Which form of vitamin B12 is best to take?
For most people with intact intestinal absorption, the form of vitamin B12 (cyano- or hydroxocobalamin) makes little difference in the long run; dose and distribution are more important. If you have an absorption disorder, discuss with your doctor whether injections are necessary.
The bioavailability of oral vitamin B12 is strongly dose-dependent. At a low dose of around 2 micrograms (comparable to your daily requirement), the body absorbs on average 46%. At a high single dose of around 18 micrograms, that drops to just 8%. If your intestines are functioning normally, smaller, spread-out doses are therefore more efficient than one large portion per day.
Which chemical form you choose probably matters less in the long run than the dose and route of administration. Cell studies show that hydroxocobalamin is absorbed twice as fast as cyanocobalamin, and intracellular activation proceeds six times faster. However, the same kinetic model predicts that both forms yield comparable amounts of the active variants in the cell over the longer term, each roughly 40% methylcobalamin and 40% adenosylcobalamin. These are outcomes from cells in the laboratory, not from human research, so do not draw firm conclusions from them.
Older adults respond surprisingly poorly to daily oral doses below 500 micrograms, even when there is no classical absorption disorder. The sometimes-recommended amounts of 1 to 10 micrograms through fortified foods are probably too little for this group. In older adults, or in people using certain antacids, a higher oral dose is therefore worth considering.
If there is an absorption disorder -- for example because the body no longer produces intrinsic factor after stomach surgery -- the situation is different. Intramuscular injections of hydroxocobalamin are then the recommended route: a standard dose of 1000 micrograms every two months, although up to half of patients require injections more frequently. Adjusting the dosage based on symptoms is the guiding principle, not on blood values alone. Notably, high oral doses of mecobalamin of 1500 micrograms per day in patients without a stomach showed comparable results to injections. This suggests that passive absorption, that is without intrinsic factor, is initiated at very high doses. Whether this is broadly applicable has not yet been sufficiently researched.
Do you smoke? Then extra vigilance is in order. Substances in cigarette smoke convert vitamin B12 into inactive forms. In male smokers, the active fraction in the blood turned out to be significantly lower than in non-smokers, while the total B12 measurement was nearly identical. A normal result on a standard blood test therefore does not fully rule out a functional deficiency in smokers.
The cell studies on absorption speed are laboratory research (HeLa cells), not human clinical research. The conclusions about dosing and injections in malabsorption are based on reviews and one clinical trial. The strength of evidence varies by sub-question: moderate for dosing and injection in malabsorption, limited for the comparison of B12 forms at the cellular level.