Genes, methylation and epigenetics

We're just starting to understand epigenetics, and we're very far from being able to target genes for expression. There aren't any supplements that have been shown to turn off genes that are contributing to ulcerative colitis (or turn on ones that "should" be on). In fact, it's not even clear which genes are contributing to colitis (in any given person), or if their higher/lower expression is due to epigenetics, or due to something farther upstream.

For example, I'm reasonably sure that my colitis may be due to high numbers of eosinophils (class of white blood cells), but I have no idea if the high number of cells would be due to a mutation in the progenitor cells, or if the progenitor cells are just receiving too many signals to become eosinophils, and those signals are from cells with mutations.

Epigenetics is an incredibly complex topic that's NOT well understood at this point. It's a very cool topic (essentially, epigenetic traits are traits that are inherited but are NOT part of the GATC genetic code), but there aren't any treatments (prescription or otherwise) known to target gene expression in ulcerative colitis.

Methylation is a major part of epigenetics (methylating regions of genes reduces their expression; methylating certain histones can either activate or inactivate whole regions of chromosomes), but unless you can target exactly what DNA or histones are methylated or demethylated, you'd either be using a substance that did nothing to address epigenetics ... or you'd risk methylating or demethylating genes that needed to be methylated or demethylated. (Not to mention, you can't even control which CELLS are being targeted).

.  It really is fascinating, isn't it?  Gives me so much hope!  I know that in the time I've been treating my polymorphisims things have really started changing.  I've only been treating since mid February.  

Now, I feel like we are working on the last layer of disease, yeasts.. Mostly non candida ones.

The autism community seems to be leading in information on genetic polymorphisms, especially ones effecting the gut.   These children are being born to folks with methylation defects and due to the toxic overstressed environment we live in, they are inheriting their parents toxic burden and turned on genes.  Add a stressful birth, a csection, no breastfeeding, poor quality gmo, engineered formulas..that provides them no micro biome protection and the heaviest load of vaccinations of any society ever.. And you've got so many possible factors to challenge methylation.  

All of these kids have serious gut problems but those dxs fall behind the more pressing ones.  Many of them have heavy metal burdens, yeast problems.. And we are just now scraping the surface of things like PANDAS/PANS (systemic, chronic strep infections) or Lyme.  All of these are signs of an undermethylator.

Methylation is imperative to health.  Every.single.second you are performing thousands of methyl transactions. CH3, is a basic building block of our body.  When it gets out of whack it's like a forest fire..  You have immune system "firefighting"...running in, dumping water and taking out any fire starters, or burning embers.. But if your methylation is impaired, there isn't enough of them, and there isn't enough water.. Slowly over the course of your life you exhaust them more and more, and they have to stop bringing water to some areas, regroup, and try saving the areas they can.  Or, a bunch of trees collapse, blocking them off, fully or partially from saving an area...

So, you gotta make some phone calls and bring in more water to help.  But it has to be water.  It can't be ice or hydrogen and oxygen you have to perform complex reactions to make useable  (folic acid) or it causes even more issues because you busy the few firefighters you have, trying to make these materials into the water you need.  You need water (l-methyltetrahydrofolate)..  You might also need pilots to traverse and shortcut the fire, pouring water (things like TMG, bh4).. And folks from the adjoining land (transulfuration cycle, NoS cycle, etc) to help bring you water, or let your methylators bring out waste.  


Imagine you have only 3 roads leading out of this fire area.  Your colon, your skin/lymph and your urinary system.  If you are an undermethylator all of these are one lane.  They might even be dirt roads or barely passable.  As the fire rages, slowly they get worn out, washed out (food, or blocked by falling trees or fire itself.  We can't restore the road (colon) till we put out the fire(this could be a pathogen, an immune system in chronic inflammation). We need water (methyl providers- and other things to help any other polymorphisms).  It doesn't matter how many firefighters you bring in (probiotics) if you don't have enough water.  And eventually the fire burns everything up..  There are acres and acres of scorched land..  And normally your body would, over time, repair that..  But the roads are impassable, and instead of good plants  regrowing to make a new forest, you have star thistle, noxious weeds... That's all that can live there because the soil is so depleted and toxic.  You have 3 park rangers with wheelbarrows coming in to replant, but as fast as they can do it the weeds take over.  You still have no water and you have a toxic cloud of air just hanging out, trapped in the valley this happened in.

So, you gotta repair the roads, bring in water, plant new plants so they can filter the toxic air..

And eventually, with enough time and support, you've got your forest back.  (you switch your genes back on, fully or at least partially).  

This is obviously very simplified.. 

The thing is, we don't know what roads are going to break down and how..  Polymorphisms aren't tied to one particular disease.  Your road to your kidneys could be broken.. Or a branch that brought in hormones, or the one to your skin ( rashes, eczema) or your colon.. 

We are the lucky ones that have poor roads leading out of our colons.  For whatever reason.  Maybe you didn't have an extensive micro biome because of repeat abx, or were fed nothing but foods in a box by your parents or self, or too much sugar, or not enough vitamin k2... Or you got food poisoning or some other pathogen like h. Pylori, strep in your intestines, yeast.. Lyme, etc.

Also, because we are all unique our needs are unique and we may have issues with polymorphisms like CbS, Comt, bhmt, mtrr, NoS that need to be addressed too that make it more complicated. There is unfortunately no magic equation for everyone. But there are many people starting to try putting the puzzle pieces together and seeing great results.

Some very smart folks who have devoted their life's work to this are saying methylation is key. In my own life I couldn't agree more. I have the very unique ability to watch my own blood while I make these changes and see if they do anything. I've done herbs before, many many different herbs and protocols.. I've done diets.. But my immune system has still sucked. When I first got the scope my whiteblood cells were few and nonmotile. After I started supplementing for my known polymorphisms I started seeing all kinds of WBCs. They moved! They ate things! Phagocytosis! I thought for sure I had some horrible new disease. But it was just my immune system, lol. On the outside of my body I saw huge changes too. I've never sweat much. Even in a sauna. But those first several weeks I sweat and SMELLED. Ive always had great skin, never had any issues with teenage acne... I broke out horribly when my detox pathways opened up. When I'd get out of a bath previously, I could always rub off lots of dead skin.. Now, I can't.

My colon has no problems except with excess carbs or processed sugar. I've been able to treat mycoplasma pneumonia, Lyme and strep.. All lab verified with herbs successfully. I'm not completely well, but I'm so much better it's insane. I had horrible joint pain on top of my UC, chronic fatigue and was sick every couple weeks. It's escalated these last few years after having my first child and stressing my body even more with lack of sleep and the immense energy requirements of growing human beings. Another plus is that when I started treating for pathogens I started getting more regular and shorter periods, after adding methylation support I'm like clockwork, no pms, cramps or heavy bleeding, I have the most normal menses of my life at 35. I also have no more brain fog, no anxiety (I struggled with postpartum turned constant anxiety) my mood is so much improved. Life is very sunny now :). I'm Hawaiian so I had tanned, never burning my whole life until UC started to escalate after I had my first child. I could no longer tan. My skin also didn't heal well. Now, I tan again :). I have no heat intolerance anymore.. My blood pressure has went from 135/90(where it has been for 4 years) to 105/60 in 3 months. My nails are LONG and strong :). My hair is down past my bra, which seemed to be the magic line it would not grow past my whole life and the baby hairs on top of my head where I had been thinning are a welcome hassle as I wait for them to completely grow in. I believe this is all due to the methylation support letting my body do it's job and allowing me to actually utilize my supplements. I've taken every herb I'm on except triphala and anatumul before, most in much larger doses.

I'll post the sites I have used to get the most information on methylation and other cycle effects as soon as I'm back on my main computer for those interested in researching more.

Post Edited (PathogenKiller) : 6/2/2013 12:13:51 PM (GMT-6)

Yup, the doc tested me for MTHFR specifically because of my chronic digestion problems and how poorly i react to meds including abx.

Butyrate is so multifaceted. It's an HDAI, ammonia detoxifier, enterocyte feeder, cytotoxic against cancer cells, killer of yeast probably many more things..it's almost as if you could search any issue + butyrate and find interesting things. I stumbled across a study on it and huntington's that has been a blessing to a suffering friend. I love that it does so many things.

Eosinophilia is basically a condition where you have elevated eosinophils, which are just one type of white blood cell involved in inflammation. I've had an elevated level for a long time, before I had colitis (I started off with skin inflammation). I haven't asked about the histology from my biopsy, but I'd assume there would be eosinophils or at least evidence of their involvement (they release inflammatory molecules that will then affect the cells in the colon).

"Mutation" doesn't equal cancer, although cancer always involves mutations. So a mutation in a cell that results in a large number of eosinophils doesn't mean that the mutated cell has cancer. A cell might have a mutation that makes it see self as not-self. It then freaks out when it sees what it PERCEIVES to be not-self and says, "MAYDAY MAYDAY" and organizes an immune response against what is essentially nothing.

Cancer involves several "hits" (mutations) that allow cells to grow uncontrollably and eventually break through membranes and invade surrounding tissue. A lot of genes folks hear about relating to cancer (BRCA1/2, p53, and Rb--retinoblastoma gene) are genes for proteins involved in either repairing mutations OR causing cells with severe defects to undergo cell death, to prevent them from growing out of control. As cells accumulate mutations, they can eventually survive in conditions where they normally would undergo cell death.

I don't know exactly what caused my colitis, or what triggers flares, although I have my own theories. What I'm saying with regards to methylation and epigenetics is that molecular biology hasn't figured out enough about epigenetics in GENERAL or about epigenetics in colitis SPECIFICALLY for there to be any treatment or supplement that has been shown to work through methylation/gene expression. If something helps you feel better, awesome--do it. It's not that I know those treatments DON'T work through methylation, just that there's no reason at this time to believe they do.

about the HDACs, butyrate would then activate a lot of gene expression, and I have no idea how that would specifically allow for "good" genes to be expressed, but not "bad" genes. And, uh, plenty of chemicals are cytotoxic to cancer cells (http://xkcd.com/1217/). Not only that, but unless something is toxic to cancer cells but not healthy cells, it's not all that different from traditional chemotherapy.

Finally, MTHFR appears to be related to a different kind of methylation than either type involved in epigenetics. It's neither a DNA methylation protein nor a histone methylation protein. That doesn't mean it's not involved in anything, just not really involved in epigenetics as far as I can see.

PathogenKiller, there are specific proteins that can methylate specific substrates. MTHFR doesn't methylate histones or DNA.

Back to the original topic.

This is an interesting study

www.ihop-net.org/UniPub/iHOP/pm/12920635.html?nr=5&pmid=18700049



Chen M, Peyrin-Biroulet L, Xia B, Guéant-Rodriguez RM, Bronowicki JP, Bigard MA, Guéant JL
Inserm, U724, Laboratory of Cellular and Molecular Pathology in Nutrition, Faculty of Medicine, Nancy-Université, Nancy- Vandoeuvre, France. [email protected]

BACKGROUND: The association of genetic polymorphisms related to metabolism of homocysteine with inflammatory bowel disease has been evidenced in Crohn disease and remains an open question in ulcerative colitis. We evaluated the association of the polymorphisms of MTHFR, MTR [?], MTRRand TCN2 genes with ulcerative colitis in Central China. METHODS: 168 patients were genotyped for these polymorphisms and compared to 219 matched controls. RESULTS: Methionine synthase 2756G allele frequency was higher in ulcerative colitis than in controls 0.15 (95% C.I. 0.11-0.19) vs 0.09 (95% C.I. 0.07 - 0.12), (P = 0.0137) and predicted ulcerative colitis risk in logistic regression, with an Odds ratio at 1.8 (95% C.I. 1.15-2.84). Methylenetetrahydrofolate reductase 677TT genotype was 2.7-fold more prevalent in individuals with pancolitis than in those with left colitis or proctitis, with respective percentages of 27.3 (95% C.I.16.4-42.0) and 10.5 (95% C.I. 6.3-17.1) (P = 0.0123). The carriage of 677TT or 677CT/1298AC genotypes of methylenetetrahydrofolate reductase was more frequent in cases with pancolitis than in subjects with left colitis or proctitis (P = 0.0048), with an Odds ratio adjusted by age and sex at 3.3 (95% C.I. 1.4-7.9), P = 0.0084) in logistic regression. CONCLUSION: Methionine synthase and methylenetetrahydrofolate reductase are genes of vitamin B12 [?] and folate cellular metabolism associated respectively with risk and extent of ulcerative colitis, at least in Central China. This finding may open new insights, particularly for the potential interest in treating patients carrying the 677TT MTHFRgenetic trait and a deficit in folate.

killcolitis, I have ulcerative colitis, and I respond to ulcerative colitis treatment meds.

PathogenKiller, I'm really, really not interested in discussing biology any further with you. I came into this thread to discuss epigenetics and what I know about the subject as a cell and molecular biologist, and I'd really appreciate it if you would treat me with respect as a fellow forum-goer.

@KillColitis,
Whatever you read on Autism forum, take it with a pinch of salt. Use it only as a direction and do your research. Autism field is probably most controversial field in scientific research and best money making machine lately. It has almost become impossible to discuss anything. Personally, I have stopped participating in those discussion because you can never convince non-science people that there are scientists with kids on spectrum and they are desperately trying to find solutions (many times working as educated slaves, Post doc salary in the US ranges from $36K to $55K, depends on the numbers of years under your belt).

The parents do all kinds of whacky stuff and announce to the world that their kids are recovered. The fact is Autism is life-long (at this moment in time.) May be someone's child is now working with NASA or what not but they are not as good as neurotypical population when it comes to their skills. Some parents want to die peacefully or some are still in denial mode but their kids 'recover', if you know what I mean.

A simple question for those who claim, their children are recovered, what do they think about Temple Grandin, is she covered? If they yes, then they have no clue of what planet they are on.... As simple as that..