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Methylcobalamin

What is Methylcobalamin?

Methylcobalamin (Methyl-B12) is one of two forms of biologically active vitamin B12. Methyl-B12 is the principal form of circulating vitamin B12, hence the form which is transported into peripheral tissue. Methyl-B12 is absorbed by a specific intestinal mechanism which uses intrinsic factor and by a diffusion process in which approximately 1% of the ingested dose is absorbed. Cyanocobalamin and hydroxycobalamin are forms of the vitamin that require conversion to Methyl-B12 via the intermediate glutathionyl- B12.

Vitamin B12 plays an important role in red blood cells, prevention and treatment of anemia, methylation reactions, and immune system regulation. Evidence indicates methylcobalamin has some metabolic and therapeutic applications not shared by the other forms of vitamin B12.

Methylcobalamin is the active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of homocysteine to methionine, thus lowering blood levels of homocysteine. Methylcobalamin acts as a methyl donor and participates in the synthesis of SAM-e (S-adenosylmethionine), a nutrient that has powerful mood elevating properties.

Why 2mg in Cerefolin®NAC?

2mg Oral Cobalamin Is Equal in Efficacy to 1mg IM Injections (Table 1):

After 120 days 7 of 14 patients who had received 1 mg IM injection of vitamin B12 had serum cobalamin levels >300 pg/mL while 18 of 18 patients on the 2mg oral vitamin B12 regimen achieved serum cobalamin levels over 300 pg/mL.

Table 1: Cobalamin: 2mg Oral vs. 1mg IM - Which Achieves Higher Blood Levels?
Endnote Reference Lead Investigator Objective Design Outcome
1 Kuzminski, A.M. To determine if high dose (2 mg/day) oral cobalamin therapy would yield similar hematologic and neurologic improvement as well as serum cobalamin levels to 1 mg of IM cobalamin given at 7 sessions thru day 30, at day 60 and day 90 to B12 deficient patients. 38 patients with serum cobalamin <160 pg/mL were randomized to either the oral or IM group. The oral treatment group (n=18) had higher serum cobalamin and lower methylmalonic acid levels at 4 mos. than the IM group. 2mg oral cobalamin daily was as effective as monthly injections of 1mg IM cobalamin in producing excellent hematologic and neurologic remissions and initial metabolic responses.

Why do Folate and B12 combination products used in homocysteine therapy require the higher amounts of B12 found in Cerefolin®NAC?

Over 1 million Americans over age 65 have or will develop pernicious anemia. Approximately 15 million elderly Americans have sub-clinical vitamin B12 deficiency.2 Its prevalence is also increasing as more and more patients are being treated with drugs and procedures that impair B12 absorption.

Serum cobalamin levels are less sensitive than elevations in methylmalonic acid and homocysteine in determining cobalamin deficiencies so that many B12 deficiencies may not be recognized.

In another study, Pennypacker screened 152 elderly outpatients and found that 25% had serum cobalamin levels =300 pg/mL and 8.5% had low levels <200 pg/mL. From his analysis of the declines in methylmalonic acid and homocysteine following cobalamin treatment, Pennypacker estimated that at least 14.5% of the elderly population had an unrecognized B12 deficiency.3

Studies have shown that high daily doses of 2mg of oral B12 can raise serum B12 to predictable therapeutic levels:

Studies with oral radioactive B12 have shown that small amounts (0.9%- 1.2%) of B12 are absorbed independent of the intrinsic factor mechanism via passive diffusion. This observation has been common to both normal and B12 deficient patients.

In a study by Berlin, 64 pernicious anemia patients were placed on long-term daily oral B12 therapy (at least 3 years at daily doses of 500µg-1000µg). 3 patients (4.7%) had serum B12 levels below 200 pg/mL (normal 200pg/mL - 900pg/mL). 23 patients (35.9%) had serum B12 levels below 300 pg/mL (low normal). This shows that a large percentage of patients with impaired B12 absorption have greater requirements for the cofactor.4

Kuzminski showed similar results when 18 patients in the (Table 11) were treated for 120 days with higher oral doses of 2mg of vitamin B12. At this dose the lowest serum B12 level was 315 pg/mL. Based on the assumption that ~1% of B12 is absorbed via passive diffusion, had the dose been reduced by 50% to 1mg daily, only 12 of 18 patients would have serum cobalamin levels >300 pg/mL.

References

  1. Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92:1191-1198.
  2. Carmel R. et al, Update on Cobalamin, Folate, and Homocysteine. Hematology 2003; 62-81.
  3. Pennypacker, L.C. et al. High Prevalence of Cobalamin Deficiency in Elderly Outpatients. JAGS, 1992; 40:1197-1204.
  4. Berlin, H. et al. Oral Treatment of Pernicious Anemia with High Doses of Vitamin B12 without Intrinsic Factor. Acta Med Scand, 1968; 184:247-258.