David
Co-Founder
Our science advisor, Judith, has been doing a lot of research on the NOD2 gene which is (along with many other genes) implicated in the manifestation of Crohn's Disease. She recently came across this journal article which discusses NOD2 and Vitamin D.
In short, tons of people with Crohn's Disease are deficient in vitamin D. There shouldn't be a person on this forum with Crohn's Disease who doesn't know what their vitamin D level is. If you don't know what it is, get it tested. If it's below 50, get it above 50. Yes, some doctors think levels below 50 are ok, but get it above 50! Sorry for being a nag but it's because I care (my mom would so be laughing right now)
For those of you who don't want to read the journal article or for those of you like me who have to read it 43 times because their brain exploded the first 42 times, let me see if I can explain. Actually, I'll use Judith's words first and add my translation below it:
My translation:
NOD2 is a gene that is busted in many people with Crohn's Disease. Think of it as part of the neighborhood watch patrol keeping an eye out for bacteria that shouldn't be in your system. If it sees some suspicious bacteria it calls 911 to tell the 911 dispatcher named NFkB to get into high gear. Only thing is, if you have Crohn's Disease chances are there aren't enough 911 dispatchers so NOD2 gets a busy signal and the NFkB (911 dispatcher) doesn't tell the police and fire department that you need help. The bad guys (bacteria) break into places they shouldn't be and start fires. There's nobody to stop them so it gets worse and worse so your neighborhood has to call in private security (your gastroenterologist) and nuke the whole place from orbit (medicate you).
Well, if you're low in vitamin D, then NOD2 never even makes that 911 phone call. If you have plenty of vitamin D, then NOD2 can keep calling back and hopefully get through to a dispatcher.
In short, tons of people with Crohn's Disease are deficient in vitamin D. There shouldn't be a person on this forum with Crohn's Disease who doesn't know what their vitamin D level is. If you don't know what it is, get it tested. If it's below 50, get it above 50. Yes, some doctors think levels below 50 are ok, but get it above 50! Sorry for being a nag but it's because I care (my mom would so be laughing right now)
For those of you who don't want to read the journal article or for those of you like me who have to read it 43 times because their brain exploded the first 42 times, let me see if I can explain. Actually, I'll use Judith's words first and add my translation below it:
Judith said:NOD2 (the gene found mutated in a huge percentage of Crohn's patients) responds when it "sees" a specific component in bacterial cell walls, MDP. Eventually NOD2 sends its signals down a chain of different proteins until finally upregulating NFkB.
In Crohn's patients, upregulation of NFkB is deficient. This is important because NFkB acts to induce gene expression of many other factors. induces inflammatory response, factors that help the cell to survive during stress (like bacterial infection), factors regulating both innate and adaptive immune response, in particular T-cell activation, and multiple factors inducing killing of the bacterial infection. If Crohn's patient has a mutation in the NOD2 gene that regulates the NFkB transcription factor, they are not able to mount an effective immune response toward these infecting bacteria.
But- Crohn's patients typically show an exacerbated and inappropriately high inflammatory response. There are a couple of reasons for this. One important one is that the NFkB induces expression of its own inhibitory molecule, so it cannot inhibit itself.
Bacteria also activate inflammatory molecules through other pathways besides NOD2/IFkB so this is why the inflammation gets out of control PLUS the bacteria werent effectively killed so they overgrow and keep activating more inflammatory pathways.
To FINALLY answer your question..... Vitamin D3 can enhance NOD2 signaling (which is defective in Crohn's). In CD patients that have only one defective NOD2 gene, vitamin D3 would be particularly valuable because it can enhance the signaling through the NOD2 gene product that is functional. In CD pateints that have both defective NOD2 genes this would be more difficult but if there were a baseline very low signaling through their NOD2, it may help to enhance it.
My translation:
NOD2 is a gene that is busted in many people with Crohn's Disease. Think of it as part of the neighborhood watch patrol keeping an eye out for bacteria that shouldn't be in your system. If it sees some suspicious bacteria it calls 911 to tell the 911 dispatcher named NFkB to get into high gear. Only thing is, if you have Crohn's Disease chances are there aren't enough 911 dispatchers so NOD2 gets a busy signal and the NFkB (911 dispatcher) doesn't tell the police and fire department that you need help. The bad guys (bacteria) break into places they shouldn't be and start fires. There's nobody to stop them so it gets worse and worse so your neighborhood has to call in private security (your gastroenterologist) and nuke the whole place from orbit (medicate you).
Well, if you're low in vitamin D, then NOD2 never even makes that 911 phone call. If you have plenty of vitamin D, then NOD2 can keep calling back and hopefully get through to a dispatcher.