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Old 31-07-09, 07:40 AM
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Default N-acetyl-carnosine effect on ocular cataract

N-acetyl-carnosine effect on ocular cataract

Question
Please cite the research reports in the professional
literature of opthomology validating or negating the
effectiveness of N-acetyl-carnosine to eliminate
ocular cataract. The objective of this inquiry is to
find independent tests by recognized reseachers
that evaluate the claims of Mark Babizhayev.

Answer
I have included a variety of report formats for you to wade through. Among the citations of published studies of this compound are also some clinical opinions rendered by critics and supporters alike. It is interesting to note that the typical response from US ophthamologists is one that discourages and doubts primarily through prima facie evidence of lack of efficacy derived by pointing out the absence of use by colleagues. The skeptical contrarian would argue that there might be self serving incentive behind such observations. For instance the current US treatment of choice seems to be surgical procedure. Perhaps there is a clear motive to protect this modality through biased awarding of available research grants. It usually is a matter of profiteering, after all.

The dipeptide l-carnosine is a well-known neuropeptide consisting of alanine and histidine (beta-alanyl-L-histidine). It is normally made in the human body and is found at high levels in brain, innervated tissues, the lens of the eye, and skeletal muscle tissue. In laboratory studies, it has been demonstrated that carnosine has the ability to protect cells against oxidative stress as well as to increase their resistance toward functional exhaustion and accumulation of senile features. Mechanisms of such protection are explained in terms of proton buffering (maintaining pH balance), heavy metal chelating (especially copper and zinc), free-radical and active sugar molecule scavenging (prevents glycation of proteins), and preventing the modification of biomacromolecules thereby keeping their native functionality under oxidative stress. Physiological concentrations (20-30 mM) in standard media prolong the in-vitro lifespan of human fibroblast cells and strongly reduce the normal features of senescence (aging). In laboratory animals, carnosine clearly improved the external appearance of experimental animals and produced apparent beneficial effects on behavioral parameters and average life span. Age-related conditions that carnosine may be useful for include: 1) Neurological degeneration, 2) Cellular senescence, 3) Cross-linking of the eye lens, 4) Accumulation of damaged proteins, 5) Muscle atrophy, 6) Brain circulation deficit, 7) Cross-linking of skin collagen, 8) LDL cholesterol oxidation, 9) DNA chromosome damage, and 10) Formation of advanced glycation endproducts (AGES). L-carnosine is nontoxic and is normally contained in meats in the diet.

The evidence for the effectiveness of N-acetyl-carnosine eye drops is based on experience on a small number of cases carried out by a Russian research team. To date, the research has not been corroborated and the results replicated by others. The long-term effect is unknown. We do not feel the evidence base for the safety and efficacy is in any way sufficient to recommend its use. More research is needed.

L-Carnosine is a naturally occurring antioxidant and anti-glycation agent has shown remarkable effects that protect the eyes in published studies. N-Acetyl- L-Carnosine acts as a time-release version (pro-drug) of L-Carnosine. This form of carnosine has access to both the aqueous parts and lipid compartments of the eye. [9] After entering the lipid compartments of the eye, N-Acetyl-L-Carnosine degrades to L-Carnosine, thus protecting the lipid tissues of the eye from light damage. [8] A recent study showed that carnosine helped to prevent light-induced DNA strand breaks. Furthermore, carnosine application to the eye allowed significant repair of all DNA strands examined. [9] In Russia, carnosine eye drops are approved for corneal erosion, trophic keratitis, postherpetic epitheliopathy, primary and secondary corneal dystrophy, and bullous keratopathy. [10]
8. Mol. Biol. Part B: (2000), 127B; (4): pp. 443-446, Clin. Chim. Acta., 1996; 254(1): pp. 1-21
9. Photochemistry and Photobiology, (2000), 71; (5): pp. 559-566.
10. Biochemistry (Moscow)(2000), 65(5): pp. 588-598.
Peptides 2001 Jun;22(6):979-94
N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts.
Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM
Innovative Vision Products, Inc., 19810, County of New Castle, DE, USA

Last edited by Peter Aldred : 31-07-09 at 07:52 AM.
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Old 31-07-09, 07:42 AM
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Peter Aldred Peter Aldred is offline
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Human trials

A long-term study observed the changes in lens clarity over a 6 to 24 month period for 49 volunteers. The average age of the participants was 65 and all suffered from senile cataract ranging from minimal to advanced opacification (clouding of the lens).

The patients received either a 1% solution of NAC eye-drops or a placebo, as 2-drops twice a day in each eye. The patients were then evaluated at 2- and 6-month periods. The tests consisted of ophthalmoscopy (glare test), stereo-cinematagraphic (slit-image) and retro-illumination (photography). A computerized digital analysis then displayed the light scattering and absorbing effects of the centers of each lens.

Here is the outcome after 6 months:

• 88.9% of the patients who were treated with NAC had an improvement of glare sensitivity (lowest individual score was a 27% improvement, all the way up to a 100% improvement)

• 41.5% had a significant improvement in the light transmission of the lens

• most importantly; 90% showed an improvement in visual acuity

• The patients in the placebo group exhibited little change in eye quality at 6-months and a gradual, significant deterioration at 12 to 24 months.

Continued improvement

This study also showed that at 24-months the NAC treated group, (who already had significant improvement to the quality of their eyesight), sustained these results with continued use of the NAC eye-drops. There were no significant side effects noted in any cases throughout the 2-year period.1

Another study evaluated two groups of 49 patients (with the average age being 65), who had advanced symptoms of cataract. After a 24-month course of treatment, the group that was treated with the eye drops had a cumulative positive change when compared with the group that did not receive the eye-drops.2
Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Doroshenko VS, Zhukotskii AV, Goldman IM. Efficacy of N-acetylcarnosine in the treatment of cataracts. Drugs R D 2002;3(2):87-103

http://www.ncbi.nlm.nih.gov/entrez/q...ed&list_uids=1...

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides 2001 Jun;22(6):979-94

http://www.ncbi.nlm.nih.gov/entrez/q...ed&list_uids=1...

Babizhayev MA, Yermakova VN, Semiletov YA, Deyev AI. The natural histidine-containing dipeptide N-alpha-acetylcarnosine as an antioxidant for ophthalmic use.

Biochemistry (Mosc) 2000 May;65(5):588-98

http://www.ncbi.nlm.nih.gov/entrez/q...ed&list_uids=1...

Carnosine for Vision
Carnosine — a dipeptide consisting of two amino acids (alanine and histidine) connected to each other by a chemical bond called the peptide bond — is one of the most exciting anti-aging nutrients that has recently become widely available.2 Based on research performed mainly by Russian scientists, it is believed that carnosine is effective both in preventing and treating cataracts.3-6

The ability of carnosine to prevent and treat cataracts is believed to be due to its antioxidant properties and its ability to inhibit a chemical process called glycation. Glycation leads to deleterious substances called AGEs (advanced glycation end products). AGEs are chemical complexes that result from common but undesirable reactions between blood sugars, such as glucose, and proteins in many parts of our bodies, including the lenses of our eyes. The sugar-protein complexes become chemically cross-linked and degrade cellular functions. The aptly named AGEs are thought to be an important factor in the aging process.

Carnosine-containing eye drops have demonstrated efficacy in treating a variety of ophthalmic conditions, including corneal diseases, cataracts, glaucoma, and increased intraocular pressure. In 1997, clinical trials with carnosine-containing eye drops were conducted on 109 ophthalmic patients. The results confirmed accelerated healing of corneal erosions, trophic keratitis, post-herpetic epitheliopathy, primary and secondary corneal dystrophy, and bullous keratopathy.7 Most striking, however, was the ability of carnosine to eliminate existing cataracts.8

Carnosine eye drops have been shown to delay vision senescence in humans, being effective in 100 percent of cases of primary senile cataract and 80 percent of cases of mature senile cataract. Scientists concluded that “carnosine seems to delay the impairment of eyesight with aging, effectively preventing and treating senile cataract and other age-related diseases.”9 Carnosine actually restores the proteins in the lens by removing cross-linked carbonyl groups, and is thought to function as a “molecular water pump,” thereby also helping to lower intraocular pressure.10 In earlier experiments it was demonstrated that applying carnosine to the conjunctiva (the membrane covering the eye) caused a decrease in normal intra-ocular pressure and reduced prostaglandin-induced ocular hypertension (related to glaucoma) in rabbits.11

Some scientists believe that carnosine is ineffective if it is metabolized (broken down) by the enzyme, carnosinase. However, studies of corneal transplants in rabbits that were treated with one of the metabolites of carnosine, histidine, indicates that the metabolite itself may be bioactive. Five percent histidine ointment was applied twice daily to 6 transplants for two months. All six transplants healed and were clear. On the other hand, transplants which were treated with daily applications of one percent cortisone became opaque, necrotic, and failed to heal. Likewise, transplantation failed completely in six control eyes.12 This indicates that histidine may be an active portion—if not the active factor—of the carnosine molecule.

Cataract-Dissolving Analog: N-Acetylcarnosine (NAC)
N-acetylcarnosine (NAC), like its parent compound, carnosine, occurs naturally throughout the human body. Both compounds are found primarily in the heart and skeletal muscles (the word carnosine is derived from the Latin word for flesh) and in the brain. Carnosine was discovered in 1900 in Russia, and it is in Russia that most of the recent research on the N-acetylcarnosine derivative has been carried out.13-15 Research with N-acetylcarnosine, as with carnosine, demonstrates that it is effective not only in preventing cataracts but also in treating them. NAC has been shown to improve vision by partially reversing the development of the cataract, thus increasing the transmissivity of the lens to light.

The structural difference between NAC and carnosine is that one hydrogen atom in carnosine replaces an acetyl group (CH3CO-), and this substitution occurs at a nitrogen atom. An important chemical difference between carnosine and N-acetylcarnosine is that carnosine is relatively insoluble in lipids (fats and fatty compounds), whereas N-acetylcarnosine is relatively soluble in lipids (as well as in water).

This means that N-acetylcarnosine may pass through the lipid membranes of the corneal and lens cells more easily than carnosine, and may thereby gain access more readily to the cells' interior, which is primarily aqueous. There, the N-acetylcarnosine is gradually broken down to carnosine (and, perhaps, to histidine), which then exerts its beneficial effects.
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Old 31-07-09, 07:44 AM
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N-Acetylcarnosine also Reduces Cataracts
In one study, Russian scientists conducted two randomized, double-blind, placebo-controlled trials of 6-months and 24-months duration, with eye drops consisting of a one percent aqueous solution of NAC administered as two drops twice daily.16 They treated a total of 49 elderly patients (average age 65) with cataracts ranging in severity from minimal to advanced (but not to the point of requiring surgery); the total number of eyes affected was 76. Using a variety of sophisticated optical techniques, they monitored the condition of the cataracts, visual acuity, and glare sensitivity.

The eyes treated with NAC were substantially improved in 6 months: the measured transmissivity of the lenses increased in 42 percent of the eyes, by 12-50 percent; in 90 percent of the eyes, visual acuity improved by 7-100 percent; and in 89 percent of the eyes, glare sensitivity improved by 27-100 percent. These improvements were sustained for the duration of the 24-month trial. In no eyes was any worsening of the condition seen. By contrast, the condition of the untreated eyes in the control group worsened. Visual acuity dropped in 89 percent of the controls by 17-80 percent after 24 months.

Another interesting study by the same team also evaluated patients between the ages of 48 and 60, who had various degrees of eyesight impairment, but who did not have the symptoms of cataract. After a course of treatment ranging from 2 to 6 months, the conclusion was that the eye drops alleviated eye-tiredness and continued to improve eyesight (i.e. there was more clear vision). The subjects reported that the treatment “brightened” and “relaxed” their eyes. This is an important indicator that the eye drops have a value both for preventive purposes, as well as medical applications.

Conclusion
Carnosine and N-acetylcarnosine eye drops appear to be a safe, effective means to prevent cataracts, and to possibly even treat cataracts that are forming. Although cataract surgery is safe and highly effective, the use of topical carnosine or NAC eye drops may give many people another option.


References
1. Block, W. N-Acetylcarnosine May Help with Cataracts. NAC eye drops show benefits in both preventing and treating this age-related condition. LE Magazine, Aug. 2003.
2. Bourassa, D., and Dean, W. M.D. Carnosine: A Remarkable Multipurpose Anti-Aging Nutrient. Vitamin Research News, Vol. 14., Num. 11, Nov. 2000.
3. Babizhayev MA, Deyev A. Free radical oxidation of lipid and thiol groups in genesis of cataract. Biophysics (biofizika), 1986, 31, 119-125, Pergamon Journals Ltd.
4. Babizhayev MA, Deyev Al, Linberg LF. Lipid peroxidation as a possible cause of cataract. Mech. Ageing Dev. 1988, 44, 69-89.
5. Babizhayev MA, Antioxidant activity of L-carnosine, a natural histidine-containing di-peptide in crystalline lens. Biochem. Biophys. Acta., 1989a, 1004, 363-371.
6. Babizhayev MA, Deyev A. Lens opacity induced by lipid peroxidation products as a model of cataract associated with retinal disease. Biochim. Biophys. Acta., 1989b, 1004, 124-133.
7. Maichuk, IUF, Formaziuk, VE, Sergienko, VI. Development of carnosine eyedrops and assessing their efficacy in corneal diseases. Vestn Oftalmol, 1997, 113(6): 27-31.
8. Yuneva, M.O., Bulygina, E.R., Gallant, S.C., et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Medicine, 2: 1999, 337-342.
9. Wang AM, Ma C, Xie H, and Shen, F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry, 2000, 65(7), 869-871.
10. Baslow, MH. Function of the N-acetyl-L-histidine system in the vertebrate eye. Evidence in support of a role as a molecular water pump. J Mol Neurosci, 1998, 10(3), 193-208.
11. Ermakova, V.N., Babizhaev, M.A., Bunin, A.Ya. Effect of L-carnosine on intraocular pressure. Byull. Eksp. Biol. Med. 1988, 105(4), 451-453.
12. Borioni, D., and Scassellati-Sforzolini, G. The action of p-aminobenzoic acid, histidine, and cortisone on the success of corneal transplants, Am J Ophthalmol, 1953, 36: 575-576.
13. Babizhayev MA, Yermakova VN, Sakina NL, Evstigneeva RP, Rozhkova EA, Zheltukhina GA. N-Acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant. Clin. Chim. Acta., 1996, 254, 1-21.
14. Babizhayev MA, Yermakova VN, Deyev Al, Seguin M-C. Imidazole-containing peptiomimetic NAC as a potent drug for the medicinal treatment of age-related cataract in humans. J. Anti-Aging Medicine 2000a, 2, 43-62.
15. Babizhayev MA, Yermakova VN, Semiletov yu A, Deyev A. The natural histidine-containing di-peptide N-acetylcarnosine as an antioxidant for ophthalmic use. Biochemistry (Moscow), 2000b, 65, 588-598.
16. Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhokotskii AV, Goldman IM. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides, 2001, 22: 979-94.

Last edited by Peter Aldred : 31-07-09 at 07:51 AM.
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