CUBN: The reason you have brain fog
Let’s talk about B12!!!
It is one of the most purchased vitamins. From the pills, to the shots, to the IVs. It has made a name for itself. “More energy, better immunity, good for hair and nails.” But let’s dive into why the pills are probably not going to work for a lot of you.
Let’s first run through what our body has to do to use it. (If you don’t understand this, that is totally fine, I’m just adding it for you to refer back to as we get into the genetic components.)
Humans can’t make B12 (well, technically we can, but it’s made by bacteria in our colon, and it can’t be absorbed there… so it’s basically useless? I plan on asking God abt this design flaw in heaven.) Nonetheless, that is why we have to get B12 from animal products.
Once we ingest it, here’s what happens:
In the stomach, B12 is first freed from food by stomach acid and enzymes.
It initially binds to a protein called haptocorrin (also called R-protein).
Then, in the small intestine, pancreatic enzymes degrade haptocorrin, and B12 binds to intrinsic factor (IF). This is a protein made by the GIF gene.
This B12-IF complex travels to the ileum, where it’s absorbed by cells expressing the CUBN gene, which produces cubilin, the receptor that recognizes B12–IF and lets it through the gates to our bloodstream.
Once inside the bloodstream, B12 binds to transcobalamin II, encoded by the TCN2 gene, which delivers B12 into cells.
Inside cells, B12 is converted into its active forms:
Methylcobalamin (used in methylation)
Adenosylcobalamin (used in mitochondria for energy metabolism)
In a perfect world, that’s how it works!!! But that is not always the case. Your genetics might be hindering you from proper absorption.
Let’s break down the genetic issues by running it back to Step 4! Yay, B12 made it to your gut! (For simplification purposes, we’ll assume your GIF gene was fine) But… your CUBN gene is impaired, and your body isn’t producing enough functional cubilin (the receptor that’s supposed to recognize and absorb the B12–intrinsic factor complex in the ileum). So instead of being absorbed, that B12 gets lost in your gut and gets excreted.
This is especially common in people with the GA or AA variant of the CUBN gene. (The GG genotype is considered optimal.) What does this look like clinically?
For Athletes:
Training fatigue, poor endurance, and slow recovery
For Executives:
Brain fog in meetings, higher stress when traveling, and burnout despite “normal” labs
Solution: Since oral supplements won’t work well. You’ll need either: Sublingual methylcobalamin, which bypasses cubilin and is absorbed directly into the bloodstream. Or Intramuscular B12 injections, which go straight into circulation for guaranteed delivery.
And this is only the beginning of what I can do for you and your genetics. There are other genes involved with B12, such as TCN2, FUT2, MTHFR, MTRR, etc, but I’ll save those for another day :)
—KB
