A GLITCH IN THE ANABOLIC MACHINERY; ACIDEMIA-INDUCED CATABOLISM AND FAILURE IN THE ADAPTIVE RESPONSE TO TRAINING.

By Brian Batcheldor

Acidosis; burn baby burn!

It’s generally accepted that the commonest pitfall for most novice bodybuilders is becoming “overtrained”, a scenario arrived at through poorly planned training regimes, insufficient rest, inadequate nutrition or a combination of any of the above. However, the absolute cluster bomb of the ensuing catabolic assault is the state of acidemia (often interchangeable, “acidosis” actually refers to the various metabolic processes leading to it). For many years now, other sports have recognized this problem and moved pro-actively with science and technology in both avoidance and nailing it at the earliest sign. Remaining largely ignorant of its relevance, bodybuilders instead resort to desperately clutching at the straws of pseudoscience and marketing hype, as they spiral downwards into an abyss of total burnout. In fairness, early signs of overtraining, such as impaired focus and reaction time, are easier to identify in performance-related sports. While there are still some unanswered questions about the chicken and egg relationship between overtraining and acidosis, one thing is clear; -acidemia represents the biggest threat to holding on to your hard-earned muscle or adding to it, - novice, intermediate and experienced pro! Characterized by depletion of the body bicarbonate stores, acidemia is reached when blood pH starts to drop below 7.4, -the normal pH of blood. Why does this occur? I’ll get to that! But first you need to understand how devastating it’s effects can be and why you could literally be wasting your time even going to the gym. There are multiple biochemical effects of metabolic acidosis, but the disturbing effects you’ll more easily relate to include nitrogen wasting, depressed protein metabolism and endocrine disruption, -hypothyroidism, increased glucocorticoid production and decreased IGF-1 levels due to peripheral growth hormone insensitivity (1, 2). In other words, an end to all anabolic processes. If you’re a hardcore bodybuilder, you probably won’t be remotely interested in the potential long-term effects, like renal disorders (nephrolithiasis, -kidney stones), bone disorders (osteomalacia and osteoporosis) or epilepsy (4, 7, 11, 14, 16, 18, 19, 20, 21, 28). Of course, if you’re really “hardcore”, you may be forgiven for thinking that anabolic steroids will still be enough to tip the balance in the favour of anabolism. Wrong, -while AS use may mitigate some of the endocrine disruption, this state isn’t totally influenced by androgen status. In fact, in the post-steroid period AS users are more vulnerable to catabolism than non-users, due to (amongst other things) increased glucocorticoid receptor concentration (3), increased renal load and the acceleration of the ATP dependant ubiquitin ñproteosome pathway (an enzymatic cannibalizing of muscle that’s influenced by falling adenosine triphosphate (ATP) levels).

Sorry, no hype this time, -recent evidence indicates that even mild degrees of acidosis induce some of these metabolic and endocrine effects. The threat is real! In the frame; Lactic acid, pH and BS Mention lactic acid to most bodybuilders and they’ll either tell you that it’s some sort of obscure recreational they think they remember taking once in their college days or it’s that pesky byproduct of exercise metabolism that causes the extreme muscle soreness they experience after an unusually intense workout or making a comeback after a layoff. Others feel that this problem is simply unique to their aerobic brethren, -those stork-legged joggers in loud baggy spandex you often see being overtaken by strolling tourists on Venice boardwalk for example. However, they’d be wrong on all counts. We seriously need to debunk a few myths before we tackle the nemesis to recovery known by the pseudonym “lactic acid”, for there is no doubt that without a game plan, the symptoms attributed to it eventually stop all of us in our tracks, -whether we recognize the real cause or not! The biggest myth is the term lactic “acid”, in skeletal muscle it doesn’t exist as an acid, it exists as “lactate”. In sports science, this is often measured when lactic acid concentration is to be determined. This is more than a moot point, as lactate and lactic acid would have two diversely different physiological effects. The lactic acidosis of exercise has been a classic explanation of the biochemistry behind metabolic acidosis for more than 80 years. The misinterpretation that lactate production causes acidosis would indicate that increased lactate production is one of the several causes of muscle fatigue during intense exercise. Read carefully: In reality, lactate production actually retards, not causes, acidosis. In fact, if muscle didn’t produce lactate, acidosis and muscle fatigue would occur far more rapidly and exercise performance would be severely impaired! This long-term confusion is at least partly understandable. You see, it’s only when exercise intensity increases beyond steady state that the body has to fall back on greater ATP regeneration from glycolysis and the phosphagen system (creatine phosphate). Picture white-knuckle, eye-popping, vein bursting leg extension/leg press supersets to failure. Lactate production increases to prevent pyruvate accumulation and supply the NAD+ needed for phase 2 of glycolysis. Now the ATP that’s rapidly being supplied (primarily) anaerobically to fuel your gut-busting efforts increases proton (hydrogen ion, -H+) release. Since proton donors are acids, the sheer amount of ATP production and rate of hydrolysis occurring simply overwhelms the body’s buffering systems (the acid-base reaction theory). A drop in pH and bingo, -the commonly termed “acidosis of intense exercise” is reached! Thus, increased lactate production coincides with cellular acidosis and remains a good marker for conditions that will induce metabolic acidosis. To recap; the purpose of lactate production is to regenerate NAD+ needed for glycolysis and thus allow ATP production to continue. “But what about that muscle soreness?”, I hear you say. Well, yes acidemia is just one factor, among many, that can cause acute muscle pain and stiffness after an intense workout. For the most part, however, this is due to microtrauma within the muscle tissue and resultant inflammatory processes. Therefore, tackling prolonged muscle soreness will likely come down to more than just addressing exercise-induced acidosis, you’ll need to review all other factors which contribute toward the overtrained state.

So to recap, we’ve taken lactate out of the frame as the perpretator; we now have to start thinking solely in terms of academia/acidosis and systemic pH. We also need to look at the other factors which influence this state, because it actually needs tackling holistically.

Exercise; the only factor? While the principles of periodization and restoration have become firmly established in the preparation of other athletes, as mentioned earlier, bodybuilders have largely been left in the dark. Without a doubt, the bodybuilding media must share the blame when it comes to the high incidence of overtraining found among novices. The perpetual churning out of unrealistic training routines misleadingly advocated as being those of the “pros” takes full advantage of the faith placed by the life blood of the sport in their heroes. With little mention of the most vital factor required for bodybuilding success, -good genetics (no, not just the medicine cabinet), there’s little wonder that frustrated beginners get drained of their seemingly limitless enthusiasm and drop out. Worse still, others that see through the masquerade go down the chemical route with only a few months training under their belt. Unfortunately, I couldn’t do justice to dealing with the exercise side of this equation within the confines of this article, but I will return to this subject in the near future. All I will say to sum up under this section is keep it “short and sweet”. Elite anaerobically trained athletes (weightlifters, sprinters, throwers, etc) demonstrate a higher buffer capacity in muscle (29), -brief high intensity anaerobic exercise itself has been shown to be responsible for this increased buffer capacity.

As metabolic acidosis isn’t the exclusive realm of elite athletes, it should be blatantly obvious that there are other factors at work here. Under normal circumstances (excluding clinical conditions), the net endogenous acid production rate (referred to as the NEAP), and the resultant degree of low-grade metabolic acidosis are determined mainly by the composition of the diet (7, 10, 18). Thus, even in healthy untrained individuals, sustained chronic metabolic acidosis can occur if there is disproportionate intake of foods high in acid precursors and those rich in base (alkaline) precursors, such as vegetable foods (7,11). Of particular note is the fact that protein metabolism yields non-carbonic acids, due mainly to oxidation of cationic and sulfur-containing amino acids (11, 12, 17). Now consider the average bodybuilder, consuming huge amounts of dietary protein that go way off the scale, topped off with protein supplements that have even higher oxidation rates. Do you think that maybe there’s a case here for chronic metabolic acidosis? Now we all know that there are scientists arguing both ways about the protein requirements of athletes (higher or very high) and, once again, that’s a whole article in itself. But across all these debates, one thing is clear, the importance of “economic” protein sources, i.e. protein sources that are not subject to high oxidation rates and that subsequently result in a sustained nitrogen balance and a higher net protein deposition. The leading work in the field of protein digestion rates and their influence on protein accretion (dietary “fast” and “slow” proteins) has been conducted by Yves Boirie and his team at the Centre for Research in Human Nutrition, in Clermont-Ferrand, France (30). The teams work revolves around nutritional intervention with wasting conditions, in particular, sarcopenia (an age-related loss of skeletal muscle that, as mentioned earlier, is largely acidosis mediated). Contrary to the work of many others in the field, Boirie is a firm believer in increasing the protein intake of these individuals, flying totally in the face of those who believed that a high protein diet could create renal overload in such a vulnerable population. He determined that while whey was able to substantially increase protein synthesis, it suffered a much higher oxidation rate than casein, which demonstrated a far better nitrogen balance over seven hours. Most importantly, Whole body protein breakdown was inhibited by 34% after casein ingestion but not at all after whey ingestion. Boirie established that by manipulating the feeding pattern, he could increase the protein intake and form the basis for a concept to be applied to catabolic situations. Higher protein intake, less oxidation, -less acidosis! Therefore, you may have noticed the trend over the last few years towards blended or casein-based protein supplements, which capitalize on the rapid protein synthesis induced by whey and the exclusively anticatabolic properties of casein. This is also the basis of a strong argument for obtaining around 50% of your dietary protein from supplemental sources, as high consumption of animal proteins is a causative factor of acidosis, as are other staples of the western diet, e.g. processed cereals and high sodium intake (22, 15).

Outside of paying more attention to our protein intake, the other dietary protocol for modulating systemic pH is through more selective consumption of vegetables and fruits, most of which increase bicarbonate production through metabolism of organic acid/alkali salts (e.g. sodium citrate, potassium citrate, potassium gluconate, etc) (11, 12, 18). Also, bicarbonate ingestion as mineral salts (sodium bicarbonate, potassium bicarbonate, etc) can increase bicarbonate concentration (4, 9, 11, 12, 18, 20). The practice of supplemental bicarbonate and citrate ingestion became popular among athletes a few years back as a way of buffering academia. However, the dosages needed to experience any effect and the unpleasant side effects related to them (gastric distress) have largely ruled this out as a practical solution for everyone but those who don’t mind training in 5 minute bursts or working from their bathroom! Just bear in mind that as your intake of protein increases, so should your consumption of base producing vegetables and fruits (8, 19). Growing in recognition, the use of probiotic bacteria in functional foods and supplements is also scientifically established to positively influence the acid-base status. There are plenty of books available on dietary induced pH adjustment, currently a fad, many list the effect of commonly available foods on acidosis. This is done by measuring the potential renal load (PRAL) of each individual food (24, 26). The PRAL (calculated over a 24 hour period), along with a relatively constant daily amount of excreted organic acids (in healthy subjects this is proportional to body surface area or body weight), gives us the daily net acid excretion (10, 12, 24, 25, 26). But there are now several ways of accurately testing the body’s acid-base status in response to diet (5, 6, 13, 17, 23, 24, 27).

The Silver Bullet; Beta-alanine! In the last 20 years, the most ground-breaking innovation in sports nutrition has been creatine supplementation, no doubt about it. Since then, we’ve had plenty of re-inventing of the wheel; arginine-AKG, considered so foul tasting in the eighties that you couldn’t give it away, back today as a “Nitric Oxide Booster”! We’ve unresearched anabolic steroids masquerading as supplements purely because they weren’t on any FDA list, some more toxic than their licensed counterparts, Halotestin and Anadrol! Sure, we’ve had a few interesting compounds pop up that may have something to offer, particularly in the fat burning category. But in reality, the world still waits for the next creatine. Creatine is established, it’s at the top of its chain, backed up by hundreds of studies supporting its use in our field and an ever-growing list of pathological states (from muscle loss to memory retention). Well, I am the bearer of good news, that wait is now over, read; the wait is now over! Let’s keep it real here; I’m not talking the “50lbs in 30 days”, “shredded”, “skin bursting pumps”, “100lbs on your bench press” b.s. bodybuilding jargon that floats other products. There’s a clear distinction; this is real, backed by real and continuing scientific studies that will, at the very least, put this compound on par with creatine.

Ironically, this introduction came from the man who was instrumental in publishing the seminal paper on muscle creatine loading, Professor Roger Harris, from the University Of Chichester, England (Harris et al, 1992, Clinical Science 83: 367-374). Although it’s probably not that ironic, -this guy is a genius. Several years ago, Roger, a long time contact of mine, approached me for some human “specimens” to perform muscle biopsies on. At that time, he was keeping tight-lipped about his work, but I went along with his request, rounded up a bunch of my freaks and assured them muscle biopsies were a very pleasurable experience. Muscle biopsies yield valuable accurate information about muscle stores and how they can be influenced. In many ways, this information reveals far more about the efficacy of a particular nutrient than performance studies, which are commonly flawed, particularly with weight trained athletes (too many variables, -genetics, poor controls, steroids, quality of training protocol, etc). I’m sure my lot will see this as water under the bridge and will start talking to me again someday soon (muscle biopsies are good preparation for going into any hostile environment)! Shortly after he got the results back, I got the opportunity to talk with Roger at length, -he was excited, (well, as excited as university professors get, -there was some lip curling and foot tapping I think). He confided in me that the carnosine contents measured in my guys were the highest recorded in human muscle and represented a 20% contribution to muscle buffering capacity! This therefore indicated a real world influence on the ability to perform high intensity exercise (31)! Here’s the twist; carnosine, not bicarbonate, is the main buffering compound in mammalian muscle, particularly in fast-twitch fibers. Thus, more carnosine, less acid build up and delayed muscle fatigue. Carnosine is a dipeptide, formed from the amino acids beta-alanine and L-Histidine. Within human skeletal muscle, carnosine level is likely related to the glycolytic capacity of muscle, which of course can be variable across different populations, e.g. aerobic athletes, anaerobic athletes, older athletes and those with pathological states. In fact, carnosine levels in athletes such as sprinters and body builders is substantially higher than those found in marathoners and untrained athletes (31, 32). Additionally, intense physical training itself can result in increased muscle carnosine levels, as demonstrated in a study with elite speed skaters who increased muscle carnosine by 84% after only 12 days of intense training (33). Thus, the big question was “is it possible to elevate carnosine levels across the board through supplementation?” While there were some previous studies on carnosine, until Roger Harris started his research in this area, the question had remained unanswered. They determined that the rate-limiting factor in carnosine synthesis was beta-alanine availability, but with supplementation of this amino acid (3.2-6.4 g/day) it was possible to substantially elevate muscle carnosine levels (34, 35, 36). In these studies, muscle carnosine concentrations increased by an average of 64%, with greater increases in Type II (fast twitch) muscle fibers compared to Type I (37, 38). Why not simply supplement with pure carnosine? Because, while it will lead to some elevation in muscle carnosine levels (39), upon ingestion, it’s rapidly hydrolyzed to beta-alanine and L-Histadine and must then be re-synthesized. The impracticality of this is easier to understand when you realize that it took 13 g/day of carnosine supplementation to elevate muscle levels by 65.8%, when a similar response (64.2%) was elicited by only 5.2 g/day of beta-alanine.

Once biopsy studies were completed and an elevation of muscle carnosine was established, it was inevitable that performance studies would follow, as would the registration of patents. The patented material, known as CarnoSynô, has been used in several of these studies, while others are still ongoing. It has for example demonstrated a 65% increase in muscle carnosine in cyclists, after only 4.8 g/day for 12 weeks (40). Anaerobic threshold and endurance also improved significantly. In another study, where subjects were first given 4 g/day for a week, followed by 6.4 g/day for a further 9 weeks, levels increased by 58% at week 4 and 73% by week 10. This was also accompanied by an increase in work output of 13% and 16% respectively. Even in untrained individuals, 6.4 g/d of CarnoSynô for 6 days, followed by 3.2 g/d for 22 days demonstrated an increase of 9% in physical working capacity and fatigue threshold when compared to a placebo group. This would thus indicate an ability to delay the onset of neuromuscular fatigue (42).

Significantly, it’s increasingly looking possible to reap the dual benefits of the two most scientifically established natural ergogenics (creatine and beta-alanine) in a “1 + 1 =3” synergism. The increased energy stores in muscle from creatine supplementation coupled with the increased buffering capacity in muscle of carnosine is indicating a dynamic one-two punch. A study using football players on 10 g/day of creatine and 3.2 g/day of Carnosynô resulted in significant increases in training volume, fat-free mass and bodyfat reduction, when compared to a placebo group and a group using creatine alone (43).

As far as dosage recommendations go, I would advise mirroring these studies. Try not to take the dosage over 1.5 g per serving, as a nicotinic acid-like tingling sensation is experienced at the higher ranges. Shoot for 2-3 servings per day, preferably spaced out, with pre and post workout being the obvious targets. Remember, as the studies showed, this is a continuous practice for full effect. As convenience is key here and beta-alanine is liquid-stable, my favorite format offers 1.5 g of proprietary CarnoSynô in a slug of protein hydrolysates and taurine. With a total of around 25g of protein, it’s enough to stimulate anabolism, yet not enough to induce the acidosis normally linked with “fast” proteins. Of course, the beta-alanine would contend with that anyway, but the added taurine will assist with osmotic transport of amino acids. For me and the strength athletes I coach, this product has been absolutely indispensable. After multiple surgeries and being on the wrong side of 40, I would ache for days after some workouts, no matter how tightly I monitored my training. Beta-alanine has virtually put an end to that. Now I heavily suggest that you go let it prove itself, -you’ll be shocked! GLOSSARY Adenosine triphosphate (ATP) is a multifunctional nucleotide primarily known in biochemistry as the mollecular currency of intracellular energy transfer. In this role ATP transports chemical energy within cells.

Glycolysis is a sequence of 11 enzyme-catalyzed reactions in which glucose or glycogen stored in the muscle is converted to lactate. At the same time, ATP is regenerated from ADP.

NAD+ (Nicotinamide Adenine Dinucleotide) is used extensively in glycolysis and the citric acid cycle of cellular respiration. The reducing potential stored in NADH (reduced form of NAD+) can be converted to ATP through the electron transport chain or used for anabolic metabolism Pyruvate (Pyruvic Acid) is the output of the metabolism of glucose, (i.e. glycolysis). One molecule of glucose breaks down into two molecules of pyruvic acid, which are then used to provide further energy.