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Aim: Few studies have explored vitamin B12 (B12) distribution in control rats and in rats treated with metformin, an anti-diabetic drug known to decrease the plasma level of B12 in humans. Here we report B12 levels in both control rats and in rats treated by two different methods of delivering metformin. Methods: Male Wistar rats aged 16 weeks at sacrifice was treated for 6 weeks with daily subcutaneous injections of either saline (n = 10) or metformin (n = 10). We collected plasma and organs for analyses of B12, and we explored the fraction of protein-bound B12 in selected organs. In addition we examined the effect of four weeks administration of metformin (n = 10) or saline (n = 10) by intra-peritoneal osmotic pumps on levels of B12 in plasma, liver, and kidneys of rats aged 14 weeks at sacrifice. Results: Median concentration of B12 in the 16 weeks old control rats was highest in the kidney (1350 pmol/g tissue) followed by the liver (74) and heart (72) and lowest in the brain (33), spleen (25), and lungs (10). The fraction of protein-bound B12 was around 0.30 in the kidney and 0.85 or higher in other organs. In 14 weeks old rats B12 concentration (pmol/g tissue) was around 0.7 of the concentration in 16 weeks old rats, both in liver and kidney. The relationship between kidney and liver B12 (pmol/g tissue) was similar for the two groups of rats. Neither subcutaneous nor intraperitoneal treatment with metformin resulted in alterations in B12 distribution or concentration as compared to the controls. This was the case for both plasma and organs. Conclusion/Interpretation: We report the kidneys of control rats to contain around two and a half fold more B12 per organ than the liver. Expressed as B12 per grams tissue, the kidney contained around fifteen fold more B12 than the liver. The total amount of B12 in these two organs increased from 14 to 16 weeks of age. Our data showed no alteration in the content or distribution of B12 upon treatment with metformin.

Vitamin B12 Levels in Rat Organs - No Change Following Prolonged Treatment with Metformin