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Carnosine
 

Carnosine Introduction

Carnosine is a naturally-occurring multifunctional dipeptide, formed from the chemical combination of amino acids beta-alanine and histidine. It is found in both animals and humans, with the highest concentrations located in the areas where long-lived cells are present. These cells are found in profusion in both the muscle and brain, and exist primarily as either neurons (nerve cells) and/or myocytes (muscle cells).

Carnosine has been well received within the medical community. Discovered nearly a century ago, its supplemental benefits regarding human physiology is a continually evolving study. The past half decade of clinical application has revealed to us its possibilities as an effective anti-aging compound. Carnosine may ultimately help to address the questions associated with the degradation of cellular integrity - a tall tale sign of the aging process.

The argument of carnosine as an ineffective agent of permanence is often dispelled through credible research. Studies have shown that levels of carnosine in neuronal and muscular tissues are in direct correlation to the life span of a given animal species. [1] Carnosine, therefore, harnesses the ability to extend the life span of vital cellular structures within the body. Carnosine acts as rejuvenator and antioxidant to cellular, protein, lipid, and DNA structures; protecting them from the destructive capabilities of senescence and free radicals. [2]

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Carnosine Food Sources

Carnosine’s main dietary sources include both fish and animal proteins. There has been a recent movement by health practitioners suggesting that all persons should attempt to drastically reduce the amount of meat in his/her diet, opting for healthier choices which are now readily available to the health conscious consumer. Realizing the physiological consequences of inadequate carnosine levels in the body, this growing trend may help to emphasize the importance of supplemental carnosine.

Carnosine Uses

Carnosine is primarily supplemented by persons for its potent antioxidant action(s). As an antioxidant, carnosine scavenges free radicals and assists in the elimination of lipid peroxidation within specific cell membranes. [3] This unique dipeptide is water soluble, as opposed to its lipid soluble counterpart, Vitamin E. Vitamin E is a perfect example of an antioxidant which is only effective in preventing free radical damage from entering bodily tissues. Carnosine, on the contrary, maintains cellular integrity when these first lines of “defense” are broken. The hydroxyl, superoxide, singlet oxygen, and peroxyl radical are all suppressed by carnosine.

Malondialdegyde, or MDA, is an example of a second tier, free radical compound which is formed by membrane lipid oxidation. This injurious compound, which is produced from the progression of free radicals within the body, can cause damage to enzymes, lipids, and DNA. It has also been shown to play a central role in atherosclerosis, joint inflammation, and cataract formation. MDA is actually made inactive by carnosine, thereby protecting the amino acids on a given protein molecule. [4, 5] Carnosine remains the only antioxidant to significantly protect chromosomes from oxidative stressors.

Coenzyme Q10 (CoQ10) and Vitamin E are often supplemented together with carnosine to offer the body “full” antioxidant protection. Vitamin E and CoQ10 are compounds that offer initial protection against the destructive characteristics of oxidation and free radical damage. Carnosine, on the other hand, is not only vital in the protection against secondary free radical damage, but also protects against the deleterious anti-glycating, aldehyde quenching, and metal chelating actions of the abovementioned elements. [2, 6] The same elements that are essential for life also possess the ability to destroy it.

Apart from free radical damage, glycosylation (or glycation), is the most influential determinant of the aging process. As humans age, the proteins of the body undergo various destructive changes because of their continuous interactions with sugars and aldehydes. This metabolic process produces Advance Glycosylation End-Products, or AGEs. AGEs are oxidized, cross-linked, abnormal endproducts that are theorized to cause widespread damage to living organisms. They are prominent in the causes of skin aging, cataracts, and neurodegeneration.

Carnosine is an effective combatant against these forms of caustic protein modifications. Carnosine provides a mechanism for inactivation against aldehydes and ketone bodies, reducing the glycosylation and formation of AGEs. It is also effective at canceling the ill effects of already formed AGEs on cellular structures, while enhancing the process of elimination via immune system response. Carnosine’s anti-glycosylation qualities may make it especially useful in the treatment and prevention of complications associated with diabetes, cataracts, kidney failure, and neuropathy.

Alzheimer's disease patients are found carrying a substance in their brains referred to as beta amyloid. Beta amyloid interacts with macrophages (immune system cells), which carry receptors known as RAGEs. This interaction causes severe damage to the arteries and nerves of the brain and often times leads to diseases associated with Alzheimer’s, such as dementia. Carnosine has proven effective at blocking, immobilizing, and preventing cell damage caused by the beta amyloid. [7] Carnosine also plays an integral role in neurotransmission.

Carnosine may also offer wound healing capabilities. Studies have shown carnosine possessing the ability to rejuvenate connective tissue cells. These effects have been observed in laboratory animals and were promising in the areas of lessened duration, and increased effectiveness in regards to wound healing. This may prove useful for those receiving treatment for burns, post-surgery wounds, or also in one’s nutritional preparation for surgery. [4]

As with carnosine levels, muscle levels consistently decline with age. Some 63% of all muscle cells are diminished from 10 to 70 years of age, and dramatically influences overall mass and functioning. [8] Studies indicate that carnosine may offer protection to muscle cells by acting as a pH buffer, protecting cell membranes from oxidation caused by the acidity produced through muscular exertion. One of the most important muscles of our body, the heart, is also directly impacted by sufficient carnosine levels. Carnosine provides more efficient contraction by increasing heart myocyte levels of calcium. [9]

Areas of ongoing research into the benefits of carnosine supplementation include:

  • Anti-neoplastic properties / Cancer prevention
  • Enhanced immunity: by stimulating the maturation of immunocompetent cells
  • Gastric Ulceration: Carnosine may provide significant protection and healing of both gastric and peptic ulcers. [10] This is done by eradicating the organism H. pylori, which has been linked to peptic ulcers and even stomach cancer.

Carnosine and Autism

Of special interest, supplemental L-carnosine has been studied in the treatment of children suffering from Autistic Spectrum Disorder (ASD). An eight week blind trial assessed thirty-one children taking either a powdered L-carnosine supplement or placebo. Various autistic rating scales and tests were used to determine carnosine’s effectiveness at treating this condition.

After the eight week trial period, oral supplementation of L-carnosine resulted in “demonstrable” improvements in autistic behaviors, including significant changes in the comprehension of language. [11] Carnosine may, in fact, provide stimulation of the frontal lobe, thereby:

  • Increasing neurotransmission, and
  • Improving the metal ion transfer of zinc and copper in the entorhinal cortex

Carnosine Dosages and Safety

Supplemental carnosine is safe. To be labeled as such (safe), a compound must adhere to certain standards. It should be naturally present, or found in the body and food sources, and must also demonstrates the ability to lengthen the life span of animals and cultured human cells. L-carnosine exhibits such potential.

There have been no reported toxicities with carnosine, even with dosages exceeding 500 milligrams per kilogram of bodyweight. [12] Smaller amounts of carnosine are neutralized within the body, and deficiencies of this nutrient are extremely rare. Supplementation ensures that the enzyme carnosinase is sufficiently saturated with carnosine, enabling the release of “free” carnosine throughout the body.

References

1. Hipkiss AR, Michaelis J, Syrris P, et al. Strategies for the extension of human life span. Perspect Hum Biol. 1995; 1:59-70.

2. McFarland GA, Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res. 1994;212(2):167-75.

3. Tarnha M, et al. Hydroxyl radical scavenging by carnosine and Cu(ii)-carm)sine complexes. Int J Radial Biol. 1999. 75(9):1, 177-1188.

4. Hipkiss A et al. Protective effects of carnosine against protein modification mediated by nialondialdchyde and hypochlorite. Bioch Biophys Acta. 1998, 1380;46-54.

5. Hipkiss A. et al. Protective effects of carnosine against MDA-induced toxicity towards cultured rat brain endothelial cells. Neuroscience Letters. 1997. 135-138.

6. Hipkiss AR, Preston JE, Himsworth DT, et al. Pluripotent protective effects of carnosine, a naturally occurring dipeptide. Ann NY Acad Sci. 1998; 854:37-53. 7. Preston J et al. Toxic effects of B-amyloid on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and B-alanine. Neuroscience letters. 1998, 242; 105-108.

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

9. Zaloga GP, Roberts PR, Black KW. Carnosine is a novel peptide modulator of intracellular calcium and contractitility in cardiac cells. Am J Physiol. 1997; 272(1 Pt 2):H462-8.

10. Nishiwaki H, Kato S, Sugamoto S, et al. Ulcerogenic and healing impairing actions of monochloramine in rat stomachs: effects of zinc, L-carnosine, polaprezinc. J Physiol Pharmacol. 1999;50:183-95.

11. Becker, Marina R.N., Buchanan, Cathleen Ph.D., Chez, Michael, Komen, Jamie. “Double-Blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorder.” Autism and Epilepsy Specialty Services. Lake Bluff, Illinois.

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