If you treat glaucoma, you likely know that patients will frequently ask about alternative therapies. Vitamins are at the top of the list of potential saviors for glaucoma. What evidence do we have that any vitamins could help? To take a closer look at the influence of B vitamin intake on exfoliation glaucoma—the most common identifiable cause of open angle glaucoma—Louis R. Pasquale, MD, looked at data from 20 years of follow-up of almost 120 000 people followed longitudinally in the Nurses’ Health Study and the Health Professionals’ Study. The study results suggested that a higher folate intake could be associated with a reduced risk of developing exfoliation syndrome or exfoliation glaucoma. Interesting… but why would folate be related to exfoliation syndrome? Well, because folate is related to a bad player named homocysteine. Homocysteine is a nonproteogenic, sulphur-containing amino acid involved in methionine metabolism. Folate, among other B6 vitamins, is required for the conversion of homocysteine to methionine or cysteine, so without B6, homocysteine builds up in the blood serum. Homocysteine is a prothrombotic factor, vasodilation impairing agent, proinflammatory factor, and endoplasmatic reticulum-stress inducer. It is toxic to vascular endothelium and induces vascular smooth muscle hypertrophy. High levels of serum homocysteine have been associated with retinal vein and artery occlusions as well as nonarteretic ischemic optic neuropathy. Years ago, Robert Ritch and Roberto Vessani reviewed 124 patients with exfoliation syndrome, exfoliative glaucoma, or normal tension glaucoma and compared them with controls and found that median plasma homocysteine levels were significantly greater in exfoliation syndrome and exfoliation glaucoma. Note that exfoliation glaucoma and high homocysteine levels are all associated with retinal vein occlusion. In my opinion, it is time for a randomized trial of folate in patients with exfoliation glaucoma—120 000 health workers can’t be wrong.