Interpreting Genetic Genie Results and Starting Supplementation

[veganmua]

Hello!

I have my Genetic Genie results but I'm not sure how to start supplementing. Now I'm not a scientist, and with my brain fog it's very hard to make head or tail of all the complicated information!
So I'm really hoping for some of the knowledgeable users on here like @caledonia and @Freddd to lend me their minds for a moment and give me their opinions/advice.

I hate to ask for favours, especially when I have nothing to offer in return, but I'm not sure who to turn to.

Here are my results

Methylation -

Homozygous mutations (+/+)

• MTHFR C677T
• VDR Taq
• MAO-A R297R
• MTRR A664A

Heterozygous mutations (+/-)

• ACAT1-02
• MTR A2756G
• MTRR A66G
• CBS C699T
• CBS A360A

Detox Profile -

Homozygous mutations (+/+)

• SOD2 A16V

Heterozygous mutations (+/-)

• CYP1A2 164A>C
• CYP1B1 L432V
• CYP1B1 R48G
• CYP2C19*17
• CYP2D6 S486T
• CYP2D6 2850C>T
• GSTP1 I105V
• NAT2 I114T
• NAT2 R197Q

GSTT1 Absent - 'It is likely that you are missing this gene and have a deletion'

Also, I take 375mg venlafaxine daily, an SNRI antidepressant. I'm not sure if and how I would have to adjust my treatment to take that into consideration.

Thanks for reading!
Emma

 

[twilightsun]

I can't comment specifically on the Genetic Genie data, but I do want to mention to be very careful with your venlafaxine. I'm on 150mg daily, and that's as high as my doc will go with this particular drug. I'm not sure if you've ever experienced withdrawal symptoms following a late dose, but it's absolute hell. (Forgetting to refill the Rx and missing my bedtime dose means having to wait until the pharmacy opens in the morning. Nine hours late, and I'm already suffering enough that I can't make the 1/4-mile drive to the pharmacy myself. My husband has to go for me.) With your higher dose it's going to be a VERY tricky balance with side effects of methylation, side effects of the venlafaxine once you no longer need as much, and the side effects of withdrawal once you start cutting down. And there likely will be a point when you need to decrease your dosage on it, because once your methylation starts working properly, your serotonin and norepinephrine (the SN in the SNRI) levels should start to increase naturally.

I haven't been doing the methylation protocol long enough to affect my other meds yet, but I'm willing to share notes with you when it comes to that.

 

[caledonia]

Methylation -
Homozygous mutations (+/+)

• MTHFR C677T
• VDR Taq
• MAO-A R297R
• MTRR A664A

Heterozygous mutations (+/-)

• ACAT1-02
• MTR A2756G
• MTRR A66G
• CBS C699T
• CBS A360A

Detox Profile -
Homozygous mutations (+/+)

• SOD2 A16V

Heterozygous mutations (+/-)

• CYP1A2 164A>C
• CYP1B1 L432V
• CYP1B1 R48G
• CYP2C19*17
• CYP2D6 S486T
• CYP2D6 2850C>T
• GSTP1 I105V
• NAT2 I114T
• NAT2 R197Q

GSTT1 Absent - 'It is likely that you are missing this gene and have a deletion'

Also, I take 375mg venlafaxine daily, an SNRI antidepressant. I'm not sure if and how I would have to adjust my treatment to take that into consideration.

Hi Emma. We're all in the same boat here, so no problem with asking for help.

Methylation

You have two First Priority mutations. ACAT and CBS. For ACAT you can take bile salts. That's one of the "leaky gut genes", so it's more likely you may have gut issues. If so, treat the gut and ACAT at the same time, and do those first. You can use the 4R Gut Rebuilding protocol.

For CBS, it may or may not be expressed. You only have to treat it if it's expressed. If you're having trouble tolerating methyl supplements such as a stress/anxiety reaction or head pressure, or have trouble with sulfur foods, supps and meds, it could be expressed. The Heartfixer page has a good protocol which I've successfully used except I used the Free Thiol diet and no Yasko RNAs.

You have MTHFR C677T, so some methylfolate for that. You have both MTR and MTRR, which is the "B12 double whammy" - mutations in both B12 intake and recycling. You'll need B12 for that.

For your COMT/VDR combo, you actually have the least sensitive type, so all three types of B12 - methylcobalamin, hydroxycobalamin and adenosylcobalamin should be tolerated.

For MAO A, some low level 5htp could be taken to help with serotonin, but this is only after the rest of the methylation cycle is balanced. Note that this is contraindicated if you're on the SNRI.

=-=-=-=-
Detox

SOD2 affects the mitochondria. You can try a supplement with GliSODin or Biotec Extra Energy Enzymes if you can't do tiny amounts of gluten.

CYP1A2 +/- means slow caffeine metabolizer.

CYP1B1s cause estrogen dominance and could cause estrogen related cancers such as breast cancer. You can eat cruciferous veggies or take IC3, DIM or calcium deglucarate. The calcium deglucarate is best for CBS mutations like you have.

The CYP2C19 and 2D6s detoxify various medicines and you could have problems with these. See the Detoxigenomics link in my signature for more specific info.

You have two GST things going on, which affects glutathione. You're going to need more glutathione than the average person (best done by improving methylation).

The NATs detoxify smoke, so don't smoke and stay away from secondhand smoke.

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

=-==-=-=-
I have suggestions for dealing with anti-depressants in the Start Low and Go Slow document in my signature links. My suggestion would be to try one 10% reduction for 8 weeks to see how it goes. As an example, I get an increase in symptoms at the 6 week mark, which last for up to a week. This will give you an idea of how a taper off would go. If you don't get any symptoms, you might be lucky and be able to go faster.

I believe it can be done, but like twilightsun is saying, be extremely cautious as it's easy to make yourself worse.

 

[veganmua]

Thanks so much @twilightsun and @caledonia !

I'm definitely going to be careful with my venlafaxine - I accidentally missed my morning dose yesterday and by the evening I was an absolute wreck! I won't attempt to decrease my dose until I'm settled into B12 and methylfolate supplementation.

Regarding the ACAT, I suffer from extreme IBS - lots of bloating and pain. I don't know if I'd be able to take bile salts, because I can't seem to find a vegan version of it. I do take Enzymedica Digest Gold, 3 capsules per meal, and that seems to help.

I don't know what to do about the CBS. Most of the food I eat seems to be high in sulphur - tofu, soya milk, lentils, beans, green vegetables, garlic. I don't know how I would restrict them without risking becoming deficient in something.

I have Sublingual Hydroxycobalamin already, at 5 micrograms per drop, and I'm thinking of getting this methylfolate supplement. What dosages would you start with?

I'm thinking of asking Dr Sarah Myhill to help/supervise me with the gut rebuilding, CBS/low sulphur and methylation supplements. I think she offers the same kind of gut tests, and she has lots of information about the methylation protocol on her website.
I just hope I can afford it!

Thanks so much again for all the helpful info!

 

[caledonia]

I'm definitely going to be careful with my venlafaxine - I accidentally missed my morning dose yesterday and by the evening I was an absolute wreck! I won't attempt to decrease my dose until I'm settled into B12 and methylfolate supplementation.

It sounds like it has a short half life, like Paxil. Paxil is supposed to be pretty hard to get off of, but still doable.

Regarding the ACAT, I suffer from extreme IBS - lots of bloating and pain. I don't know if I'd be able to take bile salts, because I can't seem to find a vegan version of it. I do take Enzymedica Digest Gold, 3 capsules per meal, and that seems to help.

I think bile salts by definition are going to be an animal product.

I don't know what to do about the CBS. Most of the food I eat seems to be high in sulphur - tofu, soya milk, lentils, beans, green vegetables, garlic. I don't know how I would restrict them without risking becoming deficient in something.

Have a look at the Free Thiol diet (in my signature). It's much less restrictive. I only had to restrict 4 foods. Also, the diet is just temporary, 1-3 months. Again, you only need to do this if CBS is expressed. Just because you have the SNP doesn't mean it will be an issue.

I have Sublingual Hydroxycobalamin already, at 5 micrograms per drop, and I'm thinking of getting this methylfolate supplement. What dosages would you start with?

I was having trouble with 1 mcg methylcobalamin before I did the CBS protocol. Since then I've been able to do anywhere from 16 to 50 mcg methylcobalamin and 4 mcg adenosylcobalamin. I don't know if I'm more sensitive than most, probably just more willing or able to subdivide my supps into smaller doses. Anyway, starting with 5mcg seems reasonable, especially if you're already tolerating the hydroxy.

Also, not to be a jerk or anything, because I know people can have deep reasons and convictions for choosing veganism - but in general, veganism is not good for people with B12 mutations. If you haven't been supplementing with B12 all along, this is likely one cause of your problems. It takes several years for the B12 stores to be used up and for health problems to occur. You need B12 to create glutathione, and you have two GST mutations on top of MTHFR and MTR/MTRR mutations which can all cause glutathione depletion. Glutathione depletion is supposed to be at the root of ME/CFS. So you have about a quintuple whammy going on, genetically speaking, with glutathione. The gut problems would add to this, as you would have problems absorbing nutrients from food.

Here's a good article on this topic: http://chriskresser.com/b12-deficiency-a-silent-epidemic-with-serious-consequences

 

[veganmua]

Thanks for replying. At first I thought the bile salts might just help you make bile, not literally be made of bile! No wonder I couldn't find a vegan version!
How much methylfolate would you recommend starting off with?

Also, not to be a jerk or anything, because I know people can have deep reasons and convictions for choosing veganism - but in general, veganism is not good for people with B12 mutations. If you haven't been supplementing with B12 all along, this is likely one cause of your problems.

This is why I already had the sublingual B12, plus I've taken a daily multivitamin containing B12 for years. I tend to take 5 of the drops every once in a while, just to top up what's in the multivitamin. I guess it's just not enough to be effective. Herbivorous animals tend to eat their own excrement to get their B12, but I think I'll stick with the supplements!

Thanks so much for your help, I really do appreciate it.

 

[Freddd]

Thanks for replying. At first I thought the bile salts might just help you make bile, not literally be made of bile! No wonder I couldn't find a vegan version!
How much methylfolate would you recommend starting off with?


This is why I already had the sublingual B12, plus I've taken a daily multivitamin containing B12 for years. I tend to take 5 of the drops every once in a while, just to top up what's in the multivitamin. I guess it's just not enough to be effective. Herbivorous animals tend to eat their own excrement to get their B12, but I think I'll stick with the supplements!

Thanks so much for your help, I really do appreciate it.

Hi Veganmua,

I almost died from being vegetarian, not even vegan. A significant part of my problem was paradoxical folate deficiency from eating too much vegetable folates. Also there is the carnitine problem with plants being very low there.

Herbivorous animals also eat a great deal of insects and insect eggs that are rich in b12. Fermented manure is richer in b12 than fresh manure.

In studying vegetarian literature there is a 7 year and 20 year crash that are both well known. These crashes are typically methyltrap and then partial ATP block. They both come on with a crash whereas partial methylation block starts by day three without MeCbl I had the 7 year crash when I went into methyltrap (while taking CyCbl and folic acid) and then at 20 years I was on the edge of death, the ultimate crash with congestive heart failure with lots of edema that comes on and goes off with paradoxical folate deficiency and partial ATP block. Partial methyl block comes on gradually. Methyltrap is a crash. Partial ATP block starts gradually and then crashes when severe.

 

[veganmua]

Hi Veganmua,

I almost died from being vegetarian, not even vegan. A significant part of my problem was paradoxical folate deficiency from eating too much vegetable folates. Also there is the carnitine problem with plants being very low there.

Herbivorous animals also eat a great deal of insects and insect eggs that are rich in b12. Fermented manure is richer in b12 than fresh manure.

In studying vegetarian literature there is a 7 year and 20 year crash that are both well known. These crashes are typically methyltrap and then partial ATP block. They both come on with a crash whereas partial methylation block starts by day three without MeCbl I had the 7 year crash when I went into methyltrap (while taking CyCbl and folic acid) and then at 20 years I was on the edge of death, the ultimate crash with congestive heart failure with lots of edema that comes on and goes off with paradoxical folate deficiency and partial ATP block. Partial methyl block comes on gradually. Methyltrap is a crash. Partial ATP block starts gradually and then crashes when severe.

So you had methyltrap caused by eating too much plant folate? Forgive me if I'm wrong but couldn't this be remedied by upping your B12 dosage? Or is it a case of the wrong type of folate, ie not methylfolate? In this case couldn't it be remedied by cutting back on folate rich vegetables? This is very interesting, thanks for posting @Freddd

 

[Freddd]

So you had methyltrap caused by eating too much plant folate? Forgive me if I'm wrong but couldn't this be remedied by upping your B12 dosage? Or is it a case of the wrong type of folate, ie not methylfolate? In this case couldn't it be remedied by cutting back on folate rich vegetables? This is very interesting, thanks for posting @Freddd

Hi Veganmua,

I have a nice organic garden. I have had paradoxical folate deficiency since before the age of 2. The veggie folates are generally not l-methylfolate. Folic acid overpowers 10x as much Metafolin and folinic acid 10-20x as much Metafolin. Vegetable folates act like folinic acid generally. More b12 doesn't change the paradoxical folate deficiency. Since I reduced the extra B1, B2 and B3 I was taking I can get along on 4-8mg of Metafolin daily as opposed to 20+ mg before. I do have to be careful of how much folate rich veggies I eat and cut back on them.

 

[nandixon]

The veggie folates are generally not l-methylfolate.

For vegetables overall, 5-methyltetrahydrofolate ("methylfolate") is actually the predominantly occurring form of folate. But there are plenty of examples where 5-formyltetrahydrofolate ("folinic acid") or other folates (e.g., tetrahydrofolate) predominate instead.

Among common vegetables, broccoli has the highest favorable ratio of methylfolate to folinic acid I've seen, at over 50 to 1 (other folate forms, like tetrahydrofolate, are present as well). Spinach also contains predominantly methylfolate, which makes up close to 50% of the total folate pool.

Note that one may see reports in older literature giving folinic acid or other forms as being the predominant folate in certain vegetables, and while that can certainly be true, it was sometimes the result of inadequate analytical technique. Newer references must be looked at to be certain.

If you have a bad reaction to vegetables with a high methylfolate to folinic acid ratio, and a minimal amount of folinic acid, like broccoli and spinach, I wonder if it might be tetrahydrofolate causing the problem in those cases.

 

[skwag]

@nandixon

Do you have a source for the folate contents of veggies you mentioned? Thanks in advance.

 

[RosieBee]

If you have a bad reaction to vegetables with a high methylfolate to folinic acid ratio, and a minimal amount of folinic acid, like broccoli and spinach, I wonder if it might be tetrahydrofolate causing the problem in those cases.
----
After following sulphur-reduced diet for CBS I am absolutely knocked out if I eat spinach/ cabbage etc. How can I be sure this is sulphur/ thiols or folate?

 

[Freddd]

For vegetables overall, 5-methyltetrahydrofolate ("methylfolate") is actually the predominantly occurring form of folate. But there are plenty of examples where 5-formyltetrahydrofolate ("folinic acid") or other folates (e.g., tetrahydrofolate) predominate instead.

Among common vegetables, broccoli has the highest favorable ratio of methylfolate to folinic acid I've seen, at over 50 to 1 (other folate forms, like tetrahydrofolate, are present as well). Spinach also contains predominantly methylfolate, which makes up close to 50% of the total folate pool.

Note that one may see reports in older literature giving folinic acid or other forms as being the predominant folate in certain vegetables, and while that can certainly be true, it was sometimes the result of inadequate analytical technique. Newer references must be looked at to be certain.

If you have a bad reaction to vegetables with a high methylfolate to folinic acid ratio, and a minimal amount of folinic acid, like broccoli and spinach, I wonder if it might be tetrahydrofolate causing the problem in those cases.

HI Nandixon.

I grow and eat spinach. I strongly dislike broccoli and the whole family except a little cabbage in eggrolls. I grow bok choy of couple of varieties, swiss chard, lettuces, some miscellaneous greens. I also grow squash, beans etc. At a meal I might have a salad and a couple of cooked veggies and sometimes it is too much. Folinic acid accumulates for longer than folic acid and wipes out up to 20x as much methylfolate. Most veggies don't have 20x as much methylfolate as other folates. The exact ratio doesn't matter. Eating too many of a variety of veggies does it to me. Everything on my plate except a small piece of meat, 4-6 ounces, is a vegetable. I eat brown rice and whole wheat bread but not every day.

 

[caledonia]

Thanks for replying. At first I thought the bile salts might just help you make bile, not literally be made of bile! No wonder I couldn't find a vegan version!
How much methylfolate would you recommend starting off with?

This is why I already had the sublingual B12, plus I've taken a daily multivitamin containing B12 for years. I tend to take 5 of the drops every once in a while, just to top up what's in the multivitamin. I guess it's just not enough to be effective. Herbivorous animals tend to eat their own excrement to get their B12, but I think I'll stick with the supplements!

Thanks so much for your help, I really do appreciate it.

For amounts, I always suggest to Start Low and Go Slow. At a guess, 25mcg, which is 1/8 of the final dose of 200mcg (recommended by Rich Vank). Then you can adjust up or down from there depending on how well you tolerate it or not. Read the Start Low and Go Slow document in my signature for more details.

The multi with the B12 would be ineffective. Oral B12 only absorbs 1-2%. The sublingual is better. Some brands are better than others. Freddd has a brand he likes in lozenge form, and I'm having good luck with Douglas Labs liquid methylcobalamin. Yasko also makes liquid sublingual B12s (hydroxy, methyl and adenosyl) which are effective.

The figures from Kress's article are astounding. It makes me wonder how many vegans/vegetarians are taking B12 in oral multis thinking they're supplementing enough B12.

 

[nandixon]

@nandixon

Do you have a source for the folate contents of veggies you mentioned? Thanks in advance.

There are dozens of studies out there. Basically, ignore any studies prior to about the late 1990's, because they didn't understand how to analyze the different folate forms, which are present in very small amounts, difficult to separate, and easily oxidized/degraded. Here are just a very few:

Folate types and amounts in different foods (there are others more recent but without free access to the full text that I can find, or they only look at methylfolate exclusively):
2001: http://ajcn.nutrition.org/content/73/4/765.long (See Appendix A and Figure 1)

Specific to broccoli:
2008: http://www.scielo.br/scielo.php?pid=S0100-40422008000300013&script=sci_abstract ("The vitamin content varied between 413.7 and 742.2 µg/100 g for 5-methyltetrahydrofolate and from 4.8 to 12.8 µg/100 g for 5-formyltetrahydrofolate.")

Specific to spinach:
2008: http://www.ncbi.nlm.nih.gov/pubmed/18589576 ("Folate levels determined as 5-methylTHF and 5-formylTHF varied from 226 to 527 microg/100 g and 4.6 to 10 microg/100 g, respectively.")

and
2011: http://www.ncbi.nlm.nih.gov/pubmed/22004472/ ("The major folate vitamer was represented by 5-CH(3)-H(4)-folate, which on average accounted for up to 52% of the total folate pool.")

 

[Freddd]

For amounts, I always suggest to Start Low and Go Slow. At a guess, 25mcg, which is 1/8 of the final dose of 200mcg (recommended by Rich Vank). Then you can adjust up or down from there depending on how well you tolerate it or not. Read the Start Low and Go Slow document in my signature for more details.

The multi with the B12 would be ineffective. Oral B12 only absorbs 1-2%. The sublingual is better. Some brands are better than others. Freddd has a brand he likes in lozenge form, and I'm having good luck with Douglas Labs liquid methylcobalamin. Yasko also makes liquid sublingual B12s (hydroxy, methyl and adenosyl) which are effective.

The figures from Kress's article are astounding. It makes me wonder how many vegans/vegetarians are taking B12 in oral multis thinking they're supplementing enough B12.

Hi Caledonia,

I was a vegetarian for more than 20 years. Supplementing CyCbl the whole time. I could feel the difference after 24 hours without meat. My vegetarian friends said all the usual things, toxins etc. coming out. It was the very vitality draining from my body. I went from mild partial methylation block and trauma induced FMS in 1981, to having to change the way I made my living having declined so much in 2 years that I couldn't do what I used to. In 5 more years I had a total methyltrap AND ATP block crash for 17 years. NOTHING at all worked until I tried my first tablet of MeCbl (ENZY) and in 10 minutes I knew beyond doubt that my life was changed. In one hour lifelong depression lifted and energy started to be restored. In 10 days my burning bladder and burning muscles were no longer burning. 10 days after that I walked back into my new internists office and 100% of the people there were amazed at the visible differences.

I heard all the mythology and the search for the holy grail of vegetarianism, a pure vegan dietary source of real b12 which does not exist. Now if the food has enough fecal contamination and insects or insect eggs, there will be tiny amounts of active b12.

I did a lot of reading in research from India. They have done essentially 100% of the research on impaired reproduction caused by b12 deficiencies. Essentially all vegetarians are deficient in b12 and the ones who can't tolerate vegetable folate get much sicker faster. The only reason that it isn't recognized is that out of the 300+ possible symptoms of active b12 deficiencies, only fewer than 30 are even considered in the USA. as "real" b12 deficiency, mostly based on saving people from dying from pernicious anemia.

99% who take CyCbl or HyCbl will have dozens to hundreds of active b12 deficiency symptoms that have become mystery disease because it can't be b12 deficiency because "that is taken care of" by CyCbl/HyCbl. Taking it orally is not very effective but can typically absorb as much CyCbl as the body can possibly use in a day. It all has to go through a series of keyholes, lots of assumptions that often go wrong or were wrong to begin with.

 

[twilightsun]

Oh, I want to add about venlafaxine withdrawal:

I haven't tried it myself, because I haven't had to come off of it yet, but Prozac is supposed to help temper Effexor discontinuation syndrome. Prozac has a half-life of one week, as opposed to mere hours. So if you end up having issues when you start tapering your venlafaxine dose, you can ask your doctor about prescribing a Prozac bridge to help you through it.

 

[veganmua]

Thanks for replying @Freddd @nandixon @caledonia @twilightsun @skwag @RosieBee

Question - I had the results back from my blood test and I was told both my B12 and folate were on the high end of normal. I hadn't started methylation supplements then, I hadn't taken the sublingual B12 in months (I forgot I had it!) I would have expected it to be low. Can you have methylation problems but high blood B12 and folate?

 

[caledonia]

Thanks for replying @Freddd @nandixon @caledonia @twilightsun @skwag @RosieBee

Question - I had the results back from my blood test and I was told both my B12 and folate were on the high end of normal. I hadn't started methylation supplements then, I hadn't taken the sublingual B12 in months (I forgot I had it!) I would have expected it to be low. Can you have methylation problems but high blood B12 and folate?

Short answer - yes. The blood test measures folate and B12 in the blood, but not what's getting into the cells. So if it's high, it can mean lots of unmetabolized folate and B12 floating around, but not getting used.

That's why it can also be useful to go by signs and symptoms, or to do a test like the HDRI Methylation Pathways Panel, or the Nutreval.

My B12 blood test was 800 (quite normal), yet I have many signs and symptoms of deficiencies and my testing with the above two tests shows many severe problems.