Methylenetetrahydrofolate reductase homozygous A1298C variant

[Brandy]

I know I haven't been a good forum member for the last year; only popping in asking my questions and leaving. Sorry. At this stage in my surgery, I feel like I know nothing and have no business answering anybody's questions, but I can't resist myself when I'm here.

I'm three months away from being at my three year anniversary, but I'm still following up on my two year bloodwork which showed all sorts of weird liver levels and other strange things. Also, things like my blood tests showed all the bone variable all were trending better, but my bone density dropped like a stone. It is still in the OK range, but it was excellent a year ago. Meanwhile, my hair is fading at an alarming rate and I'm still losing a pound a month.

On the other hand, I feel and look awesome, never better and never stronger. I can eat anything with only the occasional small bloat. Although I never really saw a huge uptake in energy, if I eat enough and in the right mix, I can work out about three times a week. I don't think this is directly related to the DS in anyway, seeing the bloodwork just saved me in the long run.

I went to a naturopath because I couldn't get a different doctor to care, but she has been terrific. She isn't even making me talk to a nut! But her deep testing, better than I have had before, showed the genetic abnormality that is in the title. This stuff is hard to understand and I especially can't figure out how this is effected by the DS.

Is the following right??

That really long word in the subject is shortened to MTHFR. It is a digestive enzyme that is used to create certain types of proteins. These specific proteins are the ones that detox a class of toxins in the liver and because I can't make them, my body stores the toxins, eventually causing enough liver damage to show up on blood work.

The problem is noticeable now because many supplements, i.e. CENTRUM, uses chemical forms that my body can't clear, and at the doses I take, things are building much quicker now.​

----?

The only "small" change she wanted to make to my supplement program, and I give her huge kudos for her restraint, was to switch away from Centrum and to DFH Complete Multi. The problem with that is that that Multi is 6 a day for normal people and Mexicali Bariatric bases their vitamin program off of 4 multi's a day. I don't think taking 24, or even 12 of any pill a day would be good for me, but maybe that is just because I don't want to have to take 50 vitamins a day.

On the other hand, it has always bugged me to base my vits on 4 multi a day. That just seemed like it was asking for trouble in the long run. But as you guys know, once you are rolling with a system and your blood work looks good, you really don't want to start over.

I have this question sent to her, but before I make such a "small" change, or in other words, totally redo all my supplements and balances and then go through two years of close monitoring again, I was hoping this was something somebody has hit before.

Please? Anybody understand this? I don't understand (yet) how to choose things that won't hurt me and I hate being back on the sidelines about my health.

Thanks in advance!

 

[Munchkin]

I have been reading lately about a 'popular' issue in the pro-supplement community. A bunch of people are becoming proponents of 'natural' vs synthetic vites. Sort of sounds to me like your Naturopath is moving you in that direction. Anyway the basic idea is that many of the synthetics are derived from or carry with them other things that can be bad for you. One thing they discuss is supplements that carry toxins the liver can't remove so they just remain in your body.

Some of this stuff is clap trap pseudo science but other parts of it make sense and are logical. I haven't read enough to be able to offer any opinion yet. The supplement world is full of fake science and it's work to differentiate between the real thing and the fake thing. And the real science people have no money to actually study this stuff because the drug companies won't finance something that won't give them a bright shiny new pill!

Meanwhile back at the ranch, the first thing I would probably do is verify/get a second opinion to be sure you actually have this problem. MTHFR gene mutation testing through LabCorp. Or order online through 23andMe . Some Naturopaths are worth their weight in gold and others wear tinfoil hats to bed at night to keep the aliens away. Verify, verify, verify! And mutations travel with mutations. I would probably want a reasonably complete screening.

 

[Settledownnow]

Just a few questions. Can you clarify with lab results and specific examples, "weird liver levels and other strange things. Also, things like my blood tests showed all the bone variable all were trending better, but my bone density dropped like a stone" what this means?

I think you are trying to be logical and make connections from one lab result to the next, and they may not be connected at all. In reading more about MTHFR it seems to be related to high levels of homocysteine and low levels of folate. Homocysteine is created from amino acids in meat and dairy. In other words, you are eating a lot of protein and thus making a lot of homocysteine. High levels of homocysteine are also related to low levels of B6, B12, and Folic Acid. How are your B vitamins these days? Are you testing each and every B vit?

Regarding the suggested multi's, they are super high in B vits. Are you taking B complex now? Do you need that many B vits? On the other hand, if you would feel more comfortable taking natural vits rather than synthetic go for it.

 

[DianaCox]

I am having trouble tracking down what the effect is of having this mutation.

"1305AA is the "normal" homozygous, 1305AC the heterozygous, and 1298CC the homozygous for the "variant". In studies of human recombinant MTHFR, the protein encoded by 1305C cannot be distinguished from 1305A in terms of activity, thermolability, FAD release, or the protective effect of 5-methyl-THF.[16] The C mutation does not appear to affect the MTHFR protein. It does not result in thermolabile MTHFR and does not appear to affect homocysteine levels. It does, however, affect the conversion of MTHF to BH4 (tetrahydrobiopterin), an important cofactor in the production of neurotransmitters, and the synthesis of nitric oxide"

So what is the vitamin supplementation change she has proposed DO? How does it ameliorate the conversion of MTHF to BH4? Can you just take a little extra BH4? Is there a test for BH4 that shows you are deficient?

I'm sorry, but I think naturopathy and homeopathy are utter BS. Maybe because I have a PhD in biochemistry.

Oh, and here is something even MORE recent and scientific:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696357/

"Another common coding MTHFR single nucleotide polymorphism, A1298C (E429A), exists in strong linkage disequilibrium with C677T [111]. Unlike C677T which affects the active site of the protein, A1298C is located in the regulatory domain of the protein and is catalytically indistinguishable from the wild-type MTHFR [86]. The A1298C polymorphism is associated with increased red cell folate levels and does not affect homocysteine levels [90]. This polymorphism was shown to be associated with a decreased risk for acute lymphoblastic leukemia [107] and childhood acute leukemia [108]."

I don't think you should do ANYTHING based on having this "mutation" - which is basically a meaningless polymorphism.

 

[Brandy]

Thank you guys!! You are the best! I need a degree in biochemistry to understand this. I just don't have the background. 23andMe verified this along with quest labs. I think I'm going to just going to go study the MTHFB stuff for a while, until I can understand Diana's post!


In my 2 year labs liver measurements such as AST, ALT and Alkaline Phosphase slammed out of range, using labcore like usual. Specifically, things like my AST going from a steady ~28ish to 183. ALT from a steady ~40ish to 283. Also suddenly out of whack -- Platelets and Lymps. My regular doctor said that "things like this don't mean anything" and that I probably had a cold or something." He said that liver values need to be a lot more out of whack before they take them seriously. I wasn't going rest on these results. These values were all just retested at Quest Diagnostics and are still out of range, but they have a different range for their tests, so I don't think I can compare beyond that.

My bone scan went from excellent -- top of the range at 1 year post surgery to "Ok, just above the line" for my second year, but my blood work showed good levels for all the bone tests (calcium=9, D=48, phos=4, mag=2.1). All of these could be higher and are all on rising trends since surgery. The new Quest test, the PTH Intact is on the high side of the range (62 out of 14 to 64), where it has always been in the middle of the Labcore range (~40 out of 12 to 88).

My theory on the bone thing was menopause and estrogen, as in I should be getting some but keep putting that off because when I tried that last year, I went freaking crazy. Literally. Mood swings that were so violent that I had to watch myself to keep from doing violence and I am NOT like that at all. It was terrifying until it wore off in a few weeks. So the naturopath is prescribing some custom creams until we nail down doses and timing and she is addressing a few hormones. Her theory is that something, probably the weight loss but could have been anything, just knocked my hormone tree over and that with some careful tending, we can rev it back up and it should be fine on its own, or with a little estrogen cream. I hope.


Now with the rise in PTH, the bone issues show up in my bloodwork. Except it doesn't really say anything. argh.
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http://labtestsonline.org/understanding/analytes/pth/tab/sample/

Parathyroid hormone (PTH) helps the body maintain stable levels of calcium in the blood. It is part of a feedback loop that includes calcium, PTH, vitamin D, and, to some extent, phosphorus (phosphate) and magnesium. Conditions and diseases that disrupt this feedback loop can cause inappropriate elevations or decreases in calcium and PTH levels and lead to symptoms of hypercalcemia or hypocalcemia. This test measures the amount of PTH in the blood.

•If calcium levels are low and PTH levels high, then the parathyroid glands are responding appropriately, producing appropriate amounts of PTH. Depending on the degree of hypocalcemia, a health practitioner may investigate a low calcium level further by measuring vitamin D, phosphorus, and magnesium levels.

...​

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Maybe it is as simple as bringing my Vit D level (now @ 48) higher, even though that means a 100 iu dose a day. We will test again in 3 months.

Otherwise, she is going start dosing with me with t3 directly because of Wilson's Syndrome. Temperature regulation, Hair loss, lack of energy, brain fog and measured lack of t3 available in my blood. If you think the science is bad with the MTHFR stuff, this is worse because of actual fraud convictions. But these exact issues have been plaguing me since long before the DS and they are getting worse. I got nothing to lose 'cept money.

And lastly, she gave me a ton of Food-Blood sensitivities tests and they came back as I must be part goat. I can eat anything. Cranberries were the worst for me, and they didn't make above a 0.5 on a scale of 1 to 10. It was fun to watch the doctor back away from what had to be a pretty standard speech. She was still "eat sweet potatoes not candy" but you could tell her heart wasn't in it.

Other stuff from my blood work: the normal year 2 to 4 fade on Zinc @ 66 and Vit A @ .45 is at work, so I will upping those. My b6 is too high, but steadily dropping for the last two years now that the only B vits I take are the Centrums. All the rest of the B's values are good. Protein could be higher, but it is holding in there. My platelets are still low, but close enough for me to decide to worry about that next time. Upping my iron to 3 Proferin a day and a chewable and 2 liver pills turned that around.

Shew. Nothing is on fire. I think this is probably a normal DS stage. Now is when I get to see what the DS fixed (like high cholesterol) and what it didn't. I really am doing great, I just wish I understood:

1. Why are my liver values moderately bad and getting worse?
2. Why are my bone values all good, but the bone scan shows such a drastically bad change?
3. Why am I so cold, so hairless and so brain fogged, even though my thyroid values are better?? The symptoms are still getting worse.
4. Why am I still losing a pound a month, even after adding back sugar and soda and being as much as a glutton as I can handle?
5. Why am I still running on about the same level of energy as I did at 314 lbs. even though now I'm in shape?

 

[Settledownnow]

I will take a shot at this -

1. Why are my liver values moderately bad and getting worse?
I was told these are normal values during weight loss and not high enough to worry about.

2. Why are my bone values all good, but the bone scan shows such a drastically bad change?
Need your vit D level to be closer to 100.

3. Why am I so cold, so hairless and so brain fogged, even though my thyroid values are better?? The symptoms are still getting worse.
What are your B vitamin levels? Zinc? A? Iron and ferritin?

4. Why am I still losing a pound a month, even after adding back sugar and soda and being as much as a glutton as I can handle?
You are exercising 3x per week. Perhaps you just need more food. Add higher quality food such as complex carbs rather than sugar.

5. Why am I still running on about the same level of energy as I did at 314 lbs. even though now I'm in shape?

Possible Vit/Min deficiencies or thyroid problems, not getting enough sleep or quality sleep, and/or too much stress in your life.

 

[southernlady]

A D of 48 would have me at 100k a day and get retested in a month. How was your PTH?
Both correlate to bone health. http://bariatricfacts.org/threads/i-have-osteoperosis-now.906/

 

[DianaCox]

When you are losing weight, your body realizes that your bones don't need to be as dense as they used to be. Some of the shedding of bone density is normal - and pretty much can't be stopped. It will look bad because of the percentage of CHANGE. But some of it can't be avoided.

Most of us have fatty livers, and they don't heal. At almost 14 years out, my liver numbers are going up - some of it may have been that I was OVERDOING vitamins A and D - they were literally at the very top of normal. I stopped taking them for a few weeks, and my liver numbers went down (not sure it is 100% correlated, but - they went down), and restarted at half the dosages. My vitamin numbers are down a little, but still high normal. My liver numbers are still high, but less high.

Date AST (0-40) ALT (0-32) Comments
1/9/17 136 162 Initial appointment

1/27/17 126 274 Recheck

2/20/17 74 145 After stopping Vit A, D, K1, K2

5/18/17 48 184 After resuming ½ dose of Vit A, D, K1, K2

My GI doc doesn't think a liver biopsy is necessary. However, he wants me to lose 20 lbs. I'm at about 168 now. I will try to get more exercise, and if weight loss happens, it happens.

 

[Paula]

Im compound heterozygous for MTHFR mutation. This means Ive got both the A and C. This does require lab testing to make 100% sure which variation you have. For me, this translates to high homocysteine that I can keep reduced to normal levels by supplementing higher in folic acid. For me, its 2400mcg per day. Not all variations of the MTHFR mutation causes a spike in homocysteine, so some are lucky. But its not a biggie at all to nip high homocysteine in the blood.

I take 2 Centrum type multivitamins per day myself in addition to the folic acid and other DSer supplements. Not sure if I answered any questions or anything

 

[Brandy]

Thank you all!

I still haven't dug into the details of this mutation too much, but I did drill down into the details of changing from 4 doses Centrum to one dose of DFH Complete Multi and it will be OK. I did have to change a few other pills and add their DFH OsteoForce Supreme Bone Support, but after all is added and subtracted, all my vitamin totals make sense. Yeah, +100 here and -500 here, but after lining those up with my bloodwork, it's all good. Color me surprised. Should have done that before I freaked out. I wish I would hurry up and learn that life lesson.

It does hit me as weird that four times the normal dose of centrum is basically equal to one dose of from the DFH or Designed For Health brand. I mean "normal" people, not bariatric people, are told to take the same level of vits as we do. Ok, we will blast D3 and A's and our troublesome vits a lot higher, but the base vitamins are the same. If I heard of a "normal" person taking 4 Centrum a day, I would worry about them. Just when I start to think I have a good understanding of nutrition, I get blown out of the water.

I bet that I more than doubled the cost of my vitamins, but I'm not going to calculate it so I won't start crying. With elevated liver values and known problems in the supplement industry I guess it makes sense to move to brands that do a better job of testing. Oh, and it will add around 5 pills daily, but they are all big caps, so not a big deal. As long as pills don't smell, I can get whole handfuls down by now.

But the bottom line:

I feel much better as I've started implementing the naturopath's suggestions. I've only started DHEA in the AM and pregnenolone in the PM and just the DFH Multi (the bone one isn't in yet) AND direct T3 dosing, twice a day. But It is like something deep in me that has been clenched for a decade is relaxing. I'm not overly tired, but I went to bed early last night just cuz I was so relaxed and content. Then I slept through the night, which I'm not sure has happened in a few years.

I'm going to keep going down this road. Tuesday I will be able to pick up the custom creams with the rest of the hormone therapy. Last time I tried estrogen I went nuts, so keep your fingers crossed. I also haven't started the liver detox, cuz I'm wary of taking that much B6, but I think I will trust her and try it once everything else settles down.

Again, thanks to you all for all this community does. It matters.

 

[Brandy]

I'm compound heterozygous for MTHFR mutation. This means Ive got both the A and C. This does require lab testing to make 100% sure which variation you have. For me, this translates to high homocysteine that I can keep reduced to normal levels by supplementing higher in folic acid. For me, its 2400mcg per day. Not all variations of the MTHFR mutation causes a spike in homocysteine, so some are lucky. But its not a biggie at all to nip high homocysteine in the blood.

I take 2 Centrum type multivitamins per day myself in addition to the folic acid and other DSer supplements. Not sure if I answered any questions or anything

This was especially helpful to me since I was freaked about it all and you helped me to realize that it will just mean a different pill or two. Thank you.

What type / brand of folic acid do you take?

Thanks!

 

[Settledownnow]

Thank you all!
I also haven't started the liver detox, cuz I'm wary of taking that much B6, but I think I will trust her and try it once everything else settles down.

Again, thanks to you all for all this community does. It matters.

What is the liver detox she is suggesting?

 

[Paula]

This was especially helpful to me since I was freaked about it all and you helped me to realize that it will just mean a different pill or two. Thank you.

What type / brand of folic acid do you take?

Thanks!

Im glad this helped you out. It was pretty freaky for me at first after my hematologist gave me the results of the testing. I like buying the 800mcg formulation, but I have no brand loyalty. Ive used NOW, Vitamin Shoppe, etc. Before I started folic acid, my homocysteine got up in the 70's. But with folic acid, its around 8.

 

[Brandy]

What is the liver detox she is suggesting?

Thorn Research Methyl-Guard Plus

Reviews on Amazon are positive and agree with my doc to start these puppies slow. The real dose is 3 pills but because they will be flushing stuff, she said to start with one and even skip to every other day if you want. She said most of her patients take about three weeks to a month to work up to the full dose.

Because we are changing my supplements and hormones, I'm going to wait until I know how all those are working before I introduce these. I will follow up here when I start the experience and I hope if any of you do this , you will too!

..b.

 

[Settledownnow]

Thorn Research Methyl-Guard Plus

Reviews on Amazon are positive and agree with my doc to start these puppies slow. The real dose is 3 pills but because they will be flushing stuff, she said to start with one and even skip to every other day if you want. She said most of her patients take about three weeks to a month to work up to the full dose.

Because we are changing my supplements and hormones, I'm going to wait until I know how all those are working before I introduce these. I will follow up here when I start the experience and I hope if any of you do this , you will too!

..b.

These look like B vits. Not sure how they are flushing the liver -- ? I thought perhaps you might save milk thistle or something along those lines.