riboflavin (B2)

CM - you know that I respect you a great deal but this is not "goofy crape* - I have felt the effects of these B vits on me, it is real and I am reading research studies from real scientists, one after the other about the well researched c677t mutation that I have, which, I remind you, is 3x more prevalent in UC people than in the average population.

Of course I do want to hear what you have to say so please do post as it all helps with the understanding. I can assure you that I am not taking any supplements since I have been nearly killing myself with B12 and folate overdose.

Let me offer one data point here. I just experimented with Biotin -- added 5000mcg daily to my diet (there's no known upper limit, so i figured "why not start big?"). After two weeks, i have a seriously annoying case of glossitis (inflammation of the tongue). Feels like the inside of my mouth is nothing but sandpaper. And super dry mouth all the time. Anytime I eat something acidic, like salad dressing or lemonade, the "sandpaper" gets noticeably worse.

So I take biotin out. Next day, things are noticeably better. So, there definitely IS something to B-vitamins and mucosa (I no longer have this horrendously dry mouth). I can't say anything more than that. But what I do say, I say with certainty.

London, I have Canada Mark on ignore because he loves to come into threads on genetics that he understands not one whit about and challenge me, so just heads up I never address his posts. I said nothing with post after post from him of things I might not think smart..even After he advocated that crazy neurotransmitter doc who wasted thousands of dollars from the collective of users who fell for it "curing " CM.. But Just like a few months later oregano oil (which he told people was dangerous) "cured" him.. And he started attacking every post i make about One carbon metabolism which he seems to think is a funny joke on civilization?? Or a an elaborate lie or something. i dont know how to reason with someone who rejects one carbon metabolism.

Yet he loves to come into threads and pretend he has any idea of what he is talking about and attack me. I don't respond usually but can see from your response he's still up to it...but I'm rather annoyed the mods are continuing to let him harass my posts.

There are alot of places here that offer specially blended nutrient Ivs that have the "right" forms of vitamins. I've thought about trying weekly infusions instead, but feel like I've fairly dialed in my supplement regime and don't want to upset any apple carts now that we've moved on to final stage, neurotransmitter support.

Post Edited (PathogenKiller) : 4/7/2014 4:42:21 PM (GMT-6)

Path you got a lot of your facts messed up severely and because I question a lot of your posts- you totally freak out when anyone dare challenge you. You mention all this knowledge you've acquired from study the pathways and how you see the "light" and can explain everything but I don't believe this to be so. I don't think you know what Snp's are nor what carbon one means. There are far more logical explainations than any of the stuff you mention. If you are so good at this answer one simple question: after all it was what I was going to type out and explain anyway. Save me the time.

Explain how one goes from a gene let's make a random (or fake) one here:

GTACATGGCATCGCGACT

Let's assume this is a what we can call "Protein Molecule 1"

Now translate this for me from DNA to Protein Molecule. And show us or explain in all your wisdom how this becomes a fully functioning protein (albeit an imaginary one) lol, but the process is the same at base level. Then add a snp in the gene and explain how this effects the protein molecule... And how this in turn effects us...

PS - no DNA is nothing like computer code at all... It really, really isn't. It's a common misconception.

And once again I'll throw in here- I had zero and I mean zero clue about all this stuff forever, then I went back to school for a few courses and it opened my eyes to how much not only do I love it but more so how much I misunderstood, even from as little as 6 months ago,. I find it amazing how much is still not understood in general abut genes, the immune system, nutrient absorption etc etc. it's shocking how little is known actually.

Oh - and the paper OM dig up on the new immune cells is pretty cool. I didn't get around to reading it till just now. Macrophages also express folate receptors though no one knows why yet. So the two together are quite interesting. I'm sure more immune cells will pop up in this regards as well.

London, I get things wrong all the time! This is a constant learning process.

But one thing Im not wrong on is how one carbon metabolism is one of the building blocks of life. Now what I dont always know how to do is distill something down to the basics and handhold people through something as complex as what we are talking about.

You know how you can look at a math problem and know the answer sometimes, but you may not know why the answer is what it is? Since I am not a scientist by education, I do not often have the patience to start from the beginning. Especially when you go from very basic to incredibly complex. But


I like this paper.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3696357/

Anyway, back to Riboflavin and I apologize if Im covering anything that has been covered, but I grab minutes here and there to post so sometimes I cant read all the studies, especially if they have no description. if you have cox6 issues you can look at riboflavin there too as it is further upstream where as the cox enzyme comes into play at stage iv of the mitochondrial respiratory chain.

In the mitochondrial respiratory chain, we need FMN (flavin mononucleotide) for complex 1 and FAD(flavin adenine dinucleotide) for complex 2. If we dont have enough riboflavin then we have none of those key energy substrates. FAD is also very important to the Krebs cycle and when it isnt available then electron transport and oxidative phosphorylation through the Krebs cycle is impacted. So in a scenario where you are deficient in riboflavin and have a fair amount of hetero or homozygous snps through COX6C you basically have two pathways in the system not working optimally. I love that our bodies were designed as redundant systems, its when multiple pathways break down that we start seeing chronic disease. It then becomes somewhat of a domino effect.



So here is what happens with the typical person due to fortification:
They go into their doc who runs standard labcorp serum values for b-12 and folic acid. Most people come back normal or even high. So people assume that isnt an issue. Well, the problem is that yeah, you have alot of the synthetic version of these fortified vitamins in your system blocking the creation and utilization of the forms that your body really needs. That lab test is pretty much worthless.
I could have a crap ton of b-12 in my system and not be able to use any of it because my lithium levels are off and b-12 needs lithium to help it into the cell

What you need to know is how much of the vitamins are making it into the cell. The Spectracell test is much better for that. I know Genova has a test too, Nutreval that is super comprehensive and would be helpful to anyone that is looking at addressing epigenetics but I dont know if it is as comprehensive in regards to vitamin levels specifically. Nutraeval is more like what Yasko runs with the UAA.. I just have no direct experience with it and every doctor that believes in testing outside of labcorp is going to have a test that they like best.. but those are good places to start when trying to put your 23andmeresults together with what nutritional needs you have.

The epigenetics side has been coming to me from my work in mental health for a few years, it is new to me to consider it from this "methylation" side - and I definitely am looking for a genetics 101 course.

These are the sort of trials going on with mindfulness and genetics which is big news, and becoming big business in mental health

www.investigatinghealthyminds.org/pdfs/KalimanRapidPNEC.pdf

www.ncbi.nlm.nih.gov/pmc/articles/PMC3057175/

Meanwhile, on B2, I have been reading guidelines on management of anaemia in IBD. Everywhere it says to keep up B12 and folate levels yet nowhere is it said to monitor B2, yet B2 deficiency has been know to also be implicated in anaemia for many, many years, I am seeing studies on it back to the 1940s

Also, London.. What a blessing you'll be in your field if you know about this stuff! Good for you for becoming educated!

This s a great slide deck that may be up your alley.
www.foodforthebrain.org/download.asp?id_Doc=10

And I like this paper too
journals.tubitak.gov.tr/medical/issues/sag-14-44-1/sag-44-1-1-1211-39.pdf

Post Edited (PathogenKiller) : 4/8/2014 9:55:49 AM (GMT-6)

Thank you for the links PK

Canada Mark said...


Here is the statement for any interested:

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing
www.nature.com/gim/journal/v15/n2/full/gim2012165a.html

Well, one could choose to go with their review, or one could choose to go with the 2011 more cautious approach

Meta-analysis said...

Aliment Pharmacol Ther. 2011 Nov;34(10):1173-84. doi: 10.1111/j.1365-2036.2011.04864.x. Epub 2011 Oct 3.
Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases.
Oussalah A1, Guéant JL, Peyrin-Biroulet L.
Author information
Abstract
BACKGROUND:

The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD.
AIM:

To conduct a systematic review and meta-analysis to examine these issues.
METHODS:

The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD.
RESULTS:

Twenty-eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD)=3.75 μmol/L; 95% CI, 2.23-5.26 μmol/L; P<0.0001; reference ranges for plasma homocysteine level: 5-12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn's disease (CD) (WMD=0.41 μmol/L; 95% CI, -2.45 to 3.06 μmol/L; P=0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR)=4.65; 95% CI, 3.04-7.09; P<0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR=1.97; 95% CI, 0.83-4.67; P=0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P=0.006).
CONCLUSIONS:

The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia-related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.

Meanwhile - back to B2 with a bit of MTHFR thrown in - although same people seem to have brought out a conflicting study later

Dutch study said...

cebp.aacrjournals.org/content/16/2/327.abstract
Methylation of the promoter region of tumor suppressor genes is increasingly recognized to play a role in cancer development through silencing of gene transcription. We examined the associations between dietary folate intake, MTHFR C677T genotype, and promoter methylation of six tumor suppressor and DNA repair genes. Patients with colorectal adenoma (n = 149) and controls (n = 286) with folate intake in the upper or lower tertile with the CC or TT genotype were selected from a case-control study. Methylation-specific PCRs were conducted on colorectal adenoma specimens. The percentages of promoter methylation ranged from 15.7% to 64.2%. In case-case comparisons, folate was inversely associated with promoter methylation, especially among TT homozygotes. Case-control comparisons suggested that folate was not associated with the occurrence of adenomas with promoter methylation, and increased the risk of unmethylated adenomas, especially in TT homozygotes. The interactions between folate and MTHFR genotype were most pronounced for O6-MGMT: compared with CC homozygotes with low folate intake, the adjusted odds ratios (95% confidence interval) of having a methylated O6-MGMT promoter were 3.39 (0.82-13.93) for TT homozygotes with low folate intake and 0.37 (0.11-1.29) for TT homozygotes with high folate intake (P interaction = 0.02); the odds ratios for the occurrence of adenomas without methylation were 0.57 (0.16-2.11) for TT homozygotes with low folate intake and 3.37 (1.17-9.68) for TT homozygotes with high folate intake (P interaction = 0.03). In conclusion, folate intake seems to be inversely associated with promoter methylation in colorectal adenomas in case-case comparisons, and was positively associated with the occurrence of adenomas without promoter methylation in case-control comparisons, especially for TT homozygotes. (Cancer Epidemiol Biomarkers Prev 2007;16(2):327–33)

Yes over and over these studies supplement B12 and folate without B2 - yet B2 is known to be necessary to protect mucous membranes and it is known that B2 is taken up as a co-factor - so strange how it has been so little researched - and again, seems particularly relevant for those who are homoz c677t such as myself which is perhaps why it is ringing such bells.

Paper said...
www.ncbi.nlm.nih.gov/books/NBK6145/
Riboflavin and Methylenetetrahydrofolate Reductase

Steinar Hustad, Jern Schneede, and Per Magne Ueland.

The flavoenzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl group donor in the conversion of homocysteine to methionine. In rats, experimental riboflavin deficiency is associated with low MTHFR activity and reduced levels of 5-methyltetrahydrofolate. In humans, reduced enzyme activity caused by the commonly occurring 677C→T substitution of the MTHFR gene is associated with elevated plasma homocysteine. The mutant enzyme has lower affinity for its flavin cofactor than the wild-type enzyme, and recent studies show that plasma homocysteine is inversely related to riboflavin in subjects with the T-allele. This indicates that the metabolic effect of the 677C→T polymorphism is related to riboflavin status, which may have implications for future studies on the relationship between this polymorphism and various clinical and biochemical endpoints.

London, You might enjoy this
forums.phoenixrising.me/index.php?threads/b2-i-love-you.15209/page-2

It's an insanely chock full of data on b2

Post Edited (PathogenKiller) : 4/10/2014 11:59:09 AM (GMT-6)

GutsZilla said...
Let me offer one data point here. I just experimented with Biotin -- added 5000mcg daily to my diet (there's no known upper limit, so i figured "why not start big?"). After two weeks, i have a seriously annoying case of glossitis (inflammation of the tongue). Feels like the inside of my mouth is nothing but sandpaper. And super dry mouth all the time. Anytime I eat something acidic, like salad dressing or lemonade, the "sandpaper" gets noticeably worse.

So I take biotin out. Next day, things are noticeably better. So, there definitely IS something to B-vitamins and mucosa (I no longer have this horrendously dry mouth). I can't say anything more than that. But what I do say, I say with certainty.

I keep thinking about this..
You must have depleted a cofactor. Do you take magnesium?

London,

I do alot of sitting outside in the sun while typing. After being cooped up in Seattle for many years I definitely enjoy the sun now.

I think what is happening is that people are creating a functional deficiency of a vitamin. The Bs work in unison, they are like a symphony. You cant have too much of any single one of them (except maybe b12) without depleting the others. Biotin specifically needs Magnesium and ATP so if you were low in mag what would happen is you'd start taking biotin and feel great, until your body no longer had enough of the cofactor to give you and then your body would start trying to pull something that wasnt there and youd feel poorly. (alternately the atp pool could have been burned through- we need biotin for complex iv of the mitochondrial respiratory chain) I was taking large amounts of biotin because Id lost so much of my hair and it also is effective against yeast. I was not supplementing Mag. This created constipation for me in alot of exhaustion until I figured it out.

I dont believe in b complexes. I know everyone wants to take the least amount of pills possible but I think they can be bad for people. I like this chart www.acu-cell.com/bx2.html

HAH! I just got to the end of the riboflavin thread after getting frustrated at page 15 and skipping to the end. I see that this was said:

For the 30 odd pages, what I seemed to get is this:

*B2 is needed for both ATP production and processing of folates, wether fake or real
* Manganese is needed for B2 and glutamate conversion
* Vitamin K is used for Vitamin D absorption and also uses up free glutamates

So it seems that... the aim to take these three is to get rid of glutamate, fake folates and restore Krebs + Glutamate-Glutamine Cycle + Folate Cycle by processing real folates?


__________________________________________


Bam! And that, my friends is the crux of the matter. But you have to start with gaba/glutamine I think (GAD1) first or if you have another really gnarly part of your genetics like detox, you might needs to start there, I dunno. I think Yasko is right with Gaba Glutamine. Thats why I think some people respond really well to LDN.