In recent years the word neurotransmitter has become a bit of a buzz word in the sports supplement industry. ‘Modulation of neurotransmitter levels for athletic performance’ sounds a bit of a mouthful, but in reality it simply means altering the levels of chemicals in the brain so you can run faster, lift heavier or feel better. Neurotransmitters are chemicals that are used as signal molecules in the brain to control every aspect of human behaviour such as memory, motivation, movement control, mood state, sexual desire and energy levels. As such they can have a huge influence on not just athletic ability, but every aspect of life. Take a look in any health food or supplement shop and the shelves are stacked with the latest ‘nootropic formulas’, churned out by the usual suspects of bandwagon supplement companies (you know who you are and I am watching you!). These formulas promise to enhanced brain power, increase motivation and mental focus or provide tremendous gains in strength and endurance.
The brain is made up of cells (neurones) that are highly interconnected and communicate with one another by passage of electrical signals. However, there are spaces between each neurone (called synapses) that prevent the passage of this electrical signal directly from one neurone to the next. To allow free flow of the information the brain cells converts this electrical signal into a chemical signal (a neurotransmitter) which crosses the synapse and stimulates the next neurone to produce another electrical signal. By increasing or decreasing the amount of neurotransmitter released into the synapse, the brain can modulate the amount of outgoing electrical activity. This neurotransmission therefore acts as a crude volume control. If we can find a way to increase neurotransmitter levels at the synapse of noradrenaline neurones, effectively pumping up the volume, then we should be able to increase outgoing electrical activity which will lead to increases levels of motivation, energy, arousal and improve mood. If we do this regularly at training session the results should be faster gains in strength and muscle growth.
So we want to increase the amount of noradrenaline at certain synapse in the brain, But how do we do this? Well, we really have two options. Firstly, we could increase the production and release of noradrenaline into the gap between the neurones. Secondly, we could prevent the destruction and removal of noradrenaline to maintain its levels for longer. However, If we’re smart, we’ll do both. The building block for noradrenaline is the amino acid tyrosine. Tyrosine is non essential because it can be produced from the essential amino acid phenylalanine, but dietary intakes of tyrosine can boost blood levels considerably. Once in the bloodstream tyrosine is transported across the blood brain barrier where it enters neurones and is converted to noradrenaline by a series of enzymes. This noradrenaline is then packaged up in vesicles and sent along the neurones to the point of release where it is stored until it is needed for neurotransmission.
Now this sounds great. Take more tyrosine in the diet, and we get increased levels of noradrenaline. Well unfortunately it’s not that simple. Firstly, there is a problem with the transport of tyrosine into the brain, in so far as tyrosine will complete with other amino acids for transport across the blood brain barrier. In particular, tyrosine will compete with the amino acid tryptophan. Tryptophan will try to bind to the same transport proteins as tyrosine and will push some of the tyrosine out of the way resulting in less tyrosine in the brain. This is not exactly ideal. The second major problem is that once in the neurone, tyrosine is converted to noradrenaline via enzymes, one of which happens to be rate limiting. The enzyme, called tyrosine hydroxylase, will only convert the tyrosine to noradrenaline at a particular rate depending on a number of factors within the brain. The principle regulator of the rate of this reaction happens to be the amount of noradrenaline stored in the neurone ready for release. So quite cleverly the brain will not convert excess tyrosine to noradrenaline if it already has enough in store.
So it appears that our plan to increase noradrenaline by increasing dietary tyrosine is scuppered. But don’t despair. There are two things we can do to allow us to use tyrosine effectively. Firstly, we can make sure there are no amino acids in the bloodstream to compete with tyrosine for transport into the neurones. This basically means taking tyrosine on an empty stomach away from meals. We may be able to aid this process further by taking the tyrosine with a small amount of glucose. The insulin release caused by the glucose should push the tyrosine across the blood brain barrier more effectively by removing some of the competing amino acids. The second major thing we can do is to remove the noradrenaline stored in the neurone which is acting to inhibit activity of the tyrosine hydroxylase enzyme. If we can do this tyrosine conversion to noradrenaline will increase as the inhibition on the enzyme is removed. There are a number of substances known to achieve this very effectively, but for our purposes the main player is our old friend ephedrine.
Like caffeine, ephedrine is a stimulant drug that targets the noradrenaline pathway in the brain. Most serious trainers have taken a couple of ephedrine before a workout to give them a buzz and increase strength level. In fact, most people who have tried ephedrine will probably have taken it along with caffeine, and perhaps aspirin or tyrosine. These compounds all seem to compliment each other nicely. Many dieters are aware of the ACE stack, standing for aspirin, caffeine and ephedrine. Ephedrine is a compound isolated from certain plants. Ma huang is the herb from which ephedrine is extracted and this plant contains a number of other ephedra alkaloids with varying levels of effect in the human body. Ephedrine acts in a similar way to amphetamine, and in fact it is possible to manufacture amphetamine from ephedrine in the lab, and this has lead to ephedrine being classed as a controlled substance. Remember when ephedrine could be bought from a supplement shop? Ahhh those were the days.
When consumed ephedrine enters the blood and passes to the brain where it acts to displace noradrenaline from its storage location within brain cells. The displaced noradrenaline then passes into the synapse to increase synaptic levels thus giving us the desired effect. As with caffeine, the stimulatory effect of ephedrine is subject to down regulation. In other words, after taking it, as with amphetamine, some people may experience a mild ‘come down’. This is because the nerve terminal now has a shortage of noradrenaline, because vast amounts of it have just been released into the synapse. However, the depletion of noradrenaline at the nerve terminal can be countered by talking supplemental tyrosine. Remember how tyrosine hydroxylase prevented tyrosine’s conversion to noradrenaline? Well now levels are depleted somewhat the enzyme starts to work faster. Therefore noradrenaline production can be upregulated and supplemental tyrosine can now replenish the depleted stores of noradrenaline.
Caffeine is another obvious choice for anyone who wants to crank up a workout by increasing physical performance. It works so well it’s banned above certain levels in many sports. Many people down a cup of strong coffee or a caffeine drink before training for good reason. It works. No doubt about it, caffeine is the undisputed king of workout stimulants. It is cheap, readily available in a number of tasty forms such as tea, coffee, various soft drinks, chocolate and cocoa. It is even available as the herbal formula guarana or as tablets. Caffeine is a member of a group of chemicals called the methylxanthines, which have broadly similar effects. The other common methylxanthines are theobromine and theophylline. Theobromine is found along with caffeine in chocolate and theophylline is found along with caffeine in tea. Coffee is mainly plain old caffeine. So why is caffeine a useful adjunct to tyrosine and ephedrine? Well is is a useful drug because it acts to raise noradrenaline levels at the synapse by a different mechanism to ephedrine.
Caffeine is an adenosine A2 receptor antagonist, which means it has the ability to raise levels of noradrenaline at the synapse by blocking the adenosine receptor. Adenosine is well characterised for its inhibition of neurotransmitter release in the central nervous system. By inhibiting the effects of adenosine, caffeine and related drugs therefore act to increase levels of noradrenaline within the brain. Caffeine also compliments tyrosine nicely because it has the ability to upregulate tyrosine hydroxylase gene expression, thus increasing cellular levels and thus facilitating a faster conversion of tyrosine to adrenaline. Caffeine also act to raise levels of noradrenaline by inhibiting a cellular enzyme called phosphodiesterase. Phosphodiesterase is involved in the degradation of noradrenaline and by inhibiting the enzyme, methylxanthines allows more molecules of noradrenaline to escape destruction, thus prolonging its activity at the synapse. Just for good measure caffeine is also able to aid in the release of adrenaline from the adrenal medulla and thereby increase levels of adrenaline outside the central nervous system.
The main problem with caffeine however is its ubiquitous nature in foods. You see caffeine is everywhere, in food and drink, pills and potions. Unless you are careful you can easily consume 200 mg a day. Tea and coffee drinkers can consume considerably more than this. So what is the problem with that? The problem is that however good caffeine is as a stimulant, it does suffer from a downside shared by most drugs, that of attenuation. This basically means that over a period of time more of the drug must be taken to get the same effects. Prolonged use of caffeine will eventually result in minimal stimulatory effects. Therefore over time, caffeine overuse will result in diminishing benefits in terms of enhancement of athletic performance. As most regular caffeine drinkers with attest, frequent use of caffeine prevents the buzz experienced after consumption that is noticeable to most novice drinkers.
So how do you get the best out of caffeine? One option would be to inhibit the degradation pathway for caffeine in the liver, thus potentiating its duration in the bloodstream. This can be achieved in some cases by taking grapefruit which contains a chemical called naringin that decreases the oral clearance of caffeine and prolongs its half-life. However, the same effect could probably be achieved by simply taking a higher dose or prolonging the administration i.e. take a number of tablets or cups of coffee over a period of time to maintain blood levels. Therefore, by far the most effective method for increasing the effectiveness of caffeine is as so often in life is the simplest. By allowing allow down regulation of the adenosine receptors and phosphodiesterase enzyme by cutting back on caffeine when its not needed to enhance performance. Lay off the espresso during the day and go for a caffeine free alternative. Just use the caffeine kick when you want to get mental!
