L-5-methyltetrahydrofolate glucosamine salt (5-MTHF) is a biologically active form of folate, the naturally occurring form of vitamin B9. Its use in supporting or treating Age-related Macular Degeneration (AMD) is primarily based on scientific rationale rather than tradition. The scientific interest arises from the role of folate in homocysteine metabolism; elevated homocysteine levels are associated with increased risk of vascular diseases, including those affecting the retina. Some observational studies have suggested that individuals with higher dietary folate intake or higher blood folate levels may have a reduced risk of developing AMD. Furthermore, a few small clinical studies and case reports have indicated that supplementation with B vitamins, including folate, may slow the progression of AMD, particularly in combination with other nutrients.

However, direct and robust evidence supporting the use of 5-MTHF specifically for AMD is limited. Most large randomized controlled trials, such as AREDS and AREDS2, did not include 5-MTHF, although they did assess other nutrients (like vitamins C, E, zinc, copper, lutein, and zeaxanthin). There is some mechanistic plausibility—since folate may reduce homocysteine and improve endothelial function in the retinal vasculature—but clinical evidence is not yet strong. Therefore, while there is a scientific basis for interest and preliminary evidence, the overall strength of evidence remains low to moderate, justifying a rating of 2 out of 5.