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Carnosine

   Supplement Carnosine

   Description Carnosine is a dipeptide – meaning that it is a compound comprised of two amino acids linked together (alanine and histidine). Carnosine is found in high concentrations in skeletal muscles.

   Claims

Antioxidant
Enhances wound healing
Reduces lactic acid accumulation
Promotes muscle recovery
Enhances muscle contraction

   Theory Although no definite metabolic role has been ascribed to carnosine, it has been implicated in a variety of physiological processes. Perhaps the best-described function of carnosine is as a "broad-spectrum" antioxidant, where it has been shown to interact with several free radical species including singlet oxygen, hydrogen peroxide, and both peroxyl and hydroxyl radicals. In addition, carnosine is able to inhibit radical-induced cellular damage induced by iron, copper and zinc. Carnosine also appears to play a role in activating the enzymes responsible for generating muscle contractions (myofibrillar-ATPase) as well as serving as an intramuscular buffering agent to retard accumulation of lactic acid. Among athletes, muscle carnosine levels are known to be highest in those with high anaerobic demands (rowers and track sprinters), but levels are also elevated in endurance athletes (marathoners) when compared to untrained subjects. Of the potential therapeutic actions of carnosine, including antihypertensive effects, immunomodulation, wound healing and anti-tumor/chemopreventive effects, there are exist several laboratory and pre-clinical evidence to suggest benefits, but most of these claims have not been convincingly documented nor subjected to rigorous clinical evaluation.

   Scientific Support Carnosine is absorbed intact in the small intestine (jejunum) by a specific active transport mechanism. It circulates in the blood for specific transport to the kidney, liver and muscle (where the highest concentrations are found). Carnosine is either used by these tissues or is hydrolyzed (broken down) into alanine and histidine by the enzyme carnosinase (which is found in blood, liver and kidney)

As a water-soluble antioxidant, carnosine is capable of decreasing cell membrane oxidation caused by iron, zinc, copper, hydrogen peroxide, singlet oxygen, and both peroxyl and hydroxyl free radicals. The antioxidant effect of carnosine is far greater than the individual or combined activity of its constituent amino acids – indicating that the peptide linkage between alanine and histidine is involved in some unique way in the overall antioxidant activity of carnosine. In animal and test-tube experiments, carnosine has been shown to inhibit oxidation of LDL-cholesterol (a possible benefit in preventing heart disease) and reduce development of breast cancer (in rats). High doses of carnosine may also possess some immune-stimulating activity as shown by animal experiments in which survival time in x-ray irradiated mice was increased by about 50% following carnosine intake (50-200mg/kg.day – a very large dose).

Carnosine appears to promote wound healing as shown by animal experiments in which 6-20mg/kg/day for 2 weeks reduced the size and depth of gastric ulcers and accelerated regeneration of the damaged tissue.

It has been calculated that the pool of muscle dipeptides (mainly carnosine) can account for about 10%-40% of the pH-buffering capacity of muscle tissue. During intense exercise, carnosine may play an important role in preventing the reduction in pH caused by lactic acid accumulation – and thereby improving exercise performance. Although this theory has not been evaluated in clinical studies, Animal studies in racehorses have shown that muscle carnosine concentrations are higher in muscles with a high percentage of fast-twitch glycolytic fibers and lower in muscles with predominantly slower twitch oxidative fiber types. In addition to its potential effects on anaerobic metabolism (lactic acid), carnosine may enhance oxidative (aerobic) metabolism by increasing the efficiency of mitochondria to produce cellular energy.

   Safety Although no long-term safety studies have been conducted in humans, carnosine is not expected to result in any significant side effects when consumed in levels found in most commercial dietary supplements. Rodent experiments have suggested that carnosine is extremely safe – no adverse toxic effects are noted even at doses up to 500mg/kg body weight (about 35 grams for an average-sized man).

   Value Given the potential physiological benefits of carnosine outlined above, its use as a dietary supplement is generally slanted toward sports nutrition. Its possible roles in delaying fatigue, reducing stress, buffering acid buildup, wound healing, muscle contraction, and oxidative protection position carnosine as both an ergogenic aid and as a general tonic.

   Dosage The average daily intake of carnosine from foods is probably in the range of 50-250mg (based on a diet containing at least one serving, 3-4 ounces, of beef, pork or chicken). Given that carnosine is fairly well-absorbed (up to 15% of ingested dose), circulates in the blood and is quickly used by peripheral tissues, metabolized to it constituent amino acids (alanine and histidine) or filtered to the urine by the kidneys, supplements should be consumed in several divided doses throughout the day. Oral doses of 1-3 grams per day have been used with success in managing immune system function in cancer patients.

   References
1. Alabovskii VV, Boldyrev AA, Vinokurov AA, Gallant S, Chesnokov DN. Comparison of protective effects of carnosine and acetylcarnosine during cardioplegia. Biull Eksp Biol Med. 1999 Mar;127(3):290-4.

2. Bakardjiev A, Bauer K. Biosynthesis, release, and uptake of carnosine in primary cultures. Biochemistry (Mosc). 2000 Jul;65(7):779-82.

3. Dadmarz M, v d Burg C, Milakofsky L, Hofford JM, Vogel WH. Effects of stress on amino acids and related compounds in various tissues of fasted rats. Life Sci. 1998;63(16):1485-91.

4. Decker EA, Livisay SA, Zhou S. A Re-evaluation of the antioxidant activity of purified carnosine. Biochemistry (Mosc). 2000 Jul;65(7):766-70.

5. Deev LI, Goncharenko EN, Baizhumanov AA, Akhalaia MIa, Antonova SV, Shestakova SV. Protective effect of carnosine in hyperthermia. Biull Eksp Biol Med. 1997 Jul;124(7):50-2.

6. Gutierrez A, Anderstam B, Alvestrand A. Amino acid concentration in the interstitium of human skeletal muscle: a microdialysis study. Eur J Clin Invest. 1999 Nov;29(11):947-52.

7. Lee JW, Miyawaki H, Bobst EV, Hester JD, Ashraf M, Bobst AM. Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine. J Mol Cell Cardiol. 1999 Jan;31(1):113-21.

8. Mzhel'skaia TI, Boldyrev AA. The biological role of carnosine in excitable tissues. Zh Obshch Biol. 1998 May-Jun;59(3):263-78.

9. Preedy VR, Patel VB, Reilly ME, Richardson PJ, Falkous G, Mantle D. Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle. Front Biosci. 1999 Aug 1;4:e58-66.

10. Quinn PJ, Boldyrev AA, Formazuyk VE. Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Med. 1992;13(5):379-444.

11. Roberts PR, Zaloga GP. Cardiovascular effects of carnosine. Biochemistry (Mosc). 2000 Jul;65(7):856-61.

12. Stuerenburg HJ. The roles of carnosine in aging of skeletal muscle and in neuromuscular diseases. Biochemistry (Mosc). 2000 Jul;65(7):862-5.

13. Swearengin TA, Fitzgerald C, Seidler NW. Carnosine prevents glyceraldehyde 3-phosphate-mediated inhibition of aspartate aminotransferase. Arch Toxicol. 1999 Aug;73(6):307-9.

14. Zaloga GP, Roberts PR, Black KW, Lin M, Zapata-Sudo G, Sudo RT, Nelson TE. Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells. Am J Physiol. 1997 Jan;272(1 Pt 2):H462-8.

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