Has The Next Creatine Finally Arrived?

New research from the UK, the USA and Japan may be laying the path for an ergogenic aid that may even eclipse the phenomenal success of Creatine monohydrate. Still don't believe me? I don't blame you with the mounting release of bogus supplements on the market this year; but by the end of this article I am willing to bet my bottom dollar you will be convinced about the potential of this under-studied, under-exposed and under-valued muscle buffering di-peptide.

A Brief Moment In Time...

Carnosine (beta-alanyly-L-histidine) was discovered way back in 1900 showing a structure composed of a combination of two amino acids, histidine & beta-alanine. Over the past 100 or so years the focus of research has developed around assigning carnosine a biological role or biological function you may say. The search has spanned the disciplines of human physiology, biochemistry, and even neurochemistry.

But from all the documented literature it wasn't until 1995 that the first of 2 human papers were released indicating its true nature with respect to exercise performance. So what's new? Where do we go from now as regards its use? & Indeed its potential for performance enhancement? Well you're lucky this month guys, I just happen to be working in probably the most active lab in the world at this time on just these topics. So let me enlighten you and elucidate on the application of a supplement at the CUTTING EDGE of sports nutrition.

Muscle, Muscle & More Muscle...

You guessed it folks carnosine is located in relatively high concentrations in skeletal muscle but where exactly in the muscle fibre is it localized? Well first lets have a carnosine lesson 101 on how it is synthesized and taken up into the muscle cell before expanding on its preferential distribution in certain muscle fibres, including why this distribution suggests it is the perfect solution for the enhancement of high intensity exercise.

When we eat a food containing carnosine it gets hydrolysed (broken down) to its constituent amino acids by the enzyme carnosinase, which is highly active in blood. These amino acids are then taken up into the muscle where they are reassembled or resynthesized to carnosine by carnosine synthetase.

Although both histidine and beta-alanine have a variety of functions in their own right I will focus only on the role in relation to the synthesis of carnosine. Now for the real area of interest to you strength and power athletes also the implications its role & localization in skeletal muscle may have on our performance. Its definitely the case that carnosine is preferentially located in those big boy's the type II muscle fibres ^1,2. This is even more apparent in the type IIx fibres which provide us with the fast twitch characteristics needed to propel the Maurice Green's of the world to sprinting excellence, and the power to engage in high intensity resistance training. So what's the deal with carnosine and these fibre type's?

Explorers Of The Ocean Deep Pointing The Way

Although carnosine is preferential located in the type II fibres there is carnosine in type I fibres, its just the case we have double the concentration in type IIs, coincidence? Me thinks not. Suyama³ and colleagues have shown that in certain species (little piked whale) we find values of around 500 mmol.kg-1 dm (dry muscle), this value even exceeds this species muscle glycogen stores.

Human skeletal muscle contains circa 20mmol.kg-1 dm; yes 25 times less than these amazing sea mammals. So why the huge variation in values? Well its pure and simple "ecological pressures". What I mean by this is diving mammals tend to spend much of their time in a state of prolonged hypoxia (without oxygen) much like the intramuscular acidosis produced during high intensity resistance exercise (i.e. burning sensation felt in the muscle during a hard set often incorrectly describe as lactate).

This relationship between the level of hypoxia and muscle carnosine concentrations has been demonstrated in previous work ⁴. This work emphasises the adaptive responses needed to maintain pH under conditions of metabolic and respiratory acidosis.

How Carnosine Works...

Feel the burn or maybe not!

As I have just described carnosine is high in the muscle of those exposed to prolonged & low muscle pH. This decrease in pH is not due to lactate perse which you may of been told in the past, but rather the production of H+ (hydrogen ions) as part of the process of energy release from anaerobic glycolysis or oxidative phosphorylation (note: A way of supplying energy to ATP Synthesis).

As we work at higher intensities we need a equal increase in our rate of energy production as such in events such as 800m running. This turnover is high and as such the H+ formation is multiplied accordingly. As H+ are released intramuscular pH can begin to fall leading to fatigue unless we can prevent it. So how do we achieve this maintenance (buffering) of pH? Wouldn't it be fantastic if we had a system in place that can do just this...well surprise surprise we have.

The main intramuscular buffering system involves phosphates (one reason why creatine is effective), bicarbonate, and proteins of which carnosine is a constituent. At the physiological pH of which muscle contraction occurs (6.8) "carnosine can pick up H+ (associate) and prevent or should I say delay the inevitable decrease in pH increasing our ability to work harder for longer". The extent to which carnosine can delay acidosis is relative to its content in muscle, and this is where supplementation may eventually play a role.

Please Not Another Rat Study...

Although there is much research on equine & rat muscle, research is few and far between but human data on carnosine does exist. With reference to its distribution in human single fibres there is only one paper to date by Harris, Dunnett & Greenhaff ².

This was the first paper in humans to show a difference in carnosine between fibre types and carnosine content. On a separate note the sulfonated amino acid taurine has the exact opposite distribution to carnosine in single fibres (we will explore this in a future issue). The total contribution of these values represent to muscle buffering was 28% in the type II muscle fibre. To put this in perspective creatine represents 29% of the total H+ uptake during short fatiguing exercise ⁴.

Carnosine & The Strength Athlete

So let me get back to what we are here for "exercise" and how carnosine is related. Parkhouse¹ helped give us significant cause to believe that carnosine really can be a factor in exercise performance. This landmark study took a series of muscle biopsy samples from sprinters, 800m runners, rowers, marathon runners. Carnosine was significantly elevated in the power athletes (sprinters & rowers) possibly as an adaptive response to the stressors of their associated sports . This result is even more likely when we look at the other groups.

Runners showed no significant difference in skeletal muscle carnosine and buffering capacity in relation to untrained subjects. The problems with this study are they only analysed whole muscle, which is the combination of, type I and II fibres. As we now know there is less canosine in the type I so by mixing the muscle the overall value will be lower than type II alone.

The bottom line "Carnosine is highly elevated in the bodybuilder versus the untrained" this news could turn out to be legendary for three reasons:

1. It demonstrates a large physiological variation in muscle carnosine in different populations.

    

2. Shows that we can change our muscle carnosine through training.

    

3. IT BLOWS APART the previously held belief that carnosine has little influences on muscle buffering. The real application of carnosines function on muscle performance will be when data is released from supplementation studies. From recent work just completed with carnosine feeding by our group "I predict we are about to go on a fantastic ride similar to that felt after the release of creatine way back in the early 90's".

The Past, Present, & Future Of Carnosine Supplementation!
 

It's the question that has driven most of my doctoral research over the past four years can carnosine supplementation increase muscle carnosine? Feel the anticipation ok guys? The answer in short is "YES" but to what levels in humans, and what dosing? You will have to wait for a future issue. But what I can divulge is what we have seen so far in animal studies. Carnosine and other imidiazole dipeptides are absent from fasting human plasma but are detectable in very low concentrations in urine⁷.

There is a definitive increase in plasma carnosine following ingestion of meats and associated products but still at low concentrations, this is probably due to the relatively high activity of the carnosinase enzyme. Although dietary studies are rare restrictive diets where removal of one of carnosines constituent amino acids are Histidine, has been the focus of dietary restriction studies and the findings are not unexpected and show that after removal of histidine from the diet for periods as short as 24 days and as long as 12 weeks muscle carnosine levels are reduced ^8,9.

As for beta-alanine there is one very well designed study, probably the best out there in terms of analytical techniques used and the outcome of the study design i.e. GREAT NEWS FOR US. Dunnett et al² showed that after feeding a combination (yes even the biochemists use stacking) of beta-alanine (100mg/kg body weight) and histidine (12.5mg/kg body weight) for 30 days increased muscle carnosine by 13%. More recent studies by Maynard¹⁰ over in Kentucky have shown a 2-5 fold increase in rat muscle carnosine with a diet consisting of 1.8% carnosine.

More recently this year there have been two human carnosine studies released one showing an increase in human plasma but no muscle data. The other on autistic children taking 400mg of 2 times a day for 12 weeks showed significant improvement in these children's behavior¹².

Conclusion: A Word In Your Ear.

Lets tie this thing up then. Carnosine holds great promise and is of paramount importance for those of us who want to increase the intensity of our exercise; and it will no doubt elevate the training threshold especially in activities defined and characterized by prolonged periods of anaerobic work. Although carnosine's function has been attributed to other metabolic functions, its physical chemistry dictates that it will contribute significantly to hydrogen ion/ pH control, indeed in equine muscle up to 40% and in humans i.e. our bodybuilders maybe 20-30% in type II fibres.

Theoretically training or sustained oral administration of beta-alanine, histidine or even carnosine maybe effective methods for increasing endogenous muscle carnosine concentrations. Any such increase would be of benefit primarily in sports involving sprinting and as such a recent paper¹² showed muscle carnosine contents was highly correlated to peak power output during sprint cycling (such was the case with creatine in the early days).

Although success looks on the horizon with carnosine use, it will be less effective as an ergogenic aid in endurance orientated sports. As a final note, or a word in your ear, carnosine as all supplements can have powerful physiological effects especially when taken at high dose; and carnosine is no exception to the rule.

We have found that with high dose i.e. 50mg/kg beta-alanine only half that taken in the equine study mentioned earlier by Dunnett et al, significant and uncomfortable parathesis occurs. Parathesis a feeling similar to pins & needles, an intense tingling sensation like when you have been on the sun bed to long (posers one & all). To date the health consequences are unknown so caution must be advised with its use until further results demonstrating its safety and effectiveness are released. That time is approaching and as always in life "the best things are always worth waiting for".

Written By Mark Tallon.

REFERENCES

Parkhouse WS, McKenzie DC, Hochacha PW: Buffering capacity of deproteinised human vastus lateralis muscle. J Appl Physiol 58: 14-17, 1995
Harris RC, Dunnett M, Greenhaff PL: Carnosine and Taurine contents in individual fibres of human vastus lateralis muscle. J Sport Sci 16: 639 -643, 1998
Dunnett M & Harris RC: Influence of oral beta-alanine and L-Histidine supplementation on the carnosine content of gluteus medius. Equine Vet J 30: 499 - 504, 1999
Suyama M, Suzuki T, Maruyama M, Saito K: Determination of carnosine, anserine and balanine in the muscle of animals. Bullitin Jap Soc Sci & Fish 36: 1048 - 1053, 1970
Crush KG: Carnosine related substances in animal tissues. Comp Biochem Physiol 34: 3-30, 1970
Roesel RA, Kearse EC, Blankenship PR: Carnosine excretion in infants and children. Fed Proc 45: 470, 1986
Amend JF, Strumeyer DH, Fisher H: Effect of Dietary histidine on tissue concentrations of Histidine containing dipeptides in adult cockerels. J Nutr 109: 1779 -1786, 1979
Easter RA &Baker DH: Nitrogen metabolism, tissue carnosine concentration and blood chemistry of gravid swine fed graded levels of histidine. J Nutr: 120-125, 1977
Maynard ML, Bossonneault GA, Chow CK, Bruckner GA: High levels of dietary carnosine are associated with increased concentrations of carnosine and in rat soleous muscle. J Nut 131: 287-290, 2001
Chez MG, Buchanan CP, Komen JL, Becker M: Double-blind placebo-controlled study of L-Carnosine supplementation in children with autistic spectrum disorders. In press, 2002-10-04
Suzuki Y, Ito O, Mukai N, Takahashi H, Takamatsuma K: High levels of skeletal muscle carnosine contributes to the latter half of exercise performance during 30s maximal cycle ergometer sprinting. Jap J Physiol 52 (2): 199 - 205, 2002