The following is a response to a question on carnosine use:

Issue of Carnosine in Carnoware and Potential uses and side effects of Carnosine

Carnosine is a natural occurring histidine containing compound. Carnosine is found in several tissues, particularly in skeletal muscle. Carnosine was initially discovered in Russia in 1900 and there have been many theories about its biological role. However, none of the theories have been proven beyond a reasonable doubt. This compound is reported to possess antioxidant, buffering, immune enhancing and neurotransmitter actions. Carnosine was initially isolated from Liebig's meat extract and was subsequently identified as Beta-alanyl-histidine. Since then various aminoacyl have been isolated from excitable tissues. Just bear in mind that all these peptides are structurally similar and are synthesized by Carnosine synthetase, an enzyme with broad sub-strait specificity. Carnosine is an endogenously synthesized diapeptide, which is present in brain, cardiac muscle, kidney, stomach, and olfactory bulbs and in large amounts in skeletal muscle. Carnosine methylation give rise to anserine or ophidine. Its hydrolysis leads to histidine and beta-alanine. During decarboxilation of histidine, histamine is formed whose interaction with beta-alanine results in formation of carcinine. Carcinine is a compound with unknown functions. Beta-alanine besides being an indispensable component of co-enzyme A is a product of pyrimidine based degradation and may have a role in stimulating collagen synthesis in tissue. Tissue carcinine concentrations are influenced by diet. Dietary histidine deficiency reduced skeletal muscle carcinine concentration in rats, while high dietary histidine supplementation increases it. Supplementation with high concentration of dietary carnosine also increases skeletal carnosine concentration. However, dietary carnosine supplementation does not affect carnosine concentration in heart, liver or skeletal muscle. Supplementation with both carnosine and alpha-tocopherol results in greater carnosine concentration in liver and alpha-tocopherol concentrations in liver and heart, than supplementation with alpha-tocopherol alone. This suggests in vitro inter-relationship between carnosine and alpha-tocopherol.

Carnosine is a water-soluble natural metabolite of animal tissues. It has antioxidant properties due to its biological function of scavenging active oxygen species. Carnosine is the scavenger of hydroxyl and superoxide radicals and is a strong quencher of singlet molecular oxygen. Because of its water solubility carnosine provides cells with an antioxidant system that functions in the cytosolic environment where water-soluble oxidation mediators such as transition metals and oxygen radicals are often present in high concentrations. These studies have demonstrated both at the tissue and organelle level, that carnosine and related peptides may prevent peroxidation of model membrane systems. These have led to the suggestion that they represent water-soluble counterparts to lipid soluble antioxidant in protecting cell membranes from oxidative damage. Carnosine may inhibit lipid oxidation by a combination of free radicals scavenging and metal chelation. The ability of carnosine to suppress significantly the development of ischemic reperfusion contracture and to support the restoration of contractile force during reperfusion has been shown in isolated rat heart muscle model. As far as buffering activities are concerned, at physiological pH both carnosine and anserine exhibit remarkable buffering activity, a function which may explain some of their biological roles. In addition carnosine also exhibits heavy metal iron binding properties, which inhibit some enzymatic reactions. However, in a case control study muscle buffer capacity and carnosine concentration of biopsy sample from vastus lateralis were assessed before and after sixteen weeks of isometric endurance training. Neither muscle buffer capacity nor carnosine concentration change after training. Carnosine level falls in muscle tissue after starvation, infection, trauma and shock. Infection and trauma may be associated with cellular calcium disregulation and myocardial depression. Carnosine administration improves cardiac contractivity, increases myosite-free intracellular calcium level releases, calcium from sarcoplasmic reticulum and increases the calcium sensitivity of contractile proteins. Therefore, carnosine may have a role in the regulation of intracellular calcium and contractivity in cardiac cells.

During aging, proteins become oxidized and cross linked. These modifications are inducible by dilitarious aldahides such glucose, fructose and peroxidation product malondialdehyde. Methylglyoxal may also promote similar protein modifications, especially associated with secondary complications in diabetes mellitus. Carnosine radically react with many deleterious aldahides, presumably because it has a target amino group with proximal imidazole and carboxyl groups. Carnosine can inhibit protein modification induced by lysine-methylglyoxal-advanced glycosylation and products. This emphasizes carnosine potential as a possible non-toxic modulator of diabetic complications.

In a prospective randomized study of the affect of different enteral diets on wound healing, dietary carnosine improved wound healing when administered as part of a complete enteral formula. This may be of clinical relevance since few enteral formulas currently contain carnosine. Through its anti-glycating and anti-oxidant activities, both of which are implicated in neuronal and endothelial cell damage in Alzheimer's disease, carnosine may therefore be a useful therapeutic agent. In Russia stable eye drops of 5% carnosine have been developed and permitted by the Ministry of Health for medical use. In clinical trials on 109 patients carnosine eye drops exerted a good therapeutic effect in corneal erosion, trophic keratitis and bullous keratopathy. In rats, intraperitoneal administration of carnosine inhibited experimentally induced gastric erosion and also improved healing of mucosal defects. Carnosine may have protective functions additional to anti-oxidant and free radical scavenging roles.

Potential Side Effects : This brings us to the issue that was raised in one of the emails I got from one of my patients regarding possible toxicity. It is true that Carnosine is a potent chelator for copper and theoretically speaking can result in increased binding of copper in the gut and hence resulting in copper overload. But I would think that by measuring serum copper and cerruloplasmin (which is a protein that binds with copper) one could effectively measure any increase in the copper level. If copper levels stay normal then we don't have to worry about it.

As far as Taurine excretion is concerned, again I agree that this is increased by carnosine and taurine binds to Magnesium. However, I will presume that by doing urine and serum magnesium level and replacing magnesium this problem can be eliminated.

Caution : I want to be clear that this doesn't mean that I am endorsing this product. Any one who wants to try will have to make this decision based on there sole judgment. I have not seen this product researched and therefore any use will have to be purely on experimental bases and with clear understanding that this is purely experimental use and each individual is responsible for there own decision. I am presenting this information so it will allow people to make informed decision.

Contact me if any further info is needed.

Regards

S. Khattak