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The Case for Active B12

Vitamin B12 deficiency is estimated to affect 10 to 15% of people over the age of 60 1, and approximately 40% of all adults may have B12 levels at or below the "low normal" range.2 The confusion is that people with low, low-normal, or even normal levels of the inactive form of B12 circulating in their blood can be deficienct in the required active forms of B12.3

As we grow older, absorption of all forms of B12 diminishes. Weak stomach acid and other gastrointestinal conditions, medications, acid blockers, and reduced production of a protein called "intrinsic factor" all impair B12 absorption. Use of laxatives depletes storage of B12.4

When Vitamin B12 succeeds at entering the bloodstream it then must be converted to an active coenzyme before it is beneficial to our health.5 It takes at least three steps to convert the manmade B12 you encounter in most vitamin supplements (called cyanocobalamin) into methylcobalamin, the only form of B12 your body can use to neutralize homocysteine 6:

As the name implies, cyanocobalamin contains a cyanide molecule, a substance most people recognize as poisonous. Step one of the conversion sequence above is for your body to remove the cyanide, although the amount of the poison is not considered toxic.

Dose for dose, there is substantially greater retention of useable B12 when taking methylcobalamin as a supplement ingredient. The amount of B12 (simple cobalamin) excreted in the urine after a dose of methylcobalamin is about one-third that of a similar dose of cyanocobalamin.7 Also, it takes 1-2 months for cyanocobalamin to be converted to active B12, assuming an adequate supply of necessary cofactors is available.8

Research has also shown that both the oral and the sublingual forms of B12 are identically effective at doses of at least 500 mcg.9


1 Baik HW and Russell RM. Vitamin B12 deficiency in the Elderly. Annu Rev Nutr 1999; 19:357-77.

2 Tucker KL, Rich S, Rosenberg I, Jacques P, Dallal G, Wilson PW, Selhub J Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000 Feb;71(2):514-22.

3 The Coenzyme Forms of Vitamin B12: Toward an Understanding of their Therapeutic Potential Gregory Kelly, N.D.

4 Ann Pharmacother 1999 May;33:641-3.

5 Cooper BA, Rosenblatt DS. Inherited defects of vitamin B12 metabolism. Ann Rev Nutr 1987;7:291-320.

6 Pezacka E, Green R, Jacobsen DW. Glutathionylcobalamin as an intermediate in the formation of cobalamin coenzymes. Biochem Biophys Res Comm 1990;2:443-450.

7 Okuda K, Yashima K, Kitazaki T, Takara I. Intestinal absorption and concurrent chemical changes of methylcobalamin. J Lab Clin Med 1973;81:557-567.

8 Heinrich HC, Gabbe EE. Metabolism of the vitamin B12-coenzyme in rats and man. Ann NY Acad Sci 1964;112:871-903.

9 Sharabi A, Cohen E, Sulkes J, Garty M. Br J Clin Pharmacol. 2003 Dec;56(6):635-8.

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