COMPOUND HETEROZYGOUS MTHFR

[therron]

I would love to hear from others with MTHFR gene mutations and how you have approached the methylation protocol. I have two issues (677 and 1298). I have reacted very poorly to all methylation supplements tried in the past. Based on things I have read in this forum, I have a feeling that Freddd's protocol is the way to go for me because of genetic issues. I have just finished week 2 on adb12 (1/4 tablet 4 x per day). I'm starting to get that "internal pressure" feeling again, in which my stomach and intestines feels bloated/tight, blood vessels feel pressurized......same as always........

 

[Freddd]

I would love to hear from others with MTHFR gene mutations and how you have approached the methylation protocol. I have two issues (677 and 1298). I have reacted very poorly to all methylation supplements tried in the past. Based on things I have read in this forum, I have a feeling that Freddd's protocol is the way to go for me because of genetic issues. I have just finished week 2 on adb12 (1/4 tablet 4 x per day). I'm starting to get that "internal pressure" feeling again, in which my stomach and intestines feels bloated/tight, blood vessels feel pressurized......same as always........

Hi Therron,

For starters adb12 does nothing directly for methylation and like other forms of b12 other than methylb12, has to be converted to methylb12 before doing any methylation and is hence a methyl competitor. However, the folic acid in the Country Life, if that's the brand you are taking, could be causing paradoxical folate deficiency. You might want to get rid of folic and folinic acid in all supplements and go to forms that don't include them.

So far starters could you list all the things you are taking and let's examine them for problem areas. Be specific as to brand and name unless it is very basic like calcium that doesn't include other things.

 

[therron]

Hi Freddd,
Thank you for responding. My worst reactions to supplements are always insomnia and abdominal discomfort. Since my reactions to supplements usually come after a two week build-up, I will include duration in my list:
*Past 5 months-every single day: Natural Factors Olive Leaf Extract 500 mg x 5 = 2,500 mg. (Started with just a few drops then worked up. Cured 95% of my gut issues. Couldn't live without it.) Spring Valley melatonin: 3mg each night. That's it.
*Past month: Added 2 NOW Omega 3 capsules per day. (I have never had a problem with omegas). Peter Gillhams Calm + Calcium (350mg magnesium, 230 mg calcium, 115 mg potassium, 290 mg vit c, 115 iu d3, 290 mcg boron). Helped me sleep for a week or two.
*Past 2 weeks: Added 1/8-1/4 of a 3000mcg sublingual Country Life Dibencozie 3-4x per day, 1/8 of a Jarrow 1000mcg sublingual 1x per day. Immediate responses include speed-talking, increased energy, and insomnia.
*Four days ago: Added 1/4 of 800mcg Solgar folate (L-methylfolate/metafolin) tablet.
*Two days ago: Switched to Source Naturals dibencozide.
The uncomfortable feeling in my abdomen started near the 10 day mark after the first dibencozide. It is the exact same feeling that I have gotten from Sam-e, Tmg, methylcobalamin.... Lots of pressure/burning/pain beneath sternum. Increased insomnia. Feelings of vascular pressure.
I would appreciate any comments you might make.

 

[drex13]

I would love to hear from others with MTHFR gene mutations and how you have approached the methylation protocol. I have two issues (677 and 1298). I have reacted very poorly to all methylation supplements tried in the past. Based on things I have read in this forum, I have a feeling that Freddd's protocol is the way to go for me because of genetic issues. I have just finished week 2 on adb12 (1/4 tablet 4 x per day). I'm starting to get that "internal pressure" feeling again, in which my stomach and intestines feels bloated/tight, blood vessels feel pressurized......same as always........

I too am Hetero for both MTHFR (677 and 1298). At present I am having difficulty with both Metafolin and Mb12, but to be fair I don't have any of the cofactors in place.(I am taking potassium and magnesium) They both seem to cause extreme digestive upset, cramps, etc.. and a very intense flu like beginning a few days in. I think maybe I need to get a base of cofactors down before I start mehtylation.

 

[therron]

Hi Drex,
Yes, the same thing happens to me. Major digestive upset, cramps, pressure. I have tried methyl b12 sublingual, liquid, and injections. Methylfolate, TMG, Sam-e, and some others do the same thing. Even at small doses they all end up backing up in my system by the 2-week mark. My mother and sister have had amazing results with methyl b12 and methylfolate. I'm assuming they each only have one of the mutations (they've never been tested). Since I'm so sensitive, I try to start one thing at a time, but then there is the issue you cited, in that cofactors must be in place. Kind of a Catch-22. I wonder if there are any others out there who are compound heterozygous for MTHFR 677 and 1298 that have been successful. Any ideas on where else to post?

 

[Freddd]

Hi Drex,
Yes, the same thing happens to me. Major digestive upset, cramps, pressure. I have tried methyl b12 sublingual, liquid, and injections. Methylfolate, TMG, Sam-e, and some others do the same thing. Even at small doses they all end up backing up in my system by the 2-week mark. My mother and sister have had amazing results with methyl b12 and methylfolate. I'm assuming they each only have one of the mutations (they've never been tested). Since I'm so sensitive, I try to start one thing at a time, but then there is the issue you cited, in that cofactors must be in place. Kind of a Catch-22. I wonder if there are any others out there who are compound heterozygous for MTHFR 677 and 1298 that have been successful. Any ideas on where else to post?

Hi Therron,

Have you completely eliminated folic and folinic acid?

 

[lucyhem]

Hi Drex and Therron
I have two MTHFR 677 gene variants and i dont' know about the 1298. The reason that I continue to pursue this with persistance is that my medication prescriber offered me Deplin (methylfolate), and for about five days I felt like myself completely without anxiety. It was remarkable. THen it stopped working. I now understand that the detox pathways were not ready for that. So now I have discovered the methylation pathway theory and am trying to back up and clear the pathways so that methylfolate can work its magic on me. I am interested to read what you are trying and wonder if anyone has tried injecting the folinic acid or methylfolate? Would that by pass the metobolic issues at least until those pathways can be cleared?
I don't get digestive disorders except the same old constipation issue.
I wish you both well in finding the right cofactors. This is all new and I am trying to figure out where to start myself.

Lucy

 

[Freddd]

Please notice the side effects of Metafolin without NAC and with NAC (Deplin with NAC). These are severe folate deficiency symptoms, whether becasue of NAC, glutathione, folic acid or folinic acid, the last two casuing paradoxical folate deficiency.


Deplin (pure Metafolin) side effects
Are there side effects with Deplin? http://www.deplin.com/DeplinFacts,WhatToExpect
L-methylfolate was well tolerated in both short-term and long-term trials. Side effects did not differ from a sugar pill (placebo).15-18 Deplin has not been associated with weight gain, sexual dysfunction, nausea, or akathisia.15-21

http://www.drugs.com/sfx/cerefolin-w....htmlCerefolin with NAC

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Cerefolin with NAC:

Bloated feeling; headache; itching; mild diarrhea; mild fever; nausea; vomiting.
​

Seek medical attention right away if any of these SEVERE side effects occur when using Cerefolin with NAC:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); lower back or side pain.
​

So we see these side effects for Metafolin with NAC and NONE of them for pure Metafolin. These NAC side effects are commonly called "NAC detox" and are in fact identical with severe induced folate effects. Notice the increase in allergic response and the IBS onset. Also identical with "glutathione detox" effects. Also identical with paradoxical folate deficiency effects. The Cerefolin with NAC list is not a complete list, just the consumer list. I'm still chasing down that professional list.

 

[therron]

Hi Freddd, Drex, and Lucy,
I have dropped Country Life and switched to Source Naturals dibencozide + Solgar folate. I had to back down on the dosage because the digestive side effects and insomnia were not tolerable. I work full time, and cannot function with zero sleep. Also, the speed talking and OCDish side effects make working and social relationships a challenge as it takes a huge amount of energy to continually monitor myself (I don't have this problem off the supplements). Basically, now I just take a tiny crumb off of 1/4 dibencozide sublingual tab and the same for folate. It still speeds me up, but not as badly. I have added vitamin D and extra Omega 3s. The only other supplement I currently take is 3 mg melatonin every night. Insomnia and digestive discomforts have eased a lot too. I want to be able to use larger doses as suggested in order to push through the methylation block, but I really can't function physically or emotionally. I will continue to increase my crumbs and let you know how it goes. I hope to start a crumb of the B-12 complex with metafolin as well. Waiting for order. PS I discovered that if you are COMT++ or VDR taq+ you will NEED b12, but not be able to tolerate it well.

 

[drex13]

Hi Freddd, Drex, and Lucy,
I have dropped Country Life and switched to Source Naturals dibencozide + Solgar folate. I had to back down on the dosage because the digestive side effects and insomnia were not tolerable. I work full time, and cannot function with zero sleep. Also, the speed talking and OCDish side effects make working and social relationships a challenge as it takes a huge amount of energy to continually monitor myself (I don't have this problem off the supplements). Basically, now I just take a tiny crumb off of 1/4 dibencozide sublingual tab and the same for folate. It still speeds me up, but not as badly. I have added vitamin D and extra Omega 3s. The only other supplement I currently take is 3 mg melatonin every night. Insomnia and digestive discomforts have eased a lot too. I want to be able to use larger doses as suggested in order to push through the methylation block, but I really can't function physically or emotionally. I will continue to increase my crumbs and let you know how it goes. I hope to start a crumb of the B-12 complex with metafolin as well. Waiting for order. PS I discovered that if you are COMT++ or VDR taq+ you will NEED b12, but not be able to tolerate it well.

I've seen those references to COMT +/+, but I can't figure out specifically which COMT they're referring to . From what I can tell, Yasko looks at 4 (V158M or rs4680, H62H or rs4633, L136L not in 23andMe, and 61 or P1998 or rs769224) of them, and 23andMe reports on 3 of those 4. I think I am hetero for 2 (V158M and H62H) and GG for the third (61) (not sure if GG is +/+). I also don't get the VDR Taq result. They say VDR Taq +, but I have 2 letters for the result (A/G). Still trying to figure it out.

 

[rwac]

When someone refers to COMT+/+ they're usually talking about V158M, Rs4680. This is the warrior vs worrier SNP.

 

[drex13]

When someone refers to COMT+/+ they're usually talking about V158M, Rs4680. This is the warrior vs worrier SNP.

I'm +/-, hetero, so...... I'm a worrying warrior ? or a worrier that likes to fight ? (actually that's pretty close)