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My results from GeneticGenie -- thoughts welcome

SOC

Senior Member
Messages
7,849
Methylation
Homozygous

MAO A R297Rrs6323TT+/+
BHMT-08rs651852TT+/+
CBS A360Ars1801181AA+/+

Heterozygous
COMT V158Mrs4680AG+/-
COMT H62Hrs4633CT+/-

VDR Bsmrs1544410CT+/-
VDR Taqrs731236AG+/-
MTHFR C677Trs1801133AG+/-
MTRR K350Ars162036AG+/-
BHMT-02rs567754CT+/-

There were also half a dozen "not found" genes. Maybe they were eliminated in the most recent selection of genes tested by 23andme...?

Detox
Homozygous

CYP2D6 S486Trs1135840GG+/+

Heterozygous
CYP1A2 164A>Crs762551AC+/-
CYP1B1 R48Grs10012CG+/-
CYP2C19*17rs12248560CT+/-
CYP2D6 2850C>Trs16947AG+/-
SOD2 A16Vrs4880AG+/-
NAT2 I114Trs1801280CT+/-
NAT2 K268Rrs1208AG+/-

 
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PDXhausted

Senior Member
Messages
258
Location
NW US
The way you can tell whether they were eliminated by 23andme or undetermined by your sample, would be to search for the RS numbers in your raw data. If the RS numbers aren't there, then 23andme eliminated them. If they are there but say "--" rather than two letters, that just means they couldn't determine from your sample or you are missing the SNP.
 

PDXhausted

Senior Member
Messages
258
Location
NW US
I have a similar profile to you in terms of COMT/MAOA/VDR. I have a tendency toward slow breakdown of adrenaline and dopamine, and also a tendency toward anxiety/panic. I'm curious if you find similar tendencies, because from my research, it seems like these SNPs can affect that (though I'm sure its much more complicated than 2 or 3 SNPs).
 

SOC

Senior Member
Messages
7,849
I have a similar profile to you in terms of COMT/MAOA/VDR. I have a tendency toward slow breakdown of adrenaline and dopamine, and also a tendency toward anxiety/panic. I'm curious if you find similar tendencies, because from my research, it seems like these SNPs can affect that (though I'm sure its much more complicated than 2 or 3 SNPs).
I can believe that I might have a slow breakdown of adrenaline simply because when I do get an adrenaline rush it seems excessive (jittery, jumpy) and it seems to take forever to wear off. It's really annoying and uncomfortable, so I avoid it as much as possible. I also have tachy, which might be related... I dunno. :confused:

I don't have anxiety or panic, though. What are the implications of slow breakdown of dopamine?
 

PDXhausted

Senior Member
Messages
258
Location
NW US
@SOC yes- I get that same feeling with adrenaline and try to avoid it as well. The naturopath I've been seeing recently who is well-versed in the methylation stuff, says to take vitamin C to help aid in the breakdown of adrenaline. I'm not totally sure about this because I'm having a hard time finding the biochemistry to confirm it, but the one time I tried it, it did seem to help some. I'll have to experiment more to be sure though.

I'm not sure of the health/disease implications of slow dopamine breakdown, I haven't researched it too much. The way I noticed it manifesting in me, is that I was getting very subtle manic feelings from taking DIM. The reason I suspect that had to do with COMT, is because DIM supposedly diverts more estrogen metabolism through COMT, and since my COMT is down-regulated (+ is a down regulation) already, I think having more estrogen through that pathway was slowing it down even more and I was getting a backup in dopamine metabolism, thus the slight manic feelings. This is just me theorizing though. I'm not sure how much of this is this particular SNP, my CFS or whatever I have, just me in particular, or some combination thereof.

Anyway I discontinued the DIM, though I probably could have tried taking niacin or niacinamide along with the DIM-- niacin absorbs some methyl groups which theoretically would take some of the burden off of COMT which might help speed up that pathway. When I try taking niacinamide just by itself, it makes me incredibly sleepy, so I just abandoned messing with that whole pathway for now :)
 

PDXhausted

Senior Member
Messages
258
Location
NW US
It just occurred to me that maybe niacin could aid in the breakdown of adrenaline? That might be something to try as well. Experts, correct me if I'm wrong though!
 

Helen

Senior Member
Messages
2,243
It just occurred to me that maybe niacin could aid in the breakdown of adrenaline? That might be something to try as well. Experts, correct me if I'm wrong though!

I did some research earlier trying to find an antidote to adrenaline. Physical activity was the only one that I could find.
 

SOC

Senior Member
Messages
7,849
Okay, my brain exploded. :ill:

I'm overwhelmed with data and underfunctional in brain power at the moment. Good thing I'm on holiday break from tutoring -- I hate to think what garbage I'd be "teaching" with my brain in this state.:wide-eyed:

I've been trying (and failing) to do some reading up on my genetics with regard to methylation and detox, but I'm not processing any of it. :bang-head:

Please help me sort this out. Do I actually have any significant methylation issues suggested by my genetics? I'm thinking not, but I'm not confident in my conclusions.

I really, really, really, really, really hate major cognitive dysfunction. :mad:
 

Helen

Senior Member
Messages
2,243
Hi @SOC,

From my point of view the mutations (in bold) that you have that are affecting folate- and B12 metabolism are the most crucial to bypass. (Together, not bypassed with supplements, you might have a methylation blockage with a functional vit B12 deficiency).
Then other mutations might have an impact, but I have no personal experience from that so I think others might help you if you fail to be on a methylation protocol. I comment beside the mutations for what it is worth.

Homozygous
MAO A R297Rrs6323TT+/+
BHMT-08rs651852TT+/+
CBS A360Ars1801181AA+/+ Maybe this will have an impact for you. I think @caledonia can give advice. But there are people who have no problems taking B12 and methylfolate with these mutations so you have to try how you react.

Heterozygous
COMT V158Mrs4680AG+/- These two mutations might make you less tolerant to methylgroups. I am homozygote and
COMT H62Hrs4633CT+/- have no problems with extra methyl donours.

VDR Bsmrs1544410CT+/-
VDR Taqrs731236AG+/-
MTHFR C677Trs1801133AG+/- This mutation means that you need extra methylfolate. See info below Caledonias signature.
MTRR K350Ars162036AG+/- This mutation means that you don´t recycle B12 properly and B12 needs to be supplemented.
BHMT-02rs567754CT+/-

If you haven´t tried mecobalamin/B12 and or methylfolate yet they will probably be of great help for your brain fog.
Again, the information that Caledonia links to would give you a good base for how to start.

Best of luck!
 
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anne_likes_red

Senior Member
Messages
1,103
It just occurred to me that maybe niacin could aid in the breakdown of adrenaline? That might be something to try as well. Experts, correct me if I'm wrong though!

No expert here ;) but this article suggests niacin would be useful
http://www.livestrong.com/article/408424-niacin-anxiety/

Functions and Properties of Niacin
Niacin, also called vitamin B3, is needed for DNA repair, synthesis of steroidal hormones and energy metabolism within the body. A strong property of niacin is its ability to relax the muscle tissue composing arteries, which increases their diameter. This process, called vasodilation, leads to increased blood flow and reduced blood pressure. According to "Biochemistry of Human Nutrition," niacin also raises blood levels of HDL, the "good" cholesterol, and reduces levels of LDL, the "bad" cholesterol, which further improves cardiovascular health. Perhaps most important with respect to anxiety, niacin is an antidote to adrenaline, which is often over-produced in those experiencing anxiety
 

caledonia

Senior Member
Methylation
Homozygous

MAO A R297Rrs6323TT+/+
BHMT-08rs651852TT+/+
CBS A360Ars1801181AA+/+

Heterozygous
COMT V158Mrs4680AG+/-
COMT H62Hrs4633CT+/-

VDR Bsmrs1544410CT+/-
VDR Taqrs731236AG+/-
MTHFR C677Trs1801133AG+/-
MTRR K350Ars162036AG+/-
BHMT-02rs567754CT+/-

There were also half a dozen "not found" genes. Maybe they were eliminated in the most recent selection of genes tested by 23andme...?

You have one First Priority mutation, which is CBS A360A. This is the minor one. I've never seen anyone outside of Heartfixer need to treat for the minor CBS. You also have some BHMTs which can add to CBS. So I would give it a "maybe" as to whether you would need to treat for CBS first.

There are various signs and symptoms and some tests to see if CBS is expressed. See Heartfixer.

The BHMT08 is supposed to be linked to ADD, so maybe that's where the brainfog is coming from?

You have an MTHFR C677T mutation, which is the more severe one, so some methylfolate for that. You have an MTRR mutation, which is B12 recycling, so some B12 for that. With your COMT/VDR combination, Yasko suggests hydroxycobalamin and adenosylcobalamin, no methylcobalamin - so trending towards sensitive.

You have VDR Bsm, which is the Vitamin D Receptor, so check your vitamin D levels (standard lab test), and if that's low, supplement for that.

The BHMTs are the secondary "shortcut" methylation pathway, so some lecithin for that to get some TMG.

MAO A affects serotonin, so after the rest of the pathway is balanced and if you're still experiencing mental health type problems, then Yasko suggests a small sprinkle of 5htp. This is contraindicated if you're also on an SSRI/SNRI.

There are SNPs missing because 23andme doesn't have everything in Yasko's methylation panel.
 

caledonia

Senior Member
Detox
Homozygous

CYP2D6 S486Trs1135840GG+/+

Heterozygous
CYP1A2 164A>Crs762551AC+/-
CYP1B1 R48Grs10012CG+/-
CYP2C19*17rs12248560CT+/-
CYP2D6 2850C>Trs16947AG+/-
SOD2 A16Vrs4880AG+/-
NAT2 I114Trs1801280CT+/-
NAT2 K268Rrs1208AG+/-

CYP2D6, and CYP2C19 detoxify various drugs.
CYP1A2 means slow caffeine metabolizer.
CYP1B1 is estrogen dominance possibly causing estrogen related cancers. You can lower estrogen by eating cruciferous veggies, or taking DIM, IC3 or calcium deglucarate. (Calcium deglucarate being the best if you have CBS problems.)

SOD2 causes oxidative stress and affects the mitochondria. You can try a GliSODin supplement for that.

The NATs detoxify smoke and car exhaust, so avoid those.

The general advice for detox SNPs is to eat your fruits and veggies and avoid toxins.

There is more specific info on detox SNPs in my signature links.
 

caledonia

Senior Member
Okay, my brain exploded. :ill:
Please help me sort this out. Do I actually have any significant methylation issues suggested by my genetics? I'm thinking not, but I'm not confident in my conclusions.

The short answer is yes. I'd say yours are about typical for the people on this forum, many of whom are very very sick.

However, genetics aren't the whole story. You also have to take into account your history of toxin exposure, viruses, periods of extreme stress, mercury fillings, anesthesia, antibiotics, oral birth control or other meds that deplete folate, factors which deplete B12, etc. etc. It all adds up over time, causing a vicious cycle.

If you haven't watched my Methylation Made Easy video series (linked in my signature) that's a good place to start.
 

SOC

Senior Member
Messages
7,849
@Helen and @caledonia

Thank you both very much for your help! Clearly my conclusions were not very good. :)

I'll take a look at Heartfixer and decide what to do about the CBS.

I'll try methylfolate again. It didn't seem to do anything when I tried it before, but it's worth giving it a longer trial given my SNPs.

I don't know what to make of the B12 issue. My blood tests show very high B12 which is not coming down even without supplementation. My doc told me to stop taking B12. When I was taking B12, hydroxy worked best for me, which fits what we're seeing in the SNPs. I'll talk to my doc again about this now that we know about these SNPs.

Interesting about BHMT08 and ADD. Pre-ME I was very much not ADD. I could hyper-focus when I wanted to, and not when I didn't. However, a lot of my cognitive problems since ME have similarities to ADD. I wonder if this might be a gene expression issue....

I already know my vitamin D is low. 7500 IU daily increases my blood vit D levels only slightly. I'll talk to my doctor about this.

I know nothing about SOD2 or GliSODin, so I'll look into that.

I can take lecithin, but is there any reason not to take TMG directly?

Thanks again! Now I have some more specific information, I should be able to focus on the individual issues and gather info more effectively.
 

caledonia

Senior Member
@Helen and @caledonia

I can take lecithin, but is there any reason not to take TMG directly?

I think the reason is that you only need small amounts otherwise you can get overmethylated. TMG supps are huge amounts. I think lecithin also needs some conversion in the body to make TMG. So it's slower and safer.

With methylation, often less is more. See the Start Low and Go Slow doc in my signature links.
 

SOC

Senior Member
Messages
7,849
I think the reason is that you only need small amounts otherwise you can get overmethylated. TMG supps are huge amounts. I think lecithin also needs some conversion in the body to make TMG. So it's slower and safer.

With methylation, often less is more. See the Start Low and Go Slow doc in my signature links.
Thanks! I always prefer the Start Low and Go Slow method. I'll go with lecithin.

How does one know one is overmethylated? Is that in your Methylation Made Easy videos? I will get to them -- tomorrow probably -- but videos are not easy for me or my computer so I don't use them as resources as much as I probably need to.
 

caledonia

Senior Member
Thanks! I always prefer the Start Low and Go Slow method. I'll go with lecithin.

How does one know one is overmethylated? Is that in your Methylation Made Easy videos? I will get to them -- tomorrow probably -- but videos are not easy for me or my computer so I don't use them as resources as much as I probably need to.

My overmethylation symptoms are feeling overly stimulated, revved up, agitated, etc. If you have COMT mutations - mood swings.

Metal detox for me is more like flu-like symptoms - muscle and joint aches, extra tired, cold, etc. This actually good - you know you're methylating properly. Then you just need to dial it back to a level you can tolerate, which for me is, I don't feel metal detox at all (even though it's still occurring at a low level).

CBS for me was a stress/anxiety reaction - exactly like a stressful week at work with deadlines, or having a family membery seriously ill - tight painful trapezius muscles (those ones at the base of the neck), feeling stressed, butterflies in the stomach. One person on here reported an intense head pressure.
 

SOC

Senior Member
Messages
7,849
My overmethylation symptoms are feeling overly stimulated, revved up, agitated, etc. If you have COMT mutations - mood swings.

Metal detox for me is more like flu-like symptoms - muscle and joint aches, extra tired, cold, etc. This actually good - you know you're methylating properly. Then you just need to dial it back to a level you can tolerate, which for me is, I don't feel metal detox at all (even though it's still occurring at a low level).

CBS for me was a stress/anxiety reaction - exactly like a stressful week at work with deadlines, or having a family membery seriously ill - tight painful trapezius muscles (those ones at the base of the neck), feeling stressed, butterflies in the stomach. One person on here reported an intense head pressure.
Hmmmm..... I'm very mellow and don't have any feeling of overstimulation. I've never had the wired but tired feeling some people with ME/CFS talk about. I also don't suffer from stress/anxiety. Hopefully this means, 1) I'm not currently overmethylating, and 2) my CBS upregulation is relatively mild.

I'm currently trying to sort out how much, if at all, I need to deal with CBS before I tackle the other stuff. I'm still hunting in Heartfixer for the signs/symptoms/tests to see if CBS is expressed.
 

Helen

Senior Member
Messages
2,243
@Helen and @caledonia

...I'll try methylfolate again. It didn't seem to do anything when I tried it before, but it's worth giving it a longer trial given my SNPs.

I don't know what to make of the B12 issue. My blood tests show very high B12 which is not coming down even without supplementation. My doc told me to stop taking B12. When I was taking B12, hydroxy worked best for me, which fits what we're seeing in the SNPs. I'll talk to my doc again about this now that we know about these SNPs....

Did you try methylfolate together with Methylcobalamin before? If not, that might be the reason why you didn´t notice any difference according to your MTHFR and MTR/MTRR mutations.

Hydroxycobalamin has to be methylated so HyCbl consumes methyl groups and might put demand on your methylation if not working properly. The most effective combination of B12 and folate are those in Freddd´s protocol.

Many people , also with CBS mutations can handle MeCbl and as it is much more effective for a methylation issue I would prefer MeCbl if possible to take-and to start with. Then slowly add in methylfolate. The Mega B drops from Yasko allows slow titrating. Be aware of a potassium deficiency that can occur. And have some B3 ready. I have mutations like yours and need a lot of B12, injections every second day, but only a low dose folates like in Thorne´s B-complex. My CBS doesn´t seem to cause any problems as for many others that I know and follow. You will find out after some trials..

B3 , and other vitamin B´s, needs to be methylated so "they consume" methyl groups if you are overmethylated. So testing a dose of B3 if you have symptoms that you are worried about might give you a clue about an eventual overmethylation.

Some people with ME/CFS that I know have very high B12 and feel well just with the high B12. (High could be 4-5000 when reference is 200-400). I shouldn´t worry about a high B12 value. Their doctors knowledgeable about B12 treatment don´t . Only if homocystein or MMA were abnormal. B12 might be high because of your decreased ability to make use of folates when metabolising B12 . Methylcobalamin has never been found in research to be harmful even in high doses. If you could get some labwork as a Methylation Panel from your doctor, you would know what´s going on.