We thank Goodarzi (1) for his interest in our work (2) and recognize that we agree with most of the criticisms leveled at our study. Indeed, most of the points raised were acknowledged in our original work. There is a need to test the issues raised more robustly—a point on which we agree.
Goodarzi highlights that B12 levels may be unrelated to the association of metformin with cognitive function. We do not consider that any possible neurodegenerative effect of metformin use need necessarily involve vitamin B12. Researchers from The Scripps Research Institute published a study showing that AMP-activated protein kinase activation by metformin was sufficient to induce dendritic spine loss in hippocampal cells (3). Therefore, there is at least some evidence for a neurodegenerative effect of metformin that does not involve vitamin B12.
The deleterious effects of metformin on vitamin B12 levels are well documented (4,5), thus there is no harm in suggesting that patients who take metformin should also be given extra monitoring or vitamin B12 supplementation. There is no evidence that such supplementation is harmful; it may in fact be neuroprotective, though this remains to be proven by prospective studies.
We commend the lay press for taking an interest in current research and promoting new findings. We believe that patients who use metformin will not simply stop taking the medication. Such assumptions underestimate the ability of the patient and their treating clinicians to make informed decisions. That some patients may stop taking their medications is a very poor reason to not publish or communicate new findings that flag safety concerns about a widely prescribed drug. We hope the interest of the lay press will encourage patients to request monitoring of their B12 levels and to seek replacements where necessary to avoid a range of potential adverse effects of B12 deficiency.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
