ARTICLE

Association between serum

25-hydroxyvitamin D levels
and age-related cataracts
Donghyun Jee, MD, PhD, Eun Chul Kim, MD, PhD

PURPOSE: To investigate associations between serum 25-hydroxyvitamin D levels and age-related

cataracts.
SETTING: Department of Ophthalmology, College of Medicine, Catholic University of Korea,
South Korea.
DESIGN: Observational cross-sectional study.
METHODS: Participants aged 40 years or older in the fourth (2008 to 2009) and fifth (2010 to 2012)
Korea National Health and Nutrition Examination Survey (KNHANES) had evaluation of their serum
25-hydroxyvitamin D levels and ophthalmic slitlamp examinations to identify cataract. An age-
related cataract was defined as the presence of a cortical, nuclear, anterior subcapsular,
posterior subcapsular, or mixed cataract or a history of cataract surgery.
RESULTS: The study evaluated eyes of 18 804 patients. The mean levels of serum 25-
hydroxyvitamin D were 20.0 ng/mL in men and 17.5 ng/mL in women. In men, but not in
women, the odds ratio (OR) for age-related cataracts decreased statistically significantly when
the serum 25-hydroxyvitamin D levels were in the highest quintile than when they were in the
lowest quintile (OR, 0.76; 95% confidence interval, 0.59-0.99) after adjusting for potentially
confounding factors including age, sex, smoking status, diabetes, hypertension, and sunlight
exposure. However, trend analysis did not show a significant declining trend in the cataract risk
associated with higher serum 25-hydroxyvitamin D quintiles (P Z .084). In women, serum 25-
hydroxyvitamin D levels were not associated with age-related cataracts.
CONCLUSIONS: The age-related cataract risk decreased in men with higher serum
25-hydroxyvitamin D levels than in those with lower serum 25-hydroxyvitamin D levels after
adjusting for potential confounding factors. In light of previous research indicating an
antioxidative effect of vitamin D, the connection between vitamin D and age-related cataract
warrants further study.
Financial Disclosure: Neither author has a financial or proprietary interest in any material or
method mentioned.
J Cataract Refract Surg 2015; 41:1705–1715 Q 2015 ASCRS and ESCRS

Age-related cataracts are a major cause of blindness
and visual impairment worldwide.1 Although surgery
can improve visual acuity, the procedure is expensive.
Risk factors for age-related cataracts are aging, smok-
ing, exposure to ultraviolet (UV) radiation, and genetic
influences.2 Recent publications suggest that antioxi-
dant vitamins, including vitamins C and E, can reduce
the cataract risk in animal models and humans3–7
because oxidative stress is a significant factor in the
genesis of cataracts.8
Vitamin D, one of the antioxidant vitamins, is
known to decrease oxidative stress.9–11 There is evi-
dence associating low vitamin D with an increased
risk for chronic diseases such as diabetes mellitus, hy-
pertension, heart disease, multiple sclerosis, schizo-
phrenia, and rheumatoid arthritis.12 Several studies
report an inverse association of vitamin D with
several ocular diseases through its antioxidative func-
tion, including diabetic retinopathy,13,14 age-related
macular degeneration (AMD),15,16 and glaucoma.17

Q 2015 ASCRS and ESCRS http://dx.doi.org/10.1016/j.jcrs.2014.12.052 1705

Published by Elsevier Inc. 0886-3350

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1706 SERUM 25-HYDROXYVITAMIN D AND CATARACT
Recently, an inverse association of vitamin D and
AMD was reported,18 which is interesting given that
approximately 90% of vitamin D is generated in the
skin through sunlight exposure, which has been impli-
cated as a risk factor for AMD.12,19
Similarly, the mechanism underlying age-related
cataractogenesis involves photooxidation of proteins
in the lens. Thus, it is possible that vitamin D has
beneficial effect on the development of cataract.
Moreover, it is possible to uptake vitamin D without
lens damage from UV rays in sunlight through sun-
glasses or dietary supplements of vitamin D. How-
ever to our knowledge, no epidemiologic studies
have evaluated the associations between vitamin D
levels and cataracts. We hypothesized that serum
vitamin D levels play a role in age-related cataract
development. To test our hypothesis, we examined
the relationship between serum 25-hydroxyvitamin
D levels and age-related cataracts in a representative
Korean population.
PATIENTS AND METHODS
Study Population
This study used data acquired for the Korea National
Health and Nutrition Examination Survey (KNHANES),
which is a nationwide and population-based cross-sectional
study conducted by the Korean Ministry of Health and Wel-
fare and the Division of Chronic Disease Surveillance at the
Korean Centers for Disease Control and Prevention. The
KNHANES adopted a rolling sampling design that was
used to perform a stratified, complex, multistage probability
cluster survey, with proportional allocations based on the
National Census Registry for the noninstitutional Korean
civilian population. Details about the study design and the
methods used are reported elsewhere.20,21 Data from the
fourth (2008 to 2009) and fifth (2010 to 2012) KNHANES
Submitted: September 8, 2014.
Final revision submitted: November 17, 2014.
Accepted: December 15, 2014.
From the Department of Ophthalmology and Visual Science (Jee),
St. Vincent’s Hospital, College of Medicine, Catholic University of
Korea, Suwon, Gyenggido, and the Department of Ophthalmology
and Visual Science (Kim), Bucheon St. Mary’s Hospital, College
of Medicine, Catholic University of Korea, Bucheon, Gyeonggido,
South Korea.
The Epidemiologic Survey Committee of the Korean Ophthalmo-
logic Society conducted the Korea National Health and Nutrition
Examination Survey examinations and supplied the data for this
study.
Corresponding author: Eun Chul Kim, MD, PhD, Department of
Ophthalmology and Visual Science, Bucheon St. Mary’s Hospital,
College of Medicine, Catholic University of Korea, 505 Banpo-
dong, Seocho-gu, Seoul 137-040, South Korea. E-mail: eunchol@
hanmail.net.
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were used in the present study to estimate the association
between serum 25-hydroxyvitamin D levels and age-
related cataract.
The KNHANES participants were enrolled; exclusion
criteria were age 39 years or younger, not having
serum 25-hydroxyvitamin D levels measured, and not
having a slitlamp eye examination. The study adhered
to the tenets of the Declaration of Helsinki for biomed-
ical research and was approved by the institutional
review board at the Catholic University of Korea in
Seoul, South Korea. All participants provided informed,
written consent.
Age-Related Cataract Assessments
The age-related cataract examinations and grading of
KNHANES have been described.22–26 Briefly, ophthal-
mology residents performed comprehensive slitlamp eye ex-
aminations using a BQ 900 slitlamp (Haag-Streit AG). The
standard Lens Opacities Classification Systems III (LOCS
III) was used to assess cataracts.27 Cataracts were compared
with standard photographs and classified as cortical (LOCS
III score R2 for cortical cataracts), nuclear (LOCS III
score R4 for nuclear opalescence or nuclear color), anterior
subcapsular (LOCS III score R2 for anterior subcapsular cat-
aracts), posterior subcapsular (LOCS III score R2 for poste-
rior subcapsular cataracts), or mixed type (more than 1 type
per eye). All age-related cataracts were defined as the pres-
ence of any 1 or more type of cataract. For the statistical anal-
ysis, pseudophakic and aphakic eyes were included in the
same category as those with previous cataract surgery. For
participants who had unilateral lens extraction, the contra-
lateral phakic eye was used define lens opacity type. The
survey’s quality was verified by the Epidemiologic Survey
Committee of the Korean Ophthalmologic Society, and
participating resident physicians were periodically trained
by staff from this committee.
Assessment of Serum 25-Hydroxyvitamin D Levels
The analysis of serum 25-hydroxyvitamin D levels has
been described.28,29 Serum samples were collected after
an 8-hour fast, and serum 25-hydroxyvitamin D levels
were measured with a radioimmunoassay kit (Diasorin,
Inc.) using a gamma counter (1470 Wizard, PerkinElmer,
Inc.), which is often used in mass surveys such as the
KNHANES. The KNHANES participates in the Vitamin D
Standardization Program; therefore, the measurement of
25-hydroxyvitamin D was standardized in accordance
with the National Institute of Standards and Technology-
Ghent University reference procedure.30 All serum samples
were appropriately processed, promptly refrigerated, and
transported cold to a laboratory that is certified by the
Korean Ministry of Health and Welfare at the Neodin Med-
ical Institute in Seoul. Blood samples were analyzed within
24 hours after transportation. The detection limit for
25-hydroxyvitamin D by radioimmunoassay is 1.2 ng/mL,
and the inter-assay coefficients of variation were 2.8% to
6.2% for the samples from the 2008–2009 KNHANES group
and 1.9% to 6.1% for the samples from the 2010–2012
KNHANES group.
In addition to analyzing serum 25-hydroxyvitamin D
levels, fasting glucose, hemoglobin A1c (HbA1c), total
cholesterol, and triglyceride levels were measured using
a Hitachi 7600 clinical analyzer (Hitachi High-
Technologies Corp.).
 SERUM 25-HYDROXYVITAMIN D AND CATARACT 1707

Assessment of Other Variables
Demographic information was collected during health in-
terviews. Height and weight were measured with the pa-
tients wearing light clothing and no shoes. Body mass
indices were calculated as weight (kg)/height (m).2 Age
was categorized in 10-year intervals. Smoking status was
self-reported, and patients were classified as current
smokers, past smokers, or nonsmokers. Alcohol use was
self-reported, and patients were classified as drinkers or non-
drinkers. Data regarding sunlight exposure were obtained
by asking the participants whether they were exposed to
the sun for less than 5 hours or 5 hours or more per day.
Three blood pressure measurements were taken at 5-
minute intervals using a sphygmomanometer and with the
patients sitting; the average of the second and third measure-
ments was used for the analysis. Diabetes mellitus was
considered present if the fasting blood-glucose level was
126 mg/dL or more or the patient was taking antiglycemic
medication. Hypertension was considered present if the sys-
tolic blood pressure was 140 mm Hg or higher, the diastolic
blood pressure was 90 mm Hg or higher, or the patient was
taking antihypertensive medication. Heart disease was
defined as a history of myocardial infarction or angina. Is-
sues relating to strokes were self-reported.
Statistical Analyses
Statistical analyses were performed using SPSS software
(version 18.0, International Business Machines Corp.). Strata,
sampling units, and sampling weights were used to obtain
point estimates and standard errors. Participants’ character-
istics were described using means and standard errors for
continuous variables and percentages and standard errors
for categorical variables, according to the presence of cata-
ract. Analysis of variance or chi-square tests were used to
compare the patients’ demographic characteristics. Serum
25-hydroxyvitamin D levels were categorized into quintiles
to evaluate the association between this vitamin and age-
related cataract incidence.31 Simple and multiple logistic
regression analyses examined the associations between
serum 25-hydroxyvitamin D levels and age-related cataracts.
After calculating the crude odds ratios (ORs) (Model 1),
values were adjusted for age and sex (Model 2). They were
then adjusted for age, sex, and other confounding factors
including smoking, hypertension, diabetes, and sunlight
exposure times because these were established risk factors
for age-related cataracts in previous studies (Model 3).32,33
All variables considered for the logistic regression analyses
were examined for multicollinearity, and only variables
with a variance inflation factor of less than 5 were used.
The P values were 2-tailed, and a P value less than 0.05 indi-
cated statistical significance.
RESULTS
Of the individuals invited to participate in the
KNHANES for 2008 through 2012, 43 523 attended a
health interview and health examination. Of those,
24 719 were ineligible for the present study on the basis
of being 39 years or younger (22 912), not having
their serum 25-hydroxyvitamin D levels measured
(1497), or not having a slitlamp examination (310).
The remaining 18 804 patients had their eyes examined

Table 1. Demographic and clinical characteristics regarding presence or absence of cataract as reported in the Korean National Health and
Nutrition Examination Survey 2008–2012.

Cataract Status

No Cataract Cataract and Pseudophakia All Participants

Characteristic (n Z 9479) (n Z 9325) P Value (N Z 18 804)

Men (%)* 49.7 (0.5) 47.7 (0.5) .014 48.9 (0.3)

Age (year)† 49.5 (0.1) 63.6 (0.2) !.001 56.6 (0.1)
Body mass index (kg/m2)† 24.1 (0.0) 23.9 (0.0) .022 24.0 (0.0)
Systolic blood pressure (mm Hg)† 119.5 (0.2) 127.1 (0.2) !.001 123.3 (0.2)
Diastolic blood pressure (mm Hg)† 79.1 (0.1) 77.5 (0.1) !.001 78.3 (0.1)
Fasting glucose (mg/dL)† 98.8 (0.3) 104.4 (0.3) !.001 101.6 (0.2)
HbA1c (%)* 5.8 (0.0) 6.2 (0.0) !.001 6.0 (0.0)
Total cholesterol (mg/dL)† 193.6 (0.4) 193.2 (0.5) .543 193.4 (0.3)
Triglyceride (mg/dL)† 146.6 (1.6) 148.7 (1.5) .317 147.7 (1.2)
25-hydroxyvitamin D (ng/mL)† 18.4 (0.1) 19.1 (0.1) !.001 18.8 (0.1)
Diabetes (%)* 8.4 (0.4) 19.3 (0.5) !.001 12.8 (0.3)
Hypertension (%)* 30.0 (0.6) 52.6 (0.8) !.001 39.3 (0.5)
Sun exposure (O5 hours/day)† 17.6 (0.7) 25.1 (1.1) !.001 20.7.0 (0.7)
Smoking status (%)* !.001
Never 53.6 (0.6) 54.4 (0.6) 53.9 (0.4)
Former 14.0 (0.5) 17.9 (0.6) 15.6 (0.4)
Current 32.5 (0.6) 27.7 (0.6) 30.5 (0.4)
Alcohol consumption (%)* 89.1 (0.4) 78.5 (0.5) !.001 84.8 (0.3)

HbA1c Z hemoglobin A1c

*Weighted frequency (%) with standard error
†
Weighted mean values with standard error

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1708 SERUM 25-HYDROXYVITAMIN D AND CATARACT

to determine cataract status. Of these patients, 7993 had
age-related cataracts and 1332 had a history of cataract
surgery. The cataract types and their incidence were
cortical (1744 eyes [18.9%], standard error 1.1%), nu-
clear (4460 eyes [50.5%], standard error 1.2%), anterior
subcapsular (172 eyes [1.8%], standard error 0.2%), pos-
terior subcapsular (74 eyes [0.7%], standard error
0.1%), and mixed (1543 eyes [14.7%], standard error
0.7%). Table 1 gives the demographic characteristics
of these patients according to their cataract status.
Patients with age-related cataracts were more likely
than patients without them to be older (P ! .001) and
have higher serum 25-hydroxyvitamin D levels
(P ! .001), hypertension (P ! .001), higher systolic
blood pressures (P ! .001), diabetes (P ! .001), higher
fasting glucose levels (P ! .001), higher HbA1c levels
(P ! .001), and longer sun exposure (P ! .001).
The demographic and clinical characteristics of the pa-
tients according to the blood 25-hydroxyvitamin D quin-
tiles showed that as serum 25-hydroxyvitamin D levels
increased, patients were more likely to be men
(P ! .001), older (P ! .001), hypertensive (P Z .011),
and have experienced longer sun exposures (P ! .001,
Table 2). The serum 25-hydroxyvitamin D level in men
and women was categorized according to the presence
of hypertension, smoking status, the presence of diabetes,
alcohol consumption, cataract status, and sun exposure
(Table 3). Blood 25-hydroxyvitamin D levels were higher
in men than in women (P ! .001). The mean serum
25-hydroxyvitamin D levels were significantly higher
in the older age groups (P ! .001), in patients with dia-
betes (P Z .019 for men, P Z .035 for women), and in pa-
tients with more than 5 hours of sun exposure a day
(P ! .001 for both sexes). Women, but not men, showed
statistically significant differences in their serum
25-hydroxyvitamin D levels relative to the presence of
age-related cataracts (P ! .001), the presence of hyper-
tension (P Z .007), and alcohol consumption
(P Z .033). Univariate regression analysis showed that
the age-related cataract was associated with age, hyper-
tension, blood pressure, diabetes, fasting glucose levels,
and HbA1c (Table 4). As serum 25-hydroxyvitamin D
levels increased, the age-related cataract incidence signif-
icantly increased from 1784 eyes (39.5%) in the first quin-
tile to 2070 eyes (46.1%) in the fifth quintile (P ! .001)
(Table 5). This trend was apparent in women
(P ! .001) but was not apparent in men (P Z .173).
In men, the adjusted ORs for age-related cataracts
declined statistically significantly in patients whose
serum 25-hydroxyvitamin D levels were in the highest

Table 2. Demographic and clinical characteristics by serum 25-hydroxyvitamin D quintile in representative Korean adults age 40 years
or older.

Quintile

1 2 3 4 5
R13.1 and R16.4 and R19.7 and
Demographic or Clinical !13.1 ng/mL ! 16.4 ng/mL ! 19.7 ng/mL ! 24.3 ng/mL R24.3 ng/mL P Value
Characteristic (n Z 3756) (n Z 3764) (n Z 3765) (n Z 3777) (n Z 3742) for Trend

Men (%)* 34.3 (0.9) 42.2 (1.0) 50.5 (1.0) 57.0 (1.0) 61.4 (1.0) !.001
Age (year)† 54.4 (0.2) 54.1 (0.2) 54.8 (0.2) 56.1 (0.2) 57.3 (0.2) !.001
Body mass index (kg/m2)† 23.9 (0.1) 24.2 (0.1) 24.1 (0.1) 24.1 (0.1) 23.7 (0.1) !.001
Systolic blood pressure (mm Hg)† 122.6 (0.4) 121.8 (0.3) 122.2 (0.3) 123.0 (0.3) 123.4 (0.4) .011
Diastolic blood pressure (mm Hg)† 78.1 (0.2) 78.4 (0.2) 78.5 (0.2) 78.8 (0.2) 78.4 (0.2) .330
Fasting glucose (mg/dL)† 101.1 (0.5) 100.3 (0.4) 102.5 (0.5) 100.6 (0.4) 100.9 (0.4) .031z
HbA1c (%)* 6.07 (0.03) 5.98 (0.02) 6.08 (0.03) 5.99 (0.02) 6.09 (0.03) .015
Total cholesterol (mg/dL)† 192.6 (0.8) 193.5 (0.7) 194.8 (0.7) 194.8 (0.7) 191.3 (0.7) .002
Triglyceride (mg/dL)† 153.8 (3.7) 149.4 (2.6) 147.7 (2.4) 146.3 (2.3) 139.5 (1.8) .002
Diabetes (%)* 13.3 (0.7) 11.5 (0.6) 13.5 (0.7) 12.3 (0.6) 13.5 (0.7) .116
Hypertension (%)* 39.0 (1.1) 38.4 (1.0) 37.0 (1.0) 40.5 (1.0) 41.6 (1.1) .011
Sun exposure (O5 hours/day)† 11.4 (0.7) 15.0 (0.8) 18.0 (1.0) 25.0 (1.2) 35.4 (1.6) !.001
Smoking status (%)* !.001
Never 63.8 (1.0) 57.9 (1.0) 54.5 (1.0) 48.1 (1.1) 44.6 (1.0)
Former 10.7 (0.7) 14.5 (0.7) 17.4 (0.8) 20.0 (0.9) 15.3 (0.9)
Current 25.5 (0.9) 27.6 (1.0) 28.1 (0.9) 32.0 (1.0) 40.1 (1.1)
Alcohol consumption (%)* 81.6 (0.8) 85.2 (0.7) 85.9 (0.7) 85.9 (0.7) 85.6 (0.7) !.001

HbA1c Z hemoglobin A1c

*Weighted frequency (%) with standard error
†
Weighted mean values with standard error
z
Statistically significant (P ! .05)

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 SERUM 25-HYDROXYVITAMIN D AND CATARACT 1709

Table 3. Sex difference in serum 25-hydroxyvitamin D levels according to age group and other variables in representative Korean adults
aged 40 years or older.

Serum 25-Hydroxyvitamin D Levels (ng/mL)*

Men (n Z 8186) Women (n Z 10 618)

Characteristic Level P Value for Trend Level P Value for Trend

All subjects aged 40C years 20.0 (0.1, 19.7-20.2) 17.5 (0.1, 17.3-17.8)
Age (y) !.001† !.001†
40–49 19.2 (0.1, 18.9-19.6) 16.2 (0.1, 15.9-16.5)
50–59 20.5 (0.2, 19.8-20.6) 18.0 (0.1, 17.6-18.3)
60–69 20.8 (0.2, 20.4-21.3) 18.5 (0.2, 18.1-18.9)
70C 20.4 (0.2, 19.9-20.9) 18.5 (0.2, 18.1-19.0)
Cataract .111 !.001†
Without cataract 19.8 (0.1, 19.5-20.1) 17.1 (0.1, 16.8-17.3)
With cataract 20.2 (0.1, 19.8-20.5) 18.2 (0.1, 17.8-18.5)
Diabetes .019† .035†
Nondiabetic 20.1 (0.1, 19.8-20.4) 17.5 (0.1, 17.2-17.7)
Diabetic 19.5 (0.2, 19.0-20.0) 18.0 (0.2, 17.5-18.6)
Sun exposure !.001† !.001†
!5 hours/day 19.1 (0.1, 18.9-19.4) 17.1 (0.1, 16.8-17.3)
R5 hours/day 22.1 (0.2, 21.6-22.6) 20.1 (0.2, 19.5-20.7)
Hypertension .596 .007†
Nonhypertensive 20.0 (0.1, 19.7-20.4) 17.4 (0.1, 17.1-17.6)
Hypertensive 19.9 (0.1, 19.6-20.3) 17.8 (0.1, 17.5-18.2)
Smoking .020† .013†
Never 20.1 (0.2, 19.6-20.6) 17.6 (0.1, 17.3-17.8)
Former 19.5 (0.1, 19.2-19.9) 16.5 (0.3, 15.8, 17.2)
Current 20.2 (0.1, 19.8-20.5) 17.3 (0.3, 16.6-17.9)
Alcohol consumption .384 .033†
Never 20.3 (0.3, 19.5-21.1) 17.8 (0.1, 17.5-18.2)
Past or current 20.0 (0.1, 19.7-20.2) 17.4 (0.1, 17.2-17.7)

*Serum 25-hydroxyvitamin D levels are expressed as weighted estimate (standard error, 95% confidence interval)
†
Statistically significant (P ! .05)

quintile compared with those whose serum 25-
hydroxyvitamin D levels were in the lowest quintile
(OR, 0.76; 95% confidence interval [CI], 0.59-0.99), after
adjusting for potential covariates such as sex, age,
smoking, hypertension, diabetes, and sunlight exposure
(Table 6). However, trend analysis did not show a statis-
tically significantly declining trend in the incidence of
age-related cataracts in association with the higher
serum 25-hydroxyvitamin D quintiles (P Z .084). The
association between the serum 25-hydroxyvitamin D
quintiles and age-related cataract incidence was not
statistically significant after adjusting for the potential
covariates in women (OR, 0.84; 95% CI, 0.66-1.07;
P Z .208) and in both sexes (OR, 0.86; 95% CI, 0.71-
1.04; P Z .126).
The incidence of the types of age-related cataract
in men and women in relation to the serum
25-hydroxyvitamin D quintiles is shown in Table 6.
Nuclear and mixed cataracts were positively corre-
lated with higher serum 25-hydroxyvitamin D
quintiles (P Z .019 for nuclear cataracts, P Z .009 for
mixed cataracts). A positive association was apparent
between the incidence of mixed cataracts in women
and the higher serum 25-hydroxyvitamin D quintiles
(P ! .001). No statistically significant associations
were found between the serum 25-hydroxyvitamin D
quintiles and any type of cataract (Table 7).
DISCUSSION
To our knowledge, this is the first epidemiologic study
to evaluate associations between vitamin D levels and
age-related cataracts. We found the risk for age-
related cataract was significantly reduced in men whose
serum 25-hydroxyvitamin D levels were in the highest
quintile compared with those whose serum 25-
hydroxyvitamin D levels were in the lowest quintile,
and that no such reduction in risk was found in women.
However, a statistically significant linear increasing
trend in the OR for cataracts in men was not shown.

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1710 SERUM 25-HYDROXYVITAMIN D AND CATARACT

Table 4. Univariate logistic regression analysis for the association between clinical risk factors and age-related cataract (KNHANES
2008–2012).

Regression Analysis Result for Cataract

All Participants Men Women

Risk Factor Odds Ratio* P Value Odds Ratio* P Value Odds Ratio* P Value

Female 1.08 (1.01-1.15) .014 d d d d

Age (y) 1.17 (1.16-1.18) !.001 1.15 (1.14-1.17) !.001 1.19 (1.17-1.20) !.001
Body mass index (kg/m2) 0.98 (0.97-0.99) .021 0.93 (0.91-0.95) !.001 1.02 (1.01-1.04) .002
Systolic blood pressure (mm Hg) 1.02 (1.02-1.03) !.001 1.02 (1.01-1.02) !.001 1.03 (1.03-1.04) !.001
Diastolic blood pressure (mm Hg) 0.98 (0.98-0.99) !.001 0.97 (0.97-0.98) !.001 1.00 (0.99-1.00) .859
Fasting glucose (mg/dL) 1.01 (1.00-1.01) !.001 1.01 (1.00-1.01) !.001 1.01 (1.01-1.01) !.001
HbA1c (%) 1.36 (1.26-1.48) !.001 1.24 (1.13-1.36) !.001 1.55 (1.37-1.75) !.001
Total cholesterol (mg/dL) 1.00 (0.99-1.00) .543 0.99 (0.99-0.99) !.001 1.00 (1.00-1.00) !.001
Triglyceride (mg/dL) 1.00 (1.00-1.00) .329 0.99 (0.99-1.00) .001 1.00 (1.00-1.00) .001
25-hydroxyvitamin D (ng/mL) 1.06 (1.00-1.02) !.001 1.00 (0.99-1.01) .109 1.02 (1.01-1.03) !.001
Diabetes (%) 2.59 (2.29-2.93) !.001 2.15 (1.83-2.51) !.001 3.35 (2.79-4.02) !.001
Hypertension (%) 2.59 (2.39-2.81) !.001 1.80 (1.60-2.01) !.001 3.83 (3.43-4.28) !.001
Sun exposure (O5 hours/day) 1.57 (1.39-1.78) !.001 1.34 (1.17-1.54) !.001 2.12 (1.81-2.49) !.001
Smoking status (%) !.001 !.001 .585
Never Reference Reference Reference
Former 1.26 (1.13-1.41) 1.37 (1.15-1.64) 1.14 (0.83-1.58)
Current 0.83 (0.77-0.91) 0.87 (0.74-1.03) 1.07 (0.87-1.32)
Alcohol consumption (%) 0.44 (0.40-0.48) !.001 0.57 (0.45-0.72) !.001 0.39 (0.35-0.44) !.001

CI Z confidence interval; HbA1c Z hemoglobin A1c

*Odds ratio expressed as odds ratio (95% confidence interval)

Although the crude ORs for age-related cataract
increased with the rise in vitamin D levels, this
might be confounded by age, considering that the
incidence of cataract was positively associated
with age, which was positively associated with
vitamin D levels in the present study (Table 5). After
adjusting for potentially confounding factors,
including sex, age, smoking, hypertension, diabetes,
and sunlight exposure, the risk for cataracts in
men within the highest serum 25-hydroxyvitamin
D quintile (quintile 5) was 24% lower than in those
within the lowest serum 25-hydroxyvitamin D
quintile (quintile 1). The possible biological explana-
tion for this association is that vitamin D inhibits
the oxidation of proteins in the lens that is critical
to the development of cataracts.8 Vitamin D is
positively associated with plasma glutathione, a
major intracellular antioxidant, and with cysteine,
a major extracellular antioxidant.9 Moreover,
vitamin D appears to catalyze glutathione produc-
tion.34 However, the trend analysis for the OR
did not show a significant declining trend in the
risk for cataracts in association with the higher
serum 25-hydroxyvitamin D quintiles, suggesting
the possibility of a poor dose–response relationship
between serum 25-hydroxyvitamin D levels and
cataracts.
The analysis was stratified by men and women to
examine the interaction of sex with serum
25-hydroxyvitamin D levels because the average
vitamin D concentrations were statistically signifi-
cantly different between men and women. Men
with the highest serum 25-hydroxyvitamin D levels
had a 24% lower risk for cataracts than men with
the lowest serum 25-hydroxyvitamin D levels; how-
ever, after adjustment for the potentially confound-
ing factors, this statistically significant association
was not found in women. The reason for this finding
is unknown, although speculatively it might be that
men experience greater exposure to sunlight than
women, sunlight being the main driver for vitamin
D production in the skin. However, high sunlight
exposure can cause more cataract because of the sun-
light’s effect on the natural lens, although wearing
sunglasses might reduce the lens’ sunlight exposure
but maintain the amount of exposure to the skin.
Alternatively, the preventive effect of vitamin D
through skin exposure might outweigh the cataracto-
genic effect of sunlight on the eye’s lens. Potentially,
too, women might have less sensitivity to vitamin D
or they more frequently use sunlight protective mea-
sures such as exposure-blocking clothing, sunscreen
creams, hats, and sunglasses. Further studies are
required to identify the factors responsible for this

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 SERUM 25-HYDROXYVITAMIN D AND CATARACT 1711

Table 5. Prevalence and adjusted OR of age-related cataract, stratified according to quintile categories of serum 25-hydroxyvitamin D in
representative Korean adults aged 40 years or older.

Quintile
P Value
Characteristic 1 2 3 4 5 for Trend

Both sexes
Hydroxyvitamin D !13.1 R13.1 and !16.4 R16.4 and !19.7 R19.7 and !24.3 R24.3
level (ng/mL)
Group size (n) 3756 3764 3765 3767 3752
Prevalence* 39.5 (1.2, 37.2-41.9) 37.8 (1.2, 35.5-40.1) 39.4 (1.2, 37.1-41.8) 42.8 (1.3, 40.3-45.4) 46.1 (1.5, 43.2-49.1) !.001z
Odds ratio†
Model 1 1.00 (reference) 0.92 (0.83-1.03) 0.99 (0.88-1.22) 1.14 (1.00-1.29)z 1.31 (1.13-1.50)z !.001z
Model 2 1.00 (reference) 0.93 (0.80-1.09) 0.89 (0.76-1.05) 0.88 (0.73-1.05) 0.85 (0.70-1.03) .113
Model 3 1.00 (reference) 0.98 (0.84-1.15) 0.91 (0.77-1.11) 0.92 (0.77-1.11) 0.86 (0.71-1.04) .126
Men
Hydroxyvitamin D !14.5 R14.5 and !17.9 R17.9 and !21.2 R21.2 and !25.7 R25.7
level (ng/mL)
Group size (n) 1641 1634 1638 1636 1637
Prevalence* 38.4 (1.6, 35.3-41.6) 37.8 (1.6, 34.8-41.0) 41.3 (1.7, 38.0-44.7) 40.7 (1.7, 37.5-44.0) 42.5 (1.9, 38.8-46.3) .173
Odds ratio†
Model 1 1.00 (reference) 0.97 (0.81-1.16) 1.13 (0.94-1.35) 1.10 (0.91-1.32) 1.18 (0.97-1.44) .042†
Model 2 1.00 (reference) 0.93 (0.74-1.16) 0.99 (0.78-1.26) 0.88 (0.69-1.13) 0.79 (0.61-1.03) .103
Model 3 1.00 (reference) 0.93 (0.74-1.16) 0.99 (0.78-1.27) 0.91 (0.71-1.17) 0.76 (0.59-0.99)z .084
Women
Hydroxyvitamin !12.3 R12.3 and !15.3 R15.3 and !18.4 R18.4 and !22.8 R22.8
D level (ng/mL)
Group size (n) 2132 2116 2124 2124 2122
Prevalence* 39.6 (1.4, 36.9-42.4) 38.3 (1.5, 35.5-41.2) 39.3 (1.5, 36.5-42.2) 44.2 (1.6, 41.0-47.3) 49.6 (1.6, 46.5-52.7) !.001z
Odds ratio†
Model 1 1.00 (reference) 0.94 (0.81-1.09) 0.98 (0.84-1.14) 1.20 (1.02-1.41)z 1.50 (1.27-1.76)z !.001z
Model 2 1.00 (reference) 0.95 (0.81-1.20) 0.89 (0.73-1.09) 0.93 (0.76-1.15) 0.83 (0.66-1.04) .156
Model 3 1.00 (reference) 0.98 (0.79-1.21) 0.94 (0.76-1.15) 0.96 (0.78-1.19) 0.84 (0.66-1.07) .208

Model 1 Z the crude odds ratio; Model 2 Z adjusted for sex and age; Model 3 Z adjusted for sex, age, smoking, diabetes, hypertension, and sun exposure
*Expressed as weighted estimate (%) (standard error [%], 95% confidence interval)
†
Expressed as odds ratio (95% confidence interval)
z
Statistically significant (P ! .05)

difference and, particularly, to elucidate the sex-
specific biological mechanisms by which 25-
hydroxyvitamin D inhibits age-related cataract
development.
The mean vitamin D concentrations in men
(20.0 ng/mL) and women (17.5 ng/mL) were low
and in the range indicated by clinical guidelines as
mild to moderate vitamin D deficiency. Moreover,
vitamin D levels increased with patient age. It is the
reason vitamin D was positively associated with the
incidence of cataract in crude analysis before adjust-
ing for age. These findings are supported by previous
studies35–38 in which incidence of vitamin D defi-
ciency was approximately 70% or higher, and elderly
patients in countries such as Korea and Thailand had
higher vitamin D levels than young people. A
possible explanation is that older people have more
time to spend doing outdoor activities. Because of
the rapid economic development in Korea, many
young people have indoor jobs, whereas older people
have outdoor jobs.36 The results in the present study
warrant further investigation because vitamin D
levels differ according to the latitude and ethnicity
of the study population.39 Vitamin D production in
the skin varies with ultraviolet-B (UVB) exposure
from the sun, which is affected by a range of factors
including sunbathing, time spent outside, clothing
traditions, the use of sun protection agents, and
skin color.39 In addition, exposure to UVB declines
from the equator to the polar regions, creating a
gradient of vitamin D production in the skin. Thus,
the effect of vitamin D on cataract development
might differ in different parts of the world because
of the influences of latitude, skin color, and culture.

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1712 SERUM 25-HYDROXYVITAMIN D AND CATARACT

Table 6. Prevalence of any cataract by type of cataract stratified according to quintile categories of serum 25-hydroxyvitamin D in represen-
tative Korean adults aged 40 years or older.

Quintile
P Value
Characteristic 1 2 3 4 5 for Trend

Both sexes
Hydroxyvitamin D !13.1 R13.1 and !16.4 R16.4 and !19.7 R19.7 and !24.3 R24.3
level, ng/mL
Group size (n) 3756 3764 3765 3767 3752
Cataract prevalence*
Cortical 7.1 (0.6, 6.0-8.4) 6.6 (0.6, 5.6-7.9) 7.6 (0.6, 5.6-7.9) 8.4 (0.7, 7.1-9.8) 8.4 (0.7, 7.1-9.9) .081
Nuclear 19.7 (1.0, 17.9-21.7) 19.8 (1.0, 18.0-21.8) 18.5 (1.0, 16.7-20.5) 21.2 (1.1, 19.2-23.5) 22.5 (1.2, 20.2-25.0) .019†
Anterior subcapsular 0.7 (0.2, 0.4-1.1) 0.6 (0.1, 0.4-0.9) 0.8 (0.2, 0.5-1.2) 0.7 (0.2, 0.5-1.2) 0.8 (0.2, 0.5-1.2) .829
Posterior subcapsular 0.3 (0.1, 0.2-0.6) 0.2 (0.1, 0.1-0.4) 0.3 (0.1, 0.2-0.6) 0.2 (0.1, 0.1-0.5) 0.4 (0.1, 0.2-0.7) .808
Mixed 5.6 (0.5, 4.8-6.6) 4.7 (0.4, 4.0-5.6) 6.2 (0.5, 5.2-7.3) 6.2 (0.5, 5.2-7.3) 6.9 (0.6, 5.9-8.2) .009†
Men
Hydroxyvitamin D !14.5 R14.5 and !17.9 R17.9 and !21.2 R21.2 and !25.7 R25.7
level, ng/mL
Group size (n) 1641 1634 1638 1636 1637
Cataract prevalence*
Cortical 7.8 (0.8, 6.3-96) 8.0 (0.9, 6.5-10.0) 8.7 (1.0, 7.0-10.9) 7.5 (0.9, 6.0-9.4) 8.9 (1.0., 7.2-11.0) .718
Nuclear 18.9 (1.3, 16.5-21.6) 19.8 (1.3, 17.4-22.5) 20.6 (1.4, 18.0-23.4) 20.8 (1.4, 18.2-23.6) 21.1 (1.6, 18.1-24.3) .747
Anterior subcapsular 0.6 (0.2, 0.3-1.2) 1.1 (0.4, 0.6-2.1) 0.8 (0.2, 0.4-1.5) 0.7 (0.2, 0.4-1.1) 0.8 (0.2, 0.4-1.4) .576
Posterior subcapsular 0.2 (0.1, 0.1-0.6) 0.2 (0.1, 0.1-0.6) 0.4 (0.2, 0.2-0.9) 0.1 (0.1, 0.1-0.3) 0.3 (0.2, 0.1-0.8) .379
Mixed 5.2 (0.7, 4.0-6.6) 4.5 (0.5, 3.5-5.5) 5.1 (0.6, 4.0-6.5) 5.8 (0.6, 4.6-7.2) 6.1 (0.7, 4.8-7.6) .350
Women
Hydroxyvitamin D !12.3 R12.3 and !15.3 R15.3 and !18.4 R18.4 and !22.8 R22.8
level, ng/mL
Group size (n) 2132 2116 2124 2124 2122
Cataract prevalence*
Cortical 6.4 (0.6, 5.3-7.7) 6.6 (0.7, 5.4-8.1) 6.9 (0.7, 5.6-8.5) 7.7 (0.7, 6.4-9.3) 7.9 (0.8, 6.5-9.6) .361
Nuclear 20.0 (1.1, 17.9-22.3) 19.5 (1.2, 17.3-21.9) 18.9 (1.1, 16.8-21.1) 21.1 (1.3, 18.7-23.7) 23.0 (1.3, 20.4-25.7) .069
Anterior subcapsular 0.7 (0.2, 0.4-1.3) 0.4 (0.1, 0.2-0.8) 0.6 (0.2, 0.3-1.0) 0.8 (0.2, 0.5-1.4) 0.7 (0.2, 0.4-1.3) .538
Posterior subcapsular 0.4 (0.2, 0.2-0.8) 0.2 (0.1, 0.1-0.5) 0.1 (0.0, 0.0-0.3) 0.3 (0.1, 0.2-0.7) 0.5 (0.2, 0.2-1.3) .139
Mixed 5.7 (0.5, 4.8-6.9) 4.7 (0.5, 3.9-6.8) 6.6 (0.8, 5.3-8.3) 7.1 (0.7, 5.8-8.6) 8.6 (0.8, 7.2-10.3) !.001†

Number of cataracts by type: cortical Z 1744; nuclear Z 4460; anterior subcapsular Z 172; posterior subcapsular Z 74; mixed Z 1543
*Expressed as weighted estimate (%) (standard error [%], 95% confidence interval)
†
Statistically significant (P ! .05)

The action of vitamin D is mediated by its binding
to a specific vitamin D receptor, a member of the ste-
roid hormone receptor superfamily, and several
frequent polymorphisms are found in the vitamin D
receptor gene.40 This suggests the possibility of a pre-
disposing genetic susceptibility to the effect of vitamin
D on cataract formation. Unfortunately, a genetic
study was not performed in the present study.
The study design and the relatively large number of
participants were among the major strengths of this
study. Another strength was the rigorous quality con-
trol surrounding the ophthalmic examinations and the
measurements of serum 25-hydroxyvitamin D levels.
This study also had several limitations. First, it was
not possible to adjust for seasonal variations in serum
25-hydroxyvitamin D levels because the KNHANES
does not contain information about the dates on which
the blood samples were taken. One recent study41
showed that an Asian population did not display sig-
nificant seasonal variations in its vitamin D status;
however, another study42 reported significant sea-
sonal variation with lower vitamin D levels in winter.
Another limitation was that ocular vitamin D levels
were not examined. Serum vitamin D levels might
not reflect ocular vitamin D levels. Finally, the cross-
sectional design of the present study makes inferring
causality difficult; however, existing evidence about
the antioxidative effects of vitamin D has been used
to explain the effects of 25-hydroxyvitamin D on cata-
ract development. It is unlikely that the different levels
of 25-hydroxyvitamin D seen in the serum were
caused by age-related cataracts.
In conclusion, we believe that this is the first study to
generate population-based epidemiologic data about

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 SERUM 25-HYDROXYVITAMIN D AND CATARACT 1713

Table 7. Adjusted OR* of any cataract by type, stratified by quintile categories of serum 25-hydroxyvitamin D among representative Korean
adults aged 40 years or older.

Quintile
P Value
Characteristic 1 2 3 4 5 for Trend†

Both sexes
Hydroxyvitamin D !13.1 R13.1 and !16.4 R16.4 and !19.7 R19.7 and !24.3 R24.3
level (ng/mL)
Group size (n) 3756 3764 3765 3777 3742
Cataract odds ratioz
Cortical 1.00 (reference) 0.95; 0.76-1.17 1.04 (0.84-1.30) 1.07 (0.84-1.35) 0.96 (0.76-1.22) .858
Nuclear 1.00 (reference) 1.00 (0.83-1.21) 1.06 (0.89-1.26) 0.90 (0.77-1.06) 1.01 (0.87-1.19) .803
Anterior subcapsular 1.00 (reference) 0.85 (0.45-1.60) 1.02 (0.54-1.95) 0.95 (0.48-1.85) 0.99 (0.54-1.84) .892
Posterior subcapsular 1.00 (reference) 0.77 (0.32-1.83) 1.06 (0.38-0.90) 0.79 (0.28-0.21) 1.30 (0.54-3.11) .600
Mixed 1.00 (reference) 0.94 (0.74-1.18) 1.12 (0.87-1.43) 1.01 (0.78-1.31) 1.04 (0.80-1.35) .637
Men
Hydroxyvitamin D !14.5 R14.5 and !17.9 R17.9 and !21.2 R21.2 and !25.7 R25.7
level (ng/mL)
Group size (n) 1641 1634 1638 1636 1637
Cataract odds ratioz
Cortical 1.00 (reference) 1.04 (0.78-1.38) 1.12 (0.82-1.55) 0.91 (0.65-1.27) 1.00 (0.73-1.36) .742
Nuclear 1.00 (reference) 1.07 (0.84-1.36) 1.06 (0.83-1.35) 1.05 (0.82-1.35) 0.96 (0.73-1.26) .792
Anterior subcapsular 1.00 (reference) 1.77 (0.71-4.39) 1.15 (0.47-2.82) 0.97 (0.42-2.23) 1.11 (0.47-2.63) .605
Posterior subcapsular 1.00 (reference) 1.56 (0.28-8.50) 2.77 (0.57-13.46) 0.62 (0.12-3.05) 1.89 (0.34-10.38) .730
Mixed 1.00 (reference) 0.84 (0.57-1.23) 0.82 (0.56-1.20) 1.01 (0.69-1.47) 0.95 (0.65-1.39) .859
Women
Hydroxyvitamin D !12.3 R12.3 and !15.3 R15.3 and !18.4 R18.4 and !22.8 R22.8
level (ng/mL)
Group size (n) 2132 2116 2124 2124 2122
Cataract odds ratioz
Cortical 1.00 (reference) 0.91 (0.68-1.22) 0.91 (0.68-1.23) 0.85 (0.64-1.12) 0.92 (0.69-1.22) .481
Nuclear 1.00 (reference) 1.01 (0.83-1.21) 0.95 (0.79-1.14) 0.98 (0.80-1.20) 0.98 (0.79-1.22) .823
Anterior subcapsular 1.00 (reference) 0.61 (0.23-1.60) 0.71 (0.30-1.65) 1.13 (0.49-2.58) 0.93 (0.38-2.23) .691
Posterior subcapsular 1.00 (reference) 0.50 (0.16-0.54) 0.26 (0.07-0.86) 0.70 (0.22-2.21) 1.20 (0.43-3.34) .614
Mixed 1.00 (reference) 0.84 (0.63-1.13) 1.18 (0.85-1.64) 1.14 (0.83-1.55) 1.08 (0.80-1.46) .212

Number of cataracts by type: cortical Z 1744; nuclear Z 4460; anterior subcapsular Z 172; posterior subcapsular Z 74; mixed Z 1543
*Odds ratios adjusted for sex, age, smoking, diabetes, hypertension, and sun exposure
†
P ! .05 statistically significant
z
Expressed as odds ratio (95% confidence interval)

the associations between serum 25-hydroxyvitamin D

levels and age-related cataracts in a representative
Korean population. We found that men, but not
women, with higher serum 25-hydroxyvitamin D
levels had a lower risk for cataract development than
men with lower serum 25-hydroxyvitamin D levels,
after adjusting for potentially confounding factors.
However, the study’s findings are inconclusive about
the existence of a relationship between the 2 variables
because we could not confirm a linear trend in the OR
for age-related cataract development in association
with the higher 25-hydroxyvitamin D quintiles.
Considering the antioxidative effect of vitamin D, the
connection between vitamin D and age-related cata-
racts warrants further study.
WHAT WAS KNOWN
 Vitamin D has a beneficial effect on ocular diseases such
as diabetic retinopathy and age-related macular disease
by its antioxidative function. Vitamin D has not been stud-
ied in cataract patients.
WHAT THIS PAPER ADDS
 The risk for cataract decreased in patients with high
serum vitamin D levels.
 Increasing serum vitamin D levels, such as with dietary
vitamin D supplementation, might be beneficial for pre-
venting cataract development.

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1714 SERUM 25-HYDROXYVITAMIN D AND CATARACT
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First author:
Donghyun Jee, MD, PhD
Department of Ophthalmology
and Visual Science, College
of Medicine, Catholic University
of Korea, Suwon, South Korea