Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome... (Russel-Jones, 2022)

[Hip]

Oral, sublingual, as well as injectable MB12, AB12, and HB12 have been helpful In many patients, without Greg's oil.

There is nothing special Greg's B12 oils. B12 injections would be just as good.

But Greg's B12 oils are more convenient to administer (it literately takes 10 seconds to apply one dose from the pump bottle to your skin), and this B12 oil works out cheaper than injections (less than $1 for a dose of the oil, whereas an injection would be several dollars).

One dose of the oil is equivalent to about four 500 mcg B12 injections.


But we need to take any claims that major chronic diseases like ME/CFS are due to a vitamin deficiency with a pinch of salt.

 

[Jadzhia]

OK so Part Deux of my epic post on creatine, CoQ10, ATP and CFS, according to Greg Russell-Jones (and this does link to B12 as well via B2). He believes that the dreadful fatigue felt is down to lack of creatine and CoQ10 production over a long period of time. This all gets back to methylation - Methyl B12 is part of the methylation cycle that goes to make SAM, and over 40% of SAM goes to make creatine, part of this relies on vitamins B2 and B6, so if you are deficient in either/both then your creatine production will suffer. Methylcobalamin is also essential in the production of CoQ10 via SAM, and levels of CoQ10 drop when b12 is deficient.

Mitochondria metabolise fats, sugars and proteins via glycolysis and the Krebs' Cycle and in doing so produce ATP, this ATP then needs to be transported from inside the mitochondria through the membrane to the cytoplasm of the cell. My understanding is that creatine is needed in order for this to happen. Therefore if you don't have enough, you will not get this ATP from inside the mito to where it's needed. So if your methylation is poor, you cannot produce enough creatine to achieve this.

My understanding from Greg is that vits B2 and B6 need to be phosphorylated to become active, which of course requires ATP as the phosphate group donor. The ATP is in part stuck in the mito due to lack of creatine so these vitamins aren't activated as they should be. And if your B2 is functionally deficient, so your B12 won't be doing well, either, as the abstract states:

Maintenance of vitamin B12 functional activity is critically dependent upon functional B2 sufficiency, and hence resolution of CFS there must first be resolution of functional B2 deficiency before treatment with vitamin B12 can be effective.

There is nothing special Greg's B12 oils. B12 injections would be just as good.

B12 injections are good, provided they are of the right type of B12 (methyl/adenosyl). Their drawback is the frequency of administration, and this is where the transdermal oils are superior - you get a constant absorption of B12 using the oils, whereas via injection you are getting a large dose then nothing for... a week? A month? Little and often is probably better. Also, some of us are needle-phobes!

I mean, it all makes sense, but I'm not sure people with CFS want to hear that it's 'just B12 deficiency' as that seems rather dismissive! However it is worth investigating at an individual level to see if one can make any difference by attempting to fix these deficiencies if they exist.

 

[Hip]

My understanding from Greg is that vits B2 and B6 need to be phosphorylated to become active, which of course requires ATP as the phosphate group donor. The ATP is in part stuck in the mito due to lack of creatine so these vitamins aren't activated as they should be. And if your B2 is functionally deficient, so your B12 won't be doing well, either, as the abstract states:

Thanks for fleshing out Greg's ideas.

I've found high dose B12 beneficial for my ME/CFS brain fog, but I think it is implausible that ME/CFS is due to a nutritional deficiency, functional or otherwise.

B12 injections are good, provided they are of the right type of B12 (methyl/adenosyl). Their drawback is the frequency of administration, and this is where the transdermal oils are superior - you get a constant absorption of B12 using the oils, whereas via injection you are getting a large dose then nothing for... a week? A month? Little and often is probably better. Also, some of us are needle-phobes!

The systemic absorption of B12 from these oils is a little slower than you get from an injection. With an injection, the B12 hits the system almost all at once. With Greg's B12 oils, the absorption is a little slower, probably over a period of several hours.

However, if you are taking Greg's oils once a week, like I am, then even with the oils, you are still getting the B12 just on one day, but not on any other days.


Though I came across one ME/CFS patient who found that the slow absorption of Greg's oils was not as effective for his ME/CFS symptoms as the flood dose you get from an injection. So he preferred injections.

 

[Jadzhia]

However, if you are taking Greg's oils once a week, like I am, then even with the oils, you are still getting the B12 just on one day, but not on any other days.

Any reason why you take them that way? I use them daily, last thing at night, being on a 'full dose' which is quite a large 'squirt' from one of the dispenser bottles. The emphasis in his FB group is daily or even twice daily use of the protocol supplements (I/Se/Mb, B2 and B12).

 

[Hip]

Any reason why you take them that way? I use them daily

I took Greg's B12 oil daily initially, and noticed an improvement in brain fog. Then after some time, I tried weekly dose instead, and obtained the same brain fog improvement. So for me, once a week works well. And obviously once a week saves money.

It's only after around 10 to 14 days that I notice the effects of once B12 dose wearing off, and the brain fog creeping back up again.

 

[Oliver3]

I'm in Greg's Facebook group(s) re B12 deficiency. I joined a couple of years ago when I stumbled across them by chance, and was immediately attracted by the Kreb's Cycle of the group's banner! Anyway I have been (attempting to) follow his protocol during that time and still do so.

There's a lot to unpack, really. The group consists of a large mix of people, some have CFS/ME, many have hypo (or occasionally hyper) thyroidism (I am hypo with Hashi's and think I have some degree of CFS, am still investigating that). Others there have autistic children whom they are trying to help or are diagnosed with B12 deficiency but can't get well.

The protocol has a very definite 'order' to it, in terms of the 'cascade of energy' - from Iodine through Selenium, Molybdenum, B2 and B12. The thyroid is crucial to this as it requires both Iodine and Selenium, and Greg monitors the thyroid by using TSH along with total T4 and T3 measurements (rather than the 'frees').

As doctors misuse TSH all the time to assess one's thyroid function (by using it on its own without looking at thyroid hormone levels), I am very resistant to monitoring one's thyroid via TSH (which is a pituitary hormone after all), and aiming to get it to a value of 1.0 in lab tests. Not everyone's TSH 'set point' is the same, plus there is diurnal variation in TSH, plus some folk have problems with their pituitary that causes their TSH to not respond properly. I have never seen any of those points mentioned. I do see people post how their TSH is, say, 1.3 and they can't seem to get it lower, how much more Iodine do they need to take. I feel there can be an over-emphasis on TSH which doesn't help.

The 'functional' deficiencies have been nicely covered by @Hip above. You may have a very high top of the reference interval value for B12 in your blood but yet be 'paradoxically' deficient - this is because it is in an inactive form and cannot be utilised, yet you will think you are replete in it and so will your doctor. Greg says that sublingual supplementation is ineffective and serves to increase this paradoxical level in the blood, and he invented his B12 oils for transdermal application to overcome this.

I definitely had signs of B12 deficiency - peripheral neuropathy - despite taking B12 sublingually in large doses. I have been using B12 transdermal oils and was just thinking last night how my feet are now free of neuropathy. I also take B2 as it seems to be the cornerstone of so many enzymes - via FAD.

Greg claims that both histamine intolerance and oxalate issues (which I have) can be remediated via fixing B2 deficiency (as it's needed to metabolise these) but as yet I have not seen the back of these unpleasant conditions. Some in the group have done so, and have gone from only being able to eat a few foods to back to a normal diet. I can't speak to how many have been 'cured' of CFS/ME, I'll have to take his word for it.

The OAT is Greg's favourite analytical tool along with thyroid labs, full blood count and iron panel. He has accumulated hundreds of OAT tests from many people who've contacted him. I don't doubt for a minute that he has helped people, but of course everyone is different. He is not a fan of many supplements (e.g. magnesium) preferring that people get their nutrition from food. This of course can be extremely difficult if you have food intolerances.

I think I will pause here or my post will reach epic proportions, if it hasn't done so already! I do recall Greg mentioning Creatine as important in CFS but will put that in another post.

If I'm not mistaken, I think they presented to Ron...not sure of the outcome

 

[Oliver3]

I took Greg's B12 oil daily initially, and noticed an improvement in brain fog. Then after some time, I tried weekly dose instead, and obtained the same brain fog improvement. So for me, once a week works well. And obviously once a week saves money.

It's only after around 10 to 14 days that I notice the effects of once B12 dose wearing off, and the brain fog creeping back up again.

Hip did you try the whole protocol or just the b12 oil out of interest?

 

[Hip]

Hip did you try the whole protocol or just the b12 oil out of interest?

I followed the full protocol, taking the B12 oils, B2, selenium, iodine and molybdenum daily for about a month. I noticed improvements in brain fog and mental focus.

I then switched to taking the B12 oils less frequently (around once a week) to save money. I continued with the daily B2 and selenium long term (for years), along with the weekly B12; but eventually dropped the iodine and molybdenum after the second month.

 

[Hip]

I'm in Greg's Facebook group(s) re B12 deficiency. I joined a couple of years ago when I stumbled across them by chance, and was immediately attracted by the Kreb's Cycle of the group's banner! Anyway I have been (attempting to) follow his protocol during that time and still do so.

There's a lot to unpack, really. The group consists of a large mix of people, some have CFS/ME, many have hypo (or occasionally hyper) thyroidism (I am hypo with Hashi's and think I have some degree of CFS, am still investigating that). Others there have autistic children whom they are trying to help or are diagnosed with B12 deficiency but can't get well.

Did you come across anyone in Greg's Facebook groups who were clearly ME/CFS patients (eg, satisfy the Canadian consensus criteria or Fukuda criteria), and who had substantially benefited from Greg's protocol?

 

[Learner1]

But we need to take any claims that major chronic diseases like ME/CFS are due to a vitamin deficiency with a pinch of salt

It is prudent to test for such deficiencies and treat them rather than blindly following some generic protocol just because one has a diagnosis. We are unique individuals with unique genetic and environmental factors. It is ridiculous to think that any one size fits all protocol or problem solves all our issues.

One dose of the oil is equivalent to about four 500 mcg B12 injections

Doesn't do much if you do a 10 mg injection typically. Personally, I don't like oil all over my clothes and ruining my furniture.

He believes that the dreadful fatigue felt is down to lack of creatine and CoQ10 production over a long period of time. This all gets back to methylation - Methyl B12 is part of the methylation cycle that goes to make SAM, and over 40% of SAM goes to make creatine, part of this relies on vitamins B2 and B6, so if you are deficient in either/both then your creatine production will suffer.

For many of us, the dreaded fatigue is due to viruses, toxicity, autoimmunity, immunodeficiency, mitochondrial dysfunction, hormonal, imbalances, and for some, nutritional deficiencies.

I mean, it all makes sense, but I'm not sure people with CFS want to hear that it's 'just B12 deficiency' as that seems rather dismissive! However it is worth investigating at an individual level to see if one can make any difference by attempting to fix these deficiencies if they exist.

Agreed. Comprehensive nutrient testing can provide some great insight, and help solve problems. It's unlikely to be an isolated B12 deficiency.

I've found high dose B12 beneficial for my ME/CFS brain fog, but I think it is implausible that ME/CFS is due to a nutritional deficiency, functional or otherwise.

The systemic absorption of B12 from these oils is a little slower than you get from an injection. With an injection, the B12 hits the system almost all at once. With Greg's B12 oils, the absorption is a little slower, probably over a period of several hours.

It's highly unlikely ME/CFS is caused by one single problem. Most of us have a plethora of different problems contributing to our illness, which is why it has been so difficult to run studies and solve problems across the board- - we are all unique genetic beings with unique environmental factors which cause a different variation of this illness, so that one simple solution is unlikely to cure almost all of us.

Did you come across anyone in Greg's Facebook groups who were clearly ME/CFS patients (eg, satisfy the Canadian consensus criteria or Fukuda criteria), and who had substantially benefited from Greg's protocol?

The point being missed here. Is that all of those patients, if they did meet those criteria, would have different genetics from one another, different amounts of toxicity from environmental factors, different amounts of active viruses running around in their systems, different amounts of different factors in their immune system working in different ways. We are not widgets in a widget factory, and this is where the science fails.

 

[Hip]

Doesn't do much if you do a 10 mg injection typically.

I've never come across a 10 mg = 10,000 mcg vitamin B12 injection. Where are these sold?

Comprehensive nutrient testing can provide some great insight, and help solve problems.

I've not come across anyone on this forum who benefited from such comprehensive nutrient tests. I don't see any advantage they give over standard medical blood tests, which check important things like electrolytes, vitamin D and vitamin B12.

The point being missed here. Is that all of those patients, if they did meet those criteria, would have different genetics from one another, different amounts of toxicity from environmental factors, different amounts of active viruses running around in their systems, different amounts of different factors in their immune system working in different ways. We are not widgets in a widget factory, and this is where the science fails.

Standard medical science is good at treating patients by their individual needs. That's why for example we have different antivirals and different antibiotics, which are prescribed according to the infection you have. That's why we have thousands of different surgical procedures, which are deployed according to individual patient needs.

But this is taking this thread off topic.

 

[pattismith]

I've never come across a 10 mg = 10,000 mcg vitamin B12 injection. Where are these sold?

.

Yes, you can find it, I use it:

 

[Hip]

Yes, you can find it, I use it:

Wow, that is an incredibly high dose! The B12 injections I have seen are typically around 100 to 500 mcg.

Do you know what is the purpose of such high doses? And do you actually notice any difference using this very high doses, compared to an injection of say 500 mcg.

 

[Jadzhia]

I followed the full protocol, taking the B12 oils, B2, selenium, iodine and molybdenum daily for about a month. I noticed improvements in brain fog and mental focus.

I then switched to taking the B12 oils less frequently (around once a week) to save money. I continued with the daily B2 and selenium long term (for years), along with the weekly B12; but eventually dropped the iodine and molybdenum after the second month.

That's really interesting - perhaps you are now 'replete' in B12! For me, taking T3 has been the only thing that has dispersed brain fog. Molybdenum is the other thing that has really benefitted me, by improving my stomach acid so that I no longer need to take Betaine HCl with each meal. If I stop it for even 2 days, I notice reflux coming back, so know for sure it's the Moly.

 

[Jadzhia]

Did you come across anyone in Greg's Facebook groups who were clearly ME/CFS patients (eg, satisfy the Canadian consensus criteria or Fukuda criteria), and who had substantially benefited from Greg's protocol?

Hmm not off the top of my head but I can search the group and see if anything pops up.

 

[Oliver3]

Did you come across anyone in Greg's Facebook groups who were clearly ME/CFS patients (eg, satisfy the Canadian consensus criteria or Fukuda criteria), and who had substantially benefited from Greg's protocol?

Yes, a fellow Brit. He was a kid. His mum was liasing with British people who wanted advice on how he did it. I just can't afford the protocol

 

[pattismith]

Wow, that is an incredibly high dose! The B12 injections I have seen are typically around 100 to 500 mcg.

Do you know what is the purpose of such high doses? And do you actually notice any difference using this very high doses, compared to an injection of say 500 mcg.

I tried several dosages but found no difference.

Here another one I use:

 

[Jadzhia]

how would a virus cause a functional deficiency in these vitamins?

I am thinking via its effect on the immune system. Greg says that one's immune system is a huge user of B12/folate/B2/iron and biotin. So it's not the virus itself, but our immune system's response to it, which naturally requires resources from our body to deal with any invader. Thinking about it, this could also be because B2 is involved in the activity of so many enzymes as FMN/FAD. Also imagine if you can't quite clear a viral infection, and it lurks and comes back - puts a lot of stress on one's body.

@pattismith - the hydroxycobalamin you are showing above isn't a good form to supplement with as it must be converted by your body to the active forms of B12 (adenosyl and methyl cobalamin). The conversion rate isn't great - about 25% of what you take. Also it relies on your body having enough B2. Genetics can also get in the way if you have MTRR +/+ or +/- SNPs, which are common.

 

[nataliemarie]

I am thinking via its effect on the immune system. Greg says that one's immune system is a huge user of B12/folate/B2/iron and biotin. So it's not the virus itself, but our immune system's response to it, which naturally requires resources from our body to deal with any invader. Thinking about it, this could also be because B2 is involved in the activity of so many enzymes as FMN/FAD. Also imagine if you can't quite clear a viral infection, and it lurks and comes back - puts a lot of stress on one's body.

@pattismith - the hydroxycobalamin you are showing above isn't a good form to supplement with as it must be converted by your body to the active forms of B12 (adenosyl and methyl cobalamin). The conversion rate isn't great - about 25% of what you take. Also it relies on your body having enough B2. Genetics can also get in the way if you have MTRR +/+ or +/- SNPs, which are common.

Hi Jadzhia! Do you see anything wrong with a b complex that includes hydro, adeno and methylcbl? I found this one that gave me a lot of clean energy https://rawrevelations.com/b-complex/ until I took too many days in a row and had a methyl trapping situation... but im thinking if i spread out dosing it might be good.

i am slow COMT and homo MTHFR c677t. The only b vitamin that is showing to be low for me is folate, but I figured I should take all of the bs instead of just the folate. now with the methyl trap.. im assuming b12 might be appearing as normal on test but truly isnt functioning properly?

Thanks so much for the help!

 

[Hip]

I am thinking via its effect on the immune system. Greg says that one's immune system is a huge user of B12/folate/B2/iron and biotin. So it's not the virus itself, but our immune system's response to it, which naturally requires resources from our body to deal with any invader. Thinking about it, this could also be because B2 is involved in the activity of so many enzymes as FMN/FAD. Also imagine if you can't quite clear a viral infection, and it lurks and comes back - puts a lot of stress on one's body.

I tend to see nutritional deficiency theories of ME/CFS as a kindergarten medical science.

Nutrition involves just tiny a handful of vitamins, minerals, fatty acids, etc. But there are millions of pathways in the body which can become dysfunctional, and these dysfunctions are nothing to with nutritional levels. The area of nutrition is just a drop in the ocean compared to the full complexity of the body. Thus very unlikely that nutritional factors would be involved in ME/CFS, especially given how easy it is to correct these factors with supplements.

Having said that, I found that taking high-dose selenium substantially improved my ME/CFS just on its own (see this thread), so supplements can help in ME/CFS.