Opinion on ApoE4 plus MTHFR heterozygous

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SianM
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Opinion on ApoE4 plus MTHFR heterozygous

Post by SianM »

Hello there and firstly I'd like to say how amazing it feels to be in a forum of people who are thinking about the same things that I'm thinking a lot about and who are doing so in such an intelligent and measured way. I already feel much more positive about my situation in future.

I'm new on here because it's taken me awhile to find you but I'd like to introduce myself. I am a 51-year-old doctor living in the UK. I am female and I found out about four years ago that I have one copy of the ApoE4 gene. The reason I got tested is because I have a strong family history of Alzheimers disease, my maternal grandmother, mother, aunt and uncle. In my family it tends to start in the mid 60s and by mid to late 70s everyone who has had it so far has died of dementia. So I always knew there was something going on in the family and that it was genetic but I didn't think that one copy of the ApoE4 gene alone could account for the extent of the severity of the dementia.

Even though I've only been on this site for a few days I've been reading avidly and discovered the MTHFR gene and gone through the raw data on my 23 and me profile and now understand that I am a heterozygote for this. It makes complete sense because my blood film has always looked like I'm B12 deficient despite having quite high blood levels of vitamin B12.

What I'd really like to know from the community is whether you think that this combination maybe combined with poor health and hypertension could be enough to account for the severity of dementia in my family. I'd be really relieved if it was because if it is then maybe something I can do something about it and up until till now I've felt that this disease was my destiny. I've already bought the strong B12 and folate supplements and done this in line with what is recommended on the side here and in line with the Bredesen Protocol.

Also, I already feel my memory is a dulled and retrieval is hard work, has anyone ever found this to improve not he B12/folate etc supplements?

With my gratitude to you all

SIanM
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Re: Opinion on ApoE4 plus MTHFR heterozygous

Post by lucytownsend »

SianM wrote:Hello there and firstly I'd like to say how amazing it feels to be in a forum of people who are thinking about the same things that I'm thinking a lot about and who are doing so in such an intelligent and measured way. I already feel much more positive about my situation in future.

I'm new on here because it's taken me awhile to find you but I'd like to introduce myself. I am a 51-year-old doctor living in the UK. I am female and I found out about four years ago that I have one copy of the ApoE4 gene. The reason I got tested is because I have a strong family history of Alzheimers disease, my maternal grandmother, mother, aunt and uncle. In my family it tends to start in the mid 60s and by mid to late 70s everyone who has had it so far has died of dementia. So I always knew there was something going on in the family and that it was genetic but I didn't think that one copy of the ApoE4 gene alone could account for the extent of the severity of the dementia.

Even though I've only been on this site for a few days I've been reading avidly and discovered the MTHFR gene and gone through the raw data on my 23 and me profile and now understand that I am a heterozygote for this. It makes complete sense because my blood film has always looked like I'm B12 deficient despite having quite high blood levels of vitamin B12.

What I'd really like to know from the community is whether you think that this combination maybe combined with poor health and hypertension could be enough to account for the severity of dementia in my family. I'd be really relieved if it was because if it is then maybe something I can do something about it and up until till now I've felt that this disease was my destiny. I've already bought the strong B12 and folate supplements and done this in line with what is recommended on the side here and in line with the Bredesen Protocol.

Also, I already feel my memory is a dulled and retrieval is hard work, has anyone ever found this to improve not he B12/folate etc supplements?

With my gratitude to you all

SIanM
SianM, welcome to Apoe4.Info. I'm so glad you found our community. I'm sorry to hear you're memory has dulled and your retrieval is hard work. Many of us here are at a genetically increased risk of Alzheimer's or caring for loved ones who are, and I continue to be encouraged by both the support of this community and the up-to-date research it provides. As an Intern is my job to welcome you to our community. One of our subject matter experts will respond to your question regarding ApoE4 plus MTHFR heterozugous.

This linkPrimeris an amazing introduction and was written by a member of our community who is doctor and APOE4/4. She is so knowledgable and optimistic!

The How to guideis another link that will be resourceful.

I hope this helps you on your journey. We look forward to hearing from you and thank you for being a part of our community.

Warmly,
Lucy
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SusanJ
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Re: Opinion on ApoE4 plus MTHFR heterozygous

Post by SusanJ »

SianM wrote:Also, I already feel my memory is a dulled and retrieval is hard work, has anyone ever found this to improve not he B12/folate etc supplements?
If you haven't already, you might want to check out Dr. Bredesen's Recode Protocol, which shows there are many possible underlying problems for cognitive issues. Fixing your methylation pathway is definitely one and certainly can't hurt.

There is a section in the Methylation Wiki that talks about cognition and ApoE4 with regards to one's homocysteine levels. Have you checked your homocysteine levels?

I always suggest people look at their family history, and given the high blood pressure comment, do you have problems with that? And what else causes poor health for your family? Any source of inflammation can be bad for cognition.

Personally, just tackling the methylation problems, while extremely helpful, didn't address my brain fog and memory issues. I have many variants in the methylation pathway, including being homozygote for MTHFR (and an ApoE3/4). Over time I lowered my homocysteine by taking TMG (see wiki for strategies) and tackled gut health. I finally nailed down my memory issues by lowering oxalates in my food. Goes back to family history. Three of four of my brothers have calcium-oxalate kidney stones and although I didn't have kidney stones, oxalates were causing other inflammatory problems for me.

So, give the supplementation a try. And if it doesn't quite work for you, at 51, it seems you might want to start with looking at your hormonal status. Memory can certainly be affected by changing hormone levels (and the sleep problems that menopause often brings).

And also check out the other labs that Bredesen includes in his protocol. There might be something in there that matches up to you or your family that is worth pursuing.

Good luck and keep reading!
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Re: Opinion on ApoE4 plus MTHFR heterozygous

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SianM wrote:Hello there and firstly I'd like to say how amazing it feels to be in a forum of people who are thinking about the same things that I'm thinking a lot about and who are doing so in such an intelligent and measured way. I already feel much more positive about my situation in future.

I'm new on here because it's taken me awhile to find you but I'd like to introduce myself. I am a 51-year-old doctor living in the UK. I am female and I found out about four years ago that I have one copy of the ApoE4 gene. The reason I got tested is because I have a strong family history of Alzheimers disease, my maternal grandmother, mother, aunt and uncle. In my family it tends to start in the mid 60s and by mid to late 70s everyone who has had it so far has died of dementia. So I always knew there was something going on in the family and that it was genetic but I didn't think that one copy of the ApoE4 gene alone could account for the extent of the severity of the dementia.

Even though I've only been on this site for a few days I've been reading avidly and discovered the MTHFR gene and gone through the raw data on my 23 and me profile and now understand that I am a heterozygote for this. It makes complete sense because my blood film has always looked like I'm B12 deficient despite having quite high blood levels of vitamin B12.

What I'd really like to know from the community is whether you think that this combination maybe combined with poor health and hypertension could be enough to account for the severity of dementia in my family. I'd be really relieved if it was because if it is then maybe something I can do something about it and up until till now I've felt that this disease was my destiny. I've already bought the strong B12 and folate supplements and done this in line with what is recommended on the side here and in line with the Bredesen Protocol.

Also, I already feel my memory is a dulled and retrieval is hard work, has anyone ever found this to improve not he B12/folate etc supplements?

With my gratitude to you all

SIanM
Hello there to You! So glad you found us and shared your story with this awesome community. I am a 52yo female naturopathic doc, health coach and a senior intern on this forum. I love it here! I do not carry an E4 gene but my partner is heterozygous like you. I also have a variety of other genetic dementia issues present in my own family. There is a strong presence of vascular dementia on both sides of my family tree and my dad passed away last year of Lewy Body Dementia. There are SO many factors that come in to play with dementia! Dr Bredesen says there are "36 holes to patch" with Alzheimers Dementia alone. His protocol helps to patch them in an individualized way. I am just now enrolled in a course to help people with that. His book is amazing and there is a lot of information on it within this forum if you are interested.

I am also trying to take a closer look at my own epigenetics and which SNP's might come into play with Lewy Body Dementia, Parkinsons Dx, etc...It also appears the compromise of cerebral vasculature is an issue within my family and I do not know from where that would be derived. Down the rabbit hole I go! I would be happy to combine forces if that sounds like fun to you.

Warmly,

Jenny B-C
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SianM
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Re: Opinion on ApoE4 plus MTHFR heterozygous

Post by SianM »

Wow and thank you for such good responses and so quickly.

I've read the primer and I've also read the recode book a couple of times already and taken notes, trying to patch up those holes as DB suggests. The information on methylation and potentially oxalates is another new interesting line for me to go down and I've already started looking at that. Paragraph the dietary aspect does feel a little overwhelming as when I think about what I can actually still eat when you take out the oxalates it starts to become really restrictive, but I guess that's how it feels to start with and I just need to learn how to cook with the things that I can't eat. I've also ordered the TMG which should be arriving today so I'll add that to the methyl folate and B12 supplements. Unfortunately I think I do have inflammatory issues combining with this problem. I've got some kind of arthritis in my spine which is potentially inflammatory and I take an anti-TNF drug for that. I've also had recurrent UTIs and cold sores which I don't think I was aggressive enough about treating before I realised the relevance to Alzheimer's disease. Yet again another reason to be tested and I'm persuading my sister to do so at the moment so watch out you might see her on here soon.

Jenny, yes I'm really interested in what you're doing, really ahead of the curve but I'm sure this is the direction that medicine is going to take over the next few decades. I would be really interested in combining forces and looking at the literature and trying to work out what some of this means.

Even though some of my memory doesn't feel as good as it was I'm certainly using my brain at the moment, and spending a lot of time researching this at a molecular level and also going back and doing my ancestry family tree to try and work out whether I think that some of my relatives might actually have been homozygotes. If nothing else this is definitely going to be good mental stimulation.

With warm wishes to you all and look forward to more conversations

Sian
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Re: Opinion on ApoE4 plus MTHFR heterozygous

Post by SianM »

Also another quick question. When you're trying to do intermittent fasting and reducing the number of hours which you consume food in each day how do you manage to get your supplements in without breaking this fast? Do you restrict taking the supplements to the time when you're eating or do you take the supplements on an empty stomach or have you found another way of getting around this? I'd love to know
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Re: Opinion on ApoE4 plus MTHFR heterozygous

Post by TheresaB »

SianM wrote:Also another quick question. When you're trying to do intermittent fasting and reducing the number of hours which you consume food in each day how do you manage to get your supplements in without breaking this fast? Do you restrict taking the supplements to the time when you're eating or do you take the supplements on an empty stomach or have you found another way of getting around this? I'd love to know
I take my supplements during my fasting period. As discussed in the Facebook video from yesterday, "Special Considerations for ApoE4s, Part 2" (see viewtopic.php?f=15&t=7586) Dr Bredesen said as a general rule you can remain in a fasted state with up to 50 calories, that the insulin response is minimal.
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Re: Opinion on ApoE4 plus MTHFR heterozygous

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I am 76 y E3/E4 ,MTHFR 677 CT following the Bredesen protocol since 5 years for AD prevention. I am doing cognitevely well., feel that I improved now after 5 years of following the protocol : mentally, cognitively and physically. I have to work hard to lower my homocystein, take a bp lowering drug since 25-30 years to keept it within normal limis, now at 130/80. The homocystein level varies between 11 and 13 um/l, I take regularly (twice an year) B12 injectitons to keep blood level optimal, besides taking 1 mg methyl-folate, vitamin B-complex (B2, B6 etc) Mg, 500 mg choline, 3-5 g taurin and 2 g betain - ie everything needed for good methylatation - but could not get my hcy lower. Now I increased betain to 5 g and methylfolate to 4 mg daily for even better methylation and will see if hcy levels sink. I have the feeling that having both SNPs makes it more difficult to keep hcy optimal, but also have to watch my blood lipids and the diabetes risk factors....We have to look at the whole picture of the ReCode protocol and try to keep all physiologically relevant levels optimal, do ketogenic intermittent fasting and work on all relevanr lifestyle factors. I think (and hope) that hcy alone is just one factor...Keep tweaking....
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Re: Opinion on ApoE4 plus MTHFR heterozygous

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Stefan wrote: Sun Mar 20, 2022 12:58 pm I am 76 y E3/E4 ,MTHFR 677 CT following the Bredesen protocol since 5 years for AD prevention. I am doing cognitevely well., feel that I improved now after 5 years of following the protocol : mentally, cognitively and physically. I have to work hard to lower my homocystein, take a bp lowering drug since 25-30 years to keept it within normal limis, now at 130/80. The homocystein level varies between 11 and 13 um/l, I take regularly (twice an year) B12 injectitons to keep blood level optimal, besides taking 1 mg methyl-folate, vitamin B-complex (B2, B6 etc) Mg, 500 mg choline, 3-5 g taurin and 2 g betain - ie everything needed for good methylatation - but could not get my hcy lower. Now I increased betain to 5 g and methylfolate to 4 mg daily for even better methylation and will see if hcy levels sink. I have the feeling that having both SNPs makes it more difficult to keep hcy optimal, but also have to watch my blood lipids and the diabetes risk factors....We have to look at the whole picture of the ReCode protocol and try to keep all physiologically relevant levels optimal, do ketogenic intermittent fasting and work on all relevanr lifestyle factors. I think (and hope) that hcy alone is just one factor...Keep tweaking....
Congratulations on your improvement, Stefan! It is great that you are feeling better both physically and cognitively since following the Bredesen protocol over the last five years.
Yesterday the topic of lowering homocysteine came up in the Meet Up (Virtual Book Club).
It seems that you are already doing most, if not all, of what is recommended for lowering homocysteine, but it is still persistently higher than optimal level. If you have optimized all of your B Vitamins and also have added betaine without bringing down your levels, focusing on choline might be another avenue. You mention you are taking 500 mg of choline, but choline deficiency is very common. Chris Masterjohn had a genetic choline calculator that showed egg day equivalent of choline needed per day based on individual SNP's. https://chrismasterjohnphd.com/tools/20 ... alculator/.

Dr Bredesen mentions the importance of choline in the section, “How Can I lower my homocysteine” (Pg 299, The End of Alzheimer’s Program:

“Adequate choline is also helpful and this can be obtained from your diet (e.g. egg yolks, liver)or via supplementation with citicoline, GPC choline , or lecithin.”
Also on pg 188. “Inadequate choline status can also put you at risk for elevated homocysteine.”

Dr. Dayan Goodenowe, who has been a guest on an ApoE4.Info podcast and also been interviewed by Dr. Bredesen, cites both creatine and choline for lowering homocysteine, “ Dietary supply of choline and creatine naturally reduces methyltransferace demand and naturally lowers SAH and homocysteine” (pg 186 Breaking Alzheimer’s).
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Re: Opinion on ApoE4 plus MTHFR heterozygous

Post by mcpemberton2000 »

floramaria wrote: Sun Mar 20, 2022 1:27 pm
Stefan wrote: Sun Mar 20, 2022 12:58 pm I am 76 y E3/E4 ,MTHFR 677 CT following the Bredesen protocol since 5 years for AD prevention. I am doing cognitevely well., feel that I improved now after 5 years of following the protocol : mentally, cognitively and physically. I have to work hard to lower my homocystein, take a bp lowering drug since 25-30 years to keept it within normal limis, now at 130/80. The homocystein level varies between 11 and 13 um/l, I take regularly (twice an year) B12 injectitons to keep blood level optimal, besides taking 1 mg methyl-folate, vitamin B-complex (B2, B6 etc) Mg, 500 mg choline, 3-5 g taurin and 2 g betain - ie everything needed for good methylatation - but could not get my hcy lower. Now I increased betain to 5 g and methylfolate to 4 mg daily for even better methylation and will see if hcy levels sink. I have the feeling that having both SNPs makes it more difficult to keep hcy optimal, but also have to watch my blood lipids and the diabetes risk factors....We have to look at the whole picture of the ReCode protocol and try to keep all physiologically relevant levels optimal, do ketogenic intermittent fasting and work on all relevanr lifestyle factors. I think (and hope) that hcy alone is just one factor...Keep tweaking....
Congratulations on your improvement, Stefan! It is great that you are feeling better both physically and cognitively since following the Bredesen protocol over the last five years.
Yesterday the topic of lowering homocysteine came up in the Meet Up (Virtual Book Club).
It seems that you are already doing most, if not all, of what is recommended for lowering homocysteine, but it is still persistently higher than optimal level. If you have optimized all of your B Vitamins and also have added betaine without bringing down your levels, focusing on choline might be another avenue. You mention you are taking 500 mg of choline, but choline deficiency is very common. Chris Masterjohn had a genetic choline calculator that showed egg day equivalent of choline needed per day based on individual SNP's. https://chrismasterjohnphd.com/tools/20 ... alculator/.

Dr Bredesen mentions the importance of choline in the section, “How Can I lower my homocysteine” (Pg 299, The End of Alzheimer’s Program:

“Adequate choline is also helpful and this can be obtained from your diet (e.g. egg yolks, liver)or via supplementation with citicoline, GPC choline , or lecithin.”
Also on pg 188. “Inadequate choline status can also put you at risk for elevated homocysteine.”

Dr. Dayan Goodenowe, who has been a guest on an ApoE4.Info podcast and also been interviewed by Dr. Bredesen, cites both creatine and choline for lowering homocysteine, “ Dietary supply of choline and creatine naturally reduces methyltransferace demand and naturally lowers SAH and homocysteine” (pg 186 Breaking Alzheimer’s).
Great info. I too have been struggling with lowering my homocysteine. I'm 3/4. January 2020 by homocysteine had gotten down to 7.7 (B12 was 1040 at the time of test) from 8.9 in June 2019 because I believe I was taking 500 mcg of B12 and maybe 2000 mcg of methylfolate (can't remember if I took the methyl with it or not). March 2021 it jumped to 9.4 and then I retested in August 2021 because I upped my methlyfolate dosage and it went up to 10.1. After this, I realized I had dropped my B12 dosage down to 200 mcg from the original 500 mcg. Therefore, I raised my B12 dosage to 1000 mcg but have not been including methylfolate. My latest reading on April 21, 2022 was 10.5. So it continues to climb despite the extra B12. I'm trying to figure out what to do next. I'm thinking testing my B12 levels would be wise here. Thoughts? Are there any other B vitamins you would check as well? Add back methylfolate? I'm taking 500 mg of Citicholine per day (Jarrow). Everything else looks good but I can't seem to stop this Homocysteine train! Although the B12 seems to have lowered the increase.
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