Substance review: Piracetam

One of the most popular substances purported to have a nootropic effect is Piracetam. UCB Laboratories in Belgium invented Piracetam in 1964 as a derivative of GABA, the neural system responsible for inhibiting neurotransmission the speed of the chemical reactions that trigger thought. Unlike the GABA pathways, the research team found no apparent evidence of it sedating the brain. The substance had such an impact on lead researcher Corneliu Giurgea that he coined the term "nootropic" itself in 1972 after observing the individual cases of enhanced mental functions.

The exact mechanism of Piracetam is unknown and it is not recognised as being a stimulant or a sedative. Various theories about its mechanism tend to focus on increasing neurotransmission through increasing permeability of the blood brain barrier, increasing the rate at which ion transfers occur and manipulating the receptors of various neurotransmitters such as acetylcholine. It has a similar structure to levetiracetam, which is used in epilepsy and while different it may have an effect on the part of the brain that connects the hemispheres, called the corpus collosum.

Before we continue to purported effects I want to reiterate that properly conducted trials on this substance are rare and that the content based here is opinion based on incomplete information.

Physical effects:
Although there is anecdotal evidence of Piracetam causing insomnia, nausia and gastrointestinal discomfort, various studies of piracetams applications outside of memory have not shown side-effects. This short term epileptic trial and this stroke trial from Belgium on high dosages of Piracetam reported no significant physical differences from a placebo. Piracetam at the time of posting is presumably safe.

Cognitive effects:
Despite its history and usage over the last 40 or so years there is a limited range of mostly positive trials. In the 70s a trial on post-concussive effects of piracetam was conducted and found significant benefits. A German study showed quick cognitive recovery after bypass surgery and another large Ukrainian trial showed children's cognitive recovery improving after piracetam dosages. A large trial on dislexic patients found an increase in processing ability and for those with existing poor memory as did a few other trials around the mid 80s, but effective trials on the broader population are missing.

Conclusion:
Piracetam is a promising sports nootropic. The nootropic seems particular useful for contact sports and any sports where a head clash might occur. Research indicates its restorative effects would reduce the amount of time required to restore brain function, which is could be of substantial benefit to fight sports. A sports cognition boost in general is also promising. The anecdotal evidence and numerous animal studies point to benefits in learning and focus. Combine that with no obvious side-effects from several large studies and the risk/reward profile seems ideal.

Further reading:
http://www2.cochrane.org/reviews/en/ab001011.html

Cognition and sports

Cognition in general is a tricky thing to test. Its not particularly clear what people mean when they say "I want to increase cognition" so it makes sense to categorise it. In the 70s a pharmacologist name Cornelius Giurgea coined the term nootropics in his search for a drug or substance that could generally enhance cognition. He came up with the following framework:

-Enhance learning and memory, especially under conditions of disturbed neural metabolism resulting from a lack of oxygen, electroshock or age-related changes
-Facilitate information flow between the cerebral hemispheres
-Enhance the general resistance of the brain to physical and chemical injuries
-Be devoid of any other psychological or physiological effects

Looking at his definition we see it lacking in sophistication. The facilitation of information flow between hemispheres seems extremely vague and the requirement to be devoid of side effects seems overly ambitious. More importantly it doesn't seem that relevant to sport. Far better to instead use a framework that included some of the established concepts of brain function and to include features that were testable in some quantitative way.

It is way outside the scope of this blog to define intelligence, but for its purposes we will assume it to be the efficient use of the brain to achieve the best results in any particular sport. When you consider what would help you build as a sportsman you are most likely thinking of long term memory retrieval: the ability to draw on expertise gathered from training. There are broadly two types of long term memory:

1. Acting on learned phenomena, called "procedural" or "implicit" memory
2. Understanding what phenomena is, called "declaritive" or "explicit" memory

For example there is something called the "mirror test" in which Alzheimers patients will be asked to learn a hand-eye coordination skill by drawing. The patients cannot recall performing the test because of their declarative memory impairment however their skill level at drawing in reverse is retained so their procedural memory is in tact.

When you consider specific sports you can see they often involve a delicate combination of both. On one hand you have something like golf, whereby the procedural action is working overtime, however there will still be declarative instances when you find yourself playing a new course with odd terrain. On the other hand you are playing tennis you will probably not only want to be able to recall procedurally your server, but also facts about how your opponent deals with backhands, whether she has a powerful serve etc.

Short-term memory hardly seems to be a factor in sport other than perhaps communicating a play or strategy so it will be largely ignored by this blog. Rather working memory is applicable as it encompasses short term memory and involves manipulation of stored short term data. In the examples above working memory would allow the golfer to quickly adapt to a change in wind and the tennis player to react to her opponent's better than expected backhand.

In this case any ingredient that successfully improves procedural, declarative and/or working memory in a siginificant fashion will be identified as a prime candidate for a mental enhancement supplement in sports.

Conflicting Evidence in Substance Studies

One of things that struck me as I looked into the use of caffeine as a sports supplement was the lack of a study that you would consider as definitive as well the conflicting nature of many reports. In particular caffeine's efficacy in interval type sports was varied as well as the debate around how caffeine and creatine interact with each other.

Considering caffeine is almost certainly going to be one of the most studied and popular supplements I look at, I imagine it will be hard to draw accurate conclusions on the definitive nature of their effects.

This doesn't dissuade me from the quest to find a sports nootropic, it just reinforces that I will have to be vigilant in my reviews, particularly in some of the more out-there supplements and herbs.

Here's a few things I plan to keep in mind while reading the research:

• Publicly available. That way you can check it out too and hopefully I can get some insight from any interested readers.
• I want it to be designed well i.e. double-blind, placebo research. Research where the subjects or experimenters can sway the result isn't likely to impress me or provide the greatest results.
• I want decent sample sizes. Testing only 10 or so people wont exactly represent an substance's effect on the wider population.

Edit: I came across this a bit in my current research reviews so I'm adding it in now:

• Human trials. The value of testing a cell in a labratory or even just in rats is of little application until further, specific research is carried out.

Sources and further reading:
http://www.ncbi.nlm.nih.gov/pubmed/19088794

Substance review: Caffeine part II

Continued from Part I.

Knowing how caffeine works we can hypothesise about how it will effect our body and mind during sport. Combining this with what has already been formally tested and gather a good idea of how to use caffeine or whether to use it at all.

Physical effects:

Caffeine is usually absorbed at around 15 minutes after oral consumption and intuitively the adrenaline rush it produces seems to be ideal for surges of power. Sports like football, tennis and basketball constantly use a number of repetitive bursts that could benefit. Apart from being quickly absorbed, caffeine has a half-life of around 4-6 hours, all other things being equal. That kind of time is generally longer than your average football match and so it follows that caffeine could have potential benefit in endurance sports too.

A number of older articles (eg this one) have suggested that caffeine was unsuitable for short burst events, but since then reasearch has indicated significant advantages. Swimmers found that their VO2 max and velocity increased. In more universally applicable research, short sprinting bursts also displayed improved performance in both sprinters and the same group of reasearchers found similar advantages in a similar test with team athletes.

For endurance athletes the evidence is more consistent over a greater period of time, with significant increases witnessed as far back as the 70s. Apparently the first studies were on cyclists by David Costill who showed an approximate 20% decrease in fatigue, however I have been unable to source this article. There are several more recent studies which back this original research up. A Kalmar and Cafferelli study showed increased endurance in leg extensions of more than 16% in voluntary contractions. It has been shown that caffeine increases an endurance athelete's perception of fatigue and the placebo effect of caffeine has also been measured to significantly improve performance even in the absence of caffeine.

There are a number of other studies (I reccomend a quick search on PubMed) to a point where you could reach information overload. Generally the various studies' usefulness is limited due to the sample size or methodology flaws. This review of the existing caffeine literature sums it up rather nicely:

these benefits [of caffeine] are likely to occur across a range of sports, including endurance events, stop-and-go events (e.g., team and racquet sports), and sports involving sustained high-intensity activity lasting from 1-60 min (e.g., swimming, rowing, and middle and distance running races). The direct effects on single events involving strength and power, such as lifts, throws, and sprints, are unclear.

There is also the question of Caffeine's interaction with other supplements, in particular one of the most popular of modern supplements: creatine. Research by Vandenberghe et al has shown that caffeine has a very detrimental effect on creatine use for dynamic power, however both a Doherty et al study and a very recent Smith et al study showed that caffeine had no detrimental effect when combined with creatine. Smith's showed a creatine and caffeine (amongst other supplements) stack improved performance over a placebo. At first glance you might take the modern research over the later, but I would argue that the negative effects on creatine are still a significant concern.

Articles have raised concerns about Vandenberghes' methodology, focusing on a lack in wash-out periods for creatine. This is completely misplaced when you observe the placebo was in fact just creatine and so the methodology was sound. By contrast the stack tested by Smith et al does not isolate which ingredient is contributing to the performance so it could be any portion that is enhancing performance or even being held back by other ingredients. More damning is the fact the trial is single blind only and using a proprietary supplement. It is better to point to Doherty et al, who allows us to see that caffeine is useful in short sprint situations which leads us to an interesting situation. It appears as though caffeine negates the explosive power of creatine but not the mass and increases endurance in repeated interval exercise.

Cognitive effects:

If caffeine puts the body into an adrenaline fuelled state and constricts blood vessels in the brain, it could easily be expected that it would have negative effects on cognition. Some meta-analysis (an analysis of existing results from papers) paints a comprehensive picture of the effects. Perhaps surprisingly it appears that while there is no positive impact on memory recall, there is generally no negative effect either. Of specific interest to sports is that generally caffeine improves concentration, reaction time and passive learning, but not in intentional learning. Similarly its ability to improve mood is relative to dosage.

A negative side of caffeine's use as a supplement is using to the point of tolerance build up. As you would intuitively expect, individuals that regularly consume caffeine display less of the symptoms and withdrawal from heavy usage commonly results in side effects like headaches as blood vessels expand in the brain, tiredness and a lack of motivation. This is something athletes should certainly avoid. An increase in drowsiness is not beneficial physically or mentally, nor is a dependence on caffeine to operate at a previous baseline level of performance.

In Part III we will analyse the usefulness of caffeine as a sports supplement.

Sources and further reading:
http://www.ausport.gov.au/ais/nutrition/supplements/supplement_fact_sheets/group_a_supplements/caffeine
http://www.trifuel.com/triathlon/nutrition/caffeine-and-endurance-000402.php

What's in a name?

The blog title Nootrients is a combination of nutrients and nootropics. Nutrients should be obvious to most people reading, but it never hurts to qualify for those pendants out there. Princeton defines a nutrient as "any substance that can be metabolized by an animal to give energy and build tissue".

A nootropic you may not be as familiar with. The most succinct and reputable source I could find for a description of nootropics was the scientific journal Nature: "agents that enhance memory or other cognitive functions."

Combining the two isn't exactly logical because nootropics seems to already encase the nutrient concept. Nevertheless its a good way to bring what the more of a theoretical and out-there concept of nootropics into the more readily understood field nutrition.

Why a mental supplement?

Think about the mental aspect of your sport.

If you participate in a team sport like football this should be easy - what move to play when and how the other team is playing. The number of times an individual has choked or had a brain-snap, giving away points or territory unnecessarily.

In solo sporting pursuits it may be less obvious, but is still prevalent: the martial artist who needs to overcome his opponent's strategy, the car driver who needs to hit the turn perfectly or the runner who needs to implement her race plan with absolute focus.

If sportsmen are using protein, creatine and any number of other supplements to boost muscle power then it stands that a mental supplement should be of equal importance in sports. I can think of a few where it might even be of greater importance.

Perhaps more importantly a mental supplement is not just about cognitive enhancement during the end competition, but the potential for a compounding advantage. The benefits of accelerated learning when applied to a training program are immense. The ability to retain more plays, to learn new techniques rapidly or to adjust to a new directive from a coach is increased. When you compound that across the many training sessions of a modern athlete the results could be phenomenal.

The coming posts will consider some of the more popular supplements and hopefully find a few new ones you haven't heard of. The ingredients of energy drinks that claim mental benefits will be examined as well as some of the more traditional herbal supplements like ginko biloba. Without the resources to create a trial to any decent standard we will rely on publicly published scientific studies as the basis for findings.

By the end we should have a good idea about how to improve our game through supplements or if it is even currently possible.