Two trials of the same design gave opposite answers
The first, in 148 people whose antidepressant had not worked, escalated the dose and found nothing. The second gave 75 people 15mg throughout and beat placebo on both main outcomes.
What the study found
Added to an antidepressant, L-methylfolate worked in one trial of two
Two trials, same design, opposite answers. The first, in 148 outpatients whose antidepressant had not worked, escalated the dose and found nothing. The second gave 75 patients 15mg of L-methylfolate throughout, beat placebo on both main outcomes, and helped about one in six treated.
The caveat · 15 mg is a prescription medical food
Only the positive trial tends to get quoted. The dose difference is the authors' own explanation for the split, but it is a comparison across two separate studies rather than a randomised test of dose, and the trial that worked had 75 patients. The 15mg used is roughly forty times a periconceptional folate dose and is a prescription medical food in the United States, not the supplement sold to consumers on the same reasoning.
What we don't know
Only the positive trial tends to get quoted. The dose difference is the authors' own explanation for the split, but it is a comparison across two separate studies rather than a randomised test of dose, and the trial that worked had 75 patients. The 15mg used is roughly forty times a periconceptional folate dose and is a prescription medical food in the United States, not the supplement sold to consumers on the same reasoning.