AOR Carnosine

DISCUSSION: Carnosine is a dipeptide found in high concentrations in brain and muscle tissues. A potent inhibitor of damage to proteins from sugar (glycation) and scavenger of free radicals, carnosine has been shown to reverse cellular senescence in culture. Preliminary evidence suggests that it may provide support conditions of sub-optimal brain homocarnosine metabolism leading to impairment in social interaction, communication, stereotyped behavior, and symbolic or imaginative interaction.

60 Vegi-Caps
100% Vegetarian

SUPPLEMENT FACTS:
Serving Size: 1 Capsule
L-Carnosine ... 500 mg
Vitamin C (Ascorbic acid) ... 6 mg

*Dietary Reference Intake not established.
Other ingredients: microcrystalline cellulose. Capsule: hypromellose, water.

AOR guarantees that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, corn, nuts, dairy, soy, eggs, fish or shellfish.

Suggested Use
Take one capsule two to three times a day on an empty stomach, or as directed by a qualified health care practitioner.

Main Applications
As reported by literature:
• Anti-Aging
• Supports normal cell growth
• Supports healthy cellular function
• Possibly sports nutrition

Source
Biological fermentation.

Pregnancy / Nursing
No studies have been conducted. Best to avoid.

Cautions
• Carnosine should not be taken by persons with serum carnosinase deficiency (SCD).
• Consult with a physician in case of other pre-existing neurological disorders, such as Parkinson`s disease, multiple sclerosis (MS), or after a recent stroke.

AOR Carnosine Research

Carnosine is a simple dipeptide (that is, two amino acids joined together - in this case, beta-alanine and histidine). But don`t let that simplicity fool you: simply put, Carnosine is the most exciting anti-aging nutrient ever discovered. Carnosine is made by many cells in your body - and especially in muscle, heart, and brain cells. Longer-lived animals tend to have more Carnosine in their cells than do shorter-lived species, and preliminary research suggests that levels of Carnosine decline with aging (by 63% between the ages of 10 and 70 in humans).

Carnosine plays a central part in muscle contraction and to prevent fatigue, fending off lactic acidosis and allowing isolated muscle cells that have been pushed beyond their workload limits to contract again. In nerves, its concentration is so targeted, and its release so regular, that it was once thought to be a neurotransmitter; while it now looks as if that`s unlikely, Carnosine does play an important role in modulating brain cell function, simultaneously making neurons more sensitive to certain signals and protecting neurons from toxicity from overstimulation. In heart cells, Carnosine appears to be a central player in regulating the heartbeat through its role in regulating calcium ions. But none of that explains its ability to make old cells young.

"A Remarkable Rejuvenation"
The recent interest in Carnosine began with the work of doctors Gail McFarland and Robin Holliday at Australia`s Commonwealth Scientific and Industrial Research Organization (CSRIO). The experiment was simple. First, raise lung and skin cells in one of two standard cell culture mediums. Then keep half of the cells in the original medium, but transfer the other half into the same medium supplemented with Carnosine.

The Carnosine-supplemented cells were able to keep reproducing longer, achieving anywhere from one to seven more population-doublings. And they lived longer: in fact, the longest-lived cells lines receiving the Carnosine bath survived up to two-thirds longer than the cells in the standard mediums. But most excitingly, adding Carnosine to the cell medium made the cells younger. McFarland and Holliday described the results as "Striking effects on the cell morphology [shape and structure]," saying that, "Carnosine preserved a nonsenescent [youthful] morphology." The cells raised in the usual medium get old, blotchy, and irregular, and are broken apart into scattered islands of twisted debris. Yet clearly, the cells raised in Carnosine still have the same appearance they had when they were young: the colonies are flat, still maintaining their youthful whirling patterns; they`re still smooth, regular, and even. And, remarkably, cells bathed in Carnosine stayed youthful almost until the very end of their lives.

McFarland and Holliday later showed that they could take cells from the Carnosine medium, move them into the standard culture, and see them grow old - but then move them back into the Carnosine bath, and have them spring back into youth again. "Switching cells between media with and without carnosine also switches their phenotype [visibly observable properties] from senescent [aged] to juvenile, and the reverse." They "propose that Carnosine is an important component of cellular maintenance mechanisms," and "favor the view that it may have a very important role in controlling cellular homeostasis" - that is, in keeping cells in the tightly- regulated condition that optimizes their function.

"More Resistant to Features of Aging"
In a recent series of experiments, one group of SAM mice had Carnosine added to their drinking water (the human equivalent of about one gram each day, adjusting for metabolic considerations), while another received no supplement. Animals receiving Carnosine lived 20% longer, on average, than their non-Carnosine littermates - and more excitingly, the maximum survivorship was 6% longer, too.

Animals who got the Carnosine supplement looked and acted younger throughout their lives when held up against animals not fed Carnosine. Examined at midlife, the Carnosine-fed animals showed over 40% less loss of hair fullness and color, and suffered 61% fewer skin ulcers, than the control animals. The animals that got the supplemental Carnosine also showed significantly less of the sores around the eyes that developed in animals not given Carnosine, and 13% less senile spinal curvature.

Perhaps most excitingly, Carnosine-fed animals kept their mental faculties sharper, longer than their unsupplemented littermates. Animals fed Carnosine performed 29% better on tests of passive avoidance and nearly six and a half times better on tests of "reactivity" (a measure of youthful exploratory curiosity). In short, the scientists concluded Carnosine supplements made them "more resistant to features of aging."

When the researchers looked at the brains of the SAM animals, they discovered some of the biochemical changes that underlay these results. First, the scientists examined the binding of the brain messenger glutamate to the NMDA (N-methyl-D-aspartate) receptor, a process that is crucially involved in long-term memory formation. The scientists found that Carnosine therapy increased the binding of glutamate to this receptor.

"A Promising Agent in the Therapy of Brain Stroke"
In animal studies, Carnosine has been shown to reduce mortality, and to prevent much of the brain damage and loss of mental function, after a simulated stroke. Animals receiving Carnosine before blocking the blood vessels that feed their brains are less than half as likely to die, and the memory function and the activity of key brain enzymes is better preserved in Carnosine-supplemented survivors than in survivors who did not receive the supplement. In fact, rodent "stroke" survivors who get Carnosine perform as well on many memory tests as they did before the "stroke!"

Anti-Cancer Hopes
While performing their astounding cell-rejuvenation experiments, Holliday and MacFarland happened to find that one of their cell cultures had become contaminated with cancer cells, which quickly began to choke out the healthy ones. But when Carnosine was added to samples of this contaminated population, it was found that the cell cultures became free of cancer cells. The same results followed when Carnosine was tested against seven human cancer cell lines. The researchers found that they could add cancerous cells to a culture of healthy ones, bathe the warring tribes in Carnosine - and sit back and watch as the cancer cells slowly disappeared from the pool, even as the healthy cells thrived.

When Japanese researchers implanted cancer cells into laboratory mice, and then administered a daily injection of Carnosine two centimeters away from the implant site, Carnosine-treated animals showed reduced tumor growth and mortality compared to animals not receiving the dipeptide. In some cases, tumors regressed. The effects were further enhanced when Carnosine was combined with an immune-enhancing drug.

"Pluripotent Protective Effects"
But if we try to pin down just how it is that Carnosine can exert its other, wide-ranging anti-aging effects, we`ll have a hard time choosing among all the options. The protective properties of Carnosine have been described as "pluripotent" - that is, "many-powered." Carnosine is a highly versatile antioxidant, and also has indirect antioxidant powers through the chelation of pro-oxidant metals and the prevention of the destruction of the antioxidant enzyme superoxide dismutase (SOD) normally seen in cells exposed to hydrogen peroxide.

The power of these combined antioxidant actions was shown in experiments in which cells were exposed to toxic levels of oxygen. Carnosine treatment preserved healthy cell structure and reduced damage to the cells` DNA even though no other tested antioxidant could do so: not vitamin C, not vitamin E, not N-acetylcysteine (NAC), and not the potent synthetic antioxidant ethoxyquin.

Carnosine protects against the formation of Advanced Glycation Endproducts (AGEs), warped cellular proteins that have been damaged by sugar. Preliminary studies in animals fed a high-fructose diet suggest that Carnosine`s AGE-fighting ability helps preserve the flexibility of blood vessels, preventing some of the increase in blood pressure that is otherwise suffered under such circumstances. As well, Carnosine also maintains more youthful levels of proteolysis (the ability to tear down old, defective cellular proteins) in cells, - a process which slows down in old cells, interfering with cellular function. And Carnosine has been shown to react with certain abnormal proteins in a way which some research suggests may make them more readily broken up and disposed by the cell`s "garbage disposal" systems.

Carnosine changes gene expression in cells exposed to it, including increasing the expression of vimentin, a protein involved in maintaining the integrity and complex internal structure of the cell. Carnosine enhances various aspects of immunity, and protects cells against damage from a variety of toxins produced in the body as a part of normal metabolism. Test-tube studies have found that Carnosine also prevents amyloid beta-peptide, which forms the seed of the plaques associated with Alzheimer`s disease. One clinical study found that Carnosine supplementation benefited children with Autistic Spectrum Disorder. The list of protective functions goes on and on.

Carnosinase and Effective Dosing
The body has a family of enzymes called carnosinases, which break Carnosine down into its component amino acids. Researchers believe that this may be a way of storing histidine in a form that does not trigger inflammation, allowing it to be released as needed. Because of these enzymes, Carnosine doses below a certain threshold are rapidly metabolized away by the body. Experiments clearly show that feeding laboratory animals Carnosine in dosages equivalent to a human taking over four hundred milligrams of Carnosine a day have no effect on Carnosine levels in muscles, heart, or liver, while higher dosages increase muscle Carnosine levels and (as we have seen) have clear therapeutic benefits to the brain and body. While the exact cutoff point is uncertain, and indeed may vary from one individual to another, benefits clearly and consistently emerge at dosages equivalent to 945 milligrams per day and up for a person of average weight (70 kilograms).

Jump In - The Water`s Fine
We still haven`t explored many possible roles of Carnosine in human health, including preliminary studies suggesting that forms of Carnosine may prove to be a useful treatment for ulcers, improves wound healing, and that Carnosine is a remarkable heart-protective nutrient which increases the heart`s ability to contract and helps blood vessels to relax. As more and more research is done, the promise of this remarkable nutrient begins to shine more and more brightly.

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

McFarland GA, Holliday R. "Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts." Exp Gerontol. 1999 Jan; 34(1): 35-45.

Hipkiss AR, Brownson C, Carrier MJ. "Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups." Mech Ageing Dev. 2001 Sep 15; 122(13): 1431-45.

Yuneva MO, Bulygina ER, Gallant SC, Kramarenko GG, Stvolinsky SL, Semyonova ML, Boldyrev AA. "Effect of carnosine on age-induced changes in senescence-accelerated mice." J Anti-Aging Med. 1999 Winter; 2(4): 337-42.

Holliday R, McFarland GA. "Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine." Br J Cancer. 1996 Apr; 73(8): 966-71.

Stvolinsky S, Kukley M, Dobrota D, Mezesova V, Boldyrev A. "Carnosine protects rats under global ischemia." Brain Res Bull. 2000 Nov 1; 53(4): 445-8.

Nagai K, Suda T. "Antineoplastic effects of carnosine and beta-alanine--physiological considerations of its antineoplastic effects." Nippon Seirigaku Zasshi. 1986; 48(11): 741-7.

Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C and Komen J. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorder. J Child Neurol 2002;17;833-837.

$46.98 CDN