Carnosine: Loaded Muscles

Beta-alanine is fast becoming one of the most popular sports supplements for athletes and bodybuilders, and for good reason. When complexed with histidine as a dipeptide, which is the bonding of two amino acids, the resulting compound is called carnosine.

Carnosine functions as an antioxidant and prevents glycation, the name given to potentially dangerous reactions between sugar and protein in the body. More to the point for athletes, carnosine is a potent buffer against acidity in muscle. Increased muscle acidity, which builds up during weight training, results in muscle fatigue. High acidity cripples the activity of energy-producing enzymes in muscle. Muscle contains sufficient amounts of histidine, so the rate-limiting, or major determining factor, of carnosine synthesis is the availability of beta-alanine. Taking extra histidine would be of no value in carnosine synthesis, and the histidine can easily take several other pathways that could cause problems, such as being converted to histamine, the primary culprit in allergy symptoms.

Taking carnosine itself is useless for muscle loading because of the ubiquity of carnosinase, an enzyme that degrades carnosine in all tissues except muscle, which doesn’t have the enzyme. When degraded by carnosinase, carnosine breaks down into its constituent parts, beta-alanine and histidine. Scientists debate whether supplementing with carnosine provides any true health benefits, since most of it is broken down soon after you swallow it.

Several studies have shown that beta-alanine is effective in boosting carnosine in muscle. They showed that carnosine is most abundant in fast-twitch, or type 2, muscle fibers, the fibers most amenable to strength and size increases. The high concentration of carnosine in type 2 fibers is evident in many animals, including horses, camels, dogs and humans. That’s because fast-twitch muscle fibers, operating under anaerobic conditions, produce the most metabolic acid. An oral dose of four to six grams of beta-alanine per day can increase muscle carnosine content in humans by 20 to 30 percent after two weeks, 40 to 60 percent after four weeks and 80 percent by the 10-week mark. While creatine can also build up in muscle with supplementation, the concentrations don’t compare with beta-alanine. Loading creatine results in a relatively paltry 30 to 40 percent maximum elevated storage in muscle.

Studies have shown that once a muscle is loaded with creatine, it stays loaded for 30 days, even if no additional creatine is taken in. That raises the question of how long carnosine supplementation lasts. Since muscle lacks the enzyme that degrades carnosine, beta-alanine may last longer once it’s loaded. A recent study examined precisely how long it remains in muscle.

The subjects were 15 untrained men, average age 22, none of whom had used any supplements three months prior to the study, which had a double-blind, placebo-controlled design, meaning that neither the subjects nor the researchers knew who was getting the beta-alanine and who a maltodextrin placebo. The subjects got 2.4 grams of beta-alanine during the first two weeks, 3.6 grams a day for the next two weeks, then 4.8 grams a day until the end of the five-to-six-week study. The beta-alanine was supplied in 400-milligram capsules taken six times daily with two hours between doses.

No side effects occurred in any of the subjects during the course of the study. The carnosine content was measured in three muscles: the tibialis, a fast-twitch muscle on the front of the shin, and the two calf muscles, the fast-twitch gastrocnemius and the slow-twitch soleus. The carnosine was measured by a noninvasive procedure before and after the supplementation and at three and nine weeks after the subjects stopped taking beta-alanine.

Beta-alanine increased the carnosine content in the tibialis by 27 percent, the soleus by 39 percent and the gastrocnemius by 23 percent. The concentration of carnosine dropped by 2 to 4 percent each week after beta-alanine use stopped. At the three-week point muscle carnosine remained higher than at the start of the study; in fact, only a third of the supplementation-induced increase had disappeared. The amount didn’t return to baseline until after nine weeks. The magnitude of carnosine increase wasn’t as high as in previous studies because this study used a maximum daily dosage of 4.8 grams instead of the 6.4 grams used in previous studies.

The rate of carnosine increase in muscle appears to differ among individuals, in this study varying from 2 to 69 percent. In the high responders it took 15 weeks to return to baseline since they stored more carnosine. In the low responders, the return to baseline took six weeks—still two weeks longer than creatine.

The authors noted that it isn’t possible to reach those intramuscular measures of carnosine with normal food intake, so here’s one case where you’d need to use a supplement. On the other hand, those who habitually eat foods rich in creatine, such as red meat, are often nearly replete with muscle creatine. That explains why regular red-meat eaters often show little benefit from creatine supplements.

The study also confirmed that carnosine increases more in fast-twitch muscles. Fast-twitch fibers may have a higher expression of carnosine transport mechanisms or more abundant activity of the enzyme that produces carnosine from beta-alanine and histidine, namely carnosine synthase. In truth, however, carnosine increases in both slow-twitch and fast-twitch fibers within the same muscle, which is good for training purposes.

So beta-alanine appears to last for a long time in muscle, depending how a person reacts to the supplementation. That brings up another unanswered question: Why do some people store so much more carnosine in muscle than others? That question that will no doubt be answered by future studies. In the meantime, bodybuilders can rest assured that beta-alanine is one of the few supplements that fulfill their promise.

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Baguet, A., et al. (2009). Carnosine loading and washout in human skeletal muscles. J Appl Physiol. 106:837-42.