I'm new here; I'm posting GG methylation profile, esp. B12 (double whammy) and low ferritin

[PWR (Peace without Rest)]

I'm new here. I will upload my (and my husband's) GG methyl. profile obtained through 23andme testing. I have very low ferritin now (9 mg/dL). I have iron-deficiency anemia and have recently been low in hemoglobin, though not now. My iron is now 118, and my hemoglobin is now 13-14. I am having trouble with tolerating iron in any supplement or IV form. My doctor says I may have a rare parasite from when I was on a missions trip in Africa 30 years ago (I know, hard to believe), but if that turns out negative, she's at a loss what to do to raise my ferritin. My husband found some info through this website and www.stopthethyroidmadness.com/ferritin/ about other possible explanations such as high copper, high heavy metals (this is true of me), etc.

Recently, we got our results back and it looks like I have the B12 double whammy, both a homozygous MTR and a homozygous & heterozygous MTRR. According to @caledonia's Guide (if I understood correctly), this means the double whammy. I'm wondering if anyone knows the role of the B12 cycle and iron/ferritin and if I could find scientific articles to help my doctor?

My file is the first, my husband's is the second. We also have the detox panel but that was less bad for me. I can upload it if needed.

 

[Valentijn]

First File:
The MTR variation which you have (rs1805087) is the extremely common version, so being +/+ just means you didn't get lucky and end up with the optimal version. It also looks like it just indicates a small variation in gene function, not a moderate or large variation.[1]

MTRR A66G (rs1801394) has very little or no impact when +/- ... it's only a nasty one when it's +/+. So since that gene is acting normally, there's nothing for the mild MTR mutation to "double whammy" with here.[2]

MTRR A664A (rs1802059) is actually a mild and beneficial upregulation when +/+. So Yasko and Genetic Genie are reporting that one completely backwards.[3]

MTHFR A1298C +/+ (rs1801131) indicates a 39% decrease in gene function - that sounds bad, but it's very common for that gene. Eating a decent amount of vegetables or supplementing a normal dose (400mcg) of methylfolate should be more than sufficient to compensate for it.[4]

Second File:
MTHFR C677T +/- (rs1801133) indicates a 35% decrease in enzyme function. The same notes apply as above for MTHFR A1298C.[5]

MTRR A66G +/- isn't a problem. See notes above.

MTRR A664A +/+ is the good version. See notes above.

...

When someone posts something which contradicts the above information, ask them to cite the research which supports their claims. They won't be able to, because it all tracks back to "Yasko Says ...." But Yasko is frequently wrong and apparently incapable of reading or interpreting straightforward research.

Here's the sources for the above information:
[1] http://www.ncbi.nlm.nih.gov/pubmed/10520212
[2] http://www.ncbi.nlm.nih.gov/pubmed/12416982?dopt=Abstract
[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299910/
[4] http://www.cell.com/AJHG/retrieve/pii/S0002929707615249
[5] http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1123&context=lawfacpub

 

[WillowJ]

It seems like iron-deficiency anemia and B12-deficiency anemia tend to have opposite readings on the TIBC test.

but if that turns out negative, she's at a loss what to do to raise my ferritin.

Is it possible to get a referral to hematology?

I'm wondering if anyone knows the role of the B12 cycle and iron/ferritin

On iron in general:

http://labtestsonline.org/understanding/analytes/iron/tab/test/
http://library.med.utah.edu/WebPath/TUTORIAL/IRON/IRON.html

 

[Helen]

I'm wondering if anyone knows the role of the B12 cycle and iron/ferritin and if I could find scientific articles to help my doctor?

Did you get tested for B12 deficiency? The tests may end up negative/normal, as there aren´t any 100 % valid tests for B12 deficiency.

My doctor says I may have a rare parasite from when I was on a missions trip in Africa 30 years ago (I know, hard to believe), but if that turns out negative, she's at a loss what to do to raise my ferritin.

I think your doctor should know about the possible connection between B12 deficiency and difficulties raising ferritin. At least this possibility should be excluded.

http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/signs

 

[Gondwanaland]

I have been researching about how to balance iron because my husband has iron overload. I found the info from this site particularly interesting:
http://www.acu-cell.com/femn.html
It at least gives you hints of what to avoid. I guess that testing for manganese and copper can be revealing.

To raise iron levels I have read that lactoferrin is the best supplemental form and @Changexpert posted about it just recently. Perhaps freeze-dried liver supplements? Or eating liver?

I think that supplementing B12 with low iron can be dangerous. Heme generation needs iron and copper. In addition, B9 and B12 lower potassium, and potassium is "copper-freindly" and both are highly needed for heme formation.

Regarding transferrin, from Wikipedia:

The amino acids which bind the iron ion to the transferrin are identical for both lobes; two tyrosines, one histidine, and one aspartic acid. For the iron ion to bind, an anion is required, preferably carbonate (CO2−
3).[4]

For better absorbing iron I would first try to balance electrolytes and minerals and improve gut absorption.

 

[stridor]

@JRG
In terms of your 23 results, people's input can only point you in a general direction. For example, mine confirmed that taking methyl supports was.....well,.... supportable. Only through experimentation do we make any headway beyond this. If mB12 makes you feel better, then you likely will benefit from continuing to take it. That is regardless of what your 23 results say or don't say.

My iron has "skyrocketed" from 9 to 14 with twice daily supplementation. So, I switched to an expensive form called Proferrin and this is a "heme iron polypeptide". I have a lot of gut problems (colon removed) and can not seem to absorb B2 or mfolate well either.

You mentioned that you have heavy metals. I chelated mercury and continue to chelate lead. I have wondered whether chelation has messed with iron metabolism as well. I am taking longer breaks now and will see if it helps.

 

[PWR (Peace without Rest)]

@Helen, @stridor

I'm going to reply to you two first because I partially got the idea to ask this question by reading a post (I will try to add in later this link) from '13 where you both were involved. Thank you.

In that post, Helen said "A low ferritin might be caused by a vit B12 deficiency. A doctor said to a friend: 'without enough B12 the iron will not stay in the body"- or something like that.'"

Maybe I was barking up the wrong tree here but I was curious as to whether some B12 SNPs (see above) could affect my ability to process B12 and thus cause low ferritin. However, as I stated above, my iron is normal and, as you will see below, my B12 was HIGH, though I was taking it at the time of the blood test (in an iron supplement containing 30 mcg./dose).

So, I'm looking for information, if it exists, that discusses low ferritin due to B12 problems WITHOUT low iron or low hemoglobin or pernicious anemia. Maybe this is a lost cause? I should mention here that I have trouble taking much B12. I started the Fredd protocol a few months ago VERY SLOWLY and only 1 suppl. at a time. I am only able to take 1000 mcg./day of B12 and only in the a.m. If I take more, I get extremely jittery and can't sleep.

Here's the best info I can give you.
1) About 1 yr ago, I was coming up with my Hemoglobin (11.9L) from my previous 9.7L that Jan. (In Jan, I was hospitalized for morbid hypertension, which has been well controlled with 3 BP meds [losartan, amlodipine and spironolactone ever since).

2) So, a yr ago, my Ferritin was 20, my B12 was actually high at 1306 (ref. 211-946). My doctor (N.D.) asked me if I was taking B12 and that if I was, not to worry about the high number. (see above for iron tablet I was taking.)

3) As I stated above, my hemoglobin has returned to normal, iron returned to normal, but ferritin has remained in the 20's and teens.

4) The reason why I am not taking iron in any form, including the IVs which I've done several times, is that, when I do, I have symptoms of the iron feeding whatever pathogens I have in my colon, whether bacterial (though nothing significant showed up on my stool test that could cause this degree of problem) or possibly parasitic. In order to bring my iron blood test numbers up, I have been eating iron-rich foods: Raisins, Blackstrap molasses, dark turkey & chicken, beef 1x/week, spinach and beets & beet greens. With betaine HCL tabs and white wine vinegar, I am able to digest these things and keep my iron levels stable, though not quite high enough yet.

My doctor acknowledges that the iron can feed the pathogens but she doesn't have any alternative explanations or alternative ways of raising the ferritin, so it's kind of like, "Well, we have to do SOMETHING, even if it makes you worse." She does say that if the parasite test comes back positive, that would explain most everything and the iron could wait since it is know that this parasite (Schistosoma Haematobium) affects iron/ferritin.

For now, she's reluctantly agreed to postpone any iron IV's (and I'm not taking any iron supplements except for above foods) until the test results come back. I raised the hypothetical causes of NON-iron-related low ferritin with her and she's willing to explore those. But I don't have much time.

So, can a person have low B12 functionally without having pernicious anemia since I know I have the iron-related anemia (like my mom and sister)? The Dr. wants to run a test for the copper issue but I'm not sure if she has one for B12.

Thanks to all. BTW: when my latest iron level (118) was taken a month ago, TIBC was 314, transferrin was 38.

 

[Changexpert]

JRG,

You mentioned that you cannot tolerate iron supplements, but I am just curious if you have tried ferrous furmarate? I was on FF for about 3 months and my ferritin level skyrocketed to 291 ng/mL.

As far as lactoferrin goes, it is touted as the best iron boosting supplement without taking iron. Lactoferrin has strong affinity to iron, so with tight binding, it carries iron to necessary parts of the body instead of letting iron get excreted through waste or parasites binding to iron. One thing to keep in mind is that lactoferrin not only strengthens immune system, but also affects immune response (th1 vs th2). Unless you know for sure that you cannot tolerate ferrous furmarate, I would not try lactoferrin. Also, I have not seen any information in regards to ferritin level for lactoferrin.

I have not tried LF and FF in combination, but that could work for you in theory since LF would bind to FF and carry iron to serum instead of feeding the pathogen. It might be worthwhile to ask your physician about using these two simultaneously.

I am not very knowledgeable in genetic profile, so I will not make any comments about them. To stridor's point, the only way you can figure out if you truly need certain supplements or not is to try them out. Of course, trying out supplements can be very tricky because of dosage, combination (compliments), and timing. My best advice for you is listen to your body as you add or subtract different supplements.

 

[stridor]

@JRG
Sounds like we have a couple of things in common. It's a long story but I drank water from the Nile when I was young and reckless.
I have always had high B12 and it was therefore a bit of a surprise to respond the way I did to mB12 supplementation. I know that Valentijn does not endorse this idea, but I still attribute part of my B12 issues to the TCN2++ status (pending a better explanation).
It is one thing to analyse individual SNPS potential impact but perhaps not as easy to interpret the interplay of various combinations of SNPs, environmentally influenced gene expression and other factors such as the health of the gut biome. We are far more than a sum of our parts.

Your mB12 response is pretty common amongst the COMT community. I don't think that there is necessarily anything inherently wrong with 1000 mcg if that is what you need. We only need a couple of mcg a day if we can use it properly.

I don't have anything for you on B12 and ferritin with normal Hgb. My hemoglobin is in the normal range as well and I do not have pernicious anemia. For these reasons I shelved this until I had some other issues sorted out. I did not have the foresight to predict how slowly it would respond to augmentation.
It was ferrous fumerate that I took for months without benefit.

Why is your Dr so worried about this while mine doesn't seem to care, I wonder? Can low ferritin contribute to fatigue outside of formation of heme? I guess it helps with skin and I could use all that I can get with that. Do you have an abundance of skin problems?

 

[PWR (Peace without Rest)]

@stridor, @Changexpert, @WillowJ, @Gondwanaland,@Helen

Thank you all for your responses. I will try to separate these out individually but I want to make sure you know it's coming, whether I get to it in this post or the next!

@Helen, you said in '13

In that post, Helen said "A low ferritin might be caused by a vit B12 deficiency. A doctor said to a friend: 'without enough B12 the iron will not stay in the body"- or something like that.'"

I have been looking but have been unable to find out how B12 helps keep iron in the body. As I stated earlier, my iron is within normal and B12 high but I can't bring up ferritin. Maybe I'm unable to use my B12 well enough? Have you ever seen documention in addition to that quote? As you can imagine, this piece of info could be pivotal. Thanks.

@stridor,

Do you know (based on that '13 post I referenced earlier) about the role of B12 in ferritin synthesis? That is something I'm trying to check into. If I could link my B12 SNPs to that part of the equation, it might help my Dr. let up for a while on the IV iron which I'm "supposed" to take but makes me feel awful (feeds bacteria/parasites in my colon, massive bloating, etc.).

Re: high B12, aree you referring to the "normal" blood test for B12 or something else? It seems like you mean the "normal" one. A former Dr. used to order "RBC B12" and "RBC folate" which he said indicated these nutrients making into the Red cells. I am relieved to know I am not the only one. Of course, it is not considered "extra-healthy" to have high B12! When the current Dr. asked me if I was taking it, I initially answered, "No," because I ddin't realize it was in the iron formula. Then, she got a concerned look on her face. My husband looked it up online and found out why (among other causes, cirrhosis of the liver and leukemia). Of course, that wasn't true of me and I'm sure it's not of you, but I just had to mention that in case someone else needs that info.

Do you think that, because of your difficulty processing B12, that you have excess running around in your bloodstream that should be put in its proper places in the body instead? Even though I was taking a tiny amt of B12 in that iron formula (30 mcg/day), it seems insufficient to explain why my # was so high. As far as i know, that was the first and only time my B12 was tested via blood. Your thoughts? Could you summarize your response to the B12

You mentioned your hunch re: TNC++ gene. I don't see that on either Methyl or Detox panel. How did you find that one? I fully understand what you're saying about our environment being another major factor, not just our genes. I have not mentioned here (until now) that I was born and raised in WV and have been described by Dr. William Rea of TX when I was hospitalized there as "one of the most severe cases of MCS (Multiple Chemical Sensitivities) I've seen." He didn't mean that other people didn't have more life-threatening responses when exposed to chemicals (such as seizure, passing out, etc.) but that my severe vasculitis in response to a very wide range of chemicals was significantly affecting my life.

Actually, in regards to MCS, 20 years ago, I made a dramatic improvement compared to where I was before. I won't belabor the details here, but if anyone is interested, I can pass on the info.

You mentioned drinking the water from the Nile. If you don't mind my asking, have you ever been evaluated for tropical parasites or thought you might have signs/symptoms?

BTW: I think my Dr. is so worried about the ferritin because of my history of iron-deficiency anemia AND because she, as a Naturopathic Doctor, is trying to keep good relations with the MD's she has to deal with. No, I don't have skin problems, though that was a good insight.

My detox is #1, my husband's is #2. I noticed some discrepancies between mine and a Genovations gene test done 10+ years ago. I will follow up.

 

[stridor]

I had been under the impression that B12 was involved with iron metabolism beyond the formation of heme. Sorry for the misinformation. This is not the first time that I have discovered that my interpretation of what I was reading when sick has needed adjustments.

The funny thing is that there is a girl at work who regularly thanks me for helping her get her iron levels up by suggesting that she try B12. I have no clue.

I have 2 Drs. One will never have heard of RBC B12 or MMA and could not give a credible explanation of what B12 does. The second one doesn't care because he is more interested in treating symptoms than lab results. So yes, it is regular serum B12 and it is my contention that it was high because it could not get into the cells. I might end up being wrong about that too....

TCN2 = transcobalamin and it has been coined "The Frailty Gene" in some studies. I got this from Sterling Hill's app at MTHFR.net. mB12 was a turn around event. I had returned to work sick and limped along for 7 months until they just sent me home as "incapable". They had given me 7 months to assume full duties but I was unable.

Genes are turned activated and told to shut-up through a variety of ways. One is methylation and this second use of this word throws some people off. But it is not just our environment and methylation - things like cortisol and medications and chemicals are capable of affecting gene expression as well.

I was so sick with OI and fog...plus, I was depressed. After starting B12 I was able to return to work and assume full-duties and a month later they put me in charge of my work area.

You sure sound like someone with mercury toxicity, BTW. Consider sending hair test results to my brother over at Frequent Dose Chelation. He's the one with MCS. I just went crazy.
I have to go to work. This has been kinda rushed. Let me know if you have any more questions that I can give you the wrong answer to

 

[PWR (Peace without Rest)]

@stridor,

Don't be so sure that the info is incorrect, maybe just unconfirmed. I only have a minute but I wanted to mention that there could be a very logical/medical reason why you were able to help your friend with her iron by suggesting B12. If she needed help with methylation, then the B12 could have helped her detoxify heavy metals, thus relieving her burden on her iron/mineral metabolism, thus enabling her to raise her iron. So, your idea might not have been so "crazy" as you think!

 

[PWR (Peace without Rest)]

To all,

I just got back recent Thyroid tests (TSH, Free T3 and T4) and they were worse than 6 months ago, even though I have maintained the same dose of Armour Thyroid and been extremely consistent. Thus, my N.D. upped my dose from 1/2 grain (30 mg) to 3/4 grain (45 mg). I forgot to mention above that the www.stopthethyroidmadness.com link I put above described that low thyroid leads to low stomach acid, therefore low iron absorption (and thus lower ferritin). So, I am hoping that the Dr. will be ok postponing the iron IV's further.

Also, I found an old (2008) Spectracell nutritonal panel which revealed a "significant elevation" of my metabolic copper level (52 vs. the upper limit of normal as 42) and my zinc was deficient (right @ 37 which is the lower limit of normal, which they said was deficient). I will be repeating the test soon to see if this is still going on. If so, it could point to this common imbalance due to MTHFR (I am homozygous 1298) mentioned on the thyroid website.

@WillowJ,

I read the links you provided. It was all excellent info. Yes, it does seem that I am squarely in the IDA (Iron-deficiency anemia) camp, not the B12 anemia.

I assume you're mentioning the referral to hematology to do iron Iv's right? If there's another idea there that I'm missing, let me know.

@Changexpert,

Thanks for your ideas re: ferrous fumarate and lactoferrin. I haven't tried the fumarate (just the ferrous sulfate) but I suspect that I would have the same trouble. I forgot to mention above that the iron supplement tablet I was taking (that had the B12) was a food-based iron. It seems that, no matter what type (natural or synthetic) of SUPPLEMENT I take, it causes a problem.

I have never tried lactoferrin by itself. When I read about it after your post, I realized that it's a component of the colostrum which was part of my MAF314. I was on this for 3 years. I know I could take the lactoferrin anyway, but it seems like it would have helped a little if it was "the missing link." Thanks for the idea.

 

[WillowJ]

I assume you're mentioning the referral to hematology to do iron Iv's right? If there's another idea there that I'm missing, let me know.

Hematology to figure things out in general. I'm not sure what that would look like, as I'm not a doctor. But hematology is one possible type of specialist that might be able to work out how to help. As there is anemia and things seem complicated and the primary doc doesn't seem to know what else to do, that seems like an appropriate place to go.

A lot of times I've found that when docs seem stuck, suggesting a referral can get things moving. If the specialist can't help, sometimes they can suggest a better type of specialist.

It takes patience and an open mind to be a "nobody's problem" patient, but chances are, someone will be able to help at least a little. You just have to find them.