• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

methylcobalamin vs hydroxocobalamin

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Actually, in Rich's protocol he says to start with hydroxocbalamin and if you don't experience improvement then switch to methylcobalamin and adenosylcobalamin. He says this because he is concerned about overdriving the methylation cycle which can cause adverse symptoms and even be counterproductive to the healing process. However, if you are already having success with methylcobalamin you might just want to stick with that. Be aware that methylcobalamin is more potent than hydroxocobalamin so you wouldn't want to start out with 2000 mcg of methylcobalamin like Rich says with hydroxocobalamin. 1000 mcg of methylcobalamin might even be too much for some people here. Especially if you're using Enzymatic Therapy's which is reported to be significantly stronger than other brands of methylcobalamin.

Also, be aware that once you add folinic acid and methylfolate the combination of those and the B12 will create a stronger reaction and possibly cause overmethylation so be prepared to lower your dose of B12 if necessary. That's why Rich recommends starting with B12, then adding folinic acid if the B12 is tolerated, and then finally methylfolate of those two are tolerated. I would actually recommend starting with 250 mcg methylcobalamin until you have added both folinic acid and methylfolate. Especially if you're using Enzymatic Therapy's brand. Low potassium is a common and potentially lifethreatening effect of overmethylation and overdriving the methylation cycle so you might want to consider supplementing with potassium even if you are taking hydroxocobalamin. Capsules and tablets are not recommended for potassium supplementation because those can damage the stomach and GI tract. Now Foods sells potassium gluconate and potassium chloride in powder form. Those are both available at iHerb which ships internationally.

If you are interested in trying hydroxocobalamin, the only two sublinguals available at iHerb are by Biotics and AOR. I don't know much about either one.
http://www.iherb.com/Advanced-Orthomolecular-Research-Hydroxy-B12-60-Tablets/33061

The one from Biotics is cheaper, but also has 800 mcg of folinic acid which may or not be a good thing.
http://www.iherb.com/Biotics-Research-Corporation-B12-2000-60-Lozenges/45148


As for adenosylcobalamin, I would wait until you get the methyl b12, folinic acid, and methylfolate in place before adding it. If you take hydroxocobalamin instead of methyl b12 then you might not need adb12 at all because most people are able to convert hydroxocobalamin into methylcobalamin and adenosylcobalamin. Adenosylcobalamin is sometimes also referred to as dibencozide. The only two I know of without folic acid are Source Naturals and Anabol Naturals. Anabol's is in capsule form so people empty it into their lower lip and gum area to absorb it sublingually. I would recommend starting at a very low dose (1/4 tablet or less) and maybe start off taking it orally first. There are some lower dose adb12 sublinguals, but they have folic acid which some people are avoiding. Country Life has one and Source Naturals also has a sublingual b complex with adb12.

Hi Lotus,

B12 will create a stronger reaction and possibly cause overmethylation so be prepared to lower your dose of B12 if necessary

It just doesn't work that way. Healing can turn on at about 100mcg absorbed per day for most layers. Below that it's "iffy", not proportional. The curve shows that at about 10mcg there is a minute effectiveness that never really gets going the absorbed dose increases the effectiveness increases at an increasing rate, goes over the knee on the way up at a bit bellow 100mcg (estimated) and goes up very slowly after that. I would predict that in a well controled study that virtually nobody could distinguish between 250 mcg absorbed and 5000mcg absorbed on the basis of reactions.


As for adenosylcobalamin, I would wait until you get the methyl b12, folinic acid, and methylfolate in place before adding it. If you take


And I'm finding it most effective in a lot of people to microtitrate both AdoCbl and MeCbl with methylfolate for predictable results. Then, as soon as healing turns on, cease titration of those and bring everything else into balance before continuing. That way one doesn't bounce all over the place alternating back and fort on and off methyltrap and partial ATP block.

Low potassium is a common and potentially lifethreatening effect of overmethylation and overdriving the methylation cycle so you might want to consider supplementing with potassium even if you are taking hydroxocobalamin.

The percentage of hypokalemia with HyCbl is lower but is NOT a result of over methylation. It is the result of turming methylation on enough to start making a backlog of cells from years of delayed healing. With AdoCbl, MeCbl and l-methylfolate hypokalemia is a dependable and predictable occurance and ois the first sign of gneralized healing. Excessive potassium need as Dbkita pointed out can happen and is something else entirely different which does need to be identified.

Capsules and tablets are not recommended for potassium supplementation because those can damage the stomach and GI tract.


This warning applies to prescription time release forms of a non-disperable type that has 500mg in a single capsule/pill that can sit in a dissolving mass against the stomach causing tissue necrosis. It is not a hazzard of OTC capsules or fast dissolving low dose pills. But it is well worth warning. Also, don't take too much at a time. More smaller doses with a full gass of water are more effective and safer.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I don't understand why some of the people in this thread are comparing Rich and Freddd's protocol. Rich recommends starting with hydroxocobalamin for the reasons Adreno and I mentioned earlier, but he says to switch to methylcobalamin and adensylcobalamin if hydroxocobalamin isn't working. As far as Freddd's cofactors go, they're all good supplements and I recommend them to anyone with CFS. I'm taking almost all of them myself (although just for the record I was already taking all of Freddd's cofactors before I knew about his protocol:nerd: ). I have no doubt Rich's protocol would be more effective with Freddd's cofactors (although I'd caution people about adding additional methyl donors such as TMG, SAMe, and choline), but this doesn't have anything to do with B12. I think it's kind of silly to say "which protocol are you following? YOU MUST CHOOSE!" I learn what I can from both Rich and Freddd and then figure out what works best for me. I'm planning on switching over to methylcobalamin and adenosylcobalamin at some point. Mainly to save money, but also because I want to increase my dose of that Source Naturals sublingual b complex I mentioned earlier which has adb12 along with active/coenzymated forms of B1,B2, B3, and B6 (but also folic acid:eek:).
 

Xara

Senior Member
Messages
135
Location
The Netherlands
I'd like to see the focus on improving, on suggestions, not on taking sides, on being (not) backed up by ..., on language (not) used, etc. MB12 or hB12: as long as it helps you, fine by me.
HB12 did not help me, alas, I got worse. With mB12 and methylfolate things started to improve.
Wish improving methylation was easy - it is not. That's the only warning I'd like to give to a newcomer at the moment. :)
My two cents: read a lot.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Sex. :) Well, if you're fit enough.

I'm a practioner, and teacher, of Tantric Alchemy. Four hours of ecstacy a week can have one feeling better much of the week. It's been my secret ingrediant for 20 years or more now. Preparation of the Elixer of Eternal Life is of course one of the things practiced. However nowhere in all that is there any indication of non aging that I can find. Tantric Alchemy is one of the things that led me to the Deadlock Quartet. In alchemy, as in so many things, there is a lot of wishful thinking and non-functional hypotheses. A distinction needs to be made. "Eternal" life is not synonomous with ""Immortal" life. So, if there is a "fountain of youth" I can use it. Right now I use MSM, glucosimine and chondroitin for my hips, knees, back, neck and ankles at least, all things damaged by falling down mountains, hit by cars, beaten up by people who disliked anti war protesters in the 60s, and the various things banged up by the nature of life.
 

alice

Senior Member
Messages
109
Location
No. CA, USA
A

Capsules and tablets are not recommended for potassium supplementation because those can damage the stomach and GI tract. Now Foods sells potassium gluconate and potassium chloride in powder form. Those are both available at iHerb which ships internationally..

Lotus97, What is the preferred way of taking the potassium powder - mixed with food? What is a reasonable dose? Thanks.
alice
 

Plum

Senior Member
Messages
512
Location
UK
Actually, in Rich's protocol he says to start with hydroxocbalamin and if you don't experience improvement then switch to methylcobalamin and adenosylcobalamin. He says this because he is concerned about overdriving the methylation cycle which can cause adverse symptoms and even be counterproductive to the healing process. However, if you are already having success with methylcobalamin you might just want to stick with that. Be aware that methylcobalamin is more potent than hydroxocobalamin so you wouldn't want to start out with 2000 mcg of methylcobalamin like Rich says with hydroxocobalamin. 1000 mcg of methylcobalamin might even be too much for some people here. Especially if you're using Enzymatic Therapy's which is reported to be significantly stronger than other brands of methylcobalamin.

Also, be aware that once you add folinic acid and methylfolate the combination of those and the B12 will create a stronger reaction and possibly cause overmethylation so be prepared to lower your dose of B12 if necessary. That's why Rich recommends starting with B12, then adding folinic acid if the B12 is tolerated, and then finally methylfolate of those two are tolerated. I would actually recommend starting with 250 mcg methylcobalamin until you have added both folinic acid and methylfolate. Especially if you're using Enzymatic Therapy's brand. Low potassium is a common and potentially lifethreatening effect of overmethylation and overdriving the methylation cycle so you might want to consider supplementing with potassium even if you are taking hydroxocobalamin. Capsules and tablets are not recommended for potassium supplementation because those can damage the stomach and GI tract. Now Foods sells potassium gluconate and potassium chloride in powder form. Those are both available at iHerb which ships internationally.

If you are interested in trying hydroxocobalamin, the only two sublinguals available at iHerb are by Biotics and AOR. I don't know much about either one.
http://www.iherb.com/Advanced-Orthomolecular-Research-Hydroxy-B12-60-Tablets/33061

The one from Biotics is cheaper, but also has 800 mcg of folinic acid which may or not be a good thing.
http://www.iherb.com/Biotics-Research-Corporation-B12-2000-60-Lozenges/45148


As for adenosylcobalamin, I would wait until you get the methyl b12, folinic acid, and methylfolate in place before adding it. If you take hydroxocobalamin instead of methyl b12 then you might not need adb12 at all because most people are able to convert hydroxocobalamin into methylcobalamin and adenosylcobalamin. Adenosylcobalamin is sometimes also referred to as dibencozide. The only two I know of without folic acid are Source Naturals and Anabol Naturals. Anabol's is in capsule form so people empty it into their lower lip and gum area to absorb it sublingually. I would recommend starting at a very low dose (1/4 tablet or less) and maybe start off taking it orally first. There are some lower dose adb12 sublinguals, but they have folic acid which some people are avoiding. Country Life has one and Source Naturals also has a sublingual b complex with adb12.

Hi Lotus97

That was awesome info and very helpful. Thank you for that.

How do you know if overmethylation is happening?

Plum
 

Plum

Senior Member
Messages
512
Location
UK
Apologies if this question has been answered elsewhere - been searching through the forum:

How do you know you need to take potassium? Why do you need to take it? I'm feeling like I've missed something really obvious as it isn't listed in the short protocol of Rich's.....

Thanks :)
 

Lotus97

Senior Member
Messages
2,041
Location
United States
What brand(s) of hydroxycobalamin do those who use it like best?
There hasn't been a lot of testing as far as brands. People have said that Perque's sublingual works better than hydroxy drops, but that's about it. When placed under the tongue Perque's hb12 sublingual at first doesn't dissolve at all, but then dissolves rather quickly which isn't good for optimal absorption so I hold it between my upper lip and gum so it dissolves slowly. After an hour or longer it stops dissolving so I transfer it to my lower gum/lip area or under my tongue so it can finish dissolving. However, the people in the study seemed to get good results and I assume they did the standard under-the-tongue approach. I mentioned two other brands earlier in this thread, but I don't know of anyone who has tried either of them. The AOR is more expensive than Perque (per mg) and the Biotics one has 800 mcg of folinic acid which may or may not be a good thing.
 

Plum

Senior Member
Messages
512
Location
UK
Wow! The solgar methylcobalamin I take is dissolves in about 10 mins. Very annoying.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Lotus97, What is the preferred way of taking the potassium powder - mixed with food? What is a reasonable dose? Thanks.
alice
You can mix the potassium with water. I'm not sure if it matters whether you take it with food or an empty stomach. I would recommend spreading out the dose because potassium can have a laxative effect in high amounts for some people. You might also want to check how much potassium you're getting from food.

I can't say how much extra potassium you'll need. If you're following Freddd's protocol you're most likely going to need more than Rich's so if you're following Freddd's you should ask him about the dosage. If you're following Rich's, you might need more if you decide to switch to methylcobalamin and raise your dosage of folinic acid and methylfolate (moreso with the methylfolate than folinic acid, but you do convert some folinic acid into methylfolate so that's why I mentioned both). If you're following Rich's protocol and decide to switch to methylcobalamin, I wouldn't recommend also raising your methylfolate dose right away.

I'm probably getting at least 3000 mg of potassium a day. At least 2/3 of that is from my food, but my diet varies from day to day so I really don't know for sure. You also want to make sure you're getting enough magnesium because magnesium deficiency can increase the likelihood of hypokalemia (low potassium).
http://jasn.asnjournals.org/content/18/10/2649.full
You might also want to consider supplementing with taurine which helps with electrolyte balance and helps your cells retain magnesium and potassium. Taurine and magnesium also help with excitotoxicity which can be exacerbated during the methylation process. Some people have problems with sulphur containing supplements so I'd recommend starting on a low dose of Taurine. Now Foods sells taurine in powder form which is the most affordable. Taurine and all free form amino acids are recommended to be taken on an empty stomach or at least without protein.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Apologies if this question has been answered elsewhere - been searching through the forum:

How do you know you need to take potassium? Why do you need to take it? I'm feeling like I've missed something really obvious as it isn't listed in the short protocol of Rich's.....

Thanks
The only thing I noticed in myself was heart palpitations and tachycardia. You can check out this thread which discusses the symptoms of low potassium:
http://forums.phoenixrising.me/index.php?threads/identifying-low-potassium-symptoms.20729/

As far as why low potassium/hypokalemia occurs, there are some explanations in this thread:
http://forums.phoenixrising.me/inde...entation-needed-in-methylation-treatmt.18670/
However, I believe that the explanations might be somewhat theoretical in nature and no one really knows exactly what the mechanism is behind this phenomenon.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Hi Lotus97

That was awesome info and very helpful. Thank you for that.

How do you know if overmethylation is happening?

Plum
The most common symptoms from overmethylation result from excitotoxicity or low potassium. I already mentioned potassium earlier. Symptoms from excitotoxicity would be anxiety, overstimulation, wiredness, insomnia, etc. This is what Rich says about the subject
A lot of people experience it when they start this protocol. It's due to too much glutamate in the synapses of the neurons in the brain. The glutamate is supposed to be pumped out and converted to glutamine by the astrocytes, and sent back to the neurons for re-use, but this takes ATP, and when glutathione is low, the mitochondria do not produce ATP as fast as normal. When this protocol is started, I suspect that glutathione initially drops even more, and that is what causes the excitotoxicity. Various things have been recommended by Amy Yasko to counter this, including GABA, theanine, magnesium, Valerian root, grape seed extract, pycnogenol, progesterone cream, and taurine.

Inflammation, release of toxins, and the reactivation of the immune systme can also occur during the methylation process which is another reason why Rich warns against overdriving the methylation cycle and recommends taking things at a reasonable pace. Rich explains this in more detail here:
http://forums.phoenixrising.me/inde...depletion-rich-vanks-posts.21563/#post-332839
 

Symptomatic

Senior Member
Messages
197
What brand(s) of hydroxycobalamin do those who use it like best?

I'm just getting started with the methylation protocol, didn't know what exactly to order (given my SNP and HDRI methylation results) and couldn't find too much info so just ordered the Perque from Amazon yesterday.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
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:
Excitotoxicity seems to be a complex phenomenon. Lowering the intake of foods high in glutamate is one thing that can be done. Taking supplements that calm the NMDA receptors is another, and Amy Yasko has given lists of them. I've suggested that L-cystine (not L-cysteine) might raise glutathione in the brain, and help with this (but not if there is a high mercury body burden, because it can move mercury into the brain). Another possibility would be supplementing manganese, if it is low, because it supports glutamine synthetase, which converts glutamate to glutamine. I don't think it's a good idea to try to "push through" excitotoxicity, because it may be killing neurons.

Best regards, Rich
---------------------------------------------------------------------------------------------------------------------------
Hi Rich, thank you for your input.
In that case, what happens to the manganese? Would a continuous supply of glutamates bring on a manganese depletion, or is that same manganese used over and over again?
Sorry that I am not able to ascertain this by myself.
Best regards,
Asklipia
---------------------------------------------------------------------------------------------------------------------------
Hi, Asklipia.

Yes and yes. The manganese is used over and over, but it is also excreted, so there is a continuing need for it, as is true of the other essential minerals. If a person's diet is too low in manganese, or if the digestive system does not absorb it in normal amounts, a person will become deficient in it.
Best regards, Rich
 

Shoesies

Senior Member
Ok Miss Lotus. I have purchased the supplements on Rich's revised protocol. I am waiting until mid-april to begin as I am just coming out of a hellish relapse. Can you simply and plainly (brain fog x 1000) tell me what I need to look for as far as symptoms and how I would adjust? Or should I just begin and document, coming back when or if I have an issue. It all seems rather complicated and I have so many coinfections, I get confused.
 

Plum

Senior Member
Messages
512
Location
UK
Thanks for the info again Lotus97 - very helpful.

Shoesies - I've just started the protocol and have taken some methylcobalamin. I wanted to check how this felt as cyanocobalamin did not agree with me. I made sure I was in a stable state before starting so I could check properly to see what side effects are occurring just from the methylcobalamin. I will start adding in 1 more supplement in a few days and see how that goes.

It seems that people have all sorts of side effects so it's best to learn a bit, try 1 supplement at a time and then keep learning along the way. I feel comfortable with the side effects mentioned that I at least know what to look out for.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
Thanks Lotus for pasting in the chart of the results from the RichVank/Nathan study. There is one part that I found both surprising and a little disturbing -- the fact that s-adenosylhomocysteine (SAH) levels increased from 43.5 to 51.7, instead of dropping.

It's my understanding that SAH is a more accurate predictor of atherosclerosis than regular ol' homocysteine. There's a discussion here...

http://mthfr.net/mthfr-mutations-are-more-than-high-homocysteine/2011/09/20/

And this study concluded that...

http://www.ncbi.nlm.nih.gov/pubmed/12881445

"...Patients with vascular disease had significantly higher plasma tHcy and AdoHcy (SAH) concentrations..."
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Ok Miss Lotus. I have purchased the supplements on Rich's revised protocol. I am waiting until mid-april to begin as I am just coming out of a hellish relapse. Can you simply and plainly (brain fog x 1000) tell me what I need to look for as far as symptoms and how I would adjust? Or should I just begin and document, coming back when or if I have an issue. It all seems rather complicated and I have so many coinfections, I get confused.
It's hard to say. Most of the supplements aren't going to cause problems, but some people here (including myself) are very sensitive to certain things so I'll try to list a few. The most likely to cause problems would be the methylfolate so I'd save that for last (Rich suggests an order to do things so I'll post that below).

Maybe the B12 would also cause problems, but I'd start that before folinic acid like Rich recommends. The Perque is tricky to cut in half or quarter, but I use an exacto knife to cut mine up. I'm not taking 2000 mcg yet, but when I do get up to that dose I'm still going to divide up my doses so I can spread it out during the day. If 1/4 tablet of B12 is too much I suppose you could try taking a whole tablet orally (swallowing it instead of taking sublingually), but B12 taken orally has a very low absorption rate compared to taking it sublingually so only do that if 1/4 is too much. Even 2 or 3 tablets taken orally probably wouldn't be equivalent to 1/4 tablet taken sublingually. I've seen some estimates suggesting an even bigger difference between oral and sublingual than what I mentioned, but I'm not sure if anyone knows for sure what the difference is. There are a lot factors that affect absorption rate so any estimates are going to be iffy at best.

A certain amount of folinic acid will be converted to methylfolate so that's another reason to start with that before adding methylfolate. If you buy the brands Rich recommends, make sure to take 1/4 tablet (200 mcg each of folinic acid and methylfolate). I misread his protocol initially and was taking 800 mcg of folinic acid a day. Luckily I didn't make the same mistake with methylfolate.

Lecithin is usually made from soy, so if you have a soy sensitivity you should get the sunflower lecithin instead. Also, one tablespoon of lecithin has around 225 mg of choline. Since choline is a methyl donor it could contribute to overmethylation. It also stimulates the BHMT pathway which can convert dopamine to norepinephrine. I'm not sure that amount of choline is enough to affect most people, but it's worth mentioning. If you're also taking TMG, betaine hcl, SAMe, and/or phosphatidylserine (especially Seriphos which is similar to PS, but more potent) which have the same effect as choline on the BHMT pathway and as methyl donors then possibly the combination those could affect some people. Especially once you add B12 and folate. The amount of TMG in the multiple isn't enough to do much of anything though so don't worry about that.

As far as the other ingredients in the multiple. Most of the ingredients are relatively low doses so they aren't likely to cause problems for that many people. My biggest complaint about the multi is that the doses of many of the ingredients seem too low to be effective, but I wonder if that's part of the reason Rich picked it was because he was afraid adding too many things to the protocol would be more likely to cause problems. 12.5 mg of P5P is relatively low, but some people are sensitive to it so that's partially why I recommend dividing up the dose of the multi. Another reason why it's good to divide the dose is because certain B vitamins only stay in your body a certain amount of time so it's good to spread it out. Pine bark extract and curcumin are listed as Th2 stimulants and some people here are Th2 dominant, but again, the dosages are low and I'm not even sure they'd cause problems for people who are Th2 dominant. Milk thistle extract is an iron chelator, but as I said with the other ingredients it's a relatively low dose. I noticed that the multi has 400 iu of vitamin E in the form of alpha tocopherol. If finances allow, I'd recommend taking a gamma tocopherol supplement in addition because alpha tocopherol depletes your body of gamma tocopherol (as well as tocotrienols). While alpha tocopherol is a good supplement to take, gamma tocopherol has additional benefits such as being anti-inflammatory, protects against LDL oxidation, and has a positive effect on nitric oxide and peroxynitrite. If you do decide to take gamma tocopherol, Jarrow's Gamma E would be the best since it has mostly gamma tocopherol and it's also a good price.

Methylfolate is the most likely to cause problems and maybe the B12 after that. It would still be better to start the B12 before the folinic acid like Rich recommends. This is what Rich says as far as the order goes
Different times of the day work better for different people, in regard to effects on sleep. 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.