Why do I keep getting worse?

[Critterina]

I'll give the Healthy Origins a try. If I don't see good results from that, I'll try the Probulin.

Which raises the question: what ARE good results from a probiotic? You described some signs of overdoing it, but not what a proper and effective dose should do for you. I don't think I have any overt signs of gut problems so I'm not sure what a "good result" would be??

You must live in Tampa/StPete. That seems to be where all the Vitamin Discount Centers are.

I'm seconding this question, especially in response to the comments on fiber. This is my gut story:

I normally had 35-50 g of fiber in my diet before I got sick (not CFS, but histamine intolerance, hypothyroid, and adrenal insufficiency/low hormones). After I got sick, stools were solid but loose and orangish with lots of stuff (I assume undigested stuff) to the point of needing to cut way back on fiber. Stool tests showed not pathogens or SIBO. When I take probiotics or digestive enzymes, or both, stools firm up and darken, but when I quit, it's a day before I'm back to orange and loose.

I decided today to go whole hog and buy some of all the 4R gut rebuilding supplements that were on sale at the discount outlet in my area. I still need arabinogalactans and glutamine (which I'll be careful with, because of low cortisol) and probably a couple of other things, but I scored on lots of supplies...And I didn't punch out the other customer who thought I should do what he does so that I can be just like him - how judgmental :thumbdown: and ignorant and not prone to a long life if he can't get a clue as to when to get out of other people's faces. (Although I did fantasize about asking him to write down his name so that I could then tell him it's so I can get a restraining order. )

 

[whodathunkit]

@Critterina, LOL! Good for you for not punching out the other customer. Unfortunately I have also had a terrible, terrible time with reigning in that impulse lately. Some people really don't get the fundamental right of personal choice.

When I take probiotics or digestive enzymes, or both, stools firm up and darken, but when I quit, it's a day before I'm back to orange and loose.

That's pretty much the answer. Things just get better, even if it's subtle. But sometimes the benefits are almost instantaneously noticeable, and sometimes it takes a little while.

Even if your poops aren't bad, when you find the right combo of probiotics or digestive supps, they get better.

Even if you only very occasionally get heartburn, with the right combo of digestive supps, you stop getting it at all.

Your immune system functions better, and you notice that after a month or two.

Etc.

Improvement can be very subtle, but it's there.

the thing about fixing your gut is it takes a while for the results to last. Minimum six months of supplements and other things daily. Frequently it takes longer than six months.

And it's not something you can ever really abandon again. After you reach maximum improvment (whatever that is for you) you may not need to take probiotics every day, but you still want to take them once per week, at least. We can't count on a constant replenishment of bacteria and beneficial organisms from our soil or water any more. Food is too well washed and water is too processed. Plus we're constantly bombarded with toxins and things that like to beat up the good bacteria in our guts. So we have to take a probiotic supplement on a regular basis, even if we get well enough so that we don't have to do it every day.

I don't think it's that we don't need *any* fiber, but rather that we need a healthy gut more. Metamucil or psyllium husks or even acacia fiber are just bandaids. If your gut flora isn't balanced and you do well on these fibers, when you stop taking the fiber you quickly go back to square one.

Plus, as you age, there may reach a point where the fiber doesn't work that well.

But if you can rebuild your gut flora, you won't need these fibers. You can stop taking them. When your gut is healthy you can just eat a normal healthy diet (meat, fruit, veggies, potatoes, occasional grain if you can tolerate that, etc.), and all will be well.

I haven't taken fiber in several years, although I used to need it.

HTH.

 

[garyfritz]

Hi @liverock,

Not sure when I said --. I'm ++ A1298C but -- A677T.

I have high ammonia, and I'm about to start taking yucca for it. The Jarrow Liver Optimizer contains ALA and NAC, which are sulfur compounds. I wonder if that's a good idea for someone with CBS++? I don't show any signs of leaky gut so maybe I'm OK on the ammonia backup?

I believe I had my homocysteine checked years ago and it was OK. Probably should check it again, given what I know now.

My BP runs low-ish (usually about 110/70). I had a sonogram on my arteries a year ago and it said I had "the arteries of a 28 yr old" (and he wants them back!! ). Pretty good considering I was 56 at the time. My MD was a bit shocked.

But my cholesterol runs high. It typically runs in the 230-240 area, but in the last year it has jumped dramatically. Last test was 280, yikes. I'm not sure if the jump was due to the greater amount of meat I've been eating for the past year (dabbling with a semi-paleo diet, but given my ammonia/sulfur I probably need to cut way back on meat), or something to do with my B12 regimens, or just getting old, or what. If not for my clean arteries and good HDL/LDL ratio I'd be pretty worried, but I would still like to bring it down.

 

[liverock]

@garyfritz

Not sure when I said --. I'm ++ A1298C but -- A677T.

Post # 16 and # 18, you appear to switch from ++MTHFR (with 4 variants which is shown on your test results) to - -MTHFR. What exactly are the 4 variants on ++MTHFR?

I have high ammonia, and I'm about to start taking yucca for it. The Jarrow Liver Optimizer contains ALA and NAC, which are sulfur compounds. I wonder if that's a good idea for someone with CBS++? I don't show any signs of leaky gut so maybe I'm OK on the ammonia backup?

The liver supplement isnt just to help clear out the liver, it contains nutrients that can help repair damaged liver cells RLS can be to a symptom of liver scarring which may not always show on liver tests.

B12 is stored in the liver,(usually up to 2 years worth normally), and low B12 storage could indicate liver problems. The fact that RLS is getting worse after eating and drinking when the liver is working its hardest could indicate a liver B12 storage problem, requiring high B12 supplements to ease symptoms. If taking the liver supplement eases symptoms then that could help narrow down the source of the problem.
.

I believe I had my homocysteine checked years ago and it was OK. Probably should check it again, given what I know now.

It should ideally be between 6-8

My BP runs low-ish (usually about 110/70). I had a sonogram on my arteries a year ago and it said I had "the arteries of a 28 yr old" (and he wants them back!! ). Pretty good considering I was 56 at the time. My MD was a bit shocked.

Im not surprised your MD was shocked. You should get him to write an article to JAMA. For somebody with ++ACE and ++NOS3 most 56 year olds would have had a bypass by now.

But my cholesterol runs high. It typically runs in the 230-240 area, but in the last year it has jumped dramatically. Last test was 280, yikes. I'm not sure if the jump was due to the greater amount of meat I've been eating for the past year (dabbling with a semi-paleo diet, but given my ammonia/sulfur I probably need to cut way back on meat), or something to do with my B12 regimens, or just getting old, or what. If not for my clean arteries and good HDL/LDL ratio I'd be pretty worried, but I would still like to bring it down.

Yeah, you need to get cholesterol lower. Whats your triglycerides readings.?

 

[garyfritz]

Post # 16 and # 18, you appear to switch from ++MTHFR (with 4 variants which is shown on your test results) to - -MTHFR. What exactly are the 4 variants on ++MTHFR?

#16 was Critterina. But anyway -- I'm +/+ for A1298C, plus rs1476413, rs3737964, rs4846048, rs4846049.

Im not surprised your MD was shocked. You should get him to write an article to JAMA. For somebody with ++ACE and ++NOS3 most 56 year olds would have had a bypass by now.

Well she didn't know about my genetics at the time. She was just shocked to see that good a result from ANYone. Especially someone with high cholesterol.

Yeah, you need to get cholesterol lower. Whats your triglycerides readings.?

On my most recent test with total chol = 287, my trigs were 83. HDL 86, LDL 184. LDLs are too high but my chol/HDL ratio is 3.3, well below the 5.0 they recommend. I should get a more comprehensive test that checks the LDL particle size. It's possible all those LDLs are the "big fluffy" kind that are actually benign, which would explain my great arterial health.

 

[whodathunkit]

FWIW, after doing some research, I like my cholesterol a little higher and rely on the ratio rather than the numbers.

Triglycerides are the most accurate "fatty" predictor of heart disease, and they have as much to do with sugar, refined carbs, and polyunsaturated fats in the diet than with the eeeeevil saturated fat.

I predict that as soon as the "cholesterol lowering" drugs either fall out of patent, or out of favor, or we move on to a new pharmaceutical model for treating heart disease, suddenly the range for beneficial cholesterol will jump. Possibly radically. Or it just won't matter any more. In the same way we're suddenly hearing salt and saturated fats are not the big bads they've been telling us for decades.

 

[garyfritz]

I think you're right. Studies I've seen say that higher levels of cholesterol are *beneficial* for overall mortality rates. Low chol *might* lower heart disease, but other health problems crop up and you're worse off. For women the health benefits of higher chol keep increasing up into the high 200's. Unfortunately for men it's not quite as clear. The health risks do start to increase with high-200's chol, but it's still only about where it is for LOW chol (150 range).

 

[whodathunkit]

As long as the cholesterol lowering class of drugs are such money-makers for the pharmaceutical companies, the science will be said to be relatively settled. Once we move beyond that paradigm, look for it to become unsettled.

 

[liverock]

@garyfritz
Now that we are clear that you are MTHFR- - and you have no gut issues, the most likely source of your symptoms is the A1298C++ mutation.

This will lower the BH4 level by 70% and the body intelligence will direct most of this to the most vital areas, which in your case with being ACE++,iNOS ++, eNOS++ will be the heart and arterial system.
The next priority for BH4 with the CBS++ will be the Urea cycle to deal with the elimination of ammonia.

Trailing in the rear will be neuro transmitters, you can live with down graded neurotransmitters with low BH4, but not with a clogged up heart, arteries and Urea cycle.

This most likely means despite being COMT++, which normally ensures adequate dopamine, with low BH4 your going to have low dopamine and probably low serotonin.

Low dopamine is associated with RLS, ADD and 'twitchy' symptoms generally, as well as fatigue.(google dopamine+RLS).

Your probably trying to raise higher methyl groups by taking high doses of B12 (after being woken up with symptoms) to increase BH4 which will eventually raise dopamine and let you sleep. I dont know why its got worse could be higher ammonia. Could also be the MTRR A66G mutation which requires feeding with higher B12 to increase methylation.

It might be worthwhile trying a Mucunu supplement to increase dopamine(starting low and buiding up slowly).

www.iherb.com/NOW-Foods-Dopa-Mucuna-90-vcaps/8673

You could also take a Vit D supplement which could help dopamine levels. It might be worthwhile getting your levels checked to work out dosage.

If you are taking a dopamine supplement, care must be taken that as you get rid of ammonia, BH4 can go up and with a COMT++ cause high dopamine levels.


A more in depth explanation about A1298C ++ and how to raise BH4 and deal with ammonia.

http://survivingmthfr.blogspot.co.uk/2012/06/mthfr-a1298c-polymorphism_04.html

This is just a precis of what I think is going on with BH4, no doubt there could be other mutations causing low B12 such as MTRR A66G++ mutation which will ultimately affect BH4 and dopamine levels.

 

[Johnmac]

@garyfritz I was going to say what @Critterina said. She said it much better than I would have, & with a greater depth of knowledge.

I was going to say it because I am just coming out of a crash that sounds a fair bit like yours, & I did so (on the advice of Critterina & others - see my recent post) by lowering methylfolate in relation to mB12.

My original ratio was about B12/folate 3:4 - much different to yours. But some like Critterina need B12/folate 15:1. I guess it depends on the SNPs - & I noticed you have the MTRR A66G +/+, which means, as @sregan said regarding my mere +/-: "You don't recycle mb12 too good".

My crash symptoms were jitteriness & tension & lack of desire to work & plunging temps & cold hands & feet & anhedonia - absolute disinterest in everything. No focus at all, zero. I was a bit clammy.

As I said in the post, it felt like serotonin syndrome, which I've never had, but had read about. I couldn't work out why that would be (I wouldn't take SSRIs for a million dollars). Then I saw that m-folate was a co-factor in generating serotonin & dopamine. So maybe it generated too much serotonin (symptoms = increased heart rate, shivering, sweating, dilated pupils, twitching, over-responsive reflexes, hyperthermia, hypervigilance, insomnia and agitation) or dopamine (attention deficit/hyperactivity), or both?

Actually I don't know what the etiology was for my symptoms; but I sure feel better with more B12 and less folate.

You and I both need m-folate (we both have MTHFR A1298C), but I'm happy to be on less at present. Also I'm skinny. (Fat people (BMI >60) need more m-folate, at least to recover from depression.)

After a time on less folate you may get folate depletion symptoms. You can ask Critterina what to do then (as I probably will).

It's "so confusing" because none of us quite knows what we are talking about, and are feeling our way down the long dark corridor of illness by trial and error, with the guidance of a fabulously promising but partly-fleshed out science - a penlight with a couple of AA batteries in it, to complete the metaphor.

A few random points:

* The reliable metal heavy tests are hair tests. Blood and urine testing will only reveal recent exposures, not longterm or chronic toxicities: e.g. the mercury that lives in your brain or the lead that lives in your bones. Though possibly urine challenge tests are an exception to this (? I've forgotten my Cutler), provided you don't do the potentially life-destroying intravenous DMPS challenge.

* I didn't need to do a thing for my gut, which was unstable despite daily kombucha and kefir: the protocol stabilised it nicely in about a week.

I have no knowledge of SNPs, but just cutting and pasting from my Yasko notes:

* Your two COMT +/- mutations probably suggest adenosyl B12. Your VDR +/- mutations might suggest vitamin D.

* Your MAO + does suggest going easy on things that generate serotonin (snap!).

 

[Violeta]

garyfritz, if you have congenital iron overload, maybe you are having iron overload symptoms. I have seen other people come up with Parkinsonian symptoms from taking high doses of methylfolate and methyl B12. Have you seen the B2 I love you thread? You may have depleted your B2, and B2 is very important for handling iron.

 

[garyfritz]

Thanks @Violeta. I'll look through that B2 thread. But another thread on B2 warned of possible problems with high-ish doses of B2.

I've recently started taking a B complex with 20mg of B2 so hopefully that will help, but as it has all the other B's too, who knows if it's going to use up all the B2 handling the excesses of other B's....

 

[garyfritz]

Thanks @liverock!

Now that we are clear that you are MTHFR- -

You mean A677T I assume? Since I am ++ for A1298C & others.

[the A1298C++ mutation] will lower the BH4 level by 70% and the body intelligence will direct most of this to the most vital areas, which in your case with being ACE++,iNOS ++, eNOS++ will be the heart and arterial system.
The next priority for BH4 with the CBS++ will be the Urea cycle to deal with the elimination of ammonia.

Would you recommend anything to help those processes?

This most likely means despite being COMT++, which normally ensures adequate dopamine, with low BH4 your going to have low dopamine and probably low serotonin.
Low dopamine is associated with RLS, ADD and 'twitchy' symptoms generally, as well as fatigue.(google dopamine+RLS).

I have long suspected I'm low dopamine. In addition to the symptoms you mention (which are me in spades), dopamine is supposed to promote "joy in life" types of emotions. I read that "The primary role of dopamine is pleasure and motivation." I could use more of both.

Low serotonin might have predisposed me to depression after my divorce?

It might be worthwhile trying a Mucunu supplement to increase dopamine(starting low and buiding up slowly).
www.iherb.com/NOW-Foods-Dopa-Mucuna-90-vcaps/8673

Thanks, interesting sounding stuff. I will look into that.

If you are taking a dopamine supplement, care must be taken that as you get rid of ammonia, BH4 can go up and with a COMT++ cause high dopamine levels.

I wondered about that. (Even though I'm just COMT +-.) High dopamine can cause paranoia, schizophrenia, suspicious personality, impulsive behaviors, ADHD, etc. Is it a good idea to take Mucuna while messing about with my ammonia/BH4/methylation/etc systems?

You could also take a Vit D supplement which could help dopamine levels. It might be worthwhile getting your levels checked to work out dosage.

I currently take 2000iu/day of D3. With my VDR +-'s I wonder if I should take more.

A more in depth explanation about A1298C ++ and how to raise BH4 and deal with ammonia.
http://survivingmthfr.blogspot.co.uk/2012/06/mthfr-a1298c-polymorphism_04.html

I'm starting some yucca to help with ammonia, and I've taken L-glutamate for several years. Those are two of her recommended treatments for ammonia control. Other than that I'm taking 5MTHF (methyl folate) and methyl/adenosyl B12 and sundry other things. Her list is daunting, but she says she's taking methylfolate, methylcobalamin, iron, vitamin C and royal jelly as BH4 precursors. I tend to have high iron but I could add C and royal jelly.

Merci sir!

 

[liverock]

@garyfritz

First a correction,you are COMT hetero, not COMT homo (my mistake looking at the wrong column)

The main problem which seems to have afflicted you, maybe all your life, is the MTRR ++ mutation. This blighter is nullifying a lot of the B12 that the MTRR its supposed to be providing to the MTR, to enable homocysteine to be converted to methionine.

If you look at the MTRR section ( a quarter way down)on this site, you can see on the wheel diagram the problem.

http://www.heartfixer.com/AMRI-Outcomes-Non-CV-Autism-Methyl Cycle.htm

This means a lot more B12 will need to be taken compared to methylfolate to avoid 'methyl trapping' which I think is what is causing your bedtime problems.
There is however a BHMT 'short pathway' which bypasses this problem you can see which would enable a dose of TMG to assist the conversion of homocysteine.

I think it might be better to hold off any Macuna or Vit D supplements and concentrate on tackling the MTRR and B12 problem which you can do now. Once you get that working properly it will increase methylation which will help with ammonia detox.

I dont know what dosages of methylfolate and methyl B12 you are taking ATM but I think it might be better to cut down on the folate a bit, and try and keep a 10:1 B12/ methylfolate ratio and start supplementing with just 1-Trimethylglycine (TMG) 500mg (for one day only initially) and see how you respond to start with.

TMG is a methyl donor and too much might stimulate COMT too much. It would help though if you could stick with the TMG as it might help with the BHMT 08 snp which causes ADD symptoms.

This will be very much 'Try As You Go' supplementation to get the best dosages for your genetic makeup, so it may take a bit of time to get right.

 

[garyfritz]

If you look at the MTRR section ( a quarter way down)on this site, you can see on the wheel diagram the problem.

You are making the rash assumption that those diagrams make any sense to me. I see the diagram but I have no background to interpret them to understand what they mean. I'm learning slowly, but the biochemistry is still pretty much a mystery to me.

I think it might be better to hold off any Macuna or Vit D supplements and concentrate on tackling the MTRR and B12 problem which you can do now. Once you get that working properly it will increase methylation which will help with ammonia detox.

I *just* bought a bottle of Macuna. I've been taking D3 for years at my MD's recommendation.

I dont know what dosages of methylfolate and methyl B12 you are taking ATM but I think it might be better to cut down on the folate a bit, and try and keep a 10:1 B12/ methylfolate ratio and start supplementing Trimethylglycine (TMG) 500mg to start with, and titrate up as required. You only have one BHMT mutation on the 'short pathway'so the TMG should work OK.

I currently take about 4-5mg of methyl folate (Solgar) along with 20-30mg of Country Life methylB12 and 4mg of adenosylB12 (dibencozide).

However I have no idea how much of the CL B12 I am actually absorbing and able to use. One expert told me he estimated I might be absorbing and appropriately using only 1% of it.

Within a week or so I will be experimenting with a B12 system (transdermal oils) that is supposed to deliver 80% absorption and usability. We will see what that does.

I haven't seen any mention of TMG before so I know nothing about it.

Thanks @liverock!

 

[liverock]

@garyfritz

I *just* bought a bottle of Macuna. I've been taking D3 for years at my MD's recommendation.

Dont take the macuna until this is all sorted It could send you manic if there is to much methyl as well.
I was talking about the D3 I mentioned not what you were already taking.

I currently take about 4-5mg of methyl folate (Solgar) along with 20-30mg of Country Life methylB12 and 4mg of adenosylB12 (dibencozide).

I would start with lower folate after you start taking the starting TMG dose (1- 500mg cap for 1 day only) too check your reaction.Having more folate than is necessary will only create surplus methyl groups that cause trouble with dopamine

However I have no idea how much of the CL B12 I am actually absorbing and able to use. One expert told me he estimated I might be absorbing and appropriately using only 1% of it.

If you hold the sublingual in your upper lip as you should do and let it dissolve it should take over an hour and be fairly close close to the level of a B12 injection. If you just suck it and dont let it dissolve then yes, 1% is about right according to Freddd.

Within a week or so I will be experimenting with a B12 system (transdermal oils) that is supposed to deliver 80% absorption and usability. We will see what that does.

Is it Methyl B12?

I haven't seen any mention of TMG before so I know nothing about it.

http://www.iherb.com/Jarrow-Formulas-TMG-Trimethylglycine-500-mg-120-Tablets/141

 

[garyfritz]

Is it Methyl B12?

They have pure methyl, but I ordered a methyl/adenosyl blend, 1:3. Their B12 expert says that reflects the levels in the body (for a normal methylating person anyway) and that it works well on people with CFS.

CORRECTION: the blend is 3 adeno : 1 methyl, roughly 5.5mg adeno : 1.9mg methyl per daily dose. Assuming it works as well as he says, I will be doing double doses for quite a while to re-stock my B12 stores. I was surprised at that ratio but that's what he recommended for my SNPS and what they've seen good results with before, for people with similar genomes.

 

[liverock]

They have pure methyl, but I ordered a methyl/adenosyl blend, 3:1. Their B12 expert says that reflects the levels in the body (for a normal methylating person anyway) and that it works well on people with CFS.

CORRECTION: the blend is 3 adeno : 1 methyl, roughly 5.5mg adeno : 1.9mg methyl per daily dose. Assuming it works as well as he says, I will be doing double doses for quite a while to re-stock my B12 stores. I was surprised at that ratio but that's what he recommended for my SNPS and what they've seen good results with before, for people with similar genomes.

I would try the TMG with your existing supplementation (which I presume is not working well for you), to check how it works before using the new B12. If the TMG is effective you may not need very high doses of B12.
Taking this B12 oil and TMG together initially would mean your going to 'muddy the waters' about which is most effective.

As I have said before when you do get round to using this new B12, the danger is having too high a folate and creating too many methyl groups for your COMT and VDR to breakdown causing higher neurotransmitter level symptoms.

Where did you get the B12 from, if you dont mind my asking?

 

[garyfritz]

From b12oils.com. Their website isn't great -- missing lots of critical info -- but their B12 expert has been extremely helpful with deciphering my SNPs &etc.

I'll report back after I give the oils a try. If I get the kind of results he says they normally get, I think a lot of people here will be very interested.

 

[garyfritz]

BTW:

If you hold the sublingual in your upper lip as you should do and let it dissolve it should take over an hour and be fairly close close to the level of a B12 injection. If you just suck it and dont let it dissolve then yes, 1% is about right according to Freddd.

I tuck it between my cheek and lower gum, and it lasts about 45-60 minutes. When I take one at night, I'll wake up with the pasty mush on my gum the next morning, so it's there for hours. But I still don't think I'm absorbing/using much of it. I took 20 mg yesterday (4x CL), but it still took 3 more CL to make it through the night. Each of them only worked for about an hour. I don't think it really takes 35mg to get me through a day, or even 0.35mg -- I think most of it is wasted.

The b12oils guy said not only is the oral absorption extremely inefficient, but it appears rapidly in serum and is mostly lost in urine. It doesn't get bound to the "transporters" (TCII and HC) needed for the body to actually use it. He claims that much less than 1% will actually bind to a transporter, and that their oil does better. I hope so.