Treat MTHFR C677T if you have it

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LG1
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Re: Treat MTHFR C677T if you have it

Postby LG1 » Tue Feb 16, 2016 5:17 am

Hubbs wrote:Hi Laura,
I am too compound heterozygous for (C677T and A1298C) and my father had and survived a major stroke in his early 70's while traveling.
So much to learn and I am too grateful to many knowledgable people here who are very generous to help.


Hey, maybe we're cousins! lol

Yes, this is an awesome site. So thankful too.

I found the info on MTHFR pretty confusing so the info posted above from Gene and Susan is Huge.
ε4/ε4

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LanceS
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Re: Treat MTHFR C677T if you have it

Postby LanceS » Mon Feb 22, 2016 7:39 am

With Bredeson's latest research pointing toward APOE4 somehow getting into the nucleus and ???inhibiting transcription????. (I'm not sure that is what his research says. Are we still sure that treating MTHFR is a good thing for those who are homozygous? heterozygous?

I don't have a handle on the science... but it seems as if folks describe MTHFR as "disabling your DNA". And if treating MTHFR "enables it"... then it might make APOE4 more effective at shutting down processes that might be running ok in us.

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Re: Treat MTHFR C677T if you have it

Postby ApropoE4 » Mon Feb 22, 2016 9:11 am

LanceS wrote:With Bredeson's latest research pointing toward APOE4 somehow getting into the nucleus and ???inhibiting transcription????. (I'm not sure that is what his research says. Are we still sure that treating MTHFR is a good thing for those who are homozygous? heterozygous?

I don't have a handle on the science... but it seems as if folks describe MTHFR as "disabling your DNA". And if treating MTHFR "enables it"... then it might make APOE4 more effective at shutting down processes that might be running ok in us.


That research is incredibly unlikely to be valid.

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Julie G
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Re: Treat MTHFR C677T if you have it

Postby Julie G » Sat Feb 27, 2016 7:21 pm

I hope this isn't lost here, but it felt relevant in this thread... Some members are hesitant to supplement vitamin B12 when they have levels that fall within a "normal" reference range.. A new study reveals that the low end of normal is associated with both cognitive decline and hippocampal structural abnormalities.

Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment.
http://www.ncbi.nlm.nih.gov/pubmed/26912492
CONCLUSION: Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency.

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Re: Treat MTHFR C677T if you have it

Postby cdamaden » Fri Apr 01, 2016 6:22 pm

I listened to a podcast by Dr. Ruscio a few weeks ago on this topic. He came down on the side that supplementing with B vitamins can lower your homocysteine levels but that doesn't improve your cardiac risk. Here are all the references - pro and con - to using B vitamins to lower Homocysteine:
PRO ---- Studies showing lowering homocysteine improved cardiovascular outcomes: Review showing B-vitamins lower homocysteine http://www.ncbi.nlm.nih.gov/pubmed/9659410
Betaine Monograph from Thorne Research 2003 http://www.altmedrev.com/publications/8/2/193.pdf
Meta analysis showing folate and/or B12 lower homocysteine but no mention of cardiovascular disease risk http://www.ncbi.nlm.nih.gov/pubmed/9569395
Randomized control trial showing folic acid/B6/B12 lowered homo and decrease incidence of cardiovascular event http://www.ncbi.nlm.nih.gov/pubmed/12190367
Observational trial http://www.ncbi.nlm.nih.gov/pubmed/11742888
CON ---- Studies showing lowering homocysteine did not improve cardiovascular outcomes:
Meta analysis of 12 randomized controlled trials http://www.ncbi.nlm.nih.gov/pubmed/26420127
Meta analysis of 8 randomized controlled trials http://www.ncbi.nlm.nih.gov/pubmed/20937919
Randomized controlled trial http://www.ncbi.nlm.nih.gov/pubmed/18460663
Randomized controlled trial http://www.ncbi.nlm.nih.gov/pubmed/18714059
Cochrane Systemic Review http://www.ncbi.nlm.nih.gov/pubmed/25590290
Cochrane did 2 earlier Systemic Reviews with same findings:
http://www.ncbi.nlm.nih.gov/pubmed/23440809
http://www.ncbi.nlm.nih.gov/pubmed/19821378
Review http://www.ncbi.nlm.nih.gov/pubmed/16872232
Review http://www.ncbi.nlm.nih.gov/pubmed/17622392
Review http://www.ncbi.nlm.nih.gov/pubmed/20236081
Review http://www.ncbi.nlm.nih.gov/pubmed/21069462
Review http://www.ncbi.nlm.nih.gov/pubmed/24863141
Review – homocysteine is a marker rather than a cause http://www.ncbi.nlm.nih.gov/pubmed/17654449

I don't know if any of those studies included MTHFR mutation status. I am homozygous for A1298C but fine with C677T. I started taking O.N.E multivitamin (from Dr. Rhonda Patrick's podcast) just before my big lab tests that revealed my E4/E4 status. I recently added 200mg of Magnesium, which greatly improved my mood :D . The multivitamin is at about 1/2 of the B-vitamin dosage that Julie has been discussing. I did try the Active B12 Lozenge (4,000 mcg Methylcobalamin and 1,000 mcg Adenosylocobalmin) along with the multivitamin but had over-methylation symptoms. The next free weekend I get, I will experiment some by stopping the multivitamin and shifting to half a lozenge (then...) to see where my break-even point is. My one and only Homocysteine measurement was at 13 umol/L while I was on a high animal protein paleo diet (~1.5 pounds red meat a day). I've since cut that down to .3 pounds red meat every other day (want to slowly eat out all that great US Wellness Braunschweiger, head cheese, and liverwurst that is stocked in the freezer - then maybe shift to chicken livers).

If anyone gleans any insights out of those links, please let us know.

Chris
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Stavia
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Re: Treat MTHFR C677T if you have it

Postby Stavia » Fri Apr 01, 2016 6:32 pm

Chris thanks for this comprehensive information.
Even though the evidence for lowering homocysteine isn't conclusive, I personally think it's pretty harmless to do so at worst. At best we may be preventing amyloid accumulation (reference personal communication Dr Rao who is one of the scientists that work with Bredesen)

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Re: Treat MTHFR C677T if you have it

Postby Silverlining » Sat Apr 02, 2016 5:26 am

Chris, Welcome! I also wanted to chime in with my mthfr status. I'm also homo for the A, normal for the C (like you). I don't see many here with that profile. I've had my homocysteine tested twice. Once in 2010 by a neurologist who ordered a slew of labs looking for cause of nerve damage. At that time my homo was 7 something. This was long before I knew of 4/4 status and at the time I was only taking a multivitamin and broad spectrum B vitamin. I stopped taking both in the past couple of years for random reasons I won't go into. I just had my homo retested and was shocked to see it at 15! So I've added back in the exact vit b's I was taking in 2010. I retest in three months. I'm very curious to see what effect the b vitamin will have. I'll share when I get those results.

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Julie G
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Re: Treat MTHFR C677T if you have it

Postby Julie G » Sat Apr 02, 2016 2:41 pm

Chris, your plan moving forward sounds good. You may want to even consider a less active/potent form of B12. I take 1mg sublingual methylcobalamin that seems to do the trick without over-methylation.

Thanks for the impressive summary of research associating homocsyeteine with CVD. I'm much less familiar with that correlation than with the AD connection. (I could spend a full day tracking down your leads!) One thing I have learned is that much of the Vitamin B/homocysteine research has been done sloppily without pre and post test levels on appropriate subjects. Also, other confounders (like adequate Omega-3 levels/necessary for Bs to be effective) aren't taken into consideration. As carriers of a gene that predispose us to both AD & CVD, I'd be hard pressed to recommend ignoring elevated homocysteine. IMHO, it's one of the more important biomarkers for us to track and tweak as it correlates well with the inflammation associated with both pathologies. Of course, we have no guarantee that lowering it will rescue us; but combined with other strategies... it may give us a fighting chance ;).

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Re: Treat MTHFR C677T if you have it

Postby cdamaden » Sun Apr 24, 2016 1:51 pm

All,
Another Dr. Ruscio podcast is out this week. He interviewed Dr. Deborah Gordon, who treats Homocysteine issues. She maintains that the studies showing no effect of lowering homocysteine levels was because they didn't go low enough. Her target is 5-8 umol/L apparently based on a Swiss study. I asked Dr. Ruscio to post a link to the study. Her focus is to lower it for dementia, CVD, and AD.
The transcript of the podcast is here:
http://drruscio.com/homocysteine-follow ... pisode-60/

Regards,
Chris
E4/E4
Alameda, CA, USA


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