• Carnosine

    Uses

    Principal Proposed Uses

    • Anti-aging nutrient
    L-carnosine, not to be confused with L-carnitine , is a substance manufactured in the human body, made by combining the amino acids alanine and histidine. The highest levels of carnosine are found in the brain and nervous system, the lens of the eye, and skeletal muscle tissue. Its exact function in the body is not known.

    Requirements/Sources

    The body manufactures carnosine from common dietary proteins, and for this reason there is no daily requirement of this substance.

    Therapeutic Dosages

    Among advocates of carnosine, there is a controversy regarding whether the proper dose is 50–150 mg per day or nearer to 1,000 mg daily. However, until carnosine has actually been shown to have any medical benefits, this argument cannot be settled.

    What Is the Scientific Evidence for Carnosine?

    Like numerous other substances, carnosine has antioxidant properties, meaning that it neutralizes dangerous, naturally occurring substances called free radicals. 22,23
    Free radicals are thought to play a role in many illnesses. And, on this basis, many antioxidant substances have been studied for potential health-promoting properties. Some websites claim that carnosine acts as an antioxidant in a unique way, fighting the “second wave” effects that follow attacks by free radicals. However, there is no meaningful evidence to support this theory or the hypothesis that such an effect, if it truly exists, would provide any health benefits.

    Anti-Aging

    Carnosine is widely marketed as an anti-aging nutrient. There are numerous studies that hint carnosine might help slow various aspects of aging. 1-20 The quality of these studies, though, is too low to provide any reliable evidence for benefit. 1-20

    Autism

    There is some very preliminary evidence that carnosine may be helpful for children with autistic spectrum disorders . 21 In a double-blind, placebo-controlled trial, 31 children with autism were given either carnosine (400 mg twice daily) or placebo for a period of 8 weeks. The children given carnosine showed significant improvements compared to those given placebo.

    Brain Disorders

    Carnosine has been studied in Parkinson’s disease. In a small controlled trial, adding carnosine to the diet of people being treated for Parkinson’s disease improved their symptoms. 58 There is also weak evidence that carnosine may be helpful for Alzheimer’s disease and other forms of dementia. 31-50 Carnosine can be found in the olfactory tissue, which is responsible for our sense of smell. Because of this, some researchers have suggested that carnosine should be administered through the nose (rather than by mouth), especially considering that people with Alzheimer’s disease often have problems with their ability to detect odors. 57,60 This use for carnosine and this method of administering it are in need of further study.

    Sports Performance

    It has been suggested that taking supplements of the amino acid alanine can raise carnosine levels in muscle, and, in turn, enhance sports performance . In one small trial, 26 men were randomized to receive 6,400 mg daily of carnosine or a placebo over the course of 10 weeks. 54 The men then went through an exercise training program, and their physical fitness was assessed after a 10-week period. Researchers, though, did not find any significant differences between the two groups.

    Other Conditions

    Other weak evidence hints that oral carnosine might be helpful for cataracts , 24-29wound healing , 30 conditions of the digestive tract, 53,56 and various forms of heart disease, such as atherosclerosis (hardening of the arteries). 51,52 For example, one study found that carnosine may interfere with the development of low density lipoproteins (or “bad” cholesterol). 55

    Safety Issues

    The use of carnosine has not been associated with any significant side effects. However, the body deploys a range of enzymes, called carnosinases, to break down carnosine. There may be a reason for the presence of these enzymes, and overcoming them by providing large amounts of supplemental carnosine could conceivably cause harm in some as-yet unrecognized way. Maximum safe doses in young children, pregnant or nursing women, or people with severe liver or kidney disease have not been established.

    References

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    2 Yuneva AO, Kramarenko GG, Vetreshchak TV, Gallant S, Boldyrev AA. Effect of carnosine on Drosophila melanogaster lifespan. Bull Exp Biol Med . 2002;133:559-61.

    3 Hipkiss AR, Brownson C, Bertani MF, et al. Reaction of carnosine with aged proteins: another protective process? Ann N Y Acad Sci . 2002;959:285–94.

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

    5 Gallant S, Semyonova M, Yuneva M. Carnosine as a potential anti-senescence drug. Biochemistry (Mosc) . 2000;65:866–8.

    6 Boldyrev A, Song R, Lawrence D, et al. Carnosine protects against excitotoxic cell death independently of effects on reactive oxygen species. Neuroscience . 1999;94:571–7.

    7 Boldyrev, AA, Gallant, SC, Suhkich, GT. Carnosine, the protective, anti-aging peptide. Biosci Rep . 1999;19:581–7.

    8 Gille JJ, Pasman P, van Berkel CG, et al. Effect of antioxidants on hyperoxia-induced chromosomal breakage in Chinese hamster ovary cells: protection by carnosine. Mutagenesis . 1991;6:313–8.

    9 Shao L, Li QH, Tan Z. L-carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts. Biochem Biophys Res Commun . 2004;324:931–6.

    10 Ikeda D, Wada S, Yoneda C, et al. Carnosine stimulates vimentin expression in cultured rat fibroblasts. Cell Struct Funct . 1999;24:79–87.

    11 Kantha SS, Wada S, Tanaka H, et al. Carnosine sustains the retention of cell morphology in continuous fibroblast culture subjected to nutritional insult. Biochem Biophys Res Commun . 1996;223:278–82.

    12 Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res . 1997;387:147–63.

    13 McFarland GA, Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res. 1994;212:167–75.

    14 McFarland GA, Holliday R. Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts. Exp Gerontol . 1999;34:35–45.

    15 Hipkiss A, Chana H. Carnosine protects proteins against methylglyoxal-mediated modifications. BiochemBiophys Rcs Goinm . 1998.248;28–32.

    16 Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med . 2000; 28:1564–70.

    17 Schmidt AM, Yan SD, Wautier JL, et al. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res . 1999;84:489–97.

    18 Stuerenburg HJ, Kunze K. Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles. Arch Gerontol Geriatr . 1999;29:107–113.

    19 Wang AM, Ma C, Xie ZH, et al. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Moscow) . 2000;65:869–71.

    20 Yuneva MO, Bulygina ER, Gallant SC, et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Med . 1999;2:337–42.

    21 Chez MG, Buchanan CP, Aimonovitch MC, et al. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol . 2002;17:833–7.

    22 Tarnha M, et al. Hydroxyl radical scavenging by carnosine and Cu(ii)-carm)sine complexes. Int J Radial Biol . 1999;75:1177–1188.

    23 MacFarlane N, McMurray J, O'Dowd JJ, et al. Synergism of histidyl dipeptides as antioxidants. J Mol CellCardiol . 1991;23:1205–7.

    24 Quinn PL Boldyrev AA. Formaziuk VH. Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Mod , 1992;13:379–444.

    25 Yuneva, MO, Bulygina, ER, Gallant, SC, et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Medicine . 1999;2:337–342.

    26 Babizhayev MA, Deyev AI, Yermakova VN, et al. Efficacy of N-acetylcarnosine in the treatment of cataracts. Drugs R D . 2002;3:87–103.

    27 Babizhayev MA. Rejuvenation of visual functions in older adult drivers and drivers with cataract during a short-term administration of N-acetylcarnosine lubricant eye drops. Rejuvenation Res . 2004;7:186–98.

    28 Babizhayev MA, Deyev AI, Yermakova VN, et al. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides . 2001;22:979–94.

    29 Argirova M, Argirov O. Inhibition of ascorbic acid-induced modifications in lens proteins by peptides. J Pept Sci . 2003;9:170–6.

    30 Nagai K, Suda T, Kawasaki K, Yamaguchi Y. Effects of L-carnosine on blood cells and biomembrane. NipponSeirigaku Zasshi . 1990;52:339–44.

    31 Stvolinskii SL, Fedorova TN, Yuneva MO, et al. Protective effect of carnosine on Cu,Zn-superoxide dismutase during impaired oxidative metabolism in the brain in vivo. Bull Exp Biol Med . 2003;135:130–2.

    32 Preston J, et al. Toxic effects of beta-amyloid on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and beta-alanine. Neuroscience Letters . 1998,242;105–108.

    33 MV, Aksenov MY, Markesbery WR, et al. Aging in a dish: age-dependent changes of neuronal survival, protein oxidation, and creatine kinase BB expression in long-term hippocampal cell culture. J Neurosci Res . 1999;58:308–17.

    34 Atwood CS, Moir RD, Huang X, et al. Dramatic aggregation of Alzheimer Ab by Cu(II) is induced by conditions representing physiological acidosis. J Biol Chem . 1998;273:12817–26.

    35 Boldyrev AA, Stvolinsky SL, Tyulina OV, et al. Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol . 1997;17:259–71.

    36 Butterfield DA. Alzheimer's beta-amyloid peptide and free radical oxidative stress. In: Gilbert DL, Colton CA, eds. Reactive Oxygen Species in Biological Systems: An Interdisciplinary Approach . New York: Plenum; 1999:609–638.

    37 Carney JM, Starke-Reed PE, Oliver CN, et al. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha phenylnitrone. Proc Natl Acad Sci USA . 1991;88:3633–6.

    38 Cherny RA, Legg JT, McLean CA, et al. Aqueous dissolution of Alzheimer's disease Ab amyloid deposits by biometal depletion. J Biol Chem . 1999;274:23223–8.

    39 Doble A. The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol Ther . 1999;81:163–221.

    40 Forster MJ, Dubey A, Dawson KM, et al. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci USA . 1996;93:4765–9.

    41 Horning MS, Blakemore LJ, Trombley PQ. Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine. Brain Res . 2000;852:56–61.

    42 Huang X, Cuajungco MP, Atwood CS, et al. Cu(II) potentiation of Azheimer Ab neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem . 1999;274:37111–6.

    43 Mark RJ, Lovell MA, Markesbery WR, et al. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem . 1997;68:255–64.

    44 Munch G, Mayer S, Michaelis J, et al. Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of beta-amyloid peptide. Biochim Biophys Acta . 1997;1360:17–29.

    45 Munch G, Schinzel R, Loske C, et al. Alzheimer's disease—synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. Journal of Neural Transmission . 1998;105:439–61.

    46 Smith MA, Sayre LM, Anderson VE, et al. Cytochemical demonstration of oxidative damage in Alzheimer disease by immunochemical enhancement of the carbonyl reaction with 2,4-dinitrophenylhydrazine. J HistochemCytochem . 1998;46:731–5.

    47 Stvolinsky SL, Kukley ML, Dobrota D, et al. Carnosine: an endogenous neuroprotector in the ischemic brain. Cell Mol Neurobiol . 1999;19:45–56.

    48 Thomas T, Thomas G, McLendon C, et al. beta-Amyloid–mediated vasoactivity and vascular endothelial damage. Nature . 1996;380:168–71.

    49 de la Torre JC. Cerebromicrovascular pathology in Alzheimer's disease compared to normal aging. Gerontology . 1997;43:26–43.

    50 Yan SD, Chen X, Fu J, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature . 1996;382:685–91.

    51 Roberts PR, Zaloga GP. Cardiovascular effects of carnosine. Biochemistry (Mosc) . 2000;65:856–61.

    52 Stvolinsky SL, Dobrota D. Anti-ischemic activity of carnosine. Biochemistry (Mosc) . 2000l;65:849–55.

    53 Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut .2007;56:168-75.

    54 Kendrick IP, Harris RC, Kim HJ, et al. The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition. Amino Acids. 2008 Jan 4.

    55 Rashid I, van Reyk DM, Davies MJ. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett. 2007;581(5):1067-1070.

    57 Pepper E, Farrell M, Nord G, Finkel S. Antiglycation effects of carnosine and other compounds on the long-term survival of Escherichia coli.Applied and Environmental Microbiology. 2010;76(24): 7925-7930.

    58 Hipkiss AR. Could carnosine or related structures suppress Alzheimer’s disease? J Alzheimers Dis. 2007;11(2):229-240.

    59 Boldyrev A, Fedorova T, Stepanova M, et al. Carnosine increases efficiency of DOPA therapy of Parkinson's disease: a pilot study. Rejuvenation Res. 2008;11(4):821-827.

    60 Boldyrev A, Stvolinsky S, Fedorova T, Suslina Z. Carnosine as a natural antioxidant and geroprotector: from molecular mechanisms to clinical trials. Rejuvenation Res. 2010;12:156-158.

    61 Hipkiss AR. Could carnosine or a carnivorous diet help suppress aging and associated pathologies? Ann N Y Acad Sci. 2006;1067:369-74.

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