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Metabolic Maintenance 10mg 5-MTHF Quatrefolic - Startup Issues

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11
To those who are considering using Metabolic Maintenance (MM) 10mg 5-MTHF Quatrefolic, take note:
This did not give me any noticeable startup, even with a dose of 2x 10mg. 2x 800mcg Solgar Metafolin was far more effective (excitoxicity haven). In both instances I took supplements from the deadlock quartet.

Not only was this disappointing from a financial perspective (MM isn't cheap.. 100 dollars per bottle), it also made me look outside methylation for a while. I was only able to come back to methylation because I still had 2 Solgar tablets left around.

Back to Solgar and to methylation!
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
hibikijoji, now I'm confused. Are startup issues a good thing? I just added my 4th deadlock quartet element, Adenosylcobalamin today and didn't notice anything. I thought that was good that I tolerated it.
 
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11
Critterina: well, not necessarily. Methylfolate is one of those things that should work quite readily, especially with mb12 present. At the dose of 10mg, I would have least expected that it would cause a potassium drop, if not excitoxicity symptoms (specifically agitation/overhyped energy/etc.).

6 hours later, it's still no where as effective as 1.6mg of Solgar's methylfolate. I haven't even touched my potassium powder yet. MM's Methylfolate just doesn't seem to be doing its job.

As for adenosylcobalamin, I'm taking it now primarily as an anti-inflammatory for when folate deficiency symptoms rears it head. If you're finding that it allows you to tolerate higher doses of folate/mb12 without causing hives/runny nose/allergies, then its probably working.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Critterina: well, not necessarily. Methylfolate is one of those things that should work quite readily, especially with mb12 present. At the dose of 10mg, I would have least expected that it would cause a potassium drop, if not excitoxicity symptoms (specifically agitation/overhyped energy/etc.).

6 hours later, it's still no where as effective as 1.6mg of Solgar's methylfolate. I haven't even touched my potassium powder yet. MM's Methylfolate just doesn't seem to be doing its job.

As for adenosylcobalamin, I'm taking it now primarily as an anti-inflammatory for when folate deficiency symptoms rears it head. If you're finding that it allows you to tolerate higher doses of folate/mb12 without causing hives/runny nose/allergies, then its probably working.
hibikijoji,
Thanks for clarifying the exitotoxicity symptoms. I use Thorne MTHF; maybe when I'm out I'll try Solgar. I'm titrating dose just now. I was put on 1 mg MTHF and 5 mg MB12, and after 4 months developed deficiency symptom's per Freddd's description. Good to know MM is not working for you, especially considering the cost.
I've only had one pill of adenosylcobalamin so far. I bought the Anabol Naturals that Freddd though was so effective, 10 mg.
My deficiency symptoms are being stubborn this time, but seem a bit improved since yesterday. I had blood tests Tuesday 2.5 weeks ago, so I stayed on the protocol I was given (by the RN who ordered my tests) until then. At that time, when I went to 2 mg MTHF and 800 mcg folinic acid (I'm SHMT +/+) my deficiency symptoms with me since May 27 were gone in 4 days. After 7 days, I replaced the folinic acid with another 1 mg of MTHF and my deficiency symptoms returned. I'm up to 1600 mcg folinic and today 5 mg of MTHF (adding 1 mg per day now). Not sure why it's being so stubborn this time, except maybe it worked better because I was on a low sulfur diet that first week. Could that have affected it?
 
Messages
11
Not sure why it's being so stubborn this time, except maybe it worked better because I was on a low sulfur diet that first week. Could that have affected it?

Perhaps. So as long as you feel potassium drop, methylation is working.

Do you have any potassium deficiency symptons?

What sort of folate deficiency symptoms are you experiencing?

As for how to clear up deficiency symptoms: Have you tried AdoCbl again with the dose? It also seems that you're not using mb12, is that right?
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Perhaps. So as long as you feel potassium drop, methylation is working.

Do you have any potassium deficiency symptons?

What sort of folate deficiency symptoms are you experiencing?

As for how to clear up deficiency symptoms: Have you tried AdoCbl again with the dose? It also seems that you're not using mb12, is that right?

Hi hibikijoji,

Re: potassium deficiency symptoms, I had walked a bit last Saturday and my calves had stayed very tight, on the verge of cramping. I had a coconut water with each of 3 meals for 2 days, which helped, but may have overdone that. On Tuesday my blood pressure was 98/58, and while I am not really consistent in blood pressure, my previous lows have been 88/60 and 80/66, but I was in much better shape then.

My folate deficiency are mostly the acne-like lesions on the face, and they are going. The first time I had the angular chelitis, acne on face and scalp and feet, abdominal bloating (fluid not gas), and itchy rectum. The last two are as close as I get to IBS. Since I haven't had a 'normal' diet since this started, it's kind of hard to judge the other symptoms of IBS.

I just started adenosylcobalamin (AdB12) for the first time mid week last week. I just realized it's 10 mg, and I use 5 mg of methylcobalamin (MB12), not exactly the 1:1 portions that Freddd recommended. The AdB12 says to take it with meals. Is that what you understand? Also, should I take the two B12s at the same time and away from the MTHF/folinic?

Yeah, what got me into this mess was that I was using 1 mg MTHF and 5 mg MB12 for 6 months, and taking them with 1000 mg Vitamin C. So as I understand it, the C pretty much destroys the MTHF in the stomach, and the MB12 circumvents my MTRR +/+ and turns on my upregulated MTR +/- to use up my limited MTHF, so I was increasing my MTHF demand more than the amount of supplement that was getting through. And being that I'm SHMT +/+, and not eating my regular greens, which would supply the folinic acid that could be made into MTHF, I was just digging myself into deficiency.

So, now I'm taking an additional mg of MTHF per day, and today I'm at 7 mg. I am holding steady on the 1600 mcg folinic acid, 5 mg MB12, and 10 mg AdB12. I also have a host of vitamins, Mg, and a multi-mineral supplement that I take, plus BCAAs and tryptophan, CoQ10, carnitine, NADH, ribose, EPAs, and GABA. I intend to add TMG when I get my MTHF straightened out, but all in due time.
 
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11
The AdB12 says to take it with meals. Is that what you understand?
If what I understand is correct, swallowing adb12 with your meals as opposed to taking it sublingually will result in poor absorption (less than 2% at 1000mcg+ dose for b12s) [1]. According to what you're saying, you will be absorbing about 100mcg AdB12.

If according to what Freddd says is right, 15-25% of 5 star mb12 are absorbed sublingually. That would mean your adb12:mb12 ratio would be about 100:750 = 1:7.5 right now. Sublingual dose of 10mg adb12 bring the ratio to 2:1.


Also, should I take the two B12s at the same time and away from the MTHF/folinic?
Not sure, haven't come across anything that would suggest so. One point to note though, is that oxidised cobalamins cannot drive methylation. Hence, it would be reasonable to believe that one needs a constant supply of mb12s to avoid Sam-E being used to recycle colbalamin.[2] More L-MTHF may likely cause more cobalamins to become oxidised more quickly since mb12 will be turned over more rapidly.

References
[1] Blood. 2008 Sep 15;112(6):2214-21. doi: 10.1182/blood-2008-03-040253. Epub 2008 Jul 7; How I treat cobalamin (vitamin B12) deficiency. Carmel R.
[2] Protein interactions in the human methionine synthase-methionine synthase reductase complex and implications for the mechanism of enzyme reactivation., Wolthers KR, Scrutton NS., Biochemistry. 2007 Jun 12;46(23):6696-709.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Hmmm...
If what I understand is correct, swallowing adb12 with your meals as opposed to taking it sublingually will result in poor absorption (less than 2% at 1000mcg+ dose for b12s) [1]. According to what you're saying, you will be absorbing about 100mcg AdB12.

If according to what Freddd says is right, 15-25% of 5 star mb12 are absorbed sublingually. That would mean your adb12:mb12 ratio would be about 100:750 = 1:7.5 right now. Sublingual dose of 10mg adb12 bring the ratio to 2:1.

Thanks for doing the math! I knew that was true of mb12, that stomach acid destroys most of it, but I thought since adb12 occurs primarily in meats, that we probably got most of it through the diet. Freddd had said (where is Freddd, anyway?) that startup issues occurred when switching adb12 brands to the one I bought. I followed the package instructions, which follow my get-it-from-meat idea. You think he probably opened up the capsules and took a pinch? I can do that. Is that what you do?

I haven't found a good explanation of how adb12 works in the cycle. Where is it used? I mean, what chemical reaction does it participate in?

One point to note though, is that oxidised cobalamins cannot drive methylation. Hence, it would be reasonable to believe that one needs a constant supply of mb12s to avoid Sam-E being used to recycle colbalamin.[2] More L-MTHF may likely cause more cobalamins to become oxidised more quickly since mb12 will be turned over more rapidly.

Part of my problem is that I don't recycle b12 to mb12 efficiently. I'm MTRR A66G +/+. Not sure I'd be wasting a lot of SAMe anyway, with that. So, taking them together might be better. OK. I can take all my active B vitamins together either sublingually or on an empty stomach. And spread them out during the day. Another experiment for tomorrow!
 
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11
Critterina:
I haven't found a good explanation of how adb12 works in the cycle. Where is it used? I mean, what chemical reaction does it participate in?
Cobalamins are oxidised by Nitric Oxide. According to one paper, adb12 could be the prime cofactor that regulates Nitric Oxide production.

Neurological brightening is like a kid who feels the urge to remember pi to the 100th digit. It's like a strong caffeine shot that lasts and lasts, without the side effects of coffee. Not all brands of mb12 can do this though.

Let us know how you go.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Critterina:

Cobalamins are oxidised by Nitric Oxide. According to one paper, adb12 could be the prime cofactor that regulates Nitric Oxide production.

Neurological brightening is like a kid who feels the urge to remember pi to the 100th digit. It's like a strong caffeine shot that lasts and lasts, without the side effects of coffee. Not all brands of mb12 can do this though.

Let us know how you go.
Thanks so much! I woke up wondering about both of these today. So, neurological brightening is more of an alertness/brain thing/energy thing as opposed to feeling your neurons fire throughout your body, which would be... overstimulation? I think maybe I'm going to have to wait until my sinus infection subsides - the congestion affects my thinking.

I think I have NO issues, but it's hard to tell, since I consistently have low arginine and am MTHFR A1298C +/- so BH4 production is probably somewhat impaired and mostly used up on other things. I also have NOS3 rs2070744 +/+ (CC), but that's associated with coronary spasm, not with blood circulation, which is the NO problem I'm aware of. So, substrate, enzyme, cofactor - who knows why my hands and feet tend to be cold and blue? As long as a good margarita can solve that, I'll be OK. :)
 

nkm

Messages
40
That's odd. When I took the full 10mg capsule, I felt horrible! I had to back down to 5mg and currently, I'm taking 3.3mg (I split one MM Quatrefolic cap into 3 caps).