Cataracts Vitamin C, Vitamin E, and the Carotenoids

Nutritional Influences on Illness
by Melvyn R. Werbach, MD
tlp@third-Unexom
Cataracts: Vitamin C, Vitamin E,
and the Carotenoids
With its continual exposure to light and ambient
oxygen, the optical lens is at high risk of photooxidative
damage. Oxygen free radicals cause cataracts by oxidizing
the lens proteins while also impairing the proteolytic
enzymes designed to eliminate the damaged proteins.
Normal lenses of older people only show early evidence of
oxidation that is confined to the intrinsic membrane fraction
and membrane-related components; the development of
cataract is associated with progressive oxidative changes in
these components, which eventually extend beyond them
to involve the soluble components of the lens proteins.
Since vitamins C and E, as well as the carotenoids lutein
and zeaxanthin, are present in human lenses, and since all
can reduce oxidative stress, we will examine the current
evidence suggesting that supplementing them may combat
the progression of age-related cataracts.
Vitamin C
The concentration of ascorbic acid in the aqueous
humor is among the highest of all the body fluids, and
there is substantial evidence that vitamin C nutriture has a
significant effect on cataract formation. When, for example,
rat lenses were maintained in a solution designed to cause
free radical damage, the addition of vitamin C protected
them.' As to humans, the intake of vitamin C supplements
over at least the past decade has repeatedly been found
to be inversely correlated with cataract risk.^^ Even over
only a five-year period, a higher vitamin C intake has
been repeatedly associated with a reduced incidence of
cataracts.^"^
Also, a study of Italian-Americans found that higher
plasma levels of vitamin C were associated with a
decreased risk of cataract,^ and blood levels of the vitamin
in a Mediterranean population were inversely correlated
with the risk of cataract.^ Moreover, researchers examining
cataractous human lens nuclei found an inverse relationship
TOWNSEND LETTER - JANUARY 2009
between vitamin C concentration in the lens and cataract
severity.^
In two open trials performed in the 1930s, 607o to
907o of patients with incipient senile cataracts had visual
improvement following supplementation with the vitamin,
improvement that was sometimes marked.'""" Findings
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Nutritional Influences on Illness
from a more recent randomized trial, however, were far
less dramatic. A large population of rural Chinese aged
45 to 74 years received either vitamin C 120 mg daily,
along with 30 meg molyÍ3denum, or placebo daily. After
five years, there was a nonsignificant reduction of 227o in
cataract risk.'Vitamin E
Like vitamin C, the addition of vitamin E protected rat
lenses from free radical damage when they were immersed
in a solution designed to cause such damage.'^ In addition,
when added to the perfusion solution, vitamin E doubled
the survival time of isolated rabbit corneal endothelium.'*
For humans, long-term vitamin E intake has been inversely
related to the risk of cataract."'^""" The same relationship
has been noted in regard to serum levels of the vitamin.""
Moreover, a recent longitudinal study found that, in both
regular users of vitamin E supplements and persons with
higher plasma levels of vitamin E, the risk of nuclear
opacification was reduced by approximately half.'^
Despite these promising findings, two randomized trials
have failed to find evidence of the vitamin's efficacy. One
trial was of 1193 volunteers aged 55-80 years with early or
no cataract. They received either 500 IU vitamin E daily or
placebo and were followed for four years. Supplementation
failed to reduce the incidence or progression of nuclear,
cortical, or posterior subcapsular cataracts.'^
A larger trial involved 39,876 females aged 45 years
or older. They received either 600 IU of natural-source
vitamin E on alternate days, or placebo. After almost ten
years of treatment and follow-up, there was no evidence
that supplementation reduced the incidence of age-related
cataract.^"
140
Carotenoids
The intake of carotenoids - particularly alpha- and
beta-carotene, lutein, lycopene, and zeaxanthin - has
been inversely correlated with cataract risk.^''^"* Although
two epidemiological studies failed to find a relationship
between beta<arotene intake and the risk of cataract,^^"
another found that the prevalence of posterior subcapsular
lens opacities in women who never smoked was related to
the intake of alpha- and beta-carotene as well as with total
carotenoids.^ Also, the blood level of beta-carotene has
been inversely correlated with cataract risk.^^ In fact, one
study found that those with serum levels of beta-carotene
in the lowest third of the distribution had almost a threefold
risk of senile cataract."
Combined Supplementation
In a randomized trial, patients in Europe and America
with early age-related cataracts received either vitamin
C 750 mg, vitamin E 600 IU, and beta-carotene 18 mg,
or placebo. After two years, there was a small positive
treatment effect in American patients; after three years, the
positive effect was apparent in the total group, with an even
greater effect in the American group. By contrast, there was
no significant effect in the European group.^^
Other similar trials have failed to show any significant
benefits. In a randomized trial of Americans, participants
aged 55-80 years received daily tablets of either vitamin
C 500 mg, vitamin E 400 IU, and beta-carotene 15 mg, or
no antioxidants. After an average of 6.3 years, there was
no significant effect of the formula on the development
or progression of age-related lens opacities." Similarly,
residents of South India aged 35-50 years (as this population
has early progression of cataracts) received vitamin C
400 mg, vitamin E (RRR-alpha-tocopherol) 400 IU, and
15 mg beta<arotene from algae in the all-irans form
with small amounts of other carotenoids. After five years,
supplementation failed to affect cataract progression.^'^'
Thus, findings from randomized trials have so far failed to
live up to the high expectations raised by other studies.
TOWNSEND LETTER - JANUARY 2009
Notes
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2. Jacques PF, et al. Long-term nutrient intake and early dge-relatfid nuclear lo>n>.
opacities. Arch Ophthalmo!. 2001 ; 119:1009-19.
3. Taylor A, et dl. Long-term intake of vitamin*^ and rarotenoids and odds of early
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2002; 7.5:540-9.
4. Mdrei-Perlman |A, et al. Vitamin supplement use and incident catararts in a
population-based study. Arch Ophthalmoi. 2000; l18:155f>-63.
5. Yrishida M, et ¿\. Prospertivp study showing that dietary vitamin C reduced the
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vitamin G is associated with significantly reduced risk of catarad in the ItalianAmerican clinical trial of nutritional supplements and age-relatpd cataract. /nve5t
Ophlhalmol Vis Sei. 2004; 45:E-A!jstrad 3415.
8. Valero MP, et al. Vitamin C iii asi-uciateci with reduced risk of cataract in a
Mediterranean population. / Nutr. 1.12:1299-1306, 2002.
9. Tessier F, pt al. Decrease in vitamin C concentration in human lenses during
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10. Bouton SM, |r. Vitamin G and the aging eye. Ardl Intern Med. 1939; 63:930-45.
11. Muhlmann V, etal. Vitamin C therapy of incipipnt senile cataract. Arch Oñalmol
BAiref: 1939; 14:552-75.
12. 5purduto RD, et al. The Linxian cataract studies. Two nutrition intervention trials.
Arç.hOpbthalmoi. 1993; 111l9);1246-53.
13. Varmd SA, el al. Photoperoxidation of lens lipids: prevention by vitamin E.
Pimtocbem Photobiol. 1982; 36(61:623-36.
14. Neuwirth-Lux O, Billson F. Vitamin E and rabbit corneal endothelial tell survival.
Aust N 11 Ophlhäimo!. 1987;1 5(4):3O9-14.
I 5. Robertson (M, et al. Vitamin E intake and risk of cataracts in human'.. Ann N Y
AcadSci. 1989; 570:372-82.
16. lacqups PF, et al. Long-term nutrient intake and 5-year change in nuclear iens
opacifies. Arrii Ophlhalmol. 2005; 123:517-26.
I 7. Lyle B), ot al. Serum carotenoids and toi ojiherols and inc ¡derira of age-related
nuclear cataract. Am I Clin Nutr. 1999; 6912):272-7.
18. Leske MG, et al. Antioxidanl vit.imins and nuclear opacities: the longitudinal
study of cataract, Ophihalmoiogy. 1998; 105(51:831-6.
19. McNeil I], et al. Vitamin E supplementation and cataract: randomized rontrollcil
trial- Ophthalmology. 2004; in(l):75-84.
20. Christen WG, et al. Vitamin E and age-relaled Cdtarart in d randomized trial i>l
women. Opiif/ia/nio/ogy. 2008; 115{51:822-29.
21. Hankinson S, et al. Nutrient intake and cataract extradion in women: A
prospedive study. BMI. 1992; 305:335-9.
22. Mares-Perlman |A. et al. Diet and nuclear lens opacities. Am I Lpidemioi. 1995;
14l(4):322-'i4.
23. Rodrigue7-Rodriquez E, et al. The relationship between antioxidant nutrient
intake dnd cataracts in older people. Inl I Vildm Nulr Res. 2006; 76(6):359-66.
24. Gale CR, et al. Plasma antioxidant vitamins and carotenoids and age-related
cataract. Ophthalmology. 2001; 108(1 11:1992-8.
25. Carson C, et al, Antioxidant intake and cataract in the Melbourne Visual
Impairment proiect. Am I Lpidfmiot. 1994; 139(11):S18.
26. lacques PF, et al. Antioxidant status in persons with and without senile cataract.
Arch Ophthalmol. 1988; 1O6(3):337-4O.
27. Knekt P, et al. Serum antio:<idant vitamins and risk ot cataract. SM/. 1992;
305:1392-4.
28. Chylark |T, |r, et al. The Roche European American Cataract Trial (REACT): d
randomized clinical trial to investigate the efficacy of an oral antioxidant
niicronutrient mixture to slow progression of age-related c:atarad. Ophlhalmic
^pidemial. 2002; 9(1 ):49-80.
29. Age-Related Eye Disease Study Research Group, A randomized, plarebocontrolled, t linical trial of high-dose supplementation with vitamins C and E and
beta-carotene for age-related cataract and vision loss. Arch OphlhalmoL 2001;
119:1439-52.
SO. Gritz DC, et al. The antioxidants ¡n prevention of c:aiarads study: effects of
antioxidant supplements on cataract progression in South India. Br I Ophihalmol.
2006; 90:847-51.
Dr. Werbach's volumitious Nutritional Irifluences on Illness CDROM, with 4,200 pages of text and covering over 100 different
illnesses, makes it easy to search the nutritionai literature. For
information on his publications or a free brochure, contact Third
Line Press Inc., 4751 Viviana Drive, Tarzana, California 913.56;
800-916-0076; 818-996-0076; FAX: 818-774-1575; [email protected]; http://www.third-line.com.
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TOWNSEND LETTER - JANUARY 2009
141