High levels of folate require bone marrow biopsy?

[Marlene]

Hi Chirley,

Current thinking in the Functional Medicine world is that the type of Folic Acid used is critical. The folic acid found in most vitamins and in fortified foods is not recommended for those with the mutation. Even those without the mutation should avoid this form of folic acid. For those with the mutation, the body cannot utilize it, it builds up leading to other problems like cancer. For those without the mutation, they may not be converting it for other reasons...they could be lacking in the co-factors needed for the conversion. Some co-factors are B12, B6, B2, zinc and magnesium.

So even though you cannot correct the mutation, knowing you have it can provide some insight in designing a proper protocol to ensure proper methylation.

I listened to a couple of podcast on this and it was interesting to learn this doctor's approach to correcting methylation and the balance is key. Over methylation can occur so you really need a tailored protocol. Over methylation is easily dealt with and is usually a result of supplementing too aggressively. Or, there are other genetic mutations in the methylation pathway that have not been identified yet. This doctor starts with getting B12 levels up before adding in the bio-available folate. Without B12, the folate won't get to where it's needed.

Raw, green leafy vegetables is the natural way to get your good folate. If you supplement, L-methylfolate, quatrefolic or 6S-5 forms are the ones to use.

Anyone who is using nutrition as part of their recovery or treatment for their bone marrow disease would benefit greatly by understanding the methylation process at a high level.

[sbk007]

Dacogen,Vidaza, SGI112,whatever, they all demethylate DNA. The thinking being that the methyl groups bound to DNA prevents gene expression. When the methyl groups are released they do express themselves. Green Tea is known to demethylate but unfortunately not an option for a fix. I don't think taking 400 mcg of folic acid could hurt but any vitamin in high doses can do more harm than good especially the fat soluble Vities.A,E,D,K and whatever.. Thanks for the post I'm going to ask my doc about it. On another note when I was first diagnosed my platelets were at 80k, having tested Vit D deficient twice (not by much), I started taking 1000 IU a day.
Without any treatment my platelets rose to 140k and never dipped below 130k, until I started Vidaza and hit "Nadir" but still 110,000. I have doubts whether or not the Vit D was the reason for the rise but my doc says it cant hurt to take 1000IU. When I asked my GP why he didn't take a vitamin D test he said he assumes everyone in the northeast is deficient, and when I asked the rocket scientist @ Cornel-Weil he said no one goes in the sun anymore..
Regards, Steve

[Marlene]

I would still avoid the folic acid form of folate and go for either raw leafy greens or the bio-available form.

I think high doses of niacin will consume methyl donors in cases of over methylation. Also curcumin/turmeric. Didn't know about the green tea.

There really is a balance in all of this. I understand that a person can have both under methylation and over methylation simultaneously. In that DNA is over methylating while the rest of the body is under methylating. I assume the MDS drugs target DNA but I don't know enough about them at this point.

John was Vit D deficient too. Upping his level didn't have an impact on his counts though. But then, nothing really did. Probably getting the iron out was key in recovery for him.

As usual...the more I learn, the less I know .

[Chirley]

Thank you that explains a lot. I read (but didn't comprehend) a research abstract on copper transport and learnt that copper uses a methylation pathway as well. In my own mind I have been linking my MTHFR mutation with my copper problem but when I mentioned this to the Metabolic Medicine doctor he discounted any relationship.

So little is known about the basic methodology of metal and vitamin metabolism that I take the doctors denial of a relationship with a grain of salt because even he admitted that his knowledge was limited.

I will try to ask my current Physician to look at the B vitamins and their relationship to bone marrow disorders and copper. Give him some homework so to speak.

Co incidentally, I also have/had Vit D deficiency. I don't know the numbers but I was put on two capsules a day for a number of months in 2010. The haematologist wrote a letter to my GP saying that my Vit D level was significantly low. I had another test in beginning of 2011 which still showed "extremely low" levels. I continued the Vit D for another three or four months then it was stopped. I've never had another level taken. Maybe it's time for another Vit D test.


Regards

Chirley

[Marlene]

I find the medical abstracts difficult also. Almost as bad as a legal contract. And anytime they try to explain metabolic pathways it's even more difficult. Like you said, even most doctors don't have a good handle on it. It's still a very specialized area of medicine/research that is just now starting to get more attention. I think the genetic testing and the interest in epigentics is shedding more light in this area. Also, so much of this is a result of research on autism and is netting out benefits to other chronic diseases that are on the rise in our modern world. Many kids with autism have metabolic pathway issues as well as digestive problems. Correcting them or managing them can go a long way in reducing or even eliminating the severity of their symptoms.

Regarding the vitamin D. Unless you're getting at least 20 - 30 minutes of sun exposure daily, you're probably low again. Both John and I had low D and we both continue to take it. We took 5000 iu's of vitamin D3 daily for 3 months to get our levels in a normal range and continue to take it to this day but not every day. In the summer, I slack off more because of greater sun exposure. Vitamin D works best when taking Vitamin K2. You can find good formulas that combine the two now. Basically, for every 1000 iu's taken, you can expect to increase your level by 10 point over a three month period. Here's a good site on Vit D that speaks to dosage.

http://www.vitamindcouncil.org/about...my-body-needs/

Make sure you're taking vitamin D3 and not the synthetic D2. Most prescription D is D2 and doesn't work as well.

I'm so glad to hear you're doing better with the copper infusions.

M

[Lbrown]

Hi Marlene and everyone,

I started taking B12 a couple weeks ago. I suspect I've had undiagnosed celiac disease for a long time now (since the 1990s). I may have been tested for B12 but I have no record of the results (in Canada they don't give you results unless you specifically ask, which is very annoying to say the least). So I assume way back when I was first diagnosed in 2008, that B12 and folate would have been something they would have tested, but I don't know for sure.

Yesterday I did a search for Gluten in "Blood" and just happened to come across this article. http://bloodjournal.hematologylibrar...d-448bb8e8572c

I have most of the symptoms - pancytopenia, chronic diarrhea, IgA deficiency, dermatitis herpetiformis (DH). The DH started around the same time as my blood disorder, which is a normocytic anemia. At first they diagnosed PRCA, I was negative for parvo and thymomas and stuff. I thought the DH was a result of the exjade. Just recently I went on a strict gluten free diet and the rash is now gone, 100%.

I am in the process of being referred to an internal medicine specialist, someone who might be able to put 2 and 2 together and come up with 4 instead of just 3. I've been transfusion-dependent almost 4 years now. I have been treated with cyclosporine, IVIG (which was disastrous), ATG/tacrolimus (which was disastrous), and then I finally refused to do anymore treatment. I saw the transplant team in 2011 where I was told my bone marrow was normal. I was offered more immune suppression then and refused. I'm on an alternative treatment & transfusions.

It's early days for the gluten-free diet (since May 25) but already my platelets are up from 27 to 52, my WBC is up a bit from 0.6 to 1, neuts are doubled, and my HGB isn't dropping as much.

I am taking 1000 mcg B12 a day, and I am pretty sure I get lots of folate through veggies. My ferritin is around 1300. I try not to take exjade very often but sometimes I have no choice.

What do you think? Should I be supplementing something else? I'm not big on supplementing as a general rule, but I may have a long term deficiency because I have been anemic since at least 2003.

Deb

[Marlene]

Hi Deb,

Initially, I would suggest upping the B12. What form are you using now? I would increase the dose to 2000mcg now and see how you feel on it. If after a few days you feel OK, then up it again. The target would be to get to 5000mcg daily. Then you can consider adding others. I'm a advocate of the low and slow approach.

Depending on how much damage was done to your stomach and small intestines, you may have to use B12 the rest of your life. As you know, celiac interferes with your body's ability to break down and absorb nutrients. A healthy gut is sooo important to good health.

You must be very pleased uncovering the gluten connection. I don't test positive for it but I do much better off of wheat. Same with my sister. And, a good friend's mother stopped all wheat and within one week, her blood pressure dropped 40 point. What's going on with wheat these days?

[Lbrown]

Hi Marlene,

That was quick!

I bought methylcobalamin, I read that was a better form for your body to break down. I did notice you could get 5000 mcg but I thought I better start cautiously.

About 10 or so years ago I was taking some supplements, and noticed B12 did give me more energy.

The gluten connection does explain why I always felt better on a low carb diet. I do find it annoying that none of my doctors even suspected it, but all I want now is to get better. Even if I have to take it the rest of my life it would beat transfusions!

Deb

[Marlene]

I'm very close to my computer this week....working on the house and I can only wash the ceiling in small section before my shoulder acts up. Getting old has its challenges. So each time I take a break, I get on my computer. HA!!!

The methyl form is good. Some people can't handle it and have to try other forms. I think the least effective is Cyno form B12.

Let me know how you do with the increased doses. If you tolerate it well, then consider adding in l-methyl folate, then p-5-p form of B6 and then a B complex.
At some point, a good B complex and B12 may be all you need. That's it for the B's. Thorne makes a good supplement with bio-active b vitamins in a combo. That may be helpful down the road. But for right now, I think doing the key nutrients one at time is a good approach.

[Lbrown]

Hi Marlene,

Washing the ceiling?! Wow...

I'll try increasing the B12 and see what happens. It's been so long since I've been able to do much, now at least I'm able to go get groceries with my husband again and I feel stronger riding my horse. I have had no days of total exhaustion since I quit gluten. I am getting impatient to get better!

Deb

[Marlene]

All in prep of painting. The prep, then the clean up from painting is the the part I dislike.

I'm glad you're starting to feel better. It can take a long time to recover but you will get there. If there's one thing we all learn with this disease, it's patients.

[Chirley]

When I first became anaemic part of the investigation work up was an antigliadin antibody test for Celiac Disease. It was very high so I had a duodenal biopsy which came back negative for CD. I was told the gold standard for a CD diagnosis was the biopsy and that overrode the blood test results.

I was very relieved because I would hate to go without my bakery items made with wheat flour. I love ordinary white bread

Regards

Chirley

[Marlene]

I too love my breads and bakery. I could eat pasta every day. Unfortunately, wheat is very inflammatory so I stopped it 100% for six weeks to give my body a rest. (side note: It takes 21 days for your system to clear the antibodies created by wheat/grains) Now I'm more relaxed about and will have it on occasion. John found a great gluten free dessert cook book which uses mostly nut flours. So I got me a nut grinder and have been able to make some very delicious cakes and tarts.

But you can't beat a good piece of artisan bread with butter.

[Chirley]

And a nice bitey vintage cheese.

[Lbrown]

I haven't been tested, and at this point I refuse to eat wheat on purpose again just for a test. I've had symptoms of this for at least the last 10 years. I'm feeling better with more energy but it's still early days.

Marlene, that's interesting about the 21 days. So, if you have antibodies for an additional 3 weeks, I would think you could expect further damage for several weeks after going gluten free? I have noticed with my counts there seems to be a 4 - 5 week lag time. That could explain things.

Deb

[Marlene]

That is an interesting conclusion. It will also take time for the cells in the lining of the GI track to heal and be replaced. Depending on severity of damage, it may not completely regenerate right away.

Your GI track needs zinc, iodine and l-glutamate for healing. Zinc, can be difficult to breakdown. And good bacteria replacement would be helpful too.

You may want to look into bitters like Swedish Bitters. There's are quite a few variations of bitter herbs specifically for digestion and GI health.

[Lbrown]

Here's the conundrum now.

My digestion seems to slowly improve (the chronic diarrhea is not so chronic), but then I take exjade and it starts up again. How do I judge if things are healing under these circumstances? Or - are they? Because I know exjade is pretty harsh on the GI tract.

I am taking 1500 mg at a time, but sometimes skipping weeks or only taking it a couple times a week. My last ferritin count was ~1300. At least it isn't totally out of control.

Maybe more probiotics etc would help.

Deb

[Marlene]

We never figured out how to battle the GI issues Exjade caused. John was mostly nauseated from it. He never got to a full dose and would still have to take a break every three weeks until he felt better. He had the opposite problem you're experiencing. It really slowed down his motility.

I think taking breaks is smart. Have you thought of reducing the dose? And 1300 is not that bad but I understand wanting to keep it in check and reduce it if possible.



On another note....I just read an interesting article on B12 that talked about the difference between two active forms of B12, the methyl form and adenosylcobalamin form. The takeaway was that the later form was utilized more by the blood than the methyl form. Methyl seems to be more effect for the brain/cns. Both will work systemically so I'm not sure if this is significant. But thought I'd mention it in case want to mix it up a bit and alternate between the two. We're all just our own science experiments .

[Lbrown]

Hi Marlene,

I'm supposed to be taking 2000 mg daily. The last time I tried 2000 mg I thought I was going to die. It took days to recover from severe gastro upset, but strangely enough I used to take that dose all the time. I do wonder what it does to your insides. I basically keep an eye on my ferritin and if it drops I quit taking exjade until it rises again.

Interesting about the B12. I am taking the methyl form, can you buy the other form or does it have to be shots? I am waiting to be referred to an internal medicine specialist and this is one of the things I will ask about (whenever that might be, it's been a saga trying to get referred).

Deb

[Marlene]

Yes you can. I just did a search and found it but most of them had folic acid in them except this one: http://www.highlandvitamins.com/products/vitamins/

This has all three of the bio-available forms of B12 without the folic acid.

BTW, dibencozide is another name for adenos form.

Wow, 2000mg is alot of Exjade. John never got beyond 750. And by the end, he had to reduce it to 500mg and then just stop because his kidneys had enough.

[Lbrown]

Yup, it is a lot of exjade for sure. I took that much for ages. I hate taking that nasty stuff.

Glad to see the B12 said gluten-free, because when I saw Maltodextrin I wondered. I am now taking 2000 mcg of the methyl stuff with no problems.

[Marlene]

Have you verified that Exjade is gluten free. I looked at the inactive ingredients and they appear ok. The only thing that may need checking is the micorcrystalline cellulose.

Glad you're tolerating the higher dose.

[Lbrown]

On celiac.com it says that microcrystalline cellulose is GF. I figured cellulose came from wood fiber, but it was a good idea to check. Maybe I'll send an email to Novartis to make sure.

Thanks,
Deb

[Marlene]

The product itself may be not be gluten but if it's manufactured in a plant that also handles gluten additives then cross contamination can occur. So it's best to check with them to ensure it's "gluten free".

Being gluten free is a challenge. I never knew so many medications had gluten, as well as dairy in them.

[Chirley]

When I have my B12 levels tested the doctor orders a B12 level and an active B12 level. I don't know how the tests differ but I am always below normal or low normal that's why I'm on the injections.