In 1926, two Boston doctors fed their dying patients raw liver. They gave them up to half a pound a day.
The patients had pernicious anemia. Their bodies had lost the ability to absorb B12. Without B12, they couldn’t make healthy blood cells, and their nerves slowly broke down. Most of them died. George Minot and William Murphy didn’t know what was in the liver. They just knew it worked. The patients lived.
Minot had his own reason to believe in long shots. He had type 1 diabetes and was one of the first people to receive insulin in the early 1920s. A guy kept alive by a brand-new hormone went on to save other people with a plate of liver. He and Murphy shared the Nobel Prize in 1934.
Nobody knew what was in that liver until 1948, when scientists isolated B12. A few years later, a chemist named Dorothy Hodgkin mapped its structure using X-rays, one of the most complex molecules anyone had solved at the time. She won a Nobel too.
A hundred years later, you know B12 by name, it’s in every multivitamin, and plenty of people still don’t have enough. A lot of that comes down to which form you take and how your body handles it.
This one is personal for me. I don’t methylate very well. Methylation is how your body makes brain chemicals, repairs DNA, and clears toxins, and B12 is one of the vitamins that powers it. I carry variants, or less efficient versions, of a gene called MTHFR. It slows down how I activate folate, B12’s partner in methylation. They work as a team, so I’m picky about both.
Your B12 can look normal on a lab report even when your cells are low. And the form you take can change how you feel. Some people take methyl B12 and feel sharp all morning. Other people take the same pill and want to pick a fight with their coworker by lunch.
You can figure out which one you are.
Why your body needs B12
B12 has two big jobs in your body. First, it helps clear homocysteine, an amino acid linked to heart disease and memory problems when it’s too high. B12 helps turn homocysteine into methionine, and your body uses methionine to make SAMe, the compound that fuels methylation. Second, it helps your mitochondria, the energy factories inside your cells, use certain fats and amino acids for energy.
It also protects the coating around your nerves and helps you make red blood cells. When you’re low, you feel tired, foggy, down, and forgetful. Some people get numbness or tingling in their hands and feet. If you’re low long enough, the nerve damage can become permanent.
Vegans and vegetarians are at higher risk. So is anyone over 50, because up to 30% of older adults don’t make enough stomach acid to pull B12 out of food. The National Academies recommend adults over 50 get most of their B12 from supplements or fortified foods. Not everyone over 50 is deficient. Food alone is just a riskier bet.
Metformin, a common diabetes drug, lowers B12 absorption. So do acid blockers like Prilosec. In one study, people who took acid blockers for two years or more were 65% more likely to be B12 deficient. Gut surgery, celiac disease, and Crohn’s disease raise your risk too.
The four forms of B12
Walk down the supplement aisle and you’ll see four different names on B12 labels.
Cyanocobalamin is the synthetic one in most cheap multivitamins and fortified cereals. I’ve said it before and I’ll keep saying it. Most multivitamins suck. They use the wrong forms in the wrong ratios, and you end up with really expensive pee.
And yes, the “cyano” means cyanide. Before you panic, the amount is tiny and harmless for healthy people.
The bigger problem is that cyanocobalamin does nothing for you as is. Your body has to strip off the cyanide and convert what’s left into an active form before it can use any of it. Many people have genetic quirks that make it hard to process certain forms of B12. When that conversion is slow, you’re swallowing B12 your body can’t put to work.
If you’ve taken cyanocobalamin for months and felt nothing, the form is the first thing I’d change.
Kidneys are where I get cautious. In a 2010 trial, people with kidney damage from diabetes took a high-dose combination of folic acid, B6, and 1 mg of cyanocobalamin. Their kidneys declined faster, and they had more heart attacks and strokes than people who took a sugar pill. The study tested the combination, so you can’t pin it on cyanocobalamin alone. If your kidneys are in bad shape, I’d still pick a different form.
Methylcobalamin, or methyl B12, is the form your body uses in the methylation pathway that clears homocysteine. Plenty of people feel great on it. Some people report feeling anxious or wired on it, especially at high doses.
The leading theory comes down to adrenaline. Methyl B12 helps your body make more SAMe, and your body uses SAMe to make adrenaline. Your body also needs an enzyme called COMT to break adrenaline down. If you carry a slow version of the COMT gene, adrenaline hangs around longer, and extra methyl B12 can tip you into wired territory. Research hasn't nailed down the full picture yet, and I'll show you how to check your COMT status in the genetics section.
Adenosylcobalamin is the form your mitochondria use. You hear about it far less than methyl B12.
Hydroxocobalamin is another form of B12 your body uses, and it’s common in supplements and shots. Your body converts it into the active forms it needs. It also stays in your system longer, which is why doctors in Europe often inject it. And in a twist I love, hospitals use hydroxocobalamin as the antidote for cyanide poisoning. One form of B12 comes with cyanide attached. Another one cleans cyanide up.
I recommend methylcobalamin, hydroxocobalamin, or adenosylcobalamin. Which one will work best for you depends on individual genetics.
Here’s what’s coming up:
How to test your B12, and the numbers to aim for
The genes to check before picking a B12 form
What to do if you don’t have genetic data
Getting enough B12 from food
How much B12 to take
What to take with B12, and what drains it
