Metformin
Common brand names: Glucophage, Glumetza
Three nutrients listed against this medication. The most severe is marked critical.
Two of the three are marked well documented. The other one carries its own evidence level.
At a glance
- Vitamin B12 (Methylcobalamin)Critical · Well documented
- Folate (Methylfolate)Moderate · Well documented
- CoQ10Mild · Mechanism only, no human trial
Color shows how serious each listed effect is. The label beside it shows how strong the evidence is. The cards below explain each one and show its evidence.
Mechanism, Metformin reduces ileal absorption of B12 by competing with the calcium-dependent intrinsic factor-B12 receptor. In a randomized trial, about 19% of long-term users developed low or borderline-low B12 over 5 years (vs about 10% on placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received.); frank deficiency is less common.
Common signs, Peripheral neuropathy, cognitive decline, fatigue, anemia, elevated homocysteine An amino acid in the blood that rises when vitamin B12, folate or B6 are low.
Aroda VR et al. (Diabetes Prevention Program Outcomes Study, J Clin Endocrinol Metab, 2016; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed.: 26900641). Randomized trial: low or borderline-low B12 in 19.1% of long-term metformin users vs 9.5% on placebo at 5 years. ADA guidelines recommend periodic B12 monitoring.
Methylcobalamin was used at 1,000–2,000 mcg daily; sublingual forms bypass the gut-absorption issue. Serum B12 and homocysteine are commonly tested annually.
Mechanism, Metformin reduces folate absorption via similar mechanisms to B12. Compounded in individuals carrying MTHFR gene variants, which are common. Background figure, not from a trial cited on this record.
Common signs, Elevated homocysteine (cardiovascular risk), fatigue, mood disturbance
Sahin et al. (J Diabetes Complications, 2007; PMID 17331860): in type 2 diabetes, metformin significantly lowered serum folate and vitamin B12 while raising homocysteine.
L-methylfolate was used at 400–800 mcg daily. The trials used methylfolate rather than folic acid. That is a description of what was studied, not a claim that folic acid is poorly converted: CDC states that common MTHFR variants process folic acid and that 400 mcg raises folate regardless of common genotype, and there is no recommendation to change folate form on genotype alone.
Mechanism, Metformin inhibits mitochondrial Complex I, and CoQ10 carries electrons within that same chain, so a fall in CoQ10 status has been proposed as a downstream consequence. The Complex I inhibition is established; the CoQ10 step is inference from it, and no human trial has measured CoQ10 on metformin. Metformin's well-documented depletion is B12, which is a separate row.
Common signs, Fatigue, reduced exercise capacity, muscle weakness
Metformin inhibits mitochondrial Complex I (mechanistic). A 2018 reference frequently cited for this claim does not correspond to any indexed human study, so no human CoQ10-depletion trial is confirmed.
CoQ10 100 to 200 mg daily with meals is a range in common use, not from a trial cited on this row. No human trial of CoQ10 on metformin is confirmed.
Each chart turns one trial result into people, using the two percentages the number needed to treat (NNT Number needed to treat: how many people must receive a treatment for one of them to benefit, compared with the control group.) is calculated from. The counts are rounded to whole people; nothing else is estimated. These figures describe the trial population, not any one person.
Out of 1,000 people like those studied, about 289 had this outcome without the drug and 217 with it. The difference, 72 people, is the benefit. 711 did not have it in either group.
Diabetes Prevention Program (DPP), NEJM 2002 (PMID 11832527) · n=3,234 · Pre-diabetic adults
It prints or saves as a single page. Whether to add a supplement for a nutrient this medication may lower is a decision for your prescriber.
These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
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