Carnosine - Is It The Cure For Cataract?
Russia over the last several years, they have been researching a special
analogue of the di-peptide carnosine. This particular form is known as
N-acetyl carnosine or NAC and it has been proven to be highly
efficacious in the treatment of cataract and may also present a case for
the prevention of the same. This article is about the case for NAC and
the problems associated with senile-cataract.
Cataract is the leading cause of
blindness and accounts for about 42% of all such cases worldwide, and
this is in-spite of the availability of effective surgical treatment.
Today we have the appalling situation where more than 17 million people
around the world are blind because of cataract and 28,000 new cases are
reported everyday. In developing countries, there is simply not a
sufficient number of surgeons to perform cataract operations.
Cataract surgery is the most commonly
performed surgical procedure in people over 65-years of age, and 43% of
all visits to ophthalmologists by Medicare patients in the US are
directly associated with cataract.
Meanwhile, approximately 25% of the
population over 65 (and about 50% over 80) have a serious loss of vision
due to cataract. Since this is the population that is most susceptible
to lens opacification and as this section of the population is expected
to increase dramatically, the numbers of individuals with cataract is
set to explode!
For example, the World Health
Organization anticipates that within the next 25-years, that 20% of the
population will be 65 or older. Furthermore, the single largest growing
section of the population are those over 85 and their actual numbers are
expected to quadruple in about the same period. Such a rapidly
burgeoning older population can only increase the numbers of individuals
suffering from cataract.
Of course, there is also the economic
impact. Currently 1.35 million cataract operations are performed
annually in the United States alone and Medicare estimates the annual
cost at $3.5 billion! There's no doubt about it, cataract is a major
It is also becoming apparent that it
will not be possible to eliminate the overall problems (including
blindness), caused by cataract with the current procedures. With so many
people presenting the afflictions of maturity onset cataract, it appears
not to be possible to train in-time, the necessary numbers of surgeons
required. In-fact, as-it-stands, it looks likely that the total number
of people with serious eye-disorders because of cataract, will increase
There is another aspect to the problem
that is rarely discussed. While cataract surgery is generally recognised
as being one of the safest operations, there is a significant
complication rate. For example, in the United States 30% to 50% of all
patients having cataract extraction, develop opacification of the
posterior lens capsule within two years and require further lazer
Since the number of cataract operations
is so large, even a small percentage of complications represents a
significant number of people. Of the patients having cataract surgery,
0.8% have retinal detachments, 0.6% to 1.3% are hospitalized for
corneal edema (or require corneal transplantation), and 0.1% present
Thus, aside from secondary cataract,
about 2% of the 1.35 million (or approximately 27,000 individuals), just
in the US each year, develop serious complications as a result of
It is therefore difficult to support
the argument that cataract research is unimportant with statistics such
as those cited above. The large and growing number of people blind with
cataract and the significant complication rate, should be sufficient
reason to increase cataract research.
The considerable discomfort experienced
by patients as their vision diminishes, and the complete loss of
accommodation resulting in the removal of the lens should also be
recognised. Besides the possible complications, an artificial lens just
does not have the overall optical qualities of a natural lens.
A medical solution is required that
will maintain the transparency of the lens. Even if the development of
cataract can be delayed by 10-years, the overall benefits would be
Innovative Vision Products (IVP)
utilizing Russian researchers and scientists has developed and tested a
unique new form of carnosine. This form of carnosine is known as
N-Acetyl Carnosine or abbreviated to NAC.
NAC presents the first major leap
forward in the treatment and possible prevention of senile cataract.
As a bio-engineering company, IVP has
developed a proprietary method of producing extremely high purity NAC
that has proven to be a suitable ophthalmic drug for the non-surgical
treatment of age-related cataracts.
NAC has a highly statistical and very
significant clinical success rate for patients within 3-12 months of
treatment. Not surprisingly, IVP has been quick to ensure that its NAC
has worldwide patents, including its use for cataract. It is also
interesting to note that NAC eye-drops are patented for use in
open-angle glaucoma, but as yet, the research for that disorder remains
Carnosine eye-drops were used in a
clinical trial to treat 96 patients aged 60 and above. All the patients
had senile cataract in various degrees of maturity. The duration of the
disease in these patients ranged between 2 and 21 years.
Firstly, the researchers stopped the
patients use of all other anti-cataract drugs. Then the patients
instilled 1 or 2 drops into each eye 3 or 4 times a day, for a period of
3 to 6 months.
The level of eyesight improvement and
the change of lens transparency was considered as an evaluation index.
The results showed that there was a pronounced effect on primary
senile cataract, the effective rate was 100% (i.e. all patients
experienced an improvement). For the more mature senile cataract
(i.e. those who had had the cataract the longest time, in some cases
more than 20-years) the effective rate was still an extremely impressive
These are remarkable results
considering that the best that could normally be expected would be a
slight improvement, a halt to the progression and under normal (i.e.
non-treated) circumstances a continual worsening of the disease.
Importantly, it was also noted that
there were no side effects noted in any of the cases.
Another Russian study was designed to
document and quantify the changes in lens clarity over a 6 to 24 month
period for 49 volunteers. Their average age was 65 and all suffered from
senile cataract of a minimal to advanced opacification.
The patients received either a 1%
solution of NAC eye-drops or a placebo, as 2-drops twice a day into each
eye. The patients were then evaluated at 2 and 6 month periods. The
tests consisted of ophthalmoscopy (glare test), stereocinematagraphic
(slit-image) and retro-illumination (photography). A computerized
digital analysis then displayed the light scattering and absorbing
effects of the centers of each lens.
At 6-months, 88.9% of all eyes treated
with NAC had an improvement of glare sensitivity (lowest individual
score was a 27% improvement, right the way up to a 100% improvement).
41.5% of all eyes treated with NAC had a significant improvement of the
transmissivity of the lens, but perhaps most importantly 90% of
the eyes treated with NAC showed an improvement in visual acuity.
Meanwhile, in the placebo group there was little change in eye quality
at 6-months and a gradual deterioration at 12 to 24 months.
Importantly, 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.
Once again, no significant side effects
were noted in any cases throughout the 2-year period.
Another interesting study 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 preventative purposes, as well as medical applications.
At this time, it is now believed that
carnosine eye-drop treatment has been applied to over one thousand
patients with senile cataract in China and Russia, (those countries are
home to the principal researchers behind the work). Clear evidence is
emerging that NAC eye-drops are a safe, effective treatment and
potential preventative against cataract.
NAC method of action
Cataract is a glycosylation
problem. This reaction occurs when proteins became cross-linked (and
hence impaired). The result of this reaction leads to the discoloration
of the eye-lens to yellow and brown, and hence the impairment of vision.
But, carnosine is known to compete on the molecule for the glycating
agent and protect cellular structures against aldehydes. Therefore,
carnosine can slow and help to prevent proteins from becoming
cross-linked, (and in this case from becoming cataract).
NAC has been shown to be highly
resistant to carnosinase, (the natural enzyme that breaks down
L-carnosine into histamine etc.). An experiment on rabbits showed that
NAC eye drops allow themselves to be broken down into L-carnosine once
inside the eye's aqueous humor, (a process that occurs within 15 to 30
minutes after application of the eye-drops).
L-carnosine is an excellent
anti-oxidant and is particularly effective against potent free-radicals,
especially the Superoxide and the Hydroxyl. It is
therefore presumed, that the anti-oxidant role of L-carnosine (within
the aqueous humor) is a major factor, in slowing and preventing the
appearance of cataract.
However, when L-carnosine
eye-drops were used there was no presence of L-carnosine in the
aqueous humor (even after 30-minutes). This may be because L-carnosine
is broken down early into histamine etc., before it reaches the aqueous
humor. So, NAC may act as a "carrier" for L-carnosine delivering it to
where it is needed.
The powerful anti-oxidant abilities of
carnosine within the eye, and the prevention of cross-linking, helps to
explain why NAC is effective at preventing and slowing cataract, perhaps
even halting it. But it doesn't explain why NAC has been shown to
reverse cataract. But we may already know the answer.
For example, it is known that when
carnosine is delivered in high doses, that it can reverse
protein-aldehyde cross-linking, (this reaction is normally very
difficult to reverse). Under these circumstances, carnosine has been
shown to have a "rejuvenating" effect on cultured cells.
Cataract develops when anti-oxidant
defense is exhausted, leading to the cross-linking of the lens
crystallins, (producing a clouded lens, and hence impaired
eyesight). We can assume that the regular use of a 1% NAC eye-drop (as
used in the clinical trials), delivers "a high-dose of carnosine capable
of reversing the lens cross-linking," and hence the reduction and
eradication of cataract.
So in conclusion, NAC eye-drops appear
to act as a universal anti-oxidant, both in the lipid phase of the
cellular lens membranes, and in the aqueous environment. NAC eye-drops
reduce and protect the crystalline lens from oxidative stress-induced,
NAC compared to L-carnosine
We may logically ask the question; why
have NAC eye-drops been shown to have this action upon cataract, and yet
L-carnosine (which is its sister di-peptide) appears to have little
benefit? Dr. Mark Babizhayev, one of the principal Russian researchers
behind the clinical trials with NAC eye-drops gave us this reply to that
very same question:
"I believe that the application of
L-carnosine for the treatment of human cataracts is misleading. This is
because L-carnosine readily becomes a substrate for the activity of
natural peptidases (i.e. carnosinase) in the aqueous humor. So much so,
that there is no sign of L-carnosine in the aqueous humor within
15 minutes after instillation. Furthermore, I consider that L-carnosine
eye-drops may even be harmful for eyes because it gradually releases
histamine, which, located as it would be in the presence of the eye-lens
is a very toxic agent. However, NAC eye-drops are resistant to
hydrolysis with natural carnosinase. Therefore, NAC is the only
currently known agent which reverses and prevents human cataracts."
In conjunction with Dr. Hipkiss and Dr.
Kyriazis information, we can conclude that while some of the benefits of
oral L-carnosine may derive after carnosinase breaks down into
It is also interesting to note that a
study by Dr. Boldyrev et al, also concluded that the oral use of
NAC was far less likely to be broken down by carnosinase than
Dr. Mark Babizhayev also makes it quite
clear that "ordinary" NAC will not be of much use in the treatment of
senile-cataract. This is because there are many synthesized "carnosines"
and their biological and medicinal activity strongly varies and depends
on the mode of their obtention.
For example, if carnosine is extracted
from meat muscle substances, the biological and anti-oxidant activity is
very low. This is presumably due to the contamination of the "pure"
carnosine substance by heavy metal salts and proteins and other related
impurities. It is very difficult to purify carnosine
chromatographically, as the compound chelates divalent metal ions very
heavily and the biological and anti-oxidant activities can not be
regenerated during the purification procedures.
In conclusion, there were many forms of
carnosine which were abandoned in the Russian studies because of their
lack of anti-cataract and anti-oxidant ability in the human eye.
However, IVP (in conjunction with their
Japanese partner and manufacturer), has developed a synthesized pure NAC
which has biological activity and has been well controlled and proven in
human lens studies. This is the same type that has been used in the
Cataract is a widespread age-related
affliction and NAC eye-drops appear to be a highly efficacious and safe
treatment for cataract. As such, I suspect that this supplement is going
to become one of the most important new discoveries, and will have a
major impact on the way that cataract is controlled.
interview with Dr.
interview with Dr.
1. Boldyrev AA,
Dupin AM, Bunin Aya, Babizhayev MA, Severin SE "The antioxidative
properties of carnosine, a natural histidine containing di-peptide."
Biochem. Inrern., 1987, 15/6, 1105-1113.
2. Babizhayev MA et al "N-Acetylcarnosine, a natural
histidine-containing di-peptide, as a potent ophthalmic drug in
treatment of human cataracts." Peptides (USA) 2001, 22(6): 979-994.
3. Babizhayev MA, Yermakova VN, Deyev Al, Seguin M-C
"Imidazole-containing peptiomimetic NACA as a potent drug for the
medicinal treatment of age-related cataract in humans." J. Anti-Aging
Medicine 2000, 2, 43-62.
4. Babizhayev MA, Yermakova VN, Semiletov yu A, Deyev Al "The natural
histidine-containing di-peptide N-acetylcarnosine as an antioxidant for
ophthalmic use." Biochemistry (Moscow), 2000, 65, 588-598.
5. Babizhayev MA, Yermakova VN, Sakina NL, Evstigneeva RP, Rozhkova EA,
Zheltukhina GA "N-Acetycarnosine is a prodrug of L-carnosine in
ophthalmic application as antioxidant." Clin. Chim. Acta., 1996, 254,
6. Babizhayev MA, Bozzo Costa E "Composizioni farmaceutiche contenenti
N-acetilcarnosina per il trattamento della cataratta." A61K gruppo 37/00
cap 20122 MI 15.10.1993. Italian patent.
7. Babizhayev MA, Bozzo Costa E "Pharmaceutical compositions containing
N-Acetylcarnosine for the treatment of cataract." European Patent PCT/EP
94/03340 10.10.1994 Ref. SCB 238 PCT.
8. Babizhayev MA, Seguin M-C, Gueyene J, Evstigneeva RP, Ageyeva EA,
Zheltukhina GA "L-carnosine and carcinine act as natural antioxidants
with hydroxyl-radical-scavenging and lipid peroxidase activities."
Biochem J. 304, 509-516.
9. Babizhayev MA, "Antioxidant activity of L-carnosine, a natural
histidine-containing di-peptide in crystalline lens." Biochem. Biophys.
Acta., 1989, 1004, 363-371.
10. Babizhayev MA, Deyev Al "Lens opacity induced by lipid peroxidation
products as a
model of cataract associated with retinal disease." Biochim. Biophys.
Acta., 1989, 1004, 124-133.
11. Babizhayev MA, Deyev Al "Free radical oxidation of lipid and thiol
groups in genesis of cataract." Biophysics (biofizika), 1986, 31,
119-125, Pergamon Journals Ltd.
12. Kantha S, Wada S, Tanaka H, Takeushi M, Watabe S, Ochi H (1966),
Biochem. Biophys. Res. Commun. 223, 278-292.
13. Babizhayev MA, Deyev Al, Linberg LF "Lipid peroxidation as a
possible cause of cataract." Mech. Ageing Dev. 1988, 44, 69-89.
14. Boldyrev AA, "Problems and perspectives in studying the biological
role of carnosine" International Center for Biotechnology, Department of
Biochemistry, Lomonosov, Moscow State University.
15. Hipkiss A, (1998) Int. J. Biochem. Mol. Biol., 30, 863-868.
16. Boldyrev AA, Dupin A, Bunin A, Babizhayev MA, Severin SE (1987),
Biochem. Int., 15, 1107-1113.
17. Wang AM, Ma C, Xie H, F Shen "Medical application of carnosine"
Department of Biochemistry and Neurobiology, Harbin Medical University,
18. World Health Organisation, Ageing and Health, Website: