Old Mike said...
Hey Mark: I have mentioned it in a few posts that I have a nagging feeling that all the food fortification might be killing us. There are arguments both ways. Seems that the only way to get away from it is to eat whole grains foods and then you still have to watch. Other commercial foods mostly fortified especially anything with white flour. The nutrient balance in natural foods probably much better than what man can put together. My other thought is what the hell goes on with our gut bacteria with all the extra fortification,who knows.
I can't find your original thread, but had that copied in my draft email. I think I was maybe going to email you something actually... in fact I was... a study I think but have since forgotten which one.
Anyway I also wanted to take the time to type out something I’ve been thinking about
lately. And this eventually goes to the B2 issue perhaps.
My personal take based on a lot of what I have learned lately is that these Folate issues just provide further evidence and support that at the heart of IBD there is a breakdown in our mucus barrier as you suggested many a months ago. But that’s just my personal opinion for now. Opinions however always change with new information/further learning.
The whole Folate thing is odd – and personally I find the whole thing can get confusing as heck - fast. Most often (or at least to me) it seems there’s a lot of conflicting information just as you point out. So arguments both ways.
First folate has been shown to be both inflammatory and anti-inflammatory depending the concentration. Which is interesting in general.
Currently we also know that some (or perhaps most) of our immune cells possess Folate Receptors – so “activated” macropages and then there’s a new type of T-cell (MAIT or Mucosal Associated Invarient T-Cell) that you posted a link to that makes up quite the population – 10% of the T-cell population I believe it stated. So both of these respond to “invaders”. Anyway, what I find intriguing is that first in the case of the activated macrophages, there is a study on them where in the discussion at the end it asked the question “Why exactly do macrophages possess folate receptors?” and they gave an intriguing suggestion.
In inflammatory conditions like IBD or those with say Arthritis, activated macrophages that are producing TNFa also express folate receptors. When the folate receptors become activated it serves the purpose of shuttling or increasing the rate of external folate “eating” by endocytosis - so basically once macrophages are “activated” in response to a problem (bacterial, fungal or viral infection) this folate receptor is expressed and makes them gobble up external or excess extracellular Folate. The suggestion they offered is that perhaps the purpose of this is to deprive the invaders of a required nutrient source. It was also pointed out by them that macrophages need iron to produce hydroxyl radicals used to fight infections and at the same time during an infection they function as a storage site for iron – So they (activated macrophages) become ummm iron hogs as well in which they then use to produce hydroxyl radicals…
So to me, in IBD and IBS there’s a lot of people with Iron, Folate issues and oxidative stress issues… Lots and lots of bug zapping going on I guess you could say.
Vitamin B2 (Roboflavin) is utilized a little differently by bacteria for the most part. There are a few bacteria like some lacto bacteria (these little dudes are called Auxotrophs) that cannot synthesize it – so they rely on an external source, but for the most part the vast majority of bacteria and all fungus can synthesize it (so they make it when required). This understanding is why we have Sulfonamide antibiotics (to interfere with this pathway). A few of these bacteria and fungi can also actually secrete Riboflavin externally and this is why some Candida strains etc are used for the production on B2.
Now here is where things get interesting: In bacteria – Vitamins act directly as these little mRNA “switches” known as Riboswitches. So you can imagine then as like ummm little “on/off light switches”. So in bacteria Vitamins like Thiamine (b1), Riboflavin (b2) and Cobalamin (b12) turn on and off these switches directly. – so rather than explain that cause it gets a little long (google it perhaps if interested). When the pool of available Riboflavin is sufficient inside the cell, the switch is “off” but when it’s low the switch goes “on”. Now that’s not 100% correct, but easier to understand that way. In reality, Riboflavin directly binds the mRNA at a specific transcript
ional site and the mRNA literally wraps itself around the metabolite (i.e Riboflavin or whatever vitamin) and this process in turn blocks the transcript
ion of enzymes that participate in this particular biosynthetic pathway when the pool is high – and when the pool is low the Riboflavin then releases and now the mRNA is free to transcribe for the enzymes needed. So “off and wrapped around” means enzyme production is blocked and “on and not attached” means enzyme transcript
ion takes place.
Now a little more interesting.
I believe gram-negative bacteria and pathogenic fungi are incapable of Riboflavin transport umm directly into them – I don’t know the term for this but direct external uptake or external transport perhaps. Gram-positive bacteria on the other hand easily transport external Riboflavin. And what I find an interesting connection in that in cases where iron availability is depleted, the organisms that actually secrete Riboflavin externally increase the overall secretion rate in response the depletion of Iron in their external environment. This is thought to be a defense mechanism for oxidative stress.
So you can start to see some pretty big connections here between B Vitamins and IBD and so on. And to me, it’s a far simpler explanation rather than have anything to do the whole MTHFR jazz.
I was going to type more out but I have to run off for a while and get a few things done, but I thought I’d share this with you as I think some of it might interest you. All in all, many people seem just fine eating fortified foods all their lives with no issue- but, much like some of the biopsy papers show, if there’s a problem with the mucus barrier and there really is a biofilm built up there’s likely going to be issues with perhaps in eating fortified foods along with perhaps overproduction of B2 by certain bacteria and fungi in response to depleted iron etc.
Sources: Brock Biology of Microorganisms 13'th Edition, Cell and Molecular Biology (Concepts and Experiments), The Physiology and Biochemistry of Prokaryotes 4'th Edition and a few papers you posted which I don't have in front of me at the moment but will dig them up.
Post Edited (Canada Mark) : 4/17/2014 1:19:53 PM (GMT-6)