What are the implications of a patient with low Vitamin B12 (B12) levels, hyperhomocysteinemia (254), normal methylmalonic acid (MMA) and normal folate levels?

From the Guidelines

A vitamin B12 level of 254 pg/mL is considered borderline low, and given the normal methylmalonic acid (MMA) and folate levels, supplementation with B vitamins is reasonable to reduce stroke risk, as evidenced by the recent study published in Stroke in 2022 1.

Key Considerations

• The study found that B vitamins, including B12, reduced ischemic stroke by 43% in patients with diabetic nephropathy, highlighting the importance of B12 supplementation in preventing stroke.
• The normal MMA level suggests that the body is still effectively using the available B12, but supplementation can help maintain optimal levels and reduce the risk of stroke.
• The 2022 study published in Stroke 1 recommends supplementation with B vitamins, including methylcobalamin or hydroxycobalamin, to reduce stroke risk, with a class 2a (moderate) recommendation.

Recommendations

• I recommend starting with an oral vitamin B12 supplement of 1000 mcg daily for 1-3 months, then reassessing levels, as this can help maintain optimal B12 levels and reduce the risk of stroke.
• If symptoms like fatigue, numbness, tingling, or cognitive changes are present, discuss this with your healthcare provider, as they may recommend more aggressive supplementation.
• For maintenance after reaching normal levels, reducing to 500 mcg daily or 1000 mcg several times weekly may be sufficient.

Important Factors to Consider

• Dietary factors, such as a vegan or vegetarian diet, can reduce B12 absorption or intake, and ongoing supplementation may be necessary.
• Certain medications, such as metformin or acid-reducing medications, can also reduce B12 absorption, and supplementation may be necessary.
• Age over 60 can also increase the risk of B12 deficiency, and supplementation may be necessary to maintain optimal levels.

From the FDA Drug Label

Doses of folic acid greater than 0. 1 mg per 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 informed 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 Laboratory Tests During the initial treatment of patients with pernicious anemia, serum potassium must be observed closely the first 48 hours and potassium replaced if necessary Hematocrit, reticulocyte count, vitamin B12, folate and iron levels should be obtained prior to treatment.

Given the patient has low B12 levels (254), normal MMA, and normal folate levels, the patient likely has a vitamin B12 deficiency.

• The patient should be treated with vitamin B12 to prevent irreversible neurologic damage.
• Folic acid may mask the hematologic manifestations of the deficiency but will not prevent neurologic damage.
• The patient should be monitored closely, with hematocrit, reticulocyte count, vitamin B12, folate, and iron levels obtained prior to treatment and regularly thereafter 2.

From the Research

Vitamin B12 Deficiency

• A vitamin B12 level of 254 is considered low, and normal methylmalonic acid (MMA) and folate levels are noted 3, 4.
• Vitamin B12 deficiency can be treated with oral or parenteral therapy, with oral administration of high-dose vitamin B12 (1 to 2 mg daily) being as effective as intramuscular administration for correcting anemia and neurologic symptoms 4.
• The choice of treatment depends on the severity of the deficiency and the presence of neurologic symptoms, with intramuscular therapy leading to more rapid improvement in severe cases 4.

Treatment Options

• Oral therapy with 300-1000 micrograms per day may be therapeutically equivalent to parenteral therapy 3.
• A combination of methylcobalamin and adenosylcobalamin or hydroxocobalamin may be used to treat vitamin B12 deficiency, as both forms have distinct metabolic fates and functions 5.
• Parenteral regimens using 1000 micrograms cyanocobalamin, with 5 or 6 biweekly injections for loading and once-a-month for maintenance, may be necessary to meet metabolic requirements in many patients 3.

Bioavailability and Supplementation

• Vitamin B12 bioavailability is dose dependent, with a mean bioavailability of 46.2% at a low dose of 2.3 µg and 7.6% at a higher dose of 18.3 µg 6.
• Parenteral replenishment of vitamin B12 stores can increase bioavailability by 1.9-fold 6.
• Supplementation with vitamin B12 may be necessary for individuals with low dietary intake or malabsorption, particularly in elderly individuals, infants, children, and women of reproductive age 7.