Excess acetylcholine & methylation

[Cnew2this]

@drmullin30 – Tired of me yet? Another supplement to get your take on. I’m liking it as I could do away with my multi-min sup and some stand-alone vit/mins. I would add R5P and P5P separately. It has 200 mcg mfolate, which is a good number for me for now. Relatively low Niacin in the right form (right?).
Vital Nutrients Minimal & Essential
Thiamin (as thiamine HCl) 25 mg
Riboflavin 25 mg
Niacinamide 25 mg
Vitamin B6 (as pyridoxine HCl) 25 mg
Folate (as L-5-MTHF) Metafolin® 200 mcg
Vitamin B12 (as methylcobalamin) 200 mcg
Biotin 200 mcg
Pantothenic Acid (as calcium pantothenate) 25 mg

Vitamin A (as 67% beta carotene and 33% vitamin A acetate) 7500 IU
Vitamin C 375 mg
Vitamin D3 (as cholecalciferol) 400 IU
Vitamin E (as d-alpha tocopheryl succinate) 75 IU
Zinc (as zinc citrate) 10 mg
Selenium (as selenomethionine) 125 mcg
Copper (as copper glycinate) 1 mg
Manganese (as manganese aspartate) 5 mg
Chromium (as chromium polynicotinate) 100 mcg

 

[drmullin30]

Hi @Cnew2this The Douglas one looks good as far as the niacin riboflavin and folate. I've never tried it I was always worried about gluten or corn contamination with that company and I need to do more research on the intrinsic factor ingredient. Does porcine IF work? I've never heard of that one before.

One thing I forgot about the MAOA gene is that B2 is a cofactor so I find it's important to get enough to keep my NTs balanced but yes it can cause potassium almost insatiable potassium deficiency if you take too much while using b12 and folate.

Here's a screen shot from the AOR website the niacin is combined with the inositol so it's already in a methylated form and they use the generic name for folate which is folic acid. The doses are for three capsules. I've had no problems with this supplement and I've been taking it for years.

 

[Cnew2this]

Thanks for that @drmullin30 The AOR company is leading me to think I am losing my mind. Maybe there is another B Complex formula that I didn’t see. I was looking at the Advanced B Complex. So folic acid doesn’t concern you? I can’t seem to let go of my early reading on MTHFR (mostly Lynch) that drilled into my mind that it is pure evil. I guess it is probably dwarfed by the massive doses of mfolate that you take (?).

On the various forms of niacin, and their compatibility with the Freddd Protocol, is inositol hexanicotinate the best, niacinamide ok, and nicotinic acid bad?

When a supplement shows "Niacin" is that almost certainly nicotinic acid? I realize now that the Seeking Health B complexes probably do have some nicotinic acid. How bad is that at a fairly small amount?
Niacin (79% as inositol hexanicotinate and 21% as niacin) 95 mg

You are right that porcine in the Douglas really doesn’t work for me. But I’m not such a purest that I can’t look the other way occasionally for a by-product.

 

[drmullin30]

@Cnew2this I understand your confusion around "folic acid" so let me see if I can clarify. The term "folic acid" is a generic term that can mean any of the following:

- Vitamin B9
- folic acid
-folinic acid
- L-5-methylfolate
- methylfolate
- folate

Supplement companies, doctors, etc. will use these terms interchangeably which makes our life more difficult because we have a very specific need. We should only be taking L-5-methylfolate. If you look at the term in brackets in the screen shot you'll see that AOR uses L-5-Methylfolate in their formula but they call it "folic acid".

 

[drmullin30]

The term "Niacin" has the same problem as "folic acid". "Niacin" can mean any of the following:

- nicotinic acid
- niaciniamide
- inositol hexanicotinate
- nicotinate
- niacin
- vitamin B3

Nicotinic acid isn't a huge problem if it's a smaller dose. It simply uses up methyl donors to convert to bioavailable form so if you don't want to waste methyl groups it should be avoided but it may not cause a problem.

Both Niacinamide and inositol hexanicotinate are already in bioavailable forms. I don't know if there's a major difference between those two forms.

 

[Cnew2this]

@drmullin30 – thanks for those clarifications. I need to be more careful about reading supplement labels. My brain just locked in on “folic acid” on the AOR supps. The Advanced B I was looking at shows this for folate: Folate (as calcium L-5-MTHF) 835 mcg DFE (500 mcg of folic acid). So in simple terms, it actually contains 500 mcg mfolate?

And for the Seeking Health B+ if I understand correctly, I am getting 200 mcg mfolate and 200 mcg calcium folinate.
Folate [50% as Quatrefolic® (6S)-5-methyltetrahydrofolate, glucosamine salt
and 50% as calcium folinate] 680 mcg DFE (400 mcg)

I think for now I am going to finish the bottle of the Seeking Health B+ that I have, and then I will reevaluate. If it has 95 mg of niacin (79% as inositol hexanicotinate and 21% as niacin) I’m only getting 20 mg of nicotinic acid. I think for now I need to find some stability, particularly with B2 dose vs potassium supplementation.

I’ve started reading the Yasko book. It’s good. Back in those days her discussions were more complete on things to take/eat and things not to take/eat for various SNPs and conditions. My experience a couple years ago was that it was all about adding HH supplements for every SNP and anything slightly out of balance on a HH test. I could see the writing on the wall that it was going to get really expensive.

So, you may get a break from me for a while. I REALLY APPRECIATE all the time you have spent helping me out. Take care and continue with your own healing too.

 

[drmullin30]

@Cnew2this so just to make things even more confusing folinate is actually folinic acid and if you have MTHFR SNPS you may want to avoid that one as well. I can't handle any of that. So I should update the list from my previous post to say:

- Vitamin B9
- folic acid
- folinic acid
- folinate (folinic acid)
- L-5-methylfolate
- methylfolate
- folate

We still only want to take L-5-methylfolate

 

[Cnew2this]

@drmullin30 -
Yeah, I had been wondering about the calcium folinate in the Seeking Health. I was kind of hoping it would be a neutral addition (no harm, no good), but if it is counterproductive to the F protocol, that’s not good.

I just ordered some of this, which I think will be a good one for me for now. The R5P is too low, but I can add more separately. It has a bunch of other supps in addition to the Bs. Values are for 2 caps, but I will probably take just one for now, to keep niacin and mfolate low. Hopefully I haven’t overlooked something bad in this one.

I was reading more on CBS SNPs (I’m +/- for the C699T and several others), and it seems that one needs to be careful not to take too much B6. I’ve been taking 45 mg/day of P5P, so I would like to cut back on that, and this Thorne sup will work there too.

Thorne Basic Nutrients 2 per day
Per 2 caps
Thiamin (as Thiamin HCl) 50mg
Riboflavin (as Riboflavin 5'-Phosphate Sodium) 12mg
Niacin (as Niacinamide) 80mg
Vitamin B6 (as Pyridoxal 5'-Phosphate) 20mg
Folate (as L-5-Methyltetrahydrofolate* from L-5-Methyltetrahydrofolic Acid, Glucosamine Salt) 400mcg, Vitamin B12 (as Methylcobalamin) 600mcg
Biotin 500mcg
Pantothenic Acid (as Calcium Pantothenate) 45mg

 

[drmullin30]

@Cnew2this is your CBS SNP an upregulation or down?

I have CBS SNPs as well that results in an upregulation and some days I take over 100 mg per day of P5P. P5P is the form I need and it doesn't cause as much problem with CBS as the other form of B6. My most important supplement for that SNP is molybdenum. Are you taking molybdenum? You can test to see if your CBS SNP is active by measuring urine sulfite and sulfate with test strips.

Zinc was also crucial because with a CBS SNP I was molybdenum deficient and therefore copper toxic. The CBS SNP was the prime reason for my copper toxicity.

In my case, it seems the CBS SNP will upregulate during detox especially if I was eliminating mercury. I also always had an uptick whenever I increased my methyl donors e.g. folate or b12 etc. and it upregulated for a while when I started ALA. So I had to carefully monitor my urine sulfate for the first few months on the protocol to see how much molybdenum I should take. At one point I was taking 6 mg per day but I also have MOCS SNPS so that increases my need.

Many PR members don't think the CBS SNP is impactful but I have found otherwise.

 

[Cnew2this]

@drmullin30
Here are all of the CBS SNPs that I have been able to locate in the 23andMe report, with my notes on up/down based on reading. So I don’t know what my net result is.

CBS A13637G T CT +/- [down]
CBS A360A A GG -/- [up]
CBS C*351T A AG +/-
CBS C19150T A GG -/- [down]
CBS C699T A AG +/- [up]
CBS G*299A T CC -/-
CBS T*330C G AG +/-

When I did the Hair Analysis Test through Yasko, my molybdenum was off the chart low, but I had been taking high doses of MSM and glutathione, and eating a lot of high sulfur foods. After that I stopped the MSM/glutathione and started being more careful about high sulfur foods. I took 500 mcg/day of Mo for a few months, then went to 250 mcg/day. I haven’t rechecked it.

The UAA test showed that my ammonia was pretty normal (right in the middle of the range), which led me to believe at the time that my CBS SNP was probably not my dominant problem. But I just read this today, taken from an article by Mark London at MIT.
“Urinary ammonia is an even less reliable method for testing for CBS upregulation. This is because most of the ammonia (NH4+) in urine is produced by the kidneys for ph regulation. The ammonia that is produced elsewhere in the body, is usually detoxified by being converted to urea, which is then excreted. This process mainly occurs in the liver, and the liver is quite capable of handling the large amount of ammonia that is produced in the body, which occurs due to the metabolization of amino acids. The liver has to be able to do this, because the nervous system can only tolerate very low levels of ammonia. Excess ammonia, i.e., hyperammonia, only usually occurs either when liver functioning has been greatly reduced, or where a genetic defect in the urea cycle exists. Only by testing serum ammonia, can such a condition be diagnosed.”

The other thing factor that has lead me to believe that my CBS upregulation is not my dominant problem is that my homocysteine was always high (except that it went down quickly after I started taking SAMe, but I didn’t recheck to see if that held). But it was high during a period when I was taking massive doses of mfolate, and no mB12, and I may have been taking other supplements/meds during that time that were making things worse.

I did try sulfate strips a couple years ago, and as I recall it was a little high, but not crazy high. So I lost interest.

I do take zinc, but I also take copper, which I know goes against the grain for Yasko and most doctors. I suspected that after years of taking only zinc I was seeing some signs of copper deficiency. On the HA, copper was almost out of range low and zinc on the high end. But then I'm not sure I trust the HA test anyway. It showed my Li off the chart high, but Yasko recommended supplements because I was probably "dumping". So why trust anything from an HA? But, then, I shouldn't get started on that ...

Whenever I start thinking about my SNPs again, and doing research, my poor little brain feels like it is going to burst.

 

[Cnew2this]

@drmullin30
P.S. Given your experience with CBS upreg when you started the F program, I decided that I probably should start checking my urine sulfate level again.

I still have a few of the strips I had used previously so I checked it this morning. It is between 200-400 mg/L sulfate. The strips are Quantofix by a German company (Macherey-Nagel). Is that a good brand, or do you recommend something else? The strips I have expired in April, but since I haven’t been opening the bottle I would think they should still be valid (?). But I will need to get more anyway. Thanks for that heads up.

When you were going through your detox did you ever use any of Yasko’s (expensive) RNA support supps? Like Metals RNA?

 

[Cnew2this]

Hi drmullin30 – I would like to pick your brain a little more on potassium deficiency. I have seen mentioned a couple times in Freddd threads that too much B1, B2, and B3 can cause deficiency, but I seem to see more frequently the statement that just supplementing mB12 and mFolate almost always brings on a deficiency.

I know now that I was experiencing potassium deficiency long before I started mB12 and mFolate, and I’m pretty sure it was from too much B2. I was taking pretty typical doses of B1 and B3, but a lot of B2. Like 50 mg standard B2 plus 35 mg R5P.

I just want to make sure I stay on top of potassium. I think you said previously that potassium is what keeps you from taking a super high dose of B2. Did I get that right, and in your experience, which supplement do you think is the primary driver in bringing potassium down? Maybe it varies from person to person.

Thanks as always for your time.

 

[Cnew2this]

@drmullin30 (see above)

 

[drmullin30]

@Cnew2this I had found in the first year or so on the protocol that increases in B2 led to increased need for potassium but since I've gone low oxalate and started supplementing some lithium in the Trace elements supplement, this problem has reduced somewhat.

I also found I needed to be careful with B6 but I didn't notice any problems with B1 or B3. Except that B1 will cause me to need more magnesium if I take more.

For the last couple of years, I take about 40 mg per day of R5P but in the last few weeks I've experimented with raising this some days to 100 mg and I haven't noticed a major increase in potassium need.

To answer your question, high dose folate (over 5 mg per day) was the major driver for me and potassium deficiency. Before I started that, I didn't have the symptoms of severe potassium deficiency although I was likely deficient. This is likely due to the huge jump in red blood cell (and probably other cell types) synthesis which requires potassium per the research in refeeding syndrome. I believe and so does Fredd, that much of this potassium deficiency (and copper, boron and calcium as well) is driven by increased cell synthesis and higher quality of cells being produced.

As to your initial potassium deficiency, those of us with severe MTHFR SNPs are almost always potassium deficient as I think it is a cofactor in many methylation cycle reactions. In addition, something like 80% of the population is potassium deficient because you're supposed to get around 5 grams a day and if you don't eat a giant salad and several bananas or potatoes every day, your not going to reach the basic RDI.

I'm starting to show signs that potassium deficiency is temporary on the protocol. As tissues finish repairing and reach homeostasis this will improve. I suggest you look in to lithium supplementation as this was the final piece in the puzzle for Fredd and solved his potassium and copper deficiencies and it has definitely been important for my recovery. I just wish I could get lithium orotate supplements in Canada but they require a prescription and a bi-polar diagnosis so I'm stuck with the paltry few milligrams I get in the Concentrace supplement.

 

[Cnew2this]

@drmullin30 – thanks for all of that. It’s good to hear that the potassium problem tends to go away after a while on the protocol. Interesting that MTHFR SNPs and deficiency go together. I did have a tendency toward tight muscles and cramping for many years before I started taking high doses of B2. Always thought I needed more Mg, but I imagine K was my problem all along. Interesting that reducing oxalates has helped you too. I probably should do that too.

I have been taking lithium for a couple years, per Yasko (7.5 mg/day). Maybe I need more? I hadn’t read about Li in the Freddd threads. I probably should jump ahead, but I just keep plodding along, afraid that I might miss something important. I was reading B-12 - The Hidden Story, but then jumped over to THE STAGES OF METHYLATION AND HEALING.

That is CRAZY that you can’t get Li without a prescription when it is so readily available, and inexpensive, here in the US. Seems like not much is better in the US these days, but we have Li going for us.

 

[Cnew2this]

@drmullin30 – I would like to get your take on some Yasko vs F protocol issues, if you have the time. And if you really don’t have time, I totally understand.

In the Pathways book she talks about the “long way” and “short-cut” around the methylation cycle and that the short-cut “generates more norepinephrine relative to dopamine” and that supplementing with DMG helps slow the short-cut in favor of the long way. Whereas supports for the short-cut include PS, PC, and TMG. I know the F protocol does include adding some TMG, and I have been taking a very small amount of it (250 mg/day), but if Yasko knows what she is talking about, I think trying to encourage the long way might be better for me, so I’m thinking about doing DMG instead of TMG.
She also recommends NADH, B2, and adenoB12 to support MTR/MTRR (and limited ALA).

Any thoughts on all of this, particularly using DMG instead of TMG, and anything else to encourage the long way instead of the short-cut?

It’s been bothersome to me in past reading that my persistently high homocysteine levels (back when I was checking) seemed to be in conflict with my SNPs, but from reading this book I see that the MTHFR C677T does tend to produce high homocysteine, whereas A1298C does not, so I would tend to think that C677T is more dominant for me. I also read that high homocysteine is consistent with MTR/MTRR SNPs.

My relevant SNPs:
MTHFR C677T and MTHFR A1298C +/-
MTRR A66G +/- but MTRR H595Y and MTRR R415T were not done.
BHMT 2 and 8 were -/- but BHMT4 (the important one, I think) was not done.

 

[drmullin30]

Hi @Cnew2this don't worry about my time. It is truly a pleasure to help people in this community who have helped me so much.

DMG actually never did anything for me. I tried it briefly years ago but I didn't notice any impact.

The way I look at the long way and short way around the cycle is to prioritize the long way as you say. This is driven mainly by b12 and folate and with your MTHFR C677T SNP is even more important for you. I'm lucky in that I don't have that SNP and is one reason why I haven't had high homocysteine. The CBS upregulation is the other reason. However, my MTHFR gene is awash in red and I'm homozygous for 1298 so I still need to prioritize folate. As I mentioned above, in my experience I didn't think DMG had all that much influence so this is where I would disagree with Yasko.

For me, the short way around the cycle is important because of my CBS and BMHT SNPS . BMHT SNPs essentially act the same as a CBS upregulation. Because of this, I try to enhance both the shortcut (I take 1800 mg of TMG and 800 mg of PC per day) and the long way to minimize the wasting down the CBS drain. Since you don't seem to have this issue (indicated by high homocysteine), you can concentrate even more on the long way around and you might find that DMG works for you.

If you find that as you drive the full methylation cycle (through b12, folate and DMG if you use it), your sulfites/sulfates increase, you should also see a concomitant reduction in homocysteine. This would mean that you have opened the drain (upregulation) and may need to enhance the BMHT (short cut) pathway until the full cycle can ramp up and compensate. In this respect, the shortcut really is just that as it will respond much faster than the long cycle to supplementation in my experience.

My assumption, (and it may be wrong and not supported by Yasko) has always been that given all the necessary cofactors in abundance, the body will prioritize the long way around the cycle. Anecdotally this has worked in my case but I don't know if it would for everyone.

She also recommends NADH, B2, and adenoB12 to support MTR/MTRR (and limited ALA).

I also tried D-Ribose (to increase NADH) for awhile but it didn't do anything for me. Supposedly this means I don't have very serious problems producing NADH and ATP which fits with the fact that I don't always have CFS symptoms and why my main manifestation is anxiety and mental illness but, I have had PEM on occasion and there have been times in my life where I couldn't get our of bed for days due to fatigue and depression. This is also why I resisted the CFS diagnosis for so long but now I'm convinced that autism, CFS, some (or most?) mental illness, heart disease etc. may all be on the same spectrum of methylation disorders.

As we've discussed previously, B2 is an essential cofactor in the long cycle so Yasko is right about that. From my understanding adeno b12 need is mainly driven by ACAT SNPs but I may be wrong.

I believe Yasko's limiting of ALA is a precaution in case of CBS upregulation (ALA is high sulfur) and her concerns around heavy metal toxicity as well as ALA's ability to chelate good minerals as well. When I take more ALA I do notice an uptick in urine sulfur for a while until the cycle compensates I assume by speeding up the complete methyl cycle. In the beginning, I couldn't tolerate real doses of ALA without horrible anxiety so I had to do Cutler chelation for years. I literally started with tiny finger dabs of ALA and even that wasn't fun. This may also have something to do with my CPOX4 SNP which supposedly increases my sensitivity to the neurobehavioral effects of mercury, fun times! Now I'm up to 300 mg of ALA per day with great results in my energy and mental clarity so it would seem that Cutler chelation has worked for me. I just pray they don't make a Covid vaccine mandatory because that will almost certainly have thimerosal as an ingredient and will set me back maybe years if I can't can't get an exemption.

I find Yasko sometimes mixes the effects of SNPs in her analysis (which may not be incorrect since it is a system it just makes things harder to follow) and since she focuses on Autism, she really emphasizes CBS SNPs which is the main criticism against her as many claim that this SNP is harmless but that is NOT my experience. Maybe if you don't have mercury or heavy metal toxicity it's not an issue.

I hope this helps you make your decision and I wish you good health and healing.

 

[Cnew2this]

@drmullin30 – thank you for all of that info and your observations. You sure are knowledgeable about this stuff. You could be the next Yasko, if you are so inclined. I’m pretty sure she has settled in to the easy life of selling supplements, so someone needs to pick up the torch and continue to make progress in the field.

From what I can gather, it sounds like you have made huge progress with your own health, and I’m betting that you are going to eventually get it all figured out – given your knowledge, persistence, and discipline.

Me, on the other hand, I have a hard time betting on myself that this will be the time that I stick with it and make real progress. My track record isn’t good. Yesterday I had a crash – energy and mood – that was discouraging. Part of my brain had really hoped that the new energy I had been experiencing since starting the F protocol was going to be my new normal. The logical part of my brain knew that there would still be crashes, but the hopeful part was still quite disappointed when it happened. But, I’m coming out of it already, so that is progress. One thing I changed yesterday was to increase my AdB12 from 1,000 mcg to 3,000 mcg, but a crash isn’t what I would have expected from that. I’ll keep experimenting.

I think your assumption about providing the body with all the needed cofactors and it will choose the long route is sound. Of course it is possible that my body has just gotten lazy and is going to stay with the short cut no matter what I do.

I googled “Cutler chelation” and got an Andy Cutler Chelation website, which most likely is what you did. More reading and possibilities for me . . .

I will try (I really will TRY) to give you at least a short break from my questions. I’m so thankful that I found PR, and you. I have made many critical health discoveries already, and even if I don’t have the courage to go 100% with Fred’s protocol (the high doses part), many of the important discoveries were thanks to his posts. I just need to find the patience within me to keep reading, keep experimenting, and hope that something clicks. You have inspired me to do that and have pointed me in many good directions. So, again THANK YOU! But this definitely isn't "Good Bye". I won't be able to hold off for long without firing more questions your way.

 

[drmullin30]

@Cnew2this

You could be the next Yasko, if you are so inclined.

You are far too kind. I'm no doctor, I'm a middle aged engineer so I'm seriously under qualified and too old to consider a career change!

I have made progress, but I also make a lot of mistakes. For instance this week, I've realized I've placed myself into slight metabolic alkalosis and hypocalcemia (calcium deficiency) by overdosing on citrate minerals (calcium, magnesium, potassium and zinc) and lemon juice trying to deal with oxalates and kidney stones. This may also be related to my increase in ALA. This has sent my electrolytes way out of whack and I've been living with a tuque on and a blanket wrapped around me all week despite my house being heated to the point where my wife and kids are sweating! I've had to take huge doses of calcium and sodium chloride to keep my heart from beating out of my chest and I had to switch all of my minerals to non-citrate ones and I just ordered a huge quantity of magnesium citrate.

For some reason It also seems to have caused some pretty heavy depression. I'm finally starting to recover but if my potassium needs uptick for any reason I'll be in a pickle because all I have is potassium citrate. I also constantly worry about my kidneys because the supplements, electrolytes and oxalates place a heave burden on them.

Me, on the other hand, I have a hard time betting on myself that this will be the time that I stick with it and make real progress. My track record isn’t good. Yesterday I had a crash – energy and mood – that was discouraging.

I believe everyone here who has taken this approach has had the same experience. It has always been two steps forward, one back for us. It's a constant balancing act, it's not easy and is probably the main reason many don't stick to this protocol.

One thing I've found with any endeavor that requires willpower or discipline, is that once you start to see results the motivation builds momentum and eventually gets locked in and becomes almost habit. At one point you look back on where you used to be and realize you'll never go back to that and it's extremely relieving and satisfying.

I'll try to give some deeper thought on your crash after raising your adeno dose and see if I can give you some insight.

With respect to Cutler chelation, yes Andy Cutler is the doctor and his protocol is based on the serum half-life of ALA which is around 4 hours. I think the procedure details are there on the website.

even if I don’t have the courage to go 100% with Fred’s protocol (the high doses part)

The core of Fred's protocol and the genius of his work isn't the dosages it's the presence of the "deadlock quartet" namely, methylcobalamin, adenosyl cobalamin, carnitine and methyl folate. The dose is based on what you're needs are to recover and heal. Some people don't need the mega doses to accomplish this and others sometimes just need to add some missing cofactor. Even Fred's discovery around the necessity of Lithium was very late in the game and has allowed him to significantly reduce dosages of several supplements including b12 and potassium.

Keep it up and feel free to start a conversation directly with me if you like.

 

[Cnew2this]

Hi @drmullin30 – I am going to try starting a direct conversation with you. I’m a PR novice, so I don’t know anything about that. So, if you don’t see one from me shortly, then it must have been too complicated for me.

If that works out it might be better since poor jwat87 might be a little annoyed that I high jacked their acetylcholine thread.