From the Guidelines
Vitamin B12 should be replaced before folate in patients with suspected or confirmed deficiencies of both vitamins to prevent neurological complications. When a patient has both deficiencies, administering folate alone can improve anemia symptoms while masking the underlying B12 deficiency, allowing neurological damage to progress undetected [ 1, 1 ]. This occurs because folate supplementation can correct the hematologic manifestations of B12 deficiency (like megaloblastic anemia) without addressing the neurological effects. B12 deficiency leads to subacute combined degeneration of the spinal cord, which can become irreversible if treatment is delayed.
Replacement Regimen
The typical replacement regimen for B12 deficiency involves intramuscular hydroxocobalamin 1 mg administered on alternate days until there is no further improvement, then hydroxocobalamin 1 mg intramuscularly administered every 2 months for patients with neurological involvement [ 1, 1 ]. For people with no neurological involvement, hydroxocobalamin 1 mg intramuscularly should be administered three times a week for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2–3 months for life [ 1, 1 ].
Folate Supplementation
Only after initiating B12 replacement should folate supplementation (typically 5 mg daily) be started [ 1 ]. This sequential approach ensures comprehensive treatment of both deficiencies while protecting the patient's neurological health. It is essential to treat vitamin B12 deficiency immediately before initiating additional folic acid to prevent masking severe vitamin B12 depletion [ 1 ].
Key Considerations
- Seek urgent specialist advice from a neurologist and haematologist if there is possible neurological involvement, such as unexplained sensory and/or motor and gait symptoms [ 1, 1 ].
- Folic acid deficiency may indicate non-adherence with the daily multivitamin and mineral supplement or malabsorption, and some medications may affect folic acid levels [ 1 ].
From the FDA Drug Label
Doses of folic acid greater than 0. 1 mg/day may result in hematologic remission in patients with Vitamin B12 deficiency. Neurologic manifestations will not be prevented with folic acid, and if not treated with Vitamin B12, irreversible damage will result. Patients with pernicious anemia should be instructed that they will require monthly injections of Vitamin B12 for the remainder of their lives. Failure to do so will result in return of the anemia and in development of incapacitating and irreversible damage to the nerves of the spinal cord Also, patients should be warned about the danger of taking folic acid in place of Vitamin B12, because the former may prevent anemia but allow progression of subacute combined degeneration. Except during pregnancy and lactation, folic acid should not be given in therapeutic doses greater than 0.4 mg daily until pernicious anemia has been ruled out. Patients with pernicious anemia receiving more than 0.4 mg of folic acid daily who are inadequately treated with vitamin B12 may show reversion of the hematologic parameters to normal, but neurologic manifestations due to vitamin B12 deficiency will progress.
Replacing vitamin B12 before folate is necessary in patients with suspected or confirmed deficiencies of both vitamins because folate can mask the hematologic manifestations of vitamin B12 deficiency while allowing neurologic damage to progress. If folate is given first, it may correct the anemia, but irreversible damage to the spinal cord can still occur if vitamin B12 deficiency is not treated. Therefore, it is essential to replace vitamin B12 first to prevent long-term neurologic damage 2, 3, 4.
- Key points:
- Folate can mask hematologic manifestations of vitamin B12 deficiency
- Neurologic damage can progress if vitamin B12 deficiency is not treated
- Replace vitamin B12 first to prevent long-term neurologic damage
From the Research
Importance of Replacing Vitamin B12 Before Folate
- Replacing vitamin B12 before folate is crucial in patients with suspected or confirmed deficiencies of both vitamins because folic acid can mask the symptoms of vitamin B12 deficiency, leading to delayed diagnosis and potential neurological damage 5, 6.
- Vitamin B12 deficiency can cause irreversible damage to the central and peripheral nervous systems, and folic acid supplementation can correct the anaemia associated with vitamin B12 deficiency but will not prevent the progression of neurological damage 5.
- High intakes of folic acid can exacerbate vitamin B12 deficiency, worsening anaemia and cognitive symptoms, emphasizing the need to address vitamin B12 deficiency first 6.
Consequences of Not Replacing Vitamin B12 Before Folate
- Failure to replace vitamin B12 before folate can lead to a delay in diagnosing vitamin B12 deficiency, resulting in prolonged exposure to the harmful effects of the deficiency, including neurological damage and cognitive decline 5, 6.
- The combination of folic acid and vitamin B12 supplementation can reduce serum homocysteine concentrations, but the benefits of folic acid supplementation may be limited if vitamin B12 deficiency is not addressed first 5, 7.
Interconnected Metabolism of Folate and Vitamin B12
- The metabolism of folate and vitamin B12 is closely interlinked, and vitamin B12 plays a crucial role in the utilization of folate in the body 8, 9.
- Vitamin B12 deficiency can impair the body's ability to utilize folate effectively, highlighting the importance of addressing vitamin B12 deficiency before supplementing with folate 8, 9.