Nutritional Influences on Illnessby Melvyn R. Werbach, MDtlp@third-Unexom

Cataracts: Vitamin C, Vitamin E,and the Carotenoids

With its continual exposure to light and ambientoxygen, the optical lens is at high risk of photooxidativedamage. Oxygen free radicals cause cataracts by oxidizingthe lens proteins while also impairing the proteolyticenzymes designed to eliminate the damaged proteins.Normal lenses of older people only show early evidence ofoxidation that is confined to the intrinsic membrane fractionand membrane-related components; the development ofcataract is associated with progressive oxidative changes inthese components, which eventually extend beyond themto involve the soluble components of the lens proteins.Since vitamins C and E, as well as the carotenoids luteinand zeaxanthin, are present in human lenses, and since allcan reduce oxidative stress, we will examine the currentevidence suggesting that supplementing them may combatthe progression of age-related cataracts.

Vitamin CThe concentration of ascorbic acid in the aqueous

humor is among the highest of all the body fluids, andthere is substantial evidence that vitamin C nutriture has asignificant effect on cataract formation. When, for example,rat lenses were maintained in a solution designed to causefree radical damage, the addition of vitamin C protectedthem.' As to humans, the intake of vitamin C supplementsover at least the past decade has repeatedly been foundto be inversely correlated with cataract risk.^^ Even overonly a five-year period, a higher vitamin C intake hasbeen repeatedly associated with a reduced incidence ofcataracts.̂ "̂

Also, a study of Italian-Americans found that higherplasma levels of vitamin C were associated with adecreased risk of cataract,̂ and blood levels of the vitaminin a Mediterranean population were inversely correlatedwith the risk of cataract.̂ Moreover, researchers examiningcataractous human lens nuclei found an inverse relationship

between vitamin C concentration in the lens and cataractseverity.^

In two open trials performed in the 1930s, 607o to907o of patients with incipient senile cataracts had visualimprovement 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 farless dramatic. A large population of rural Chinese aged45 to 74 years received either vitamin C 120 mg daily,along with 30 meg molyÍ3denum, or placebo daily. Afterfive years, there was a nonsignificant reduction of 227o incataract risk.'-

Vitamin ELike vitamin C, the addition of vitamin E protected rat

lenses from free radical damage when they were immersedin a solution designed to cause such damage.'̂ In addition,when added to the perfusion solution, vitamin E doubledthe survival time of isolated rabbit corneal endothelium.'*For humans, long-term vitamin E intake has been inverselyrelated to the risk of cataract."'^""" The same relationshiphas been noted in regard to serum levels of the vitamin.""Moreover, a recent longitudinal study found that, in bothregular users of vitamin E supplements and persons withhigher plasma levels of vitamin E, the risk of nuclearopacification was reduced by approximately half.'^

Despite these promising findings, two randomized trialshave failed to find evidence of the vitamin's efficacy. Onetrial was of 1193 volunteers aged 55-80 years with early orno cataract. They received either 500 IU vitamin E daily orplacebo and were followed for four years. Supplementationfailed to reduce the incidence or progression of nuclear,cortical, or posterior subcapsular cataracts.'̂

A larger trial involved 39,876 females aged 45 yearsor older. They received either 600 IU of natural-sourcevitamin E on alternate days, or placebo. After almost tenyears of treatment and follow-up, there was no evidencethat supplementation reduced the incidence of age-relatedcataract.^"

CarotenoidsThe intake of carotenoids - particularly alpha- and

beta-carotene, lutein, lycopene, and zeaxanthin - hasbeen inversely correlated with cataract risk.̂ ''̂ "* Althoughtwo epidemiological studies failed to find a relationshipbetween beta<arotene intake and the risk of cataract,^^"another found that the prevalence of posterior subcapsularlens opacities in women who never smoked was related tothe intake of alpha- and beta-carotene as well as with totalcarotenoids.^ Also, the blood level of beta-carotene hasbeen inversely correlated with cataract risk.̂ ^ In fact, onestudy found that those with serum levels of beta-carotenein the lowest third of the distribution had almost a threefoldrisk of senile cataract."

Combined SupplementationIn a randomized trial, patients in Europe and America

with early age-related cataracts received either vitaminC 750 mg, vitamin E 600 IU, and beta-carotene 18 mg,or placebo. After two years, there was a small positivetreatment effect in American patients; after three years, thepositive effect was apparent in the total group, with an evengreater effect in the American group. By contrast, there wasno significant effect in the European group.̂ ^

Other similar trials have failed to show any significantbenefits. In a randomized trial of Americans, participantsaged 55-80 years received daily tablets of either vitaminC 500 mg, vitamin E 400 IU, and beta-carotene 15 mg, orno antioxidants. After an average of 6.3 years, there wasno significant effect of the formula on the developmentor progression of age-related lens opacities." Similarly,residents of South India aged 35-50 years (as this populationhas early progression of cataracts) received vitamin C400 mg, vitamin E (RRR-alpha-tocopherol) 400 IU, and15 mg beta<arotene from algae in the all-irans formwith small amounts of other carotenoids. After five years,supplementation failed to affect cataract progression.̂ '̂ 'Thus, findings from randomized trials have so far failed tolive up to the high expectations raised by other studies.

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Notes1. Varma SD, Richards RD. Light-induced damage to ocular lens cation puni|>

Prevention by vitamin C, Pror Nat! Acad So USA.] 979; 76:3504-6.2. 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

age-related cortical and posterior subcapsuLir lens opacities. Am I Clin Niilr.2002; 7.5:540-9.

4. Mdrei-Perlman |A, et al. Vitamin supplement use and incident catararts in apopulation-based study. Arch Ophthalmoi. 2000; l18:155f>-63.

5. Yrishida M, et ¿\. Prospertivp study showing that dietary vitamin C reduced therisk of dge-related cataracts in a micldle-ajied Japanese pupuldtion. Lur ! Nulr.2007; 4612):! 18-24.

6. Tan AG, et al. Anlioxidant nutrient intake and incidence of age-related cataract:Blue Mountains eye study, invest Ophthalmol Vis Su. 2007; 48:E-Abíi!ract-5455.

7. Maraini G and Italian-American Cataract Study Group. Baseline plasma level ofvitamin G is associated with significantly reduced risk of catarad in the Italian-American clinical trial of nutritional supplements and age-relatpd cataract. /nve5tOphlhalmol Vis Sei. 2004; 45:E-A!jstrad 3415.

8. Valero MP, et al. Vitamin C iii asi-uciateci with reduced risk of cataract in aMediterranean population. / Nutr. 1.12:1299-1306, 2002.

9. Tessier F, pt al. Decrease in vitamin C concentration in human lenses duringcatatad progression. Inl I VHanvn Ref.. 1998; 66(5]:.ÏO9-15.

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 antioxidantniicronutrient 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, plarebo-controlled, t linical trial of high-dose supplementation with vitamins C and E andbeta-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 ofantioxidant supplements on cataract progression in South India. Br I Ophihalmol.2006; 90:847-51.

Dr. Werbach's volumitious Nutritional Irifluences on Illness CD-ROM, with 4,200 pages of text and covering over 100 differentillnesses, makes it easy to search the nutritionai literature. Forinformation on his publications or a free brochure, contact ThirdLine Press Inc., 4751 Viviana Drive, Tarzana, California 913.56;800-916-0076; 818-996-0076; FAX: 818-774-1575; tlp@third-line.com; http://www.third-line.com.

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