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Cataracts are the
leading cause of blindness, accounting for about 42 percent
of all cases of blindness worldwide (affecting about 17
million people). Twenty-eight thousand new cases are reported
everyday. About 20 percent of all people over 60 have at
least the beginning of a cataract in one or both eyes,
and that figure rises to 80 percent for people over 75.
The most common
type of cataract — a nuclear cataract — is
characterized by a cloudy haze inside the lens. This haze
is the physical manifestation of a random clumping together
of the once beautifully ordered arrangement of lens proteins
called crystallins. As the cataract develops in size and
density, it reduces the amount of light that passes through
the lens and scatters the light that does get through.
Thus, instead of all the light rays being focused precisely
to a point on the retina, forming a sharp, clear image
of what we are seeing, many of the rays are spread out
across the retina, forming a fuzzy image. Colors may be
dulled or distorted, and there may be an annoying halo
of light around bright objects, causing a glare effect.
Causes of cataracts include cumulative ultraviolet radiation
damage from sun exposure, heredity, poor nutrition, smoking,
high blood pressure, kidney disease, diabetes, and the long-term
use of corticosteroids (the last two are major risk factors
for cataracts). Oxidative free radicals produced by the above-listed
causes are thought to damage vital biomolecules, including
lipids and proteins, resulting in the clumping together of
these proteins. The antidote to free radicals, of course,
is antioxidants, such as glutathione, lipoic acid, and vitamins
C and E. Consequently, many scientists believe that abundant
consumption of antioxidants may delay the onset of cataracts.
Good nutrition is a key element of effective prevention for
most age-related diseases, and cataracts are no exception.
A number of nutrients can benefit our eyes, and may help
prevent diseases such as cataracts, glaucoma, and macular
degeneration. These nutrients include the tripeptide glutathione
(the most abundant and important antioxidant in the human
body, critical for protecting the lens from free radical
damage); vitamins A and C; vitamin E and some of the B vitamins;
various bioflavonoids (especially quercetin and hesperidin)
and carotenoids (especially lutein and zeaxanthin); the amino
acids taurine, N-acetylcysteine (a precursor of glutathione),
and acetyl L-carnitine; the hormone melatonin; the alkaloid
vinpocetine; the herbs bilberry, ginkgo, and garlic; the
minerals zinc and selenium; and, last but certainly not least,
the saturated fatty acid, lipoic acid (“the antioxidant’s
antioxidant”), which plays a central role in maintaining
the body’s antioxidant network.1
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% 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 six 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.
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.
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.
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 eye drops 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.
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