First of all, my thanks to reader Jeg3 who put me onto this topic via a comment to the blog post Exercise, telomerase and telomeres. It seems that both younger people who participate in strenuous sports and old folks who are in danger because of loss of muscle strength can benefit considerably from increasing the carnosine levels in their muscles. And this can be accomplished to some extent by eating meat, supplementation with l-carnosine or supplementation with beta-alanine. This blog post reviews the research in this area and steps towards muscle strengthening that can be taken by both athletes and older folks like me.
I am also planning a follow-up blog post that looks at a fascinating set of similarities and relationships in behavior of beta-alanine, l-carnosine and gabapentin in terms of actions on GABA receptors in nerves and glia. This post will relate these substances to topics like pain management, maintaining mental balance, sleep and mental acuity.
I fell in love with l-carnosine over ten years ago when I learned how it could delay or reverse cellular senescence. It can triple the replicative lifespan of fibroblasts in culture. For an introduction to this fascinating substance, see the blog post The curious case of l-carnosine. L-carnosine has long been part of my personal supplement regimen and is in my suggested anti-aging Supplement Regimen.
Beta-alanine and carnosine
The research of relevance to this blog entry has to do with supplementation to increase muscle carnosine levels in two populations: those who participate in high-intensity exercise like long-distance running, and the elderly. The studies I cite are mostly concerned with beta-alanine supplementation, though I am not completely convinced that this is the best approach to building up carnosine levels in muscles. Beta alanine “is a naturally occurring beta amino acid, — is a component of the naturally occurring peptides carnosine and anserine and also of pantothenic acid (vitamin B5) which itself is a component of coenzyme A. Under normal conditions, Î²-alanine is metabolized into acetic acid. — Î²-Alanine is the rate-limiting precursor of carnosine, which is to say carnosine levels are limited by the amount of available Î²-alanine(ref).”
Another source indicates “The greatest natural dietary sources of beta-alanine are believed to be obtained through ingesting the beta-alanine containing dipeptides: carnosine, anserine and balenine, rather than directly ingesting beta-alanine. These dipeptides are found in protein rich foods such as chicken, beef, pork and fish. It is predominantly through ingesting the dipeptide carnosine that we ingest most of our beta-alanine, as the two other dipeptides are not found nearly as plentiful in our typical coniferous diet. However, obtaining beta-alanine through these dipeptides is not the only way, as our bodies can synthesize it in the liver from the catabolism of pyrimidine nucleotides which are broken down into uracil and thymine and then metabolized into beta-alanine and B-aminoisobutyrate.”
Simply put, in the body both carnosine and beta alanine create each other and the presence of one leads the body to create the other. Beta alanine has been a very popular sports and body-building supplement but carnosine itself is just now emerging to be known as a sports supplement(ref).
A 2009 study looks at how long carnosine stays in muscles, once its level has been built up by supplements, Carnosine loading and washout in human skeletal muscles. “The oral ingestion of Î²-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content both in trained and untrained humans.– The Î²-alanine supplementation significantly increased the carnosine content in soleus by 39%, in tibialis by 27%, and in gastrocnemius by 23% and declined postsupplementation at a rate of 2–4%/wk. Average muscle carnosine remained increased compared with baseline at 3 wk of washout (only one-third of the supplementation-induced increase had disappeared) and returned to baseline values within 9 wk at group level. — It can be concluded that carnosine is a stable compound in human skeletal muscle, confirming the absence of carnosinase in myocytes. The present study shows that washout periods for crossover designs in supplementation studies for muscle metabolites may sometimes require months rather than weeks.” It is remarkably persistent stuff!
Beta alanine supplementation for endurance athletes
The 2007 publication Î²-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters states “The ingestion of Î²-alanine, the rate-limiting precursor of carnosine, has been shown to elevate the muscle carnosine content. We aimed to investigate, using proton magnetic resonance spectroscopy (proton MRS), whether oral supplementation with Î²-alanine during 4 wk would elevate the calf muscle carnosine content and affect exercise performance in 400-m sprint-trained competitive athletes. Fifteen male athletes participated in a placebo-controlled, double-blind study and were supplemented orally for 4 wk with either 4.8 g/day Î²-alanine or placebo. — In conclusion, 1) proton MRS can be used to noninvasively quantify human muscle carnosine content; 2) muscle carnosine is increased by oral Î²-alanine supplementation in sprint-trained athletes; 3) carnosine loading slightly but significantly attenuated fatigue in repeated bouts of exhaustive dynamic contractions; and 4) the increase in muscle carnosine did not improve isometric endurance or 400-m race time.”
The 2007 study Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity concludes: “Muscle carnosine was significantly increased by +58.8% and +80.1% after 4 and 10 wks beta-alanine supplementation. Carnosine, initially 1.71 times higher in type IIa fibres, increased equally in both type I and IIa fibres. No increase was seen in control subjects. Taurine was unchanged by 10 wks of supplementation. 4 wks beta-alanine supplementation resulted in a significant increase in TWD (total work done) (+13.0%); with a further +3.2% increase at 10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The increase in TWD with supplementation followed the increase in muscle carnosine.”
The purpose of the 2009 study Effects of beta-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial “was to evaluate the effects of combining beta-alanine supplementation with high-intensity interval training (HIIT) on endurance performance and aerobic metabolism in recreationally active college-aged men. — CONCLUSION: The use of HIIT to induce significant aerobic improvements is effective and efficient. Chronic BA supplementation may further enhance HIIT, improving endurance performance and lean body mass.”
The 2006 study Effects of twenty-eight days of beta-alanine and creatine monohydrate supplementation on the physical working capacity at neuromuscular fatigue threshold looked at non-athletes. “ — findings suggested that b-Ala supplementation may delay the onset of neuromuscular fatigue. Furthermore, there appeared to be no additive or unique effects of CrM vs. b-Ala alone on PWCFT (neuromuscular threshold fatigue test).”
Beta-alanine supplementation for the elderly
Of course there is much to the conventional wisdom that exercise is an important part of any anti-aging program for the elderly as well as for the young(ref). But what about muscular carnosine?
The 2008 study The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55-92 Years): a double-blind randomized study looked at a small sample of elderly people. In the introduction, the article makes a compelling argument for strengthening the carnosine concentrations in muscles of older people: “Carnosine (beta-alanyl-L-histidine), a dipeptide is an efficient hydrogen ion (H+) buffer over the physiological pH range [1,2]. In muscle, where its concentration is highest, carnosine makes an important contribution to the maintenance of intracellular pH, which is vital for normal muscle function during intense exercise . While the dipeptide is found in both Type I and Type II muscle, its concentration is highest in Type II muscle. Studies in humans and rats have demonstrated an inverse relationship between age and muscle carnosine content [3,4]. Sarcopenia, the loss in muscle mass with age, is associated with significant reductions in strength, power, and the ability to resist fatigue in elderly men and women [5,6]. Significant decreases in skeletal muscle and decline in muscle function are clearly evident after the age of fifty [5,7]. Deterioration of motor coordination, as a result of losses in strength and/or fatigue, is related to an increase in the frequency of falls [6,8] which repeatedly lead to injury and even deaths among the elderly .” — “Twenty-six elderly men and women (Table 1) from independent-living communities in South Florida volunteered to participate in the study. None of the participants had any previous history of BA supplementation and maintained their regular activity and dietary patterns throughout the study”
The study looked at Pre- to post-test values for physical working capacity (PWC) at fatigue threshold (PWCFT) for BA and PL groups. A significant difference was found. “Data from this study suggest that ninety days of BA supplementation may increase physical working capacity in elderly men and women. These findings may be clinically significant, as a decrease in functional capacity to perform daily living tasks has been associated with an increase in mortality , primarily due to increased risk of falls . Further, deVries et al.  and Alexander et al.  have suggested that falls may be related to fatigue-induced deterioration of motor coordination. Thus, an improved resistance to fatigue, as reported in this study, may be important to consider when working with a similar population. — The results of this study suggest that ninety days of BA supplementation may have significantly increased intramuscular carnosine resulting in a 28.5% increase in PWCFT due to a greater H+ buffering capacity.” This study also contains an excellent set of hyperlinked references relating to muscular fatigue, muscular carnosine and age-related muscle functioning.
I surmise that changing the fatigue threshold for exercise via raising muscle carnosine levels would also change the point where telomere shortening due to exercise over-stress might occur. However, none of the papers regarding muscular carnosine and beta-alanine supplementation shed direct light on this issue, an issue raised in the blog entry Exercise, telomerase and telomeres.
The new-to-me citations listed above leave me impressed with how important carnosine augmentation in muscles might be for health and functionality in the elderly. On the other hand I am not sure at this point that beta-alanine supplementation is the best way to go.
Supplementation: beta-alanine vs. l-carnosine
Studies in the literature about augmenting muscular carnosine seem to be mostly about supplementation using beta-alanine. I am not sure the reasons for that including possibly a) the sport-medicine oriented researchers have always thought in terms of using beta-alanine instead of directly taking carnosine, b) the research was motivated or influenced by commercial makers of beta-alanine supplements, no doubt large money-makers, or c) beta-alanine is in fact the best approach to augmenting muscular carnosine.
As mentioned earlier, muscle levels of carnosine can also be raised by eating meat or by directly taking carnosine supplements. I have had difficulty finding any study that systematically compares the efficacy of these approaches vs beta-alanine supplementation. I have seen claims on body-building sites that beta-alanine is possibly less expensive and more bioavailable than directly taking carnosine.
One such site recommends taking a combination of beta-alanine and Histidine. On the other hand, the 2006 report The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis states “Dietary supplementation with I) 3.2 and II) 6.4 g . d(-1) beta-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine (isomolar to II) for 4 w resulted in significant increases in muscle carnosine estimated at 42.1, 64.2 and 65.8%.”
I also found a seemingly-credible blog entry relative to beta-alanine and carnosine: “Anti-crosslinking properties of carnosine: significance of histidine. — Hobart LJ, Seibel I, Yeargans GS, Seidler NW. Department of Biochemistry, University of Health Sciences, 1750 Independence Avenue, Kansas City, MO 64106-1453, USA. Carnosine, a histidine-containing dipeptide, is a potential treatment for Alzheimer’s disease. There is evidence that carnosine prevents oxidation and glycation, both of which contribute to the crosslinking of proteins; and protein crosslinking promotes beta-amyloid plaque formation. It was previously shown that carnosine has anti-crosslinking activity, but it is not known which of the chemical constituents are responsible. We tested the individual amino acids in carnosine (beta-alanine, histidine) as well as modified forms of histidine (alpha-acetyl-histidine, 1-methyl-histidine) and methylated carnosine (anserine) using glycation-induced crosslinking of cytosolic aspartate aminotransferase as our model. beta-Alanine showed anti-crosslinking activity but less than that of carnosine, suggesting that the beta-amino group is required in preventing protein crosslinking. Interestingly, histidine, which has both alpha-amino and imidazolium groups, was more effective than carnosine. Acetylation of histidine’s alpha-amino group or methylation of its imidazolium group abolished anti-crosslinking activity. Furthermore, methylation of carnosine’s imidazolium group decreased its anti-crosslinking activity. The results suggest that histidine is the representative structure for an anti-crosslinking agent, containing the necessary functional groups for optimal protection against crosslinking agents. We propose that the imidazolium group of histidine or carnosine may stabilize adducts formed at the primary amino group.”
At this time I will not stop taking l-carnosine as a supplement and substitute beta-alanine in its place because of the multiple demonstrated benefits of l-carnosine that are independent of its effects in muscle tissues(ref)(ref). I am open, however, to the question of whether adding beta-alanine to my regimen could be useful or would be redundant, and will be on the lookout for further research on this issue. I am planning a follow-up blog entry that will go deeper into the biochemical actions of carnosine, beta-alanine and gabapentin insofar as they impact on GABA receptors in nerve cells and glia.