Oral vitamin B12 supplements are not generally associated with any side effects.

Although quite rare, serious allergic reactions to injections of vitamin B12 (sometimes even life-threatening) have been reported.^{29, 30} Whether these reactions are to the vitamin itself, or to preservatives or other substances in the injectable vitamin B12 solution, remains somewhat unclear. Most, but not all, injectable vitamin B12 contains preservatives.

In a double-blind trial, people with diabetes who also had with kidney disease received a daily placebo or 2.5 mg of folic acid, 1 mg of vitamin B12, and 25 mg of vitamin B6 for three years. Compared with the placebo, vitamin supplementation accelerated the decline in kidney function and increased the incidence of cardiovascular events (such as heart attacks) and heart disease-related deaths.³¹ Based on this study, diabetics with kidney disease should not take these vitamins without a doctor's supervision.