Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk
Decreased vitamin B12 levels, or vitamin B12 deficiency, is now considered to be a common side effect in patients on metformin treatment, especially in those receiving a higher dose or longer treatment duration and in those with existing risk factors. We are therefore advising checking vitamin B12 serum levels in patients being treated with metformin who have symptoms suggestive of vitamin B12 deficiency. We also advise that periodic monitoring for patients with risk factors for vitamin B12 deficiency should be considered.
From:
Medicines and Healthcare products Regulatory Agency
The effect of metformin in significantly lowering TSH levels in hypothyroid patients on levothyroxine therapy without causing any changes in the circulating hormone levels has raised questions regarding the complexity of monitoring such patients.
This study emphasizes the importance of taking into consideration that metformin initiation falsely lowers circulating TSH levels within a few months and may compel the treating physician/endocrinologist to bring about unnecessary dosage adjustments in levothyroxine.
If the clinician is aware of this effect of metformin, then major dosage readjustments may be successfully prevented. Therefore, the results of this study indicate that not only should there be a re-evaluation of the thyroid-pituitary axis within 6-12 months of initiating metformin in diabetic patients having concomitant hypothyroidism, but the dose of levothyroxine may also not be changed unless TSH falls below the lower reference range with a raised fT4 suggesting iatrogenic hyperthyroidism.
I think this is B12-specific - but doesn't say anything (neither good nor bad) about any impact on other nutrients.
The wording they use is:
Decreased vitamin B12 levels are a known consequence of long-term treatment with metformin. The mechanism is currently thought to be multifactorial, comprising altered intestinal motility, bacterial overgrowth, and reduced uptake of vitamin B12 within the small intestine (or a combination of these factors).
A few studies with limited patient numbers from the 70s and 80s suggested that treating patients with metformin reduces plasma Mg2+ levels (4, 50). How metformin affects Mg2+ handling remains to be elucidated. In contrast, patients taking insulin had a trend (P = 0.053) toward higher plasma Mg2+ levels than those who did not require insulin treatment. This is in concordance with experimental studies showing that insulin stimulates the renal Mg2+ channel TRPM6, resulting in increased renal Mg2+ reabsorption (23). Therefore, despite their worse glycemic control, patients on insulin treatment have slightly better plasma Mg2+ values than metformin-treated patients.
Though the metformin and b12 seems to be well known, I was interested to see the link to metformin and TSH. Being both diabetic and hypothyroid I have been on maximum doses of metformin for two decades with TSH well out of range: really ill while waiting for hypo diagnosis as TSH reached 10, and later problems with suppressed TSH and low free T4 and T3. Yet GPS and endos never suggested a link; shame as the Forum members regularly remark endos are diabetic orientated, not thyroid-interested.
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