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Original Investigation
May 2014

A Prospective Study of Folate, Vitamin B6, and Vitamin B12 Intake in Relation to Exfoliation Glaucoma or Suspected Exfoliation Glaucoma

Author Affiliations
  • 1Channing Division of Network Medicine, Department of Medicine, Brigham & Women’s Hospital, and Harvard Medical School, Boston, Massachusetts
  • 2Glaucoma Service, Massachusetts Eye and Ear, Boston, Massachusetts
  • 3Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  • 4Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
JAMA Ophthalmol. 2014;132(5):549-559. doi:10.1001/jamaophthalmol.2014.100

Importance  Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma.

Objective  To examine the association between B vitamin intake and EG or suspected EG (EG/SEG) risk.

Design, Setting, and Participants  National prospective cohort study using more than 20 years of follow-up data from the Nurses’ Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980, to May 31, 2010 (Nurses’ Health Study) and January 1, 1986, to December 31, 2010 (Health Professionals Follow-up Study). We included a subset of 78 980 Nurses’ Health Study women and 41 221 Health Professionals Follow-up Study men who were 40 years or older, free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate, >85%).

Exposures  Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) as ascertained by repeated administration of validated questionnaires.

Main Outcomes and Measures  Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis.

Results  Vitamin B6 and vitamin B12 intake was not associated with EG/SEG risk in pooled analyses (P = .52 and P = .99 for linear trend, respectively). However, a suggestive trend of a reduced risk was observed with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (≥654 μg/d) was 0.75 (95% CI, 0.54-1.04; P = .02 for linear trend). These results were not materially altered after adjustment for vitamin B6 and vitamin B12 intake. An association was observed for supplemental folate intake but not for dietary folate only (P = .03 and P = .64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ≥6 times per week vs nonuse multivariable relative risk, 0.84; 95% CI, 0.64-1.11; P = .06 for linear trend).

Conclusions and Relevance  Higher total folate intake was associated with a suggestive lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG.