Serum Homocysteine, Vitamin B12, and Folate, and the Prevalence and Incidence of Posterior Subcapsular Cataract

Tan, Ava Grace; Mitchell, Paul; Rochtchina, Elena; Flood, Victoria M; Cumming, Robert G.; Wang, Jie Jin

doi:10.1167/iovs.14-15531

Cited by 13 publications

(14 citation statements)

References 30 publications

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“…39–41 Previous observational data for these nutrients, derived from several small cross-sectional and case-control studies, generally indicate an inverse association between dietary or blood levels and risk of cataract. 16–24 Thus, our finding of no significant effect overall, but significant increases in the PSC subtype, and extraction of all 3 subtypes, in the combined treatment group contrasts with previous observational data. Given the high dose of folic acid, vitamin B 6 , and vitamin B 12 used in the WAFACS, one interpretation of these findings is that the optimal dose for cataract prevention may be lower than the high doses tested in this trial.…”

Section: Discussioncontrasting

confidence: 99%

“…Folic acid and vitamins B 6 and B 12 have also been linked with lower rates of cataract in observational studies, 16–24 but have not yet been tested in randomized trials of cataract prevention. In addition to their antioxidant capabilities, 25–28 these nutrients exhibit other physiological actions including a well-established homocysteine-lowering effect, 29 and enhanced bioavailability of nitric oxide (NO), 30,31 that might also affect cataract development…”

Section: Introductionmentioning

confidence: 99%

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Folic Acid, Vitamin B₆, and Vitamin B₁₂in Combination and Age-Related Cataract in a Randomized Trial of Women

Christen

Glynn

Chew

et al. 2016

Ophthalmic Epidemiology

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Purpose To examine incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12. Methods In a randomized, double-masked, placebo-controlled trial, 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5mg/day), vitamin B6 (50mg/day), and vitamin B12 (1mg/day), or placebo. A total of 3,925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial. Results During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90–1.33; P=0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01–1.63; P=0.04). Conclusions In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Folic Acid, Vitamin B₆, and Vitamin B₁₂in Combination and Age-Related Cataract in a Randomized Trial of Women

Christen

Glynn

Chew

et al. 2016

Ophthalmic Epidemiology

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“…We calculated the required sample size for plasma tHcy and MTHFR measurement based on results from the Tan et al's [ 11 ] study which reported a mean difference of tHcy levels of 1.9μmol/L, a standard deviation of 4.8μmol/L in their population. Under the Type I error rate of 0.05 and a statistical power of 90%, 141 ARC patients and 141 healthy controls were randomly selected from the whole samples.…”

Section: Resultsmentioning

confidence: 99%

“…Molecular studies have demonstrated that raised Hcy induced apoptosis by increasing ROS generation through activation of p38 MAPK [ 8 ], and down-regulating antioxidant enzymes such as heme oxygenase-1 and glutathione peroxidase [ 9 , 10 ]. Additionally, elevated plasma total Hcy (tHcy) levels were found to be associated with increased risk of ARC in two clinical studies [ 11 , 12 ]. Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism that catalyzes the conversion of 5, 10-methyltetrahydrofolate to 5-methyltetrahydrofolate, a methyl donor during the remethylation of Hcy [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

et al. 2015

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Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by affecting MTHFR enzyme activity and tHcy levels.

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“…Two other studies of dietary and serum levels of folate showed conflicting results. 49,50 A randomized placebo-controlled trial of Centrum found that those taking the multivitamin had a two-fold increased risk in PSC events. 51 No increased mortality risk was associated with any B vitamin or lutein/zeaxanthin intake levels.…”

Section: Discussionmentioning

confidence: 99%

The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study

et al. 2015

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Purpose To evaluate whether dietary intake of lutein/zeaxanthin and B vitamins is associated with cataract prevalence and incidence. Design Clinic-based, baseline cross-sectional and prospective cohort study designs. Participants 3115 (6129 eyes) persons enrolled in the Age-Related Eye Disease Study, aged 55 to 80 years, followed for mean of 9.6 years. Methods Participants completed baseline food frequency questionnaires. Baseline and annual lens photographs were graded centrally. Multivariable models controlling for previously identified risk factors for cataracts were used to measure the association of cataracts with reported dietary intake, using the lowest quintile as reference. Main Outcome Measures Cataract surgery, cataract status (type and severity) at baseline, development of cataracts. Results At baseline, increased dietary riboflavin and B12 were inversely associated with nuclear and cortical lens opacities. In comparisons of persons with and without cataract, persons with the highest riboflavin intake vs. those with the lowest intake had the following associations: odds ratio (OR): 0.78, 95% confidence interval (CI): 0.63–0.97 for mild nuclear, OR: 0.62, 95% CI: 0.43–0.90 for moderate nuclear, and OR: 0.80, 95% CI: 0.65–0.99 for mild cortical cataracts. For B12, the results were: OR: 0.78, 95% CI: 0.63–0.96 for mild nuclear, OR: 0.62, 95% CI: 0.43–0.88 for moderate nuclear, and OR: 0.77, 95% CI: 0.63–0.95 for mild cortical cataracts. Highest dietary B6 intake was associated with a decreased risk of developing moderate nuclear lens opacity compared with the lowest quintile, OR: 0.67, 95% CI: 0.45–0.99. Highest dietary intake levels of niacin and B12 were associated with a decreased risk of development of mild nuclear or mild cortical cataracts in participants not taking Centrum® multivitamin. For participants taking Centrum® during the study, highest intake of dietary folate was associated with an increased risk of development of mild posterior subcapsular lens opacity. No statistically significant associations were found between lutein/zeaxanthin intake and presence at baseline or development of nuclear or cortical lens opacity outcomes. Conclusions Findings from our study are consistent with earlier studies suggesting that dietary intake of B vitamins may affect the occurrence of age-related lens opacities. Further investigations are warranted.

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Serum Homocysteine, Vitamin B12, and Folate, and the Prevalence and Incidence of Posterior Subcapsular Cataract

Abstract: Higher serum homocysteine level was associated with PSC prevalence in this population. Vitamin B12 status seemed to modify this association. Lack of longitudinal association could have resulted from insufficient study power.

Cited by 13 publications

References 30 publications

Folic Acid, Vitamin B₆, and Vitamin B₁₂in Combination and Age-Related Cataract in a Randomized Trial of Women

Folic Acid, Vitamin B₆, and Vitamin B₁₂in Combination and Age-Related Cataract in a Randomized Trial of Women

Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study

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Serum Homocysteine, Vitamin B12, and Folate, and the Prevalence and Incidence of Posterior Subcapsular Cataract

Abstract: Higher serum homocysteine level was associated with PSC prevalence in this population. Vitamin B12 status seemed to modify this association. Lack of longitudinal association could have resulted from insufficient study power.

Cited by 13 publications

References 30 publications

Folic Acid, Vitamin B6, and Vitamin B12in Combination and Age-Related Cataract in a Randomized Trial of Women

Folic Acid, Vitamin B6, and Vitamin B12in Combination and Age-Related Cataract in a Randomized Trial of Women

Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study

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Product

Resources

About

Folic Acid, Vitamin B₆, and Vitamin B₁₂in Combination and Age-Related Cataract in a Randomized Trial of Women

Folic Acid, Vitamin B₆, and Vitamin B₁₂in Combination and Age-Related Cataract in a Randomized Trial of Women