methylcobalamin vs hydroxocobalamin

[Plum]

Juices would get through your digestion pretty quickly. Mine are usually digested within the hour.

 

[Plum]

As far as excitotoxicity, there are other causes besides methylation and glutamate in general. If you're already experiencing excitotoxicity from other sources then excitotoxicity from methylation will be magnified because the NMDA receptors will already be overstimulated. This is a good thread about dealing with NMDA and excitotoxicity:
http://forums.phoenixrising.me/index.php?threads/anxiety-ammonia-and-the-nmda-receptor.1460/

dbkita also had an interesting post about excitory responses in the CNS:
http://forums.phoenixrising.me/index.php?threads/b2-i-love-you.15209/page-34#post-337806

As far as glutamate induced excitotoxicity (either from methylation or foods), Rich suggested low manganese could be a factor:

When Rich says it's not good to push through with excitotoxicty does this mean that the regime should not be continued in it's current state or what? Do we lower supplements, have a day off from them, take others to try and help?

 

[Plum]

Ok. Another question this time about folinic acid. The internet tells me this is the same as 5 formyl tetrahydrofolate is that correct? And where does it fit in the folate cycle? I see a THF, MTR, SHMT, 5,10 methylene THF, MTHFR and a 5-methyl THF. Help!

 

[Lotus97]

When Rich says it's not good to push through with excitotoxicty does this mean that the regime should not be continued in it's current state or what? Do we lower supplements, have a day off from them, take others to try and help?

It depends on the individual, but lowering the dose would probably be a good idea. If things are really bad then you might need a day off or longer. One thing about dosage in methylation is that sometimes you'll feel fine the first few days, but then the symptoms will gradually get worse. There are things to do to lower excitotoxicity as I posted about earlier, but it's still good to prevent it from happening if possible. Moderate to high protein diets can increase ammonia which also contributes to excitotoxicity, but many people here need a certain amount of protein so with that they'd need to take measures to counter the ammonia rather than lowering their protein intake.

Ok. Another question this time about folinic acid. The internet tells me this is the same as 5 formyl tetrahydrofolate is that correct? And where does it fit in the folate cycle? I see a THF, MTR, SHMT, 5,10 methylene THF, MTHFR and a 5-methyl THF. Help!

5-MTFH, Methyltetrahydrofolate and a 5-methyl THF are methylfolate, not folinic acid. Methylfolate is actually what's needed for methylation. As for the other abbreviations, this from wikipedia
Methylenetetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by theMTHFRgene.[2] Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.

Folinic acid is 5-formyltetrahydrofolate. It's also referred to as calcium folinate. Your body does convert some folinic acid into methylfolate, but it's not necessary for methylation if you're also taking methylfolate. Someone did suggest that since the folinic acid is converted to methylfolate slower it's sort of like taking a timed-release version of methylfolate which would be useful since methylfolate is needed to recycle B12 and taking both folinic acid and methylfolate would assure methylfolate stays in your system longer.

However, folinic acid has other uses. Rich explains why he prefers both folinic acid and methylfolate.
I actually prefer including both folinic acid and 5-MTHF. 5-MTHF is the form needed by methionine synthase, which is the enzyme with the partial block. Many people's cells are able to convert folinic acid to 5-MTHF well, but many others have inherited genetic polymorphisms that slow this conversion down considerably. The polymorphisms in the MTHFR enzyme are a good example, and these are very prevalent in the population.

Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.

There was a study done with CFS patients which found it to be beneficial to most of the participants. The study was not about methylation, they only used folinic acid.
http://www.natural-holistic-health.com/cd19-blood-test-and-chronic-fatigue-syndrome/
They found that 81% of the patients reported improvement within two months. Folinic acid co-enzymes are responsible for several important metabolic functions. These include the formation of DNA and RNA, the formation of heme protein in hemoglobin, formation of amino acids and the formation of glutathione

 

[Plum]

Ok. So then why do we add in the folinic acid on it's own and then have to wait to make sure of no adverse reaction before staring the methylfolate? it sounds like the folinic acid shouldn't have any adverse affects as small bits of it will be used by lots of different biological processes. Just my thoughts so far.

 

[Freddd]

Ok. So then why do we add in the folinic acid on it's own and then have to wait to make sure of no adverse reaction before staring the methylfolate? it sounds like the folinic acid shouldn't have any adverse affects as small bits of it will be used by lots of different biological processes. Just my thoughts so far.

Hi Plum,

A different hypothesis and understanding will come up with completely different answers. All these things being said about folate and it's "side effrects" and all that are completely bolixed by those formulating them throught he years having no understanding of paradoxical folate deficiency/insufficiency and based on results with the inactive folates ratehr than L-methylfoalte. The results of HyCbl/CyCbl/folic-acid/folinic-acid do NOT predict or explain MeCbl, AdoCbl and l-methylfoalte healing patjways.

 

[Lotus97]

Ok. So then why do we add in the folinic acid on it's own and then have to wait to make sure of no adverse reaction before staring the methylfolate? it sounds like the folinic acid shouldn't have any adverse affects as small bits of it will be used by lots of different biological processes. Just my thoughts so far.

The folinic acid is unlikely to cause problems since only a portion of is converted to methylfolate. Rich actually doesn't say you have to start the supplements one at a time, but if you do decide to do that here's what Rich says about the order
It is best to start with lower dosages than those suggested above and to work up slowly, to check for tolerance. Some people have found that they are very sensitive to these supplements, and can take only much smaller dosages. Others find that they need somewhat larger dosages than those suggested. For those who wish to start the supplements one at a time, I suggest starting with the Neurological Health Formula first, then adding the lecithin, then the B12, and finally the folates, with FolaPro last.

This is from the paper on the study using Rich's protocol. As he says above, some people will need a higher dose, but other might need a lower dose.
http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf
• GO SLOWLY. Occasionally, as the methylation cycle blockages are released, toxins are
released and processed by the body, and this can lead to an exacerbation of symptoms.

IF THIS HAPPENS, try smaller doses, every other day. SLOWLY work up to the full
dosages. If you have questions, please call our office to discuss them.

As noted earlier, one patient dropped out of the study at 3 months for a reason not related to
response to the treatment. The remaining 29 patients completed 6 months of treatment.

Various patients reported some early exacerbation of symptoms, which in most cases was
followed by a greater improvement in symptoms. Three of the patients found it necessary to
decrease their dosage frequency to every second or third day for several days, until they could
tolerate the full daily dosage schedule.

Sixteen of 30 patients (53%) reported an initial worsening of symptoms, beginning in most of
these cases within 3 or 4 days, but in some cases beginning at up to 2 weeks. Most of the
symptoms were mild, and none of the patients discontinued usage of the supplements during the
first 3 months. The most common side effects were gastrointestinal (pain, cramps, constipation,
or diarrhea), reported by 6 out of 30 patients or 20%; increase in pain, reported by 4 out of 30 or
13%; and increase in fatigue, reported by 3 out of 30 or 10%. Other symptoms, reported by one
patient each, were a decrease in appetite, poor sleep, weak legs, flu-like symptoms, and an
increase in anxiety and depression.

For those who experienced improvement, the time to self-reported improvement on the protocol
was an average of 5.6 weeks, with a range from immediate improvement (which was rare) to as
long as 8 weeks before improvement was experienced.

 

[Plum]

Thanks Lotus97. I felt awful yesterday. Really anxious and sensitive to everything being said to me - it felt horrible. I only started on the folinic acid 200mg and the lecithin yesterday. So today I have only taken the lecithin. Then tomorrow I shall take 500mg methylco and try 100mg folinic. I did however sleep MUCH better!

 

[Lotus97]

Thanks Lotus97. I felt awful yesterday. Really anxious and sensitive to everything being said to me - it felt horrible. I only started on the folinic acid 200mg and the lecithin yesterday. So today I have only taken the lecithin. Then tomorrow I shall take 500mg methylco and try 100mg folinic. I did however sleep MUCH better!

That's interesting. I've heard from a couple other people that their sleep improved from B12 although others seem to sleep worse. You said you're going to take 500 mcg of mb12? So you were taking 1000 mcg? I'm curious how you're able to take 100 mcg of folinic acid since the tablets usually come in 800 mcg. Are you splitting it into 8 pieces or is there another brand with lower doses? The folinic is unlikely to cause problems though. It's most likely the B12. After methylfolate, methyl b12 is the second most likely to cause problems.

 

[Plum]

Thanks for the info. It was weird. I took the methylB12 for about a week and it made me feel a bit weird - more tired but not sleep so great although a little better than normal. Yesterday I added in the lecithin (which I've taken today on it's own and feel fine), AND the folinic acid. I didn't feel great so I assume it was the folinic acid and my sleep improved. I didn't think it was the methylB12 that did this but I shall have to see what happens tomorrow. The methylB12 is definitely making me tired though.

I have managed to cut my folinic acid (800mg tablet) into 4 with a kitchen knife so tomorrow I shall bit it in half again. I don't know if the methylB12 is being accentuated because of the folinic and the problem is the methylB12 or if the folinic is doing the weirdness. I feel like a grumpy monster!

 

[Dreambirdie]

I know I have asked this before... but which B-Complex is the best one to take?
B-Right is not the fave anymore, right?

I really should write these things down when read them.

 

[Lotus97]

I know I have asked this before... but which B-Complex is the best one to take?
B-Right is not the fave anymore, right?

I really should write these things down when read them.

That depends what you're looking for. Are you completely avoiding folic acid? And how much methylfolate do you want in your b complex? There's b complexes that have anywhere from 100-800 mcg methylfolate?

 

[Dreambirdie]

I think the one I am going to get is the Thorne B-complex #6.
http://www.iherb.com/Thorne-Research-B-Complex-6-60-Veggie-Caps/18129

It has: Folate (100 mcg as Calcium Folinate and 100 mcg as 5-Methyltetrahydrofolate from Methyltetrahydrofolic Acid, Glucosamine Salt)

and: Vitamin B12 (50 mcg as Adenosylcobalamin and 50 mcg as Methylcobalamin)

 

[Lotus97]

I'm planning on getting almost the same thing except it's Thorne's #5 instead of #6
http://www.iherb.com/Thorne-Research-B-Complex-5-60-Veggie-Caps/18132
It also has Folate (100 mcg as Calcium Folinate and 100 mcg as 5-Methyltetrahydrofolate from Methyltetrahydrofolic Acid, Glucosamine Salt), but it has more pantothenic and less B6. I prefer that because it's almost $4.00 cheaper and I'd rather spend the money I'd save and more P5P rather than B6. You're not able to convert B6 to P5P unless you have enough B2. Maybe I have enough B2 to make the conversion, but I'd rather not take any chances. If they were the same price though I probably would have chosen the one with extra B6.

I'm actually taking Thorne #3 right now which is like those two, but it has extra B3 (mostly niacinamide). I just realized that the Thorne #3 has extra B3, #6 has extra B6, and #5 has extra B5 I bought that one because I heard that niacin is good for overmethylation. I was following a discussion about niacin and methylation and it doesn't seems there's really a consensus about how exactly it works and how much niacin is too much and counterproductive to the methylation process.

I'm also taking 1/2 of a B125 tablet until I run out and then 1/2 or 1/3 of a B100 capsule until I run out of that. After that, the only folic acid I'll be taking is from a Source Naturals sublingual b complex. I'm taking it because it has coenzymated forms of B1, B2, B3, B6, and B12 (as adb12). I'm not sure how much folic acid is a problem for me. It's more likely to cause problems in higher doses so I'll probably keep taking it. If I could design my own b complex it would have all active forms, but low doses so I could take it 3 times a day and only folinic acid. Then I could slowly add my methylfolate when I was ready. If a person doesn't have the MTHFR SNP though or some other SNP that acts similarly I don't know if they'd even need methylfolate unless they had a need for a very high amount of methylfolate. I guess the problem with that though would be that it would be hard to know how much folinic acid you're converting to methylfolate. Especially since the conversion might happen more slowly. Still, I think I'd be willing to try that at some point just to see what would happen.

 

[Lotus97]

Plum
You had mentioned making juices with fruits and vegetables. You might be getting a lot of folate from your diet. Some people have said that plant folate is folinic acid and meat is methylfolate, but Rich seemed to think there was at least some methylfolate in plant folate. I haven't seen any sources specifying which is which so I don't know who is right, but I haven't really looked.

Those links I posted earlier in this thread about potassium in foods also have lists for folate in food. Just keep in mind that the folate for the processed food is from folic acid added by the manufacturers and not naturally occurring folinic acid/methylfolate. Also, pay attention to the weight they list because it might be different than what you consider a serving. Also, chlorella and wheat grass are relatively high in folate. I assume other grasses are too, but I haven't found sources for those yet.

In another thread, dbkita said something about the folinic acid in plants being different than supplemental folinic acid and it actually resembles folic acid in certain aspects so for certain people it might not be processed as well as supplemental folinic acid and might even block methylfolate for certain people. I don't know anything about this other than what he said.

 

[Lotus97]

I found a store that ships international and carries the Perque Hydroxocobalamin.
http://pureformulas.com/activated-b12-2000mcg-100-lozenges-by-perque.html#sthash.mIWXmygN.dpbs
They also ship free on any size order (at least for US orders I'm not sure about international). And if you use next10 as a code in your shopping cart (different from the referral code they ask for when signing up) you'll get 10% off your entire order. If that coupon code is expired there might be a new one on retailmenot, but I just checked and next10 is still valid as of this post.

 

[Lotus97]

As I mentioned earlier, in the Simplified Methylation Protocol Rich recommends starting with hydroxocobalamin and only switching to methylcobalamin and adenosylcobalamin if you don't experience any improvement after a couple of months of following the full protocol.
http://forums.phoenixrising.me/inde...ation-protocol-august-25-2012-revision.19050/

I had also considered changing the form of B12 to methylcobalamin. Some PWMEs do need to use this form, particularly if their glutathione and/or S-adenosylmethionine are very low. However, use of hydroxocobalamin is a “gentler” approach to lifting the partial methylation cycle block, and many PWMEs need such an approach. Use of hydroxocobalamin also keeps the cells in control of the rate of the methylation cycle, preventing it from being overdriven, which slows the rise of glutathione. So I have decided to stay with hydroxocobalamin as the first form of B12 to try. For people who do not get a response from the SMP within a couple of months, switching to methylcobalamin would be an option to try. Another option would be to try adding some adenosylcobalamin (dibencozide). However, I do not favor raising the overall dosage of B12 very much above 2,000 micrograms per day, and especially not when it is combined with dosages of methyfolate that are much above the RDA range of 400 to 800 micrograms per day. This combination can overdrive the methylation cycle and hinder the rise of glutathione.

Here he explains in more detail why he prefers starting with hydroxocobalamin. Rich doesn't mention it in this post, but he is also basing his decision on the results of the study he conducted with Dr. Neil Nathan.

I prefer hydroxocobalamin for several reasons. One is that it allows the cells to control the amounts of the coenzyme forms of B12 (methylcobalamin and adenosylcobalamin) that they make, so that they can be matched to the need. Taking methylcobalamin in large dosages by injection or sublingually can overdrive the methylation cycle, as evidenced by a major rise in sarcosine, which I've seen in amino acids testing on some people who have been on this treatment for a while. I am not comfortable with overdriving the methylation cycle, both because I think it slows flow down the transsulfuration pathway and thus limits the normalization of the balance of the sulfur metabolism, including cysteine, glutathione, taurine and sulfate, and also because I am concerned about the possibility of overmethylation of DNA, which could have other deleterious effects.

My other concern is that methylcobalamin is known to be chemically able to methylate inorganic mercury. Many PWCs have significant body burdens of inorganic mercury as a result of having amalgam fillings in their teeth during an extended period while glutathione has been low, so that they have not been able to detox mercury at normal rates. Methylmercury can cross the blood-brain barrier readily. Mercury is a potent neurotoxin if it gets into the brain. This problem has been observed in guinea pigs. I don't have solid evidence for it in humans, but have heard from perhaps three people who may have had this problem, based on what they have reported. So I prefer to be cautious.

This having been said, some people have had good experience with methylcobalamin. It can be especially helpful if a person has a shortage of methyl groups, though that can also be helped by taking some additional trimethylglycine (some of which is in the multi that is part of the simplified treatment). or some SAMe. It's used a lot subcutaneously by the DAN! doctors in autism treatment, and as you probably know, freddd on this forum advocates its use as well. In his case, because of a mutation in the intracellular B12 processing enzymes, his body is not able to utilized hydroxocobalamin readily. But I believe that this is a rare situation, based on the published literature. freddd does not agree that it is rare, based on his experience.

 

[shannah]

I found a store that ships international and carries the Perque Hydroxocobalamin.
http://pureformulas.com/activated-b12-2000mcg-100-lozenges-by-perque.html#sthash.mIWXmygN.dpbs
They also ship free on any size order (at least for US orders I'm not sure about international). And if you use next10 as a code in your shopping cart (different from the referral code they ask for when signing up) you'll get 10% off your entire order. If that coupon code is expired there might be a new one on retailmenot, but I just checked and next10 is still valid as of this post.

Hi Lotus,

Thought I'd let you know I tried ordering here and although they say they ship internationally, they remove the items from your cart when you fill in your out of country address. A message appears saying they don't ship this item internationally.

I ended up ordering from Holistic Heal. Years ago, there were a lot of problems ordering from them but I'm hoping those are all cleared up now.

 

[cph13]

Shannah Hello, If I may jump in here and interject. I think there has been some confusion over Pure encapsulation and the a SUPPLIER of vitamin/minerals pureforumlas.com I believe someone got confused. I read that you placed your order already however, this is an FYI for future orders. I love the service, CS and return policy that I receive from pureformulas.

There was a discussion about b-complex back in March :
http://forums.phoenixrising.me/index.php?threads/which-thorne-b-complex-is-best.22248/#post-340534
I posted and specifically checked the shipping for PURE FORMULAS. Pureformulas.com does international shipping as one of my posts states in the above thread.
I will repost that information here for simplicity below. They do carry the product you were looking for to (perque activated b12 id# pq1000) link below:
http://pureformulas.ecomm-search.com/search?catalog=yhst-37598795206756&.autodone=http://store.yahoo.com/yhst-37598795206756/&query=pq1000&x=-1138&y=-130

FYI for INTERNATIONAL SHIPPING. I just placed an order with Pure Encap (PE) They use an independent contractor to ship outside the US. The mgr. was happy to share that information. The SHIPPING company is Bangor Internationsal 201-683-4894.​

​

REWARDS and NEXT10​

Also if U accumulate rewards you have to redeem them to receive a coupon code; than place your order.​

If you use a rewards coupon code u CANNOT use the NEXT10. Only one discount per order. If you are ordering more than one item you can use your Reward Code than place a seperate order for the balance of your order and receive the "NEXT 10" discount. They are trying to change the system so one can use both codes selectively on the order cutting "their shipping costs" .​

TYPO ERROR
In checking on this for International shipping the CS # for Bangor Internation is 203-683-4894.
Your can just place the order online but I know some people would rather do this on the tele. Sorry for the TYPO.
You can just place an order online rather than calling.

I also stated the following about rewards:
They also have the best $ on NCLOil that I have found, so far. They give free shipping and RETURN (that is, in the US I don't know how they treat internationcal).
Also, an additional 10% off many items just mention to the CS rep. "NEXT10" (sorry, no disc. on the pure encapsulates B Complex.)
I did not get my disc. once, I called, it was IMMEDIATELY returned to my CC.

Please be aware of their REWARDS programs.
A friend of mine ordered and forgot to use my rewards code RNBHEX; they were happy to apply a reward to my account for her order.

I hope this clarifies things for you!
Happy Healing

 

[Plum]

I would like to add one more thing to the equation, speed of avaialbility. When a person is having symptoms RIGHT NOW in the middle of the night unable to walk, approximately 400mg of potassium glucinate is what I use, with a 12-16 oz glass of water. Relief can appear in 15-30 minutes. With food based potassium, serum peak occurs with main absorbtion, about 14 hours after consumption.

Ok! So I have been having really bad leg cramps and I took some potassium. Is it normal to feel really fatigued the day after taking it? The whole day I felt exhausted and things were about 200% harder to do. There was nothing else in my day that could've caused this as I pretty much do and take the same things every day.
I was wondering if the potassium was helping my body repair itself and as a result was making me super fatigued.
Any ideas?
I rested for 2 days and was then back to 'normal'!