence suggests a synergistic effect. This means that combined racetams are more than the sum of their parts: you’ll get more and stronger positive effects by inviting more of them into your life. Some commonly reported benefits of the other racetams that may be enhanced by aniracetam use: increased motivation, clearer thinking, augmented intelligence, and, my personal favorite, increased verbal fluency.

So what about cons? Aniracetam does have some, but they’re not too bad. First off, I should mention that this stuff tastes as bitter as anything, so be prepared to sweeten it. A lot. Stevia is great for this, since it has zero calories. You can also try citric acid.

It also often takes weeks to fully feel aniracetam’s effects, though some start feeling its benefits in a matter of days. This means that you’ve got to be patient with it, but that’s not so tough. I got through this by simply not expecting to feel anything until I’d been taking it for a month or so, and, lo and behold, I didn’t feel anything until about a month had passed, but it’s been pretty awesome for me ever since.

Fish oil and other essential fatty acids can greatly boost Aniracetam’s effect.

Aniracetam is also fat-soluble, and all that means is that you need to take it with a meal, which is easy enough. It’s best to take it with essential fatty acids like fish oil or flax seed oil, too, but this is stuff I’m taking regardless for my health, since I don’t eat a pound of fish or a truly insane quantity of flax seeds every day.

Finally, it’s necessary for most people to take choline along with your aniracetam for it to actually work. Otherwise it’s like bodybuilding without getting enough protein. Alpha-GPC is the most bioavailable choline supplement, but there’s also CDP choline, phosphatidylcholine, and choline bitartrate.

Choline can also mitigate the common ‘racetam headache’ some users get when taking racetams. This happens because racetams increase choline uptake within the brain. If there is insufficient choline, you get a headache. So be sure to take yout choline supplement.

I suggest experimenting with different choline supplements to find out what you like best, as all of them are inexpensive and safe. In fact, choline is an essential nutrient, and most people don’t get the optimal amount through diet alone (do you eat 5 eggs every single day? I sure don’t).

Consider the possibilities of what you could do with augmented creativity, and consider that you’d be better at considering those possibilities with the enhanced creativity imparted by aniracetam.

How Many Scoops of Protein?

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ProteinScoopProtein is an essential nutrient needed for growth and repair, and for the manufacture of essential functional and structural components within the body, including the muscles. The amount of protein each person needs varies according to many factors, like age and condition. The body has a heightened need for protein during times of heavy activity, and most strength athletes fall under this category.

Proteins are the building blocks of muscle, so laying down new muscle requires extra protein. While there is no established recommended daily intake for protein, many sports and nutrition bodies agree that levels of around 0.7-1g/kg bodyweight per day are appropriate for a sedentary person or recreational endurance athlete.

According to The International Society of Sports Nutrition, people engaged in frequent high-intensity exercise require between 1.2-1.8g/kg bodyweight per day, and those involved in weight and resistance training should be aiming between 1.4 and 2.0g/kg bodyweight (1).

How many Scoops of Protein Should I take?

Protein powders are the easiest and most convenient way to supplement the dietary protein intake. There are many factors that may make it difficult to obtain sufficient protein from the diet. People with very high requirements may find it difficult to consume the recommended volume of food to supply their protein needs, as may also be the case for athletes following vegetarian diets. Ideally, the amount of supplementary protein should make up the shortfall in dietary sources.

For example, according to the general guidelines outlined above, a 100kg male bodybuilder should aim to consume between 140 and 200g of protein per day. If he obtains 90g of protein through his diet, this means he has a shortfall of 50-110g of protein per day. If one scoop contains 25g of protein, he should aim to supplement his food intake with 2-4 scoops of protein per day.

How many Scoops of Protein Per Shake?

This is where it gets a bit more complicated. The body has a finite rate at which it is able to digest protein, which means that efficient protein supplementation requires a bit of planning.

Different proteins are digested and absorbed at different rates. Research has shown that the fastest proteins, such as whey hydrolysate are absorbed at a rate of about 8-10g per hour, whereas slower proteins like cooked egg white are generally absorbed at a rate of less than 3g per hour (2). This is due to a number of factors, including physical digestibility, ease of absorption, and amino acid composition. While the digestive system can detect when large amounts of protein or a slower digesting protein has been eaten and slow down, compensating to give the protein longer to digest, it is generally accepted that there is an upper limit to the amount of protein that can be absorbed from one meal, and this is about 30g, although this figure differs between people (3). Any more, and there is a significant chance that the protein will pass through without being fully digested. Apart from the waste and inefficiency, undigested protein in the lower bowel may be consumed by microorganisms, which may lead to unpleasant symptoms.

The best way to eat protein is to space out shakes and meals as much as possible to ensure maximum absorption.

The amount of protein in a single scoop is usually close to 30g, so unless your protein drastically differs from this figure, one scoop per shake is a reasonable guideline to go by.

How many Scoops of Protein Post Workout?

After a workout is one of the best times to have a protein shake to replenish amino acids such as Glutamine, which is depleted during exercise, and to provide BCAAs – Leucine, Isoleucine and Valine – which stimulate muscle growth and assist recovery. A scoop of protein in milk or water is a great after-workout snack.

How many Scoops of Protein Per Day?

As we now know, the body has a finite rate at which it can absorb protein. Is there an upper limit to the amount of protein the body can handle? The answer is yes. In metabolising protein, the body generates ammonia, a toxic by-product which is usually metabolised in the liver to a harmless compound called urea, which is excreted in the urine. If this mechanism is overloaded, it is possible for ammonia to build up in the body and cause illness and organ damage. This can be serious and severe. For this reason, maintaining the protein intake within the prescribed range is strongly recommended (3).

The total number of scoops per day will vary, and when calculating how many to take, it is important to remember to take the protein content of meals into account. Using our bodybuilder from above as an example, he might have three scoops of protein per day – one between breakfast and lunch, one between lunch and dinner, and a third after dinner. The required intake and ability to digest protein differs widely between people. While this article provides a guideline, it is up to each person to decide what works best for them.

(1) Antonio J, Kalman D, Stout JR, Greenwood M, Willougby DS, Haff GG. ‘Essentials of Sports Nutrition and Supplements’. International Society of Sports Nutrition. Humana Press 2008
(2) Dangin, M., Y. Boirie, C. Garcia-Rodenas, P. Gachon, J. Fauquant, P. Callier, O. Ballevre,and B. Beaufrere. ‘The digestion rate of protein is an independent regulating factor of postprandial protein retention.’ Am. J. Physiol. Endcrinol. Metab. 280: E340-E348, 200
(3) Bilsborough S & Mann N. ‘A Review of Issues of Dietary Protein Intake in Humans.’ International Journal of Sport Nutrition and Exercise Metabolism, 2006, 16:129-152

 

CDP Choline / Citicoline

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CDP Choline, sometimes called citicoline or simply CDP is a bioavailable form of choline that is able to cross the blood brain barrier and deliver choline directly to the brain. Inside the brain choline is vital for the production of phoshatidylcholine (PC) and the neurotransmitter acetylcholine (ACh).

Acetylcholine is a vitally important neurotransmitter than is involved with attention span, learning, memory and focus.  Phosphatidylcholine is a stored form of choline in the brain which is a major component of cell membranes.

CDP Choline’s Effects

Most stacks address choline supplementation in some way as it’s a vitally important nutrient and critical for both acetylcholine and phosphatidylcholine synthesis.

In the short term, supplementing CDP will ensure memory and general cognitive function are optimal, these effects stem from ACh being optimised. In the long term the general health of the brain is supported as CDP would provide the brain with choline for PC and cell membrane renewal.

Citicoline’s Method Of Action

After CDP choline has crossed the blood brain barrier, it provides the raw material for PC synthesis and also increases the brain’s storage “pool” of choline available for ACh creation.  We put CDP choline on par with Alpha GPC (GPC choline) in terms of ability to get choline into the brain.

GPC choline is in fact a catabolic byproduct of PC breakdown, whereas CDP is a primary building block. Both are effective at providing the raw materials the brain requires.

Dosing Citicoline

500mg taken 1-2 times though out the day is suitable for most.  Citicoline is water soluble and can taken with our without food.

Citicoline Stacks Well With…

CDP would stack very well with ALCAR as ALCAR donates it’s acetyl group for acetylcholine synthesis with CDP contributes to the choline portion of the molecule. Citicoline would also stack well with Racetams such as oxiracetam, pramiracetam or aniracetam given the increased acetylcholine turnover with these supplements.

Calming Supplements for Horses

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However well you manage horses, they are all individuals. Just like people, some horses in some situations become stressed and anxious. This may be due to genetic influences, previous unpleasant experiences or management. Once horses become anxious they may develop behaviours that make managing them difficult or even unpleasant for the horse and the owner, such as rearing, shying, biting, pulling, barging, etc. Animals that have erratic or difficult behaviour can be more likely to injure themselves or people working with them. It can also make them hard work to manage and everything becomes a challenge from riding, shoeing, clipping, traveling, etc. Tiring for the horse and tiring for the owner. For most horses exhibiting erratic or difficult behaviours also affects their health and performance in competition.

In some animals, the stress or anxiety is a contributing factor in the development of stereotypical behaviours such as wind-sucking, crib-biting, frequent pawing or stamping and box-walking. Successfully managing stress and anxiety in horses can make life easier, more enjoyable and more productive for the horse and rider, trainer and owner. Stress and anxiety over long periods can lead to immunosuppression (greater susceptibility to infections), gastric ulceration, loss of condition and poor recovery from exercise and competition, not to mention loss of performance. Anxiety and stress can also be a frequent contributing factor in bleeding (Exercise-Induced Pulmonary Haemorrhage – EIPH). When we manage horses for riding, competing or breeding, we present them with a very different environment to that in the wild. Some of the changes in these horses compared with horses in the wild may include reduced interaction with other horses, less space, being stabled, artificial diurnal (daily) rhythms that we impose through our management, larger less frequent feeds and restricted grazing. Of course there are many advantages to the horse of domestication, including potentially improved health (vaccination, worming, etc), protection from predators and access to plenty of food and clean water. But despite all this, the horse is still a “flight” animal. Its first reaction to any new or frightening experience is to run away.

There are various approaches that we use to help us manage difficult horses. Sometimes taking a horse away from something that seems to cause it anxiety can help. Sometimes a simple change in management can help. For example, removing a horse from a group where it is being “bullied”. Sedative drugs such as acepromazine (ACP, Sedalin), xylazine and romfidine are very effective for short-term management but they do not address the underlying problems of anxiety. Sedatives also commonly affect gait and coordination which may lead to decreased performance and even increased risk of injury. Of course for good reasons drugs such as these are prohibited in competition. Sedatives are also powerful drugs and like any drug can have unwanted side effects. When used under veterinary supervision for the right indications, sedatives are usually very safe and effective but they are unlikely to be a suitable medium or long-term solution to behavioural problems.

There are currently an immense number of calming supplements available in the marketplace. There is clearly a demand by horse owners for products that can be purchased without the need for a veterinary prescription. But how much evidence is there to support the effectiveness (efficacy) of these products? Sadly, very little. To carry out appropriate clinical or scientific trials is usually very costly so these are rarely done. Often we are left with the adverts that seem very compelling and use all the right words or testimonials from well-known riders or trainers extolling the virtues of a particular calmer. When a vet gives a horse a good dose of a sedative, the owner will clearly see the result in minutes with their own eyes. But can you really see this effect with your calmer? In many cases the owner wants to see an effect even if there is not one there – the placebo effect. Especially as according to the manufacturer’s instructions many products require prolonged periods of feeding, in some cases several months, before they say an effect can be expected.

So, recognising that horses do develop certain behaviours which we consider undesirable and that they are also frequently exposed to new or stressful experiences and that some horses are more susceptible to stress than others, an ideal calmer should be able to:

1) Rapidly reduce acute stress

2) Be able to reduce overall anxiety in the medium to long term

 

This should could potentially allow the horse to be able to:

1) Learn better

2) Adapt faster

3) Improve more

4) Have a lower risk of developing stereotypical behaviours

5) Have a lower risk of stress related disease (e.g. infection, gastric ulceration)

So let’s look at some common equine calmer ingredients and see how they might work and any evidence for effect in horses.

Magnesium – Probably the most common calmer ingredient. Some magnesium calmers claim to have a “better” source of magnesium than others. This sounds good but is of little significance as there is no scientific or clinical evidence of any calming effect of magnesium. Studies in mice suggested that supplementing with magnesium could have an antidepressant-like and anxiolytic-like (anxiety reducing) effect. However, the amount of magnesium given was very high and was given directly into the body cavity by injection and not fed to the mice. A different study in mice showed that feeding a deficient magnesium diet produced an increase in anxiety. However, magnesium deficiency in horses is rare and most diets contain adequate magnesium. There are currently no published scientific studies demonstrating a calming effect of magnesium supplements in horses. Magnesium supplementation can also interfere with calcium balance and lead to an increased risk of orthopaedic problems. Interestingly, magnesium is not on the FEI Prohibited substances list which should give an indication as to its likely efficacy.

TryptophanTryptophan is an amino acid and is another common active ingredient in equine calmers. Tryptophan is a precursor for serotonin, a neurotransmitter that has been associated with aggression, fear, stress and inhibition of aggression in a variety of animal species. There appear to be many factors that determine the response to tryptophan and few studies have been carried out in horses. Those that have suggest that low doses actually cause mild excitement as opposed to calming. Higher doses reduce endurance and can cause haemolytic anaemia (lowering of red blood cell count). An Australian study into the behavioural effects of tryptophan on horses published in 2008 concluded that “Plasma tryptophan increases when tryptophan is administered at a dose used in some commercial products, but this is not reflected by marked behavioural changes in the horse”. Again, like magnesium, tryptophan is not on the FEI Prohibited substances list.

Valerian (Valerenic acid) – There is a reasonable amount of scientific evidence to suggest an anxiolytic effect of Valerian (Valerenic Acid) an extract from Valerian plants. However, there are no scientific published studies of Valerian or its extracts in horses, but interestingly Valerenic acid is on the FEI Prohibited substances list.

Summary – There are calmers on the market that contain “active” ingredients other than these. At present there is no scientific evidence in the form of published, peer-reviewed studies to support the effectiveness of any of these active ingredients. This is desperately needed. Supplements are far from cheap and you should ask yourself if the products you are using really do work or whether any effect is due to “the placebo effect”. That is you paid for it, you want it to work, you believe its going to work and you might even be convinced it has worked. Whether it really works or not is a different matter.

DMAA Research

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Please find below a short description of research undertaken by Yashaswini Srinivas into methods of detection of DMAA, undertaken at Sheffield Hallam University.

ANALYTICAL METHOD DEVELOPMENT FOR DETECTION OF 4-METHYL-2-HEXANAMINE IN BIOLOGICAL SAMPLES

RESEARCHER – Yashaswini Bangalore Srinivas

RESEARCH UNIT – Sheffield Hallam University, Sheffield, United Kingdom

Date of Research – June-July, 2012
SUMMARY OF THE RESEARCH PROJECT:

4-methyl-2-hexanamine/DMAA, structural congener of 2-aminoheptane is a banned stimulant listed under WADA list of banned substances and whose use is  specifically prohibited ‘in-competition’. Claimed to be of herbal origin, obtained from the oil of Pelargonium graveolens, it is said to satisfy the definition of a ‘stimulant’ by agonistically binding at α1 adrenoceptors in the liver leading to glycogenolysis. Since, the physiological effect of glycogenolysis is to release large amount of energy instantaneously, consumption of substances containing DMAA just before the sporting event confers unfair advantages to the athlete possibly leading to enhanced sporting performance.

AmpDMAA

Worldwide, WADA accredited laboratories employ the sensitive, selective analytical techniques LC-MS and GC-MS to detect the presence of doping agents in an athlete’s urine sample.  In this research project, the foremost aim was to validate LC-MS & GC-MS techniques and assess reproducibility of the protocol as followed by Perrenoud et al. (2009) for the available analytical conditions.  Calibration experiments were performed on both LC-MS and GC-MS  instruments.

The research hypothesis was ‘the two analytical techniques can achieve separation and detect both analyte and internal standard with calibration standard solutions to check the linearity range of the instrument’.

Results

The LC-MS technique failed to achieve resolved  peaks for internal (2-aminoheptane) and reference standards (DMAA) in the calibration standard solutions dissolved in the mobile phase.  Since both DMAA and internal standards have the same mass (MW=115), and being primary amine compounds can accept a proton from the solvent and attain ion of m/z=116, without separation the interpretation is ambiguous.

Therefore, the focus of the research then shifted towards GC-MS wherein calibration was carried out employing two different internal standards- tuaminoheptane and 1-hexylamine.

Using the internal standard tuaminoheptane gave was the same issue as encountered by Perrenoud et al. (2009).  It could not be concluded whether the single peak observed in the TIC represented reference/ internal standard. On the other hand, 1-hexylamine which differs from tuaminoheptane by a methyl unit proved be a slightly better internal standard in that different ion peaks formed as a result of reaction between derivatising agent with internal and reference standards.

Summary

In summary, it became clear by the end of this research project that GC-MS could be adopted as a quantification tool for examining the drug under investigation.

GreenDeckor.com Notes:

Not mentionned here are the alternative derivatising reagents used to try and effect separation using the GC-MS.  The separation was achieved initially using cyclohexanone, as published by Perrenoud et al (Journal of Chromatography B, 877 (2009) 3767–3770), then using an alternative.

The internal standard tuaminoheptane was used by Perrenoud whilst in the above project the alternative 1-hexylamine was used with initially promising results.

Methylhexaneamine – still a problem in sports

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marathonrunners1

One year ago an athlete died while completing the London Marathon. Subsequently she was found to have used the controversial supplement Jack3d, containing methylhexaneamine (DMAA). Then in August last year the drug was banned from sale, so why are we still seeing positives now?

As I reported in my blog previously the Medicines and Healthcare Products Regulatory Agency (MHRA) ruled in August 2012 that DMAA met the criteria to be classified as a medicinal product.  My understanding of the regulations suggest that the ban is for the promotion and advertisement of the drug without authority.  This was supposed to restrict the availability of DMAA as a supplement.  This did not amount to a legal ban though, as DMAA is not listed as a controlled drug under the Misuse of Drugs Act (1971) or the The Misuse of Drugs Regulations (2001).  This means that while it is illegal to sell DMAA as a dietary supplement it is not illegal to own or take.

On the UK Anti Doping (UKAD) website there are 8 athletes listed as currently suspended (or have been in the last year) having failed tests for DMAA.  Five of the athletes are boxers and three footballers (one each of league, union and association!).  Interestingly the bans imposed range from 5 months to 2 years. This is due to a range of factors, including the intent to enhance performance and attempts to ascertain the contents of the supplement before use.

In Australia DMAA was banned by the Therapeutic Goods Administration in August last year.  The Australian Sports Anti Doping Authority lists three current suspensions from DMAA use, from bodybuilding, rugby league and boxing.  Over in the US, the Food and Drug Administration (FDA) issued similar guidelines to in the UK, where selling DMAA as a dietary substance is an offence.  In the latest listings on the US Anti Doping Agency website there are three suspensions listed from 2012 but non so far from 20113.  the three from 2012 are from cycling (x2) and track and field.  All of the US athletes received a six month ban and are free to compete again.

So why are we still seeing positives in the UK and overseas now?  Some left over stock being sold off is probably one reason.  Maybe it is because the athletes had stocked up themselves and have gradually been working through it.  A quick scout around the internet did lead me to a couple of sites still listing it as available for purchase within the UK, but strictly listed as a research chemical.  I havent trid to purchase any so I am not sure if it would go through or not.  I have enough from my purchases in January (post ‘ban’) for my research.

What does this tell us?  Sports people are still prepared to gamble with supplements that have not had their ingredients thoroughly tested before hand.  This means both tested for illegal drugs and to their safety.  The case of GW1516 tells us that many sports people are quite happy to ignore health warnings.

Lecithin, Choline & Bipolar Syndrome

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CDP-Choline-structure

Taking the nutritional supplements choline bitartrate and lecithin supplies the body with more of the raw materials it needs to make acetylcholine and the scientific literature suggests that taking lecithin can helpful during phases of mania but one should be avoided during periods of bipolar depression.  

However supplementing lecithin and its derivatives (phosphatidylcholine, choline and inositol) enhances the absorption, transportation and utilisation of oil molecules throughout the body including the antidepressant omega-3 oils. Taking omega-3 and lecithin together at the same time may give you an additional stabilising technique to help you live well with bipolar syndrome. 
 
Combining a small dose of lecithin with omega-3 fish oils enhances the antidepressant effectiveness of the oils without adding any noticeable depressant effect. Increasing the lecithin to a high dose produces an anti-mania effect while at the same time protection you from swinging into bipolar depression. 
 
A small dose would be ½ to 1 teaspoon of lecithin granules, a high dose would be 2-4 or even 6 tablespoons (to confirm ½-1 teaspoons to 2-6 tablespoons).
 
Once you have learned how to monitor you bipolar by reading the signs so you can determine the state of your condition (manic or depressed) you can adjust the dose of the lecithin to help you control it. See How to Monitor your Bipolar
 
As with all supplements I recommend personal experimentation:
 
If you are in a depressed phase or more prone to them than mania try taking your omega-3 fish oils on their own or with half a teaspoon of lecithin granules to assist the transportation of the oils to your brain, if this combination is going to improve your bipolar depression it should be observable within 3 to 5 days.  The inclusion of lecithin with your oils is especially indicated if you also tend to get dry skin; the quality of the moistness of your skin is primarily influenced by how well hydrated you are and how well your body is supplied with nutritional oils.  Some people find that even when they supplement adequate amounts of water and nutritional oils their skin remains dry and that the inclusion of lecithin along with supplemental choline and inositol solves this problem because they improve the utilisation and transportation of oil molecules through the body all the way to the skin.  (see my page on lymph cleansing in my self-help pages for information on how to hydrate your body)
 
If you are in a manic phase or more prone to them than depression try taking omega-3 fish oils and say 2 tablespoons of lecithin granules. You can try increasing the dose to 4 and then 6 table spoons every 5 days and see how it affects you. What you are looking for is the dosage that produces a useful therapeutic effect, so you know how much to take in the future when you need to treat mania. The maintenance dose you need is likely to be less than the treatment dose. 
 
Don’t worry if you overdo it and make yourself depressed the effect are only temporary and will wear off within about three days of ceasing supplementation and the experience will give you valuable experience that lecithin can affect you and at the right dose can treat your manic phases. 
 

The Cholinergic Hypothesis of Bipolar Depression

 
Acetylcholine is one of the four major neurotransmitters in the brain. It primarily appears to play a role in the memory circuits of the brain, it gives the brain quick and sharp thinking. 
 
Acetylcholine appears to play a role in mood disorders. It has been observed that administration of drugs that increase the release of acetylcholine can decrease manic symptoms during manic phases but may worsen depression during depression phases or even precipitate depression.  It has also been observed that people with bipolar syndrome, schizophrenia and depression have slight elevations in the level of choline (the precursor and metabolite acetylcholine) in their red blood cells [Stoll et al], suggesting metabolism of acetylcholine is altered in people with these conditions. 
 
During manic phases it has been observed that both drugs that increase acetylcholine activity in the brain and supplementing lecithin have useful anti-mania affects.  In a 1982 study by Cohen et al it was demonstrated that lecithin is a non-toxic and effective agent capable of reducing bipolar mania. One study found that the addition of lecithin to a prescription of lithium enhanced its effectiveness compared to a placebo plus lithium.  See below

Lecithin and Choline makes Lithium more Effective Making Very Low and Safe Doses Lithium Useful

 
I recommend trying the combination of lecithin, very low dose lithium and omega-3 fish oils to help manage both bipolar mania and bipolar depression.  
 
A properly done double-blind, placebo-controlled trial done by Cohen, Lipinskini, Altersman in 1982 showed that the combination of lecithin and lithium was more effective at controlling mania than the combination of lithium and a placebo. I believe this may be one of the reasons why I am able to achieve a useful therapeutic effect from very low doses of lithium.  The form of lithium I use is an organically bound amino acid chelate as opposed to the inorganic lithium carbonate used in pharmaceutical medicine and the dosage I use is hundreds of times lower.  
 
I find this research very interesting because in my practice I obtain therapeutic effects form very low safe doses of lithium from a product called Lithinase or Lithium Orotate. The doses I recommend and use myself are so low they would be considered ineffective by most conventional medics, I believe these low doses work because I combine them with lecithin, omega-3 fish oils, vanadium lowering vitamin C, anti-inflammatory NAC cysteine, good diet etc. etc. If you want to self-medicate and live well with bipolar syndrome I recommend you include lecithin in your medicine chest. 
 
There are several major advantages to being able to use such a low dose of lithium: firstly it’s non-toxic, in fact there’s a little evidence that a very low dose of lithium (in the range that I regularly take) has anti-ageing and life extending properties, secondly I experienced none of the unpleasant mind and personality “numbing” affects that people experiences with the higher standard doses of pharmaceutical lithium carbonate and thirdly I find no problem at all in starting and stopping the dosage on an as-and-when required basis, something you cannot do with the pharmaceutical lithium carbonate drug.  Please note stopping and starting lithium may NOT be appropriate for your version of bipolar. 
 
If you’ve been prescribed lithium carbonate for mania by a psychiatrist you should stay on it unless you have established viable alternative treatments.  
In the case of hyper-mania I would also include:
 
Glycine usual dose 2-3 g on an empty stomach once or twice per day.   
In his book Healing Nutrients Within Dr Braverman says he tried 15 to 30 g of glycine with two manic individuals during acute attacks and it caused a cessation of the manic episode and calmness within one hour.   As he says further clinical trials are warranted.   
Taurine has an anti-mania affect similar to lithium 500 mg before each meal and optionally before bed.   
Total Darkness see Bright Light and Total Darkness Treatment chapter.  
Make sure you have not forgotten to take your EPA/DHA (omega-3) supplements.   If you increase your usual dose of omega-3 by half as much again it can help antidote mania but may induce a mini depression lasting 3 days.  
Lecithin increased to 2 teaspoons per day 1 with breakfast and the other with the omega-3’s
 
For me this combination reliably starts to stop a hyper-manic within half a day and terminates it within a couple of days, after which I would continue the Lithinase for perhaps another 5 days to consolidate my balance.
 
Nothing is straightforward with regards to mental illness and brain chemistry and sometimes medications produce paradoxical or opposite affects, I always recommend real-world experimentation.
 

My Personal Prescription Includes Lecithin

 
The first time I experimented with high doses of lecithin I was in a balanced state neither depressed nor manic, what happened was it did not make me feel depressed possibly because I always take a lot of anti-depressant remedies but it made me sleepy; over about five days I started to have longer and longer sleeps, normally I sleep 7 ½ hours by the end of 5 days on the lecithin I sleep a whopping 12+ hours and even wanted a siesta in the afternoon. Obviously this was totally pointless at that time but in a manic phase when I don’t feel the need to sleep lecithin’s sleep inducing effect are very helpful. It’s totally safe and even gives your liver a little detox. 
 
On a daily basis I take omega-3 fish oil containing 900 mg of EPA along with half a teaspoon of lecithin and a very low dose of lithium as and when needed. 
 
When I notice my need for sleep becoming unhealthily diminished I take 5 mg lithium orotate and 2-4 tablespoons of lecithin a day which corrects the imbalance within a few days. 
 

Choline can have Paradoxical and Contradictory Effects on Bipolar Depression

 
If you read the literature on the relationship between mental illness, the neurotransmitter acetylcholine and the supplements choline and lecithin it presents quite a confusing picture:
 
Some of the literature suggests that supplementing lecithin and choline is beneficial for controlling the manic phase of bipolar syndrome, rapid cycling bipolar syndrome and augments the effects of lithium.  However you’ll also find contradictory information suggesting that people with bipolar syndrome have a kind of super sensitivity to acetylcholine perhaps possessing an increased number of what are called receptor sites for acetylcholine within the brain and that the effects of lithium are to dampen down and control excessive acetylcholine activity within the brain.  This implies that you would not want to supplement acetylcholine during a manic phases.  Once again brain chemistry turns out to be anything but straightforward.
 
There is a way for you as an individual to cut through this confusion and that is to conduct your own personal experiments and see what if any are of the effects of choline (sold as choline bitartrate) and lecithin on your bipolar syndrome.   Obviously you should only undertake personal experimentation with bipolar carefully and ideally with the right kind of support either from an appropriate healthcare professional or after you have developed your understanding and skills at managing your condition.
Before experimenting ask yourself:-
 
1.   Is now the right time to be experimenting with my medication, or am I currently going through a phase of instability, change or stress that would make this a bad time to experiment.
2.   Do I have an adequate understanding of my own condition and a good ability to self-medicate if I get into difficulties.  If you are not good at self-medicating you should absolutely work with the guidance and support of an appropriate medical practitioner.
3.   Do you have some regular contact with a psychologically qualified person such as a psychotherapist who can give you some outside independent professional perspective on the state of your mental health, or do you at least have five or six years of regular psychotherapy under your belt.
4.   If your mania and or depression can be so extreme that it may be harmful are you confident that you can cope with this and you have mastered the use of remedies and psychological techniques so that you can quickly bring yourself back into a safe place if the experimenting causes your condition to become unstable.
 
In the next section on my personal prescription and experiences I’ll share some pointers that you may find useful for your experimentation.
 

Supplementing Choline Bitartrate and Inositol

 
Typically choline is sold in combination with another B vitamin called inositol. Most people find choline is somewhat stimulating and that inositol has a somewhat calming effect, combined together they moderate each other. In theory one would take choline in the morning and inositol in the evening, however I’ve never observed this to be really useful. 
 
Very large doses of inositol have been found to be effective for people with OCD see my page on natural treatments for OCD.  
 
I have used choline bitartrate both personally and professionally and consider therapeutic doses to begin above 750 mg per day so I would not be at all concerned about taking the 50 mg of choline bitartrate included in let’s say a multivitamin or a B 50 complex during a phase of depression, the overall effect of a B complex is antidepressant.   
 
For me personally a large single doses of choline bitartrate (1200-1500mg) highly stimulating, inducing a short-term almost hypomanic condition with a subsequent low mood rebound effect within about 4-5 hours. I would only use such large doses immediately prior to exams for the short term memory enhancing effects it can produce.   
 
If you find that rather than helping to control the manic state choline produces a paradoxical opposite effect and is stimulating, but you want to have the memory enhansing effects of choline for let’s say a period of prolonged study I have found (at least for myself) the combination of choline with inositol -along with omega-3 fish oils- to be a balanced and worthwhile solution.   The point is that the combination of choline and inositol tends to produce a fairly neutral and balanced effect on one’s mood.  
 

Choline Inositol & Lecithin for Detoxification

 
Both choline and inositol are what are called lipotrophic substances, lipo means lipids or fats/oils and trophic means attracted to. These lipotropic vitamins attach to fats and oils and assist their transportation and utilisation throughout the body; so for example if you were to take a capsule containing 250 mg of choline and 250 mg of inositol together at the same time as your omega-3 fish oils the lipotrophic choline and inositol would assist in the transportation of the omega-3 oils through your bloodstream and into your brain where it’s needed. Supplementing high doses of choline and inositol in combination is also useful when one wants to detoxify fat soluble toxins from the liver and throughout the fatty tissues of the body. This type of detoxification programme is something I routinely do in my practice and would involve following an alcohol and fried food free diet, taking perhaps 4 X 250 mg choline and inositol capsules per day along with lecithin, supportive cofactor supplements, liver cleansing herbs, high-quality omega-3 oils and periodic therapeutic fasting. See my page on the liver detoxification for more information.
 

Choline as a Memory Enhancer

 
0046Supplementing large doses of choline bitartrate which is a precursor to acetylcholine is capable of at least temporarily enhanced mental abilities, making one sharper and improving one’s ability to quickly access information stored in your memory banks. The effect lasts for about 3 ½ hours and is highly recommended when doing exams.  Be warned however when it wears off it can tend to cause a wave of low blood sugar and tiredness, although this is largely preventable by consuming light snacks such as almonds with raisins and grape or pineapple juice. I suspect that the “rebound” low blood sugar I experienced was actually a direct consequence of my brain being so switched on and highly active for several hours of intense mental work. The brain is a massive consumer of glucose compared to other body tissues; it only constitutes approximately 2% of our total body weight yet it consumes almost half of all the glucose in the blood and just like your muscles when you’re working-out the brain uses even more glucose when it’s doing especially demanding mental work.  
 
For a longer term memory enhancing effect I recommend procaine hydrochloride in the form of ultra-H 7. I recommend buying it from a European and not American source to avoid getting an inferior product. Procaine hydrochloride can also have (mild) antidepressant effects for some people. Personally when I took procaine hydrochloride I found it to have a powerful memory enhancing effect and always produced a brief but rather severe rebound depression when I suddenly stopped taking it without gradually tailing off the dosage.
 
REFERENCES
Several theories have been proposed to explain how and why lecithin enhances the effectiveness os lithium, but this is beyond focus of this page; as I have said before I am a clinician first and foremost so my focus is on discussing practical solutions rather than an academic theories, the academic reader should refer to http://www. acnp. org/g4/GN401000095/CH. html as a good starting point.
 
Pestronk Drackman: Lithium reduces the number of acetylcholine receptors in skeletal muscle. .  Science 17 of October 1980 volume 210 number 4467 pp stop 342-343.
Cohen.  Lipinskini, Altersman: Lecithin in the treatment of mania: double-blind, placebo-controlled trials.  American Journal of psychiatry 1982 of September; 139 (9): 1162-4.  
American Journal of psychiatry 2005 January: 162 (1): 137-45.  Does sustained release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders?
This study showed a reduction in both gambling behaviour and mood instability in pathological gamblers with bipolar spectrum of 83% of the people receiving sustained release lithium compared to 29% improvement in the placebo group.
 
Biol Psychiatry. 1996 Sep 1;40(5):382-8.
Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients.
Stoll AL, Sachs GS, Cohen BM, Lafer B, Christensen JD, Renshaw PF.
Source
Psychopharmacology Unit, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA.
Abstract
This study examined choline augmentation of lithium for rapid-cycling bipolar disorder. Choline bitartrate was given openly to 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases. Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.
PMID:
8874839

[PubMed – indexed for MEDLINE]