Supplement Performance - Beta-alanine Supplementation and Athletic Performance:

An Interview with Dr. Mark Tallon

Pull Quote:

for longer is our goal. The extent to which carnosine can delay acidosis (pH decline) is relative to

its concentration in our muscles and this is where supplementation may play an important role."

®) are old news, as recent studies show the addition of protein to a®) has rather powerful anti-fatigue properties.b-alanine (beta-alanine), a nonessential23 and Harris and Greenhaff (1998)14 that4

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MT:

back and talk about the muscle itself and what it undergoes during intense exercise. From this

understanding, we can better comprehend the importance and role of carnosine.

It’s well known that increased muscle mass, strength and extended muscular

performance occur in the most effective manner when exercise routines are done to complete

exhaustion. However, it’s during intense exercise that we commonly experience a reaction in our

bodies known as "metabolic acidosis." This is the point at which our muscles reach extreme

fatigue and can no longer perform an exercise or even push out another repetition. This is

commonly referred to in the gym as "muscle failure."

If we were to take a peek inside the muscle fibers and plasma during this period of

intense exercise, what we would see is a specific chain of biochemical reactions. First, the

breakdown [hydrolysis] of ATP [adenosine triphopshate] would occur, which is the primary source

of energy production in all cells, including muscle. Next, acidosis occurs. In short, this reaction,

which is brought on by the breakdown of ATP, instigates the generation of protons or hydrogen

ions [H in the muscle cells]. Consequently, this rise in H ions causes a fall in blood and, more

detrimentally, a decline in muscle pH levels.

muscle.

With prolonged muscular activity, the decrease in pH [increased acidity] is hugely

accelerated, and thus, it’s directly linked to muscle fatigue and ultimate failure.

the acidity inhibits enzymes vital for the maintenance of ATP, energy production, as well as the

force-producing capacity of your muscles.

Before we discuss carnosine any further, I believe it’s important that we take a step20 Thereby, raising the overall level of acidity in the8 In other words,13

The good news is that after reviewing the past research, as well as carefully examining

the data I’m currently working on in my own lab regarding beta-alanine/histidine supplementation

and its ability to synthesize carnosine in skeletal muscle, I’ve found clear evidence that by binding

hydrogen ions and blocking the inevitable decline in pH levels, one can expect to experience a

positive, marked effect on their muscular performance.

[Editor Note: The acidity (or basicity) of a solution, including body fluids, is measured

using the pH scale, which corresponds to the concentration of hydrogen ions (H ) in a solution.

The pH scale ranges from zero to 14, where seven is considered neutral, below seven acidic and

above seven basic. The further from seven you are on the pH scale, the more acidic or basic the

solution. Acidosis is a condition characterized by excessive acid in the body fluids.]

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and stabilizing pH levels in muscles?

MT:

chemically associate themselves with the H ions that cause fatigue. These compounds are more

commonly known as buffers. Think of buffers essentially as compounds that attach to free H

ions. And because it’s the free concentration of these H ions in fluid (plasma or intracellular fluid

in the muscle) that causes the decrease in pH, any way of removing or combining H ions with

another compound will help maintain pH levels. In essence, this buffering effect causes a

slowdown in declining muscle pH.

effort, particularly during high-intensity exercise.

Sure. In muscle, the first line of defense is a series of compounds that canNow, could you expand on the idea behind blocking the increase in hydrogen ions22 The result is a substantially extended period of muscular24

As evidenced by clinical data, and what’s most promising for us, is that in the case of

skeletal muscle, the most effective buffer is the di-peptide carnosine (beta-alanine/histidine).

3,4

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pH? And how exactly does this happen?

MT:

known as pKa. Don’t hide just yet. What I’m about to explain is not overly complex, yet it’s very

important to further appreciate the role of carnosine in muscle metabolism. This [pKa] value is

linked to how much of a compound is bound to H ions at different pH levels.

In our bodies‚ normal pH is around 7.0. Because of this, a buffer must have a pKa close

to pH 7.0 to be beneficial. For instance, a nutrient with a pKa of 7.0 would have 50 percent of its

total hydrogen ion binding capacity bound to protons. This leaves the remaining 50 percent of the

nutrient free to attach to other circulating H ions, such as the excessive amount produced during

intense exercise.

Another way of looking at this is to imagine carnosine as a four-seated car with two

people sitting in the front (hydrogen ions), leaving two seats empty in the back to pick up two

more people (additional hydrogen ions). Therefore, the more carnosine in the muscle, the more

H ions we can pick up. As a result, this helps prevent the associated decline in pH. It just so

happens that carnosine has a pKa of 6.83. Strikingly close to the 7.0 pH found in our bodies, isn’t

it? It’s for this reason, as I stated earlier, that carnosine (beta-alanine/histidine) is one of the, if not

the, most effective buffers, or pH stabilizers, in human skeletal muscle.

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MT:

would get to this question. Well, we know from research, it’s definitely the case that carnosine is

preferentially concentrated in the Type II muscle fibers.

IIX fibers,

Maurice Greenes of the world to sprinting excellence. Or, better stated for those who lift weights,

Type II muscle fibers are what most of the top professional bodybuilders have more of, versus

Type I fibers. This, in theory, might be why it could be easier for them to build more muscular

bodies, faster and larger, than the rest of us.

We also know carnosine is high in the muscles of those exposed to prolonged and low

muscle pH (such as diving mammals). This decrease in pH isn’t due to lactate per se, as you may

have been told in the past, but rather the production of hydrogen ions (H ) as part of the process

of energy generation. Like these mammals, our own systems can be placed under conditions of

prolonged and low pH when we work at higher intensities. During the period of high-intensity

exercise, we need a huge increase in our rate of energy production, and this can cause some

problems, biochemically speaking. For instance, in events such as an 800-meter run or intense

weight training, energy turnover is high, and as such, hydrogen ion formation is multiplied

accordingly. As hydrogen ions are released, muscle pH begins to fall, leading to muscle force

loss and ultimately fatigue

Thus, creating a physiological environment to increase our ability to work harder for

longer is our goal. The extent to which carnosine can delay acidosis (pH decline) is relative to its

concentration in our muscles and this is where supplementation may play an important role.

[Editor’s Note: Originally, human muscle fiber types were called type I, type IIA and type

IIB, in accordance with the nomenclature used for experimental animals. However, scientists later

realized that the human type "IIB" gene is very similar to the rat type IIX gene, so most authors

nowadays recommend the use of the designation IIX instead of IIB. Type IIX fibers are geared to

generate ATP by anaerobic metabolic processes and have a fast contraction velocity.

Although the lactic acidosis of exercise has been a classic explanation of the

biochemistry of acidosis for more than 80 years, it’s becoming increasingly clear that lactate

production actually retards, not causes, acidosis. (

Sep;287(3):R502-16). Whatever the case, the important bottom line is that during intense

exercise muscle pH begins to fall and this is directly linked to muscle fatigue. Acidic pH can affect

muscle force production in several ways. For example, even small changes in pH can have a

large impact on enzymes and thus on cellular metabolism.]

Am J Physiol Regul Integr Comp Physiol, 2004

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specific athletic event or training?

MT:

activities or other highly intense exercises, such as resistance weight training. In a study recently

published from my lab on bodybuilders in the Journal of Strength and Conditioning Research, we

measured the greatest muscle carnosine contents to date, a level so high it may account for more

than half of skeletal muscle’s total buffering capacity.

in the range of 40 to 50 mmol/kg-1 dw, which is a value nearly three times that found in untrained

subjects.

carnosine levels in the muscles, which is highly beneficial to performance.

In another landmark study, by Parkhouse, et al., muscle samples were analyzed from a

series of athletes, and carnosine was found to be higher in the power/sprint-based athletes rather

than the longer distance endurance athletes. Research carried out in 2002 by Suzuki and

colleagues in Japan demonstrated that carnosine concentrations in Type IIX (fast-twitch) muscle

fibers were directly related to mean power output during a 30-second sprint cycling. Based on

these studies and the fact that carnosine is approximately double the concentration in Type II

muscle fibers compared to Type I (slow-twitch endurance fibers), carnosine is definitely a

compound ideally suited to bodybuilders, sprinters, or any athletes involved in high-intensity

resistance exercise.

[Editor’s Note: A 2002 study by Dr. Yasuhiro Suzuki and co-workers strongly suggest that

the muscle carnosine concentration could be one of the important factors determining highintensity

exercise performance. If you wish to read all the details, a free, full-text paper is

available at http://www.jstage.jst.go.jp/article/jjphysiol/52/2/199/_pdf.]

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MT:

I give away until they are published in their respective scientific journals and are made available

for distribution; however, what I can say is that we have biopsies from some extremely welltrained

bodybuilders, over untrained individuals, and we’ve seen around a 50 percent increase in

whole muscle carnosine,

distribution. This would have a huge impact on performance and resistance to high-intensity

fatigue if we could achieve this through supplementation.

There was also a study by Suzuki last year presented at the 2004 ACSM [American

College of Sports Medicine], which I mentioned earlier, that showed significantly higher mean

power during repeated sprints in subjects with higher muscle carnosine concentrations. Beyond

this, I have taken it myself and for any high-intensity type of workout, it appears to work

fantastically.

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MT:

electrical stimulation of the muscle and some performance tests.

For beta-alanine supplementation, we have valid performance data just presented at the

2005 ACSM scientific conference in Nashville, Tennessee. It was presented that increased

muscle carnosine contents with beta-alanine supplementation increased the ability to perform

maximal exercise at intensities experienced in the gym.

using a maximal bike test and 110 percent of the final power output was calculated. Subjects

were then tested at this 110 percent of exercise capacity, and time to fatigue was measured.

These subjects were then given either beta-alanine or a placebo and tested again, using the

same test at four weeks and 10 weeks [see figure 3]. If you look at the data, this study proves

unequivocally that "beta-alanine supplementation enhances muscle and exercise performance."

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enhanced muscle function. How could this be achieved? And have you carried out dosing

studies?

MT:

stores over here in Europe, but it’s promoted as either an antioxidant or an anti-aging agent. Yes,

we have shown that carnosine can be elevated within skeletal muscle and have carried out a

series of studies on different dosing regimens of between three and 30 grams a day. The problem

at the moment is the cost of carnosine. The production costs are by no means cheapest, or really

even cost-effective for that matter, so we have begun to do most of our work on the use of betaalanine

and histidine. Aside from the histidine component, beta-alanine’s potential for

synthesizing carnosine was first described in cell culture studies back in 1994.

same authors who identified many of the vital functions of carnosine has shown beta-L-aspartyl-

L-histidine to be the natural biological precursor for carnosine and as such, is metabolized in a

similar way as carnosine.

What’s interesting is that supplemental carnosine is already sold in a few health foodYou suggested earlier that with increased muscle stores of carnosine might comeTo date, we’ve looked at different measures of contractility using involuntaryHave you taken any performance measures to date?Well, as many of my studies are in review at present, I have to be careful how muchSo what variation have you measured or observed in human subjects or athletes?Without question, it’s most beneficial to those who participate in sprinting typeAs a follow-up from that last question then, would carnosine be beneficial to anyHow might carnosine affect performance...? I was beginning to wonder when you: So, how could increased muscle stores of carnosine increase performance?The factor that primarily influences the buffering capacity of carnosine is something14 This is even more apparent in the Type23,26 which provide us with the fast-twitch muscle characteristics needed to propel the8,20 unless we can prevent the inevitable decrease in pH, that is!27 [see figure 4]. The values measured were27 This indicates exercise, which requires high levels of ATP production, elevated27 which could be much higher in Type II fibers due to the preferential18 In this study, subjects were tested4 The work by the2

When considering dosage, we would have to start by looking at the research from Dr.

Mark Dunnett, who, incidentally, studied under Professor Roger Harris for his doctorate in

carnosine metabolism in equine physiology. Dr. Dunnett demonstrated that the use of 100 mg/kg1

of bodyweight of beta-alanine for 30 days in conjunction with histidine at 12.5 mg/kg enhanced

muscle carnosine by 18 percent in Type IIB fibers.

was performed on horses and not humans. But it did lend us more relevant insight into proper

dosages. Then in 2003, research presented at the American College of Sports Medicine on betaalanine

in humans demonstrated that by consuming 800 mg four times a day for five weeks, a

significant load or increase in muscle carnosine levels was achieved.

10 The only downside was this dosing study15

AM:

to achieve "carnosine loading"?

MT:

eat a food containing carnosine, it gets broken down into its constituent amino acids; namely,

histidine and beta-alanine, by the enzyme carnosinase, which is highly active in blood. These

amino acids are then taken up into the muscles, where they’re reassembled or resynthesized to

carnosine by carnosine synthetase. We know little of the transport system at present and are

some years away from the knowledge we have on creatine transports, but we believe it may

travel through muscle plasma using similar transporters as creatine.

AM:

carnosine synthesis in humans and maybe focus a little on the supplementation trials you hinted

at earlier?

MT:

bring you up to speed on where we are with the human work.

Although dietary studies have been rare until recently, you can find some information

within the literature. Many initial clues regarding the pathways of carnosine synthesis have

emerged from restrictive diets and specifically the removal of one of carnosine’s constituent

amino acids. In a study looking at the removal of histidine from the diet for a period as short as 24

days and up to 12 weeks, we found it to significantly reduce muscle carnosine levels. Although

this indicates that, in restrictive states, histidine is important, what about non-deficient states

where meat and other carnosine/histidine foods are consumed?

Thus far, there have been four human supplementation studies that concentrated on

enhancing muscle carnosine stores. Three of these are on beta-alanine and only one on

carnosine. These studies have ranged from a period of four to 10 weeks, and all showed

increased levels of muscle carnosine, whether supplemental carnosine or beta-alanine was used.

From these studies, we’ve learned that there’s a definite influence of feeding histidine and it

seems this combination of beta-alanine and histidine is the main nutrient for enhancing muscle

carnosine stores. We have also found out that supplementation with carnosine or beta-alanine

enhances carnosine contents in both Type I and Type II fiber types to similar degrees. This may

have implications for enhancing not only anaerobic exercise performance, but also high-intensity

aerobic exercise.

Again, what we still don’t know is what the "optimal" supplementation dose is and for how

long before we reach maximal muscle concentrations, like we know for creatine. Research

indicates that right around 3.2 grams of beta-alanine supplementation, daily, can likely impart the

desired benefits.

usage.

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MT:

L-carnosine as is potentially available from the ingestion of 80 grams of turkey. That means, in

U.S. conversions of weight and mass, you would have to eat nearly one pound of turkey to

achieve the required minimal supplemental dose of carnosine. Would you want to do that three or

four times a day?

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synthesis of carnosine, as well as looking into some novel delivery systems that may further

enhance previous levels of uptake. We are also investigating the specifics of training-induced

changes in muscle carnosine.

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uptake or usefulness of beta-alanine and histidine?

MT:

to explore this topic. Understanding basic physiology, you would know that for a muscle to

contract, calcium must be able to leave the muscle. One way of doing this is through a receptor.

Think of a receptor as a transport system. The receptor I’m referring to is called a ryanodine

receptor (RR).

a decline in the ability of your muscles to contract and produce force.

carnosine has been shown to stimulate RR-mediated calcium release from the muscle.

wouldn’t it be great if we could enhance it? In theory, this would mean more force production in

the muscle. And not surprisingly, evidence has shown carnosine is not only able to do this, but in

a recent scientific paper, it was found that these effects of carnosine can be further enhanced

with the addition of caffeine.

compounds significantly enhanced the ability of human muscle fibers to prolong the generation of

force via increased efficiency in the release of calcium by the RR system. Technical, I know. But it

provides clear evidence that caffeine works to enhance carnosine.

As an adjunct to caffeine, the addition of carbohydrates, in the form of simple sugars,

seems to show promise as well for carbohydrate oxidation and improved delivery of nutrients.

Carbohydrate oxidation is the amount of carbohydrate your body burns to produce energy. In a

study by Yeo and colleagues [2005]

compared with carbohydrates alone. The study assessed the increase in plasma glucose

between the two supplement forms and there was a 26 percent increase in carbohydrate use

when used in combination with caffeine. This substantial increase in oxidation of carbohydrates

could help maintain muscle and liver glycogen stores, enhance time to fatigue, and increase

insulin levels at a much faster rate than carbohydrates given alone.

Thus, if one were to combine carbohydrates and caffeine, it would make sense that it

would increase the uptake of beta-alanine and histidine into muscle at an enhanced rate, allowing

a faster rise in carnosine levels within skeletal muscle.

[Editor’s Note: It’s well established that caffeine ingestion can increase exercise

performance. A recent study at University of Lutton used the meta-analytic approach to examine

the effects of caffeine ingestion on ratings of perceived exertion (RPE). Twenty-one studies were

included in the analysis. In comparison to placebo, caffeine reduced RPE during exercise by 5.6

percent. Also, caffeine improved exercise performance by 11.2 percent.

2005 Apr;15(2):69-78.]

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MT:

biochemistry of high-intensity muscle fatigue. So additional research on carnosine and its related

metabolites will continue, as will its distribution in different athletic populations and, more

specifically, the localization and distribution of carnosine in individual muscle fibers.

Of equal interest, we will be conducting a trial on a new supplement I have helped

formulate, in collaboration with iSatori Technologies, which was based on my latest research with

beta-alanine and histidine. It’s called H Blocker.

In the case of H Blocker, its formulation is, in my humble opinion, the only one on the

market today where every ingredient has been verified clinically effective in its suggested role and

at the correct dosages shown by science to work. Based on the data we know so far, biochemical

changes with the nutrients included in H Blocker will be noticed after three to four weeks of

continuous use and, even more promising, will keep increasing for at least up to 10 weeks

probably for as long as you take it. Therefore, unlike many supplements, the benefits of

H Blocker will keep increasing as time goes on, allowing users to experience a significant

increase in their ability to enhance maximal exercise performance at intensities normally

experienced in the gym.

For our laboratory here in the UK, our interests are in human metabolism and theWhere do you think your research will be going in the future?Scand J Med Sci Sports,Interesting that you should ask that question, because only recently have we begun: To that point, are there any other nutrients, in your opinion, that might enhance theAt present, we’re broadening our understanding of the biochemical pathways for theWhat’s your research looking into now?Yeah, sure. But keep in mind, one gram of beta-alanine delivers the same amount ofAre you able to ingest carnosine from simply eating meat?Sure, no problem. Let me give you a little history on carnosine feeding and thenCould you give us a breakdown of the research that verifies these concepts ofTo answer that, we have to briefly hit on a bit of carnosine science 101. When we15 However, this is only achieved after at least three to four weeks of continuous21 During intense exercise, the release of calcium ions may be prevented, causing21 What’s interesting is that5 So11 This study demonstrated that the combination of these two28 a mix of carbohydrates in conjunction with caffeine was17 and17

[Editor’s Note: iSatori H Blocker contains beta-alanine, histidine, citrulline malate,

caffeine and a host of other ingredients. H Blocker contains enough servings for 30 workouts, is

fruit punch flavored, and is priced at $64.99. H Blocker is backed by 60-day money-back

guarantee. That is if, for any reason, you are not totally satisfied, you can return it for a full

refund.]

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MT

I’m truly excited by the role beta-alanine, histidine and carnosine synthesis may be able to play in

helping fitness enthusiasts, bodybuilders and serious weight trainers increase their muscular

performance.

: It’s been a pleasure and I appreciate you allowing me to share my recent findings.Thank you for sharing your knowledge and insights with us.That explains a lot, but just to step back a second, what’s happening biochemicallyDoes this explain then how we would achieve a maintenance, or buffering effect, ofWhat role does carnosine play in muscle metabolism?"Creating a physiological environment to increase our ability to work harder

We sense fatigue when we exercise to the point where we feel the task requires greater

effort than it should. Fortunately, certain sports supplements have anti-fatigue properties. For

example, it’s crystal clear that muscle creatine phosphate depletion leads to fatigue and creatine

supplementation can increase creatine phosphate concentration. Consequently, creatine

supplementation improves maximal power/strength, work performed during sets of maximal effort

muscle contractions, single-effort sprint performance and work performed during repetitive sprint

performance.

It’s also well established that carbohydrate ingestion during prolonged exercise can delay

fatigue. However, it’s becoming increasingly clear that traditional sports drinks containing only

carbohydrates (e.g., Gatorade

carbohydrate supplement enhances endurance performance above that which occurs with

carbohydrate alone. There are also numerous studies indicating that caffeine and bicarbonate

loading reduces fatigue. More recently, it was shown that glycine-arginine-alphaketoisocaproic

acid (GAKIC

The latest addition to our arsenal appears to be

amino acid that’s found in many foods we eat. Recent preliminary reports suggest that betaalanine

supplementation can increase muscle carnosine levels and exercise performance. A

double-blinded study by Dr. C.A. Hill and co-workers, presented at 2005 American College of

Sports Medicine Annual Conference, examined the effects of beta-alanine supplementation (four

to 6.4 grams per day) on muscle carnosine levels and exercise performance in untrained

subjects. Mean carnosine levels increased by 58 percent at week four and by an additional 15

percent at week 10. Also, the investigators noted a 16 percent increase in total work done during

cycle ergometry at weeks four and 10.

In another study, presented at the 2005 International Society of Sports Nutrition Annual

Conference, Dr. Jeff Stout and colleagues examined the effects of beta-alanine supplementation

(1.6 to 3.2 grams per day) on physical working capacity at fatigue threshold in untrained men.

The authors reported a greater increase in fatigue threshold of nine percent over placebo (fake

supplement), suggesting that beta-alanine supplementation may delay the onset of

neuromuscular fatigue.

We tracked down the world’s leading carnosine researcher, Mark Tallon, PhD, to provide

us with answers to our questions about the potential of beta-alanine supplementation, its effects

on carnosine and its role in muscle metabolism. Dr. Tallon has worked with some of the world’s

leading international and Olympic teams from the triathlon to the English national karate squad.

He has a BSc in exercise physiology and an MSc in sports nutrition from Liverpool University and

recently earned a doctorate in nutritional biochemistry under leading creatine researcher

Professor Roger Harris. MD interviewed Dr. Tallon, who first described how his research on

carnosine metabolism began.

MT:

Harris, is when I first started to review the research on carnosine metabolism. During this time,

the issues of carnosine and muscle performance and other areas of a more pathological nature,

such as age-induced muscle loss, were only in their infancy. Basically, it was just beginning to

reveal that it could potentially play a functional role in skeletal muscle function. Previously, its

primary role had pretty much been believed to be as an antioxidant; although there were two

studies, namely those from Parkhouse, et al. (1995),

had started to lay the foundations for my doctoral work in human physiology and nutrition

surrounding carnosine.

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MT:

and histidine.

In simple terms, carnosine is a di-peptide composed of the amino acids beta-alanineWhat is carnosine?Back in 1999, after securing a doctorate under the guidance of Professor Roger