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SHMT or CBS first?

Messages
69
Should one address CBS before SHMT? I've been taking SHMT spray for about a month and initially didn't seem to have any negative effects from it.

But now that my sulfur & ammonia levels have increased, it seems that just half a dose of the SHMT spray may be causing some detox effects. Does this mean that I won't do well on the SHMT ingredients, or is the problem that CBS issues should be addressed before SHMT?

Thank you.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Mindy,

How do you know your sulfur and ammonia have increased? Do you have MTHFR C677T also? What are your detox symptoms? Did you add anything else in the meanwhile, like methylcobalamin, methylfolate, etc?

I'm no expert, but it seems like you'd want to treat by your symptoms.

Yasko and Heartfixer say to treat SHMT before CBS, but (1) Valentijn has pointed out elsewhere (I can find it if you need me to), that there are no studies that show SHMT causes problems if you don't have C677T, (I'm not sure there are studies that show it causes no problems, so take that for what it's worth) and (2) the whole CBS 10x upregulation in people theory stems from misreading of the data - it's for a lab condition where they chopped of the end, not the SNP mutation that exists in people. That's not to say that you don't have sulfur problems. 23andMe doesn't test for SUOX, which converts sulfites to sulfates. If you have sulfur problems, you have sulfur problems, no matter what the cause.

Sorry if this isn't much help. Doesn't seem that SHMT ingredients would be a problem now if they weren't then. (BTW, I'm apparently the only person who thought they had an allergic reaction to SHMT spray...turns out it was to kombucha, and probably histamine intolerance, not the spray at all.)
 

caledonia

Senior Member
SHMT spray ingredients:

Vitamin B12 (as Hydroxycobalamin) 1200mcg
Folate (as folinic acid) 50mcg
Proprietary Blend: 59.2mg
~Deoxyribonucleic Acid Sodium
~Lactoferrin
(bovine)
~Larch Arabinogalactan
~Thymidine 5'-Monophosphate Disodium Salt
~Deoxycytidine 5'-Monophosphate
~Deoxyguanosine 5'-Monophosphate Disodium Salt
~Rosemary Extract
~DeoxyAdenosine Monophosphate
~Proline-rich Polypeptode
(as Immulox®)
Other Ingredients
Purified water, Trehalose (Treha™) , Vegetable Glycerine (palm), Xylitol, Natural Orange Cream Flavor, Citric Acid (beet/cane), and Potassium Sorbate as a natural preservative.
Contains: Milk
Does not include yeast, sugar, wheat, corn, soy, artificial colors or flavors. Gluten free.

=-==-=-=-==-

Are you saying that these ingredients are starting up methylation such that you're getting a rise in ammonia and sulfur?

Is the rise consistent or does it go up and down?

How would you define "detox effects"? Are you getting a stress/anxiety response?
 
Messages
15,786
23andMe doesn't test for SUOX, which converts sulfites to sulfates.
Actually it does test 4:
rs11171718 (A = 4%)
rs705703 (T = 2%, TT = 0)
i5000977 (A is normal)
i5000976 (A is normal)

But there's no research into any of them unfortunately, just prevalence data on two of them.

I've got AG, CC, AA, AA when listed in the same order.
 
Messages
69
Mindy,

How do you know your sulfur and ammonia have increased? Do you have MTHFR C677T also? What are your detox symptoms? Did you add anything else in the meanwhile, like methylcobalamin, methylfolate, etc?

I'm no expert, but it seems like you'd want to treat by your symptoms.

Yasko and Heartfixer say to treat SHMT before CBS, but (1) Valentijn has pointed out elsewhere (I can find it if you need me to), that there are no studies that show SHMT causes problems if you don't have C677T, (I'm not sure there are studies that show it causes no problems, so take that for what it's worth) and (2) the whole CBS 10x upregulation in people theory stems from misreading of the data - it's for a lab condition where they chopped of the end, not the SNP mutation that exists in people. That's not to say that you don't have sulfur problems. 23andMe doesn't test for SUOX, which converts sulfites to sulfates. If you have sulfur problems, you have sulfur problems, no matter what the cause.

Sorry if this isn't much help. Doesn't seem that SHMT ingredients would be a problem now if they weren't then. (BTW, I'm apparently the only person who thought they had an allergic reaction to SHMT spray...turns out it was to kombucha, and probably histamine intolerance, not the spray at all.)
Critterina, I am fairly certain that ammonia and sulfur have increased based on the symptoms I get after eating and after taking a sleeping pill that has sulfur preseratives. These are the same symptoms that I had in March when these problems started. Apparently my CBS hetero was activiated when I started the active b12 and m-folate at normal dosing (I didn't start slow b/c I wasn't advised to by my dr. and didn't know any better).

My symptoms are dizziness, esp. after eating and a terrible head pressure (though not a headache). They are reduced somewhat when I take charcoal and/or molyb. Interesting on the SHMT, b/c I do not have c677 mutation, just the a1298. Inflammation is also up as well as insomnia.

Ok, that's good to know that the shmt spray doesn't seem to cause a problem. Are there any active forms in this spray? If so, I want to stay away from them :) Thanks.
 
Messages
69
SHMT spray ingredients:

Vitamin B12 (as Hydroxycobalamin) 1200mcg
Folate (as folinic acid) 50mcg
Proprietary Blend: 59.2mg
~Deoxyribonucleic Acid Sodium
~Lactoferrin
(bovine)
~Larch Arabinogalactan
~Thymidine 5'-Monophosphate Disodium Salt
~Deoxycytidine 5'-Monophosphate
~Deoxyguanosine 5'-Monophosphate Disodium Salt
~Rosemary Extract
~DeoxyAdenosine Monophosphate
~Proline-rich Polypeptode
(as Immulox®)
Other Ingredients
Purified water, Trehalose (Treha™) , Vegetable Glycerine (palm), Xylitol, Natural Orange Cream Flavor, Citric Acid (beet/cane), and Potassium Sorbate as a natural preservative.
Contains: Milk
Does not include yeast, sugar, wheat, corn, soy, artificial colors or flavors. Gluten free.

=-==-=-=-==-

Are you saying that these ingredients are starting up methylation such that you're getting a rise in ammonia and sulfur?

Is the rise consistent or does it go up and down?

How would you define "detox effects"? Are you getting a stress/anxiety response?

I'm not sure if the SHMT spray is starting up methylation or not; do you know if it could do that? I just felt an increased head pressure shortly after taking the spray, which I haven't noticed before. But the other thing to consider is that I'm certain my ammonia/sulfur levels are up again. So is there some interaction between the spray and these levels?

The rise definetly goes up and down based on when I eat and if I take butyrate, charcoal and molyb (forgot to mention I'm also taking butyrate in my previous posts). These supplements help to reduce the effects. I'm trying to eat low sulfur and ammonia, but even the slightest amount is affecting me right now.
 

caledonia

Senior Member
I'm not sure if the spray could start methylation by itself, but the hydroxycobalamin in combination with folate in the diet could be feeding methyl donors into CBS, causing an effect. Based on my experience, even tiny amounts of methyl donors can do this.

My suggestion would be to do a trial of folinic acid by itself, instead of doing the spray and see if that's any better. Or if you'd rather do the spray, then treat CBS first, then go back to using the SHMT spray.

Note that SHMT is one of the "leaky gut genes", so you should also look at your gut before going past SHMT and CBS. The reason is that once you restart methylation, there will be an increased need for magnesium and/or potassium, and with leaky gut, it will leak out as fast as you're putting it in. This can become a dangerous situation (speaking from experience here).

You would do a stool test and then if it shows imbalances, treat the gut with a 4R gut rebuilding program.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Note that SHMT is one of the "leaky gut genes", ...You would do a stool test and then if it shows imbalances, treat the gut with a 4R gut rebuilding program.
caledonia, I haven't heard of leaky gut genes - what are the other ones?
What stool test would show imbalances? I did all the pathogens, overgrowths, ova and parasites - all was good. Is there something else I should have tested? Thanks!
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
I'm not sure if the SHMT spray is starting up methylation or not; do you know if it could do that? I just felt an increased head pressure shortly after taking the spray, which I haven't noticed before. But the other thing to consider is that I'm certain my ammonia/sulfur levels are up again. So is there some interaction between the spray and these levels?

The rise definetly goes up and down based on when I eat and if I take butyrate, charcoal and molyb (forgot to mention I'm also taking butyrate in my previous posts). These supplements help to reduce the effects. I'm trying to eat low sulfur and ammonia, but even the slightest amount is affecting me right now.
Mindy,
Folinic acid is a form of folate that can be turned to methylfolate and start methylation, depending on your other mutations. If you're MTHFR C677T -/- and MTRR A66G -/-, I'm guessing the spray could start methylation (and maybe even if you're hetero for those). I'm guessing that folinic acid will have the same effect, but matching doses would be challenging, as folinic acid is usually swallowed and I don't know how much gets absorbed. From what I've read, folinic acid is like a reservoir form of folate, so your body can keep it around for when it needs it. If you're in need, maybe it's going directly to methylfolate.
 

caledonia

Senior Member
caledonia, I haven't heard of leaky gut genes - what are the other ones?
What stool test would show imbalances? I did all the pathogens, overgrowths, ova and parasites - all was good. Is there something else I should have tested? Thanks!

SHMT and ACAT are supposed to be the leaky gut genes. In other words, people with those SNPs have more problems with their gut, and supporting SHMT and ACAT along with a gut rebuilding protocol will help them fix their gut. They may have problems fixing things without supporting SHMT and ACAT.

Yasko uses the Doctor's Data Comprehensive Stool Analysis with Parasitology X1 and the Metametrix GI Effects Stool Test. I have links to those in my signature. They both work in different ways, which is why she uses two.

There is also an Intestinal Permeability test which is specificially for leaky gut.

If you have done stool testing and killed off all the bad bugs and gotten the good flora back in balance, and rebuilt the stomach lining with glutamine, you should be all right.
 
Messages
69
Mindy,
Folinic acid is a form of folate that can be turned to methylfolate and start methylation, depending on your other mutations. If you're MTHFR C677T -/- and MTRR A66G -/-, I'm guessing the spray could start methylation (and maybe even if you're hetero for those). I'm guessing that folinic acid will have the same effect, but matching doses would be challenging, as folinic acid is usually swallowed and I don't know how much gets absorbed. From what I've read, folinic acid is like a reservoir form of folate, so your body can keep it around for when it needs it. If you're in need, maybe it's going directly to methylfolate.

That is interesting. I suspect that could be happening b/c I stopped the spray for the past 2 days and did not get the same head pressure that I've been having in the morning (after the spray). But what's interesting is that the issue with the spray happened over time, but only now that my sulfur and ammonia levels are sky high again.

BTW - I am MTHFRc677-/-; not sure about MTRR a66g, doesn't look like 23andme tested for it. Given that I am hetero for 3 CBS mutations, BHMT and COMT, I don't want to take methyl supplements again (that's what has gotten me in this issue; sulfur foods were NOT a problem for me prior to taking methyl supplements). So would folinic acid be a good one for me (I'm willing to try the spray again after CBS calms down)? And what type of B12 is good for these SNPs?

Thanks so much for your input.
 
Messages
69
I'm not sure if the spray could start methylation by itself, but the hydroxycobalamin in combination with folate in the diet could be feeding methyl donors into CBS, causing an effect. Based on my experience, even tiny amounts of methyl donors can do this.

My suggestion would be to do a trial of folinic acid by itself, instead of doing the spray and see if that's any better. Or if you'd rather do the spray, then treat CBS first, then go back to using the SHMT spray.

Note that SHMT is one of the "leaky gut genes", so you should also look at your gut before going past SHMT and CBS. The reason is that once you restart methylation, there will be an increased need for magnesium and/or potassium, and with leaky gut, it will leak out as fast as you're putting it in. This can become a dangerous situation (speaking from experience here).

You would do a stool test and then if it shows imbalances, treat the gut with a 4R gut rebuilding program.

I am willing to try the spray again once CBS is under control. Question about that...do you know if people have been able to go back to eating sulfur foods once CBS is addressed? How long does it take to address it?

I'm on round II of trying to address CBS. I started by completely eliminating sulfur and had great results. I started slowly adding sulflur foods back in without a reaction. But once I added in RX drugs in addition to the sulfur foods, the sulfur/ammonia are creating worse problems than before. This is really scary b/c I can't seem to get rid of my current UTI and I need more ABX but am afraid to take them b/c of the head symptoms.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
That is interesting. I suspect that could be happening b/c I stopped the spray for the past 2 days and did not get the same head pressure that I've been having in the morning (after the spray). But what's interesting is that the issue with the spray happened over time, but only now that my sulfur and ammonia levels are sky high again.

BTW - I am MTHFRc677-/-; not sure about MTRR a66g, doesn't look like 23andme tested for it. Given that I am hetero for 3 CBS mutations, BHMT and COMT, I don't want to take methyl supplements again (that's what has gotten me in this issue; sulfur foods were NOT a problem for me prior to taking methyl supplements). So would folinic acid be a good one for me (I'm willing to try the spray again after CBS calms down)? And what type of B12 is good for these SNPs?

Thanks so much for your input.
Mindy,

I have read about head pressure being associated with overdosing of B6 or P5P. A tight band of pressure around the head. Are you taking either of those?

I got MTRR A66G from my 23andme results. I used Genetic Genie to find it:
MTRR A66G rs1801394 GG +/+ need 3-4X for MTR

But with the rs number you can look it up in your raw data. My note at the end is shorthand for saying that, because of this mutation, I need 3 to 4 times the methylcobalamin (methyl-B12) for the MTR enzyme to work. MTR is the one that uses up methylfolate when recycling homocysteine to methionine. For me, the lack of methylB12 is the rate-limiting step.

I know some people have sulfur problems, but if you read PubMed, the research has generally acquitted the CBS gene. The 10x upregulation that Yasko attributes to the CBS was not for any of the human mutations, it was a laboratory artifact. What I wonder is if you have a SUOX mutation. That is one that 23andme doesn't test for. Have you used sulfite and sulfate urine test strips to quantify your sulfur problem and track your progress? If it's SUOX, sulfite will be high. Sulfates follow my dietary intake - can't say if that will be true for you.

Folinic acid may be a good choice for you, since it is not a methylfolate. But since your MTHFR C667 is a CC, you can use it to make methylfolate. So, it may be a good choice, it may not. Since you associate the reaction with the spray that has folinic acid, at least by doing the test, you will find out if it's the folinic acid or the other ingredients.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
If you have done stool testing and killed off all the bad bugs and gotten the good flora back in balance, and rebuilt the stomach lining with glutamine, you should be all right.
Ha! I think my gut was doing pretty well until I was Rx'ed megadoses of NAC, which I think was what upset it initially, then 14 days of Levaquin followed by Augmentin in progress...I'm back to an unbalanced flora if it ever was balanced. we will start over fixing the gut after we fix the sinuses.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
I am willing to try the spray again once CBS is under control. Question about that...do you know if people have been able to go back to eating sulfur foods once CBS is addressed? How long does it take to address it?

I'm on round II of trying to address CBS. I started by completely eliminating sulfur and had great results. I started slowly adding sulflur foods back in without a reaction. But once I added in RX drugs in addition to the sulfur foods, the sulfur/ammonia are creating worse problems than before. This is really scary b/c I can't seem to get rid of my current UTI and I need more ABX but am afraid to take them b/c of the head symptoms.
Mindy,
I think how long it takes depends on two things - 1) what other SNPs you have and 2) how strictly you can follow a low-sulfur diet. I am hetero for two of the CBS mutations, C699T and A360A. I did a week of low-sulfur diet after which my urine tests showed no problems. I also felt much better and lost almost 7 lbs, most of it belly bloat. Some people will take much longer. What I didn't know at the time was that I was histamine intolerant, and that cutting out sulfur I also cut out histamines. So, what was sulfur, what was histamine? Hard to tell.
 

Shellbell

Senior Member
Messages
277
Critterina, careful of Levaquin. Look up fluoroquinolone toxicity! I have had all sorts of problems because of those drugs. Hope you feel better soon!
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Critterina, careful of Levaquin. Look up fluoroquinolone toxicity! I have had all sorts of problems because of those drugs. Hope you feel better soon!
Thanks for the warning. It was not my first choice, but my doctor's. I have asked him since to use it only as a last resort. Since I'm allergic to Z-packs and bugs are sometimes resistant to older drugs, they often go for that first hoping only to have to use one round. I have read the toxicity, and a family member who used fluoroquinolones long term had severe depression for a couple of years after stopping.
 
Messages
69
Mindy,

I have read about head pressure being associated with overdosing of B6 or P5P. A tight band of pressure around the head. Are you taking either of those?

I got MTRR A66G from my 23andme results. I used Genetic Genie to find it:
MTRR A66G rs1801394 GG +/+ need 3-4X for MTR

But with the rs number you can look it up in your raw data. My note at the end is shorthand for saying that, because of this mutation, I need 3 to 4 times the methylcobalamin (methyl-B12) for the MTR enzyme to work. MTR is the one that uses up methylfolate when recycling homocysteine to methionine. For me, the lack of methylB12 is the rate-limiting step.

I know some people have sulfur problems, but if you read PubMed, the research has generally acquitted the CBS gene. The 10x upregulation that Yasko attributes to the CBS was not for any of the human mutations, it was a laboratory artifact. What I wonder is if you have a SUOX mutation. That is one that 23andme doesn't test for. Have you used sulfite and sulfate urine test strips to quantify your sulfur problem and track your progress? If it's SUOX, sulfite will be high. Sulfates follow my dietary intake - can't say if that will be true for you.

Folinic acid may be a good choice for you, since it is not a methylfolate. But since your MTHFR C667 is a CC, you can use it to make methylfolate. So, it may be a good choice, it may not. Since you associate the reaction with the spray that has folinic acid, at least by doing the test, you will find out if it's the folinic acid or the other ingredients.

According to my dr, I also will need high levels of b-12. He wanted me to work my way into taking it in multiple forms, starting with the other 2 besides methyl. (I can't remember offhand if he wanted me to work my way to the m- form).

I have tested my sulfate levels, and they are always high when I get the head pressure resulting from food intake. I could pretty much guess the range they'd be at based on my symtpoms. A few days ago, I was at 1200-1600. What's worrisome for me is that I've been on a low sulfur diet for FOUR months; yet these medications caused the levels to skyrocket again. And it's so odd b/c, as I mentioned, before ever taking the methyl supplements, I basically lived off sulfur with no problems.

So now I'm wondering if maybe I can't tolerate ANY methyl-related supplements, and if the SHMT spray contributed to me being so sensitive to sulfur again? I added the spray in nearly 2 months after being low sulfur.

As for b6, there is likely a small amount in the multi that I'm taking, but I'm not even taking the full dose, so I don't think it's that. Good to know though. Thank you.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
According to my dr, I also will need high levels of b-12. He wanted me to work my way into taking it in multiple forms, starting with the other 2 besides methyl. (I can't remember offhand if he wanted me to work my way to the m- form).

I have tested my sulfate levels, and they are always high when I get the head pressure resulting from food intake. I could pretty much guess the range they'd be at based on my symtpoms. A few days ago, I was at 1200-1600. What's worrisome for me is that I've been on a low sulfur diet for FOUR months; yet these medications caused the levels to skyrocket again. And it's so odd b/c, as I mentioned, before ever taking the methyl supplements, I basically lived off sulfur with no problems.

So now I'm wondering if maybe I can't tolerate ANY methyl-related supplements, and if the SHMT spray contributed to me being so sensitive to sulfur again? I added the spray in nearly 2 months after being low sulfur.

As for b6, there is likely a small amount in the multi that I'm taking, but I'm not even taking the full dose, so I don't think it's that. Good to know though. Thank you.
I agree with you: the B6 in the multi is probably not causing the symptoms. I think the doses that cause head tightness are over 100 mg.

There are 4 available forms of B12: cyano, adenosyl, hydroxo/hydroxy, and methy. The cyano form is considered the least desirable, I think it's because it doesn't occur in nature and not everybody can convert it (like me). So, your doctor probably means the other three. You might check with him.

There really is no such a thing as a no-sulfur diet, just like there's no such thing as a histamine-free diet, but we do our best. For low sulfur, I did quinoa (buckwheat and amaranth are OK, too), carrots, celery, zucchini, and greenbeans, sweet potatoes, nuts except peanuts and Brazil nuts, coconut and olive oil, fruits (except four on the list that I forget.) Dairy-free, soy-free, egg-free, nothing with eyes. I forget what dairy substitute I used, probably almond since I don't think rice was on the list.

Mindy, you never said whether the antibiotics contained sulfur - is that the source? It could have nothing to do with the spray, if that's the case.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Actually it does test 4:
rs11171718 (A = 4%)
rs705703 (T = 2%, TT = 0)
i5000977 (A is normal)
i5000976 (A is normal)

But there's no research into any of them unfortunately, just prevalence data on two of them.

I've got AG, CC, AA, AA when listed in the same order.
Valentijn, if I knew this, I could have saved $70! Thanks!
I'm GG, CC, AA, and no call - the last one is probably normal, too.

Mindy, have you checked out these and your MTRR A66G?