From the Guidelines
Yes, calcium supplementation can help reduce metformin-induced vitamin B12 deficiency. Taking 1000-1500 mg of calcium carbonate daily while on metformin therapy has been shown to prevent or mitigate the B12-lowering effect of metformin. Metformin causes B12 deficiency by interfering with calcium-dependent absorption of vitamin B12 in the ileum. The drug alters the function of the calcium-dependent membrane that's responsible for B12 absorption. By providing additional calcium, this interference can be partially overcome, allowing for better B12 absorption despite metformin use. This approach is particularly important for patients on long-term metformin therapy (over 1-2 years) or those taking higher doses (≥1500 mg daily), as these factors increase the risk of B12 deficiency. For patients already experiencing B12 deficiency, calcium supplementation should be combined with B12 supplementation to restore levels. It's advisable to take calcium supplements with meals for better absorption and to consult with a healthcare provider before starting any supplement regimen, especially for those with conditions affecting calcium metabolism 1.
Some key points to consider:
- Metformin is associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy 1.
- Long-term use of metformin may be associated with vitamin B12 deficiency; consider periodic assessment of vitamin B12 level in those taking metformin chronically, especially in those with anemia or peripheral neuropathy 1.
- The risk of vitamin B12 deficiency increases with time on metformin therapy, and patients on long-term metformin therapy should be monitored for vitamin B12 deficiency annually 1.
Overall, calcium supplementation can be a useful strategy to reduce the risk of metformin-induced vitamin B12 deficiency, and patients should consult with their healthcare provider to determine the best approach for their individual needs.
From the FDA Drug Label
In metformin hydrochloride tablets clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients Such decrease, possibly due to interference with B 12 absorption from the B 12-intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin hydrochloride tablets or vitamin B 12 supplementation Certain individuals (those with inadequate vitamin B 12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B 12 levels.
Calcium intake or absorption is mentioned as a factor that can predispose individuals to developing subnormal vitamin B12 levels. However, the label does not explicitly state that calcium can reduce metformin-induced vitamin B12 deficiency. Therefore, no conclusion can be drawn about the effect of calcium on metformin-induced vitamin B12 deficiency 2.
From the Research
Calcium and Metformin-Induced Vitamin B12 Deficiency
- Metformin is a widely used medication for the treatment of type 2 diabetes, but it has been associated with an increased risk of vitamin B12 deficiency 3, 4.
- Vitamin B12 deficiency can lead to various clinical consequences, including hematologic abnormalities, progressive axonal demyelination, and peripheral neuropathy 3.
- Studies have shown that metformin can cause a decrease in vitamin B12 levels, and this effect may be mitigated with calcium supplementation 5, 6.
Effect of Calcium on Vitamin B12 Bioavailability
- A pilot study found that calcium supplementation can reverse the metformin-based inhibition of vitamin B12 bioavailability in healthy adults 5.
- Another study found that increased intake of calcium can reverse vitamin B12 malabsorption induced by metformin 6.
- The mechanism of this effect is thought to be related to the calcium-dependent membrane action affected by metformin, which can be reversed with supplemental calcium 6.
Clinical Implications
- Patients using metformin may be at risk of vitamin B12 deficiency, and calcium supplementation may be a strategy to prevent this condition 5, 6.
- Further studies are needed to confirm the effectiveness of calcium supplementation in preventing metformin-induced vitamin B12 deficiency 5.
- Healthcare providers should be aware of the potential risk of vitamin B12 deficiency in patients using metformin and consider calcium supplementation as a potential preventive measure 3, 4.