3 yrs on - methylfolate and muscle wasting roadblock

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After starting the methylation protocol about 3 years ago, I’ve made some significant progress and steps forward in health. I'm no longer bound to the house, but I am at another roadblock so I’m creating this post to get feedback as to how to overcome it.

My specific problem with the protocol is certain things (EDIT: result in muscle wasting, teeth/gum wasting, and exhaustion. The effect is quick, beginning within minutes to a day when I really notice it. Now that I consider it further, it may initiate with scavenging of Nitros Oxide because of how quickly it happens). If think the first 3 are most relevant to my current situation in this list, but I'm including the other 3 for perspective:
  • Adenosylcobalamin causes a run down feeling, muscle and gum wasting, and my teeth get dry, yellow, and extremely sensitive. I have low bone density so this is a serious issue for me. Even with low doses I start to look like a meth addict. I tolerated this well in the first 2 weeks, since I have discontinued it due to the side effects.
  • Methylfolate (metafolin) caused a run down feeling, muscle wasting, anxiety and a dry, scratchy throat.
  • Carnitine in tiny doses feels like it overrevs my system then I get extended fatigue and muscle wasting.
  • ...
  • Trace Minerals Complex II causes a feeling that my liver is shutting down, takes days/weeks to get out of my system. Stop eating and get fatigued.
  • Trace Minerals No Muscle Cramps causes brainfog, anxiety, and it feels like I’m slow to process it in VERY small amounts: 2 mg magnesium, 10 mg chloride, 4 mg sodium, 5 mg potassium, 1 mg sulfate. I stop urinating as much as I should and get fatigued and stop eating.
  • Calcium: I am not producing enough stomach acid to absorb calcium to increase bone density, which I believe is part of the methylation problem I face. Small calcium doses cause extended constipation which stop me from eating.
I did not continue taking TMG because it caused digestive issues. I did take plain glycine for a while with great results, then got a build up which caused fatigue and my brain to get slow. It’s something I’ll add back if I can get over this hump.

I never got to try SAMe, which I’m considering trying again, but the mood warnings kind of freak me out because I get anxiety and I don’t like all of the extra ingredients in the NatureMade brand.

On to what’s worked: after a long process of trial and error I got to a plateau with these daily supps about 6 months ago:
  • · 1200 mg Alpha GPC (choline)
  • · 1000-3000 mcg Hydroxycobalamin (metabolix brand liquid - yes it's good and I know I absorb it)
  • · 6000-8000 IU Vitamin D
  • · 500 mg Panthothenic Acid
  • · 17 mg Riboflavin 5 Phosphate
  • · 20 mg Benfotiamine
  • · 50 mg P5P
  • · 800 mcg Biotin
  • · 300 mg Magnesium
  • · 3-4 g Pharmaceutical grade through fish oil and caviar
  • · 2000 mg Vitamin C
I compound my own B vitamins with a mix of active ones sourced from Thorne, Pure Encapsulations, and other high quality brands without fillers. Nothing that I take is cheap.

With these supplements after I plateaued, I wasn’t getting worse, but I wasn’t getting better. 6 months ago I switched to the carnivore diet with regular fasting and time-restricted eating to quell joint stiffness issues, and it worked for the most part. However I noticed a general fatigue/depression starting in again recently. My annual physical showed low folate for the first time ever, so I decided to try introducing supplements again after the doc recommended methylfolate. I had put most of my methylation supplements on hold because I was only eating fatty meat and fatty fish, and B vitamins don’t absorb well with this. After about a week of going back on them, I tried methylfolate again.

Here’s the problem. Methylfolate has the same damn effect as it did before. Anxiety, muscle wasting, teeth sensitivity. I cannot have this as my health is too close to the precipice. It’s the same feeling I get with acetyl l carnitine.

My muscles get weak and tight and I get anxiety and I start to crave sugar/carbs, which help but they increase inflammation. It’s like ATP ramps up and then runs out of something and keeps ramping up, and if I feed it what my body craves my joints get stiffer.

Any ideas on what I’m missing? My next thoughts are:
  • force myself to try calcium/strontium again with the magnesium, though this always left me exhausted, depressed and constipated
  • Switch methylfolate to Folinic Acid
  • Take higher doses (Freddd recommended levels) of potassium despite the anxiety/brain fog/detached feeling it causes (EDIT: potassium also causes stiffness in the skeletal muscles/joints. I haven't isolated it yet, but when I take potassium supplements it gets much harder for me to move).
  • Try SAMe despite the ingredient concerns
  • Try L-ornithine again despite it always causing cold sores
I have to stick to the carnivore diet for now with a few apples thrown in for when I take supplements. Going off causes too many joint problems right now.

I’m really confused on this one :-/
 
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Dechi

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I have no suggestion regarding supplements, as I’ve stopped them all, but about muscle wasting, do you do ME adapted exercises to maintain your muscle mass ?

It really doesn’t take a lot. I’ve been doing about 45-60 seconds of exercise per day (not even everyday, just when I can) and I have kept a certain amount of muscle mass.

Nothing compared to what I had before, but enough to be strong, although with no endurance.
 
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@Dechi After I started the carnivore diet I was able to exercise again, after about 2 weeks, and I do band exercises and walk regularly, and ride bicycle seriously every couple of weeks. Since taking methylfolate, literally crumbs and dipping my finger in the dust of a crushed tablet, I don't believe it's possible because my joints are locked up again. I just walked a couple of blocks to the grocery store and I wouldn't do it again due to the pain, which is really different from how I was 2 weeks ago.

So for over 5 months I was exercising and able to move. Now for 2 days I'm not able to again.
 

Dechi

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@wookielove that is unfortunate. So sorry about that. I hope you find a solution, sorry I don’t have the knowledge to help. Hoping somebody will.
 

Victronix

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I could not tolerate methylfolate or folinic, and the high levels of potassium I was having to take were not sustainable over time, so eventually I stopped and now I just try to include high folate foods regularly (black eyed peas, asparagus, artichoke hearts, romaine, etc (https://nutritiondata.self.com/foods-000112000000000000000.html).

However, one thing that happened to me when I stopped methylfolate was that my hormones tanked, and it was pretty awful, but I have one copy of APOE4, and I've heard that that can create problems with hormones with women in general.

Assuming you don't want to stop folate, it sounds like the next step is to TRY folinic. It had an identical effect for me that methylfolate had.

I have one banana a day to address the muscle issues with B12 and then add in a large can of coconut water if I get leg cramps (which happens during my period sometimes). Methyl folate really destabilized everything for me and was very intense so that I would get euphoria and then paranoid with low K+, etc.

To me the sensitive teeth issue happens with low potassium - very bizarre. One time I was sure I had some kind of major tooth issue and was ready to go to see a dentist. Then after potassium - gone.
 
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@Victronix I just got some folinic acid to try, but I'm waiting for my symptoms to even out a bit so I can judge the reaction better.

The sensitive teeth issue is very weird, I agree. Good to know potassium helped you, I'll keep it around and try in low doses. I suspect it has something to do with collagen also, which I can't take due to my specific autoimmune issue. I also bought some Natural Vitality Natural Mag + Calcium, which has a bit of potassium also. Previously when I took even a little calcium it would just block my system up so there gets to be a multi-day delay in excreting. There's a much higher dose of magnesium here, so hopefully it works for me. I'm going to start with very small doses this time.

Unfortunately on the carnivore diet I can't eat any of the other foods you mentioned, I'm really just stuck with beef, particularly ribeye and some ribs.

I figured I'd also mention as some people probably won't visit my other thread, MethylB12 gives me debilitating headaches, and my SNPs direct me to take hydroxycobalamin instead, which is why I'm not on MB12.

I'm reading through the guides again and one thing mentioned is digestive issues due to poor methylation. I tried to work on digestion first (4R Gut Rebuilding Program) but got nowhere. This makes more sense to me now:

https://howirecovered.com/active-b12-therapy-faq/

Should I fix my digestive issues before starting methylation?

For example, the development of a partial methylation cycle block may be what leads to the gut dysfunction in many cases. However, when the gut dysfunction has developed, it can lead to poor digestion and absorption of substances that are important to get the methylation cycle running again, such as amino acids. So even though the methylation cycle block may have led to the gut dysfunction, it may be necessary in some cases to work on the gut first. In other cases, the gut may still be working well enough to bring in enough of the essential nutrients, and in those cases, of which yours might be two, fixing the methylation first works well.

Yesterday I had a conversation with Dr. Richard Kunin, the president of the Orthomolecular Health-Medicine Society, a person who has studied methylation issues for many years. He pointed out to me that when methylation goes down, one of the first things to suffer is the exocrine pancreas function, i.e. the part of the pancreas that normally produces digestive enzymes. I did a little literature searching, and he appears to be right. That might be one way (or maybe it’s THE way) that a partial methylation cycle block leads to gut dysfunction.

When you can’t digest food for lack of digestive enzymes, I think the bacteria are going to respond by consuming the food and overgrowing. This may account for low chymotrypsin or pancreatic elastase in some of the stool tests from PWCs that I’ve seen. In the past, I’ve suspected that this might be due to low stomach acid production, which would lead to lack of a signal to excrete the digestive enzymes from the pancreas when the food moves into the duodenum. But maybe the problem really is with the pancreas itself, because of the methylation cycle block. velha: My gut shut down at the same time I became very ill – July/August 09. Digestion just stopped. So, mine has been short term also.

It is hard to say what has helped my gut the most. I can say the I noticed no effect with increasing doses of mB12 and methylfolate (at least not immediate). My gut began to improve in late December. I did a number of things at that time, two being increasing my adB12 (to daily) and carnitine dosages (~4g/day). Suzy: I just wanted to share another possible reason for improvement of gut function on Rich’s or Freddd’s protocol. This abstract shows that oxidative stress can lead to pancreatitis and Rich’s protocol has been shown to raise glutathione in his study.

Superoxide dismutase and catalase: a possible role in established pancreatitis.
Guice KS, Miller DE, Oldham KT, Townsend CM Jr, Thompson JC.

The mechanism of cerulein-induced acute pancreatitis may involve the production of free radicals in excess of the capacity of endogenous intracellular scavengers. These radicals destroy the cellular membranes, releasing digestive enzymes and cellular proteins into the interstitium. Thereafter, a cascade of events, including polymorphonuclear infiltration and complement activation, leads to pancreatic destruction.

The present study demonstrates that superoxide dismutase and catalase reduce the ultrastructural and biochemical injury associated with cerulein-induced acute pancreatitis in rats. Pretreatment with superoxide dismutase and catalase 30 minutes before injury did not appear to be protective, presumably because the half-life of intravenous superoxide dismutase is only 6 minutes. This and similar studies suggest a potential clinical role for free radical scavengers in acute established pancreatitis.

 

Kathevans

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Who knows if it would help, but I have had amazing results for the supplement Boron. It has taken seven months now from titrations of 180 mcg of a 3 mg tablet, but I have felt changes in my muscles, as well as had a huge shift in the amount of folate that I can tolerate. As Fred says, all these supplements work in concert.
 
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Who knows if it would help, but I have had amazing results for the supplement Boron. It has taken seven months now from titrations of 180 mcg of a 3 mg tablet, but I have felt changes in my muscles, as well as had a huge shift in the amount of folate that I can tolerate. As Fred says, all these supplements work in concert.
Hi. Can I ask how you get the 180mcg titrations like that? I've got Radience Boron capsules in 3mg but I see a lot of people just spoon out the 20 Mule Team Borax straight into water and that seems to work for them. Thanks. Rob
 

Kathevans

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Can I ask how you get the 180mcg titrations like that? I've got Radience Boron capsules in 3mg but I see a lot of people just spoon out the 20 Mule Team Borax straight into water and that seems to work for them.
Divide the 3 mg capsule in half--now it's 1500mcg, then again--now it's 750mcg, then again--now it's 375, then again--now it's something like 180mcg. It's tedious...

I wouldn't take straight Borax, though I've heard that people do. I've got enough problems that I'd rather use a chemical compound where I don't have to worry about one more thing.
 
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Divide the 3 mg capsule in half--now it's 1500mcg, then again--now it's 750mcg, then again--now it's 375, then again--now it's something like 180mcg. It's tedious...

I wouldn't take straight Borax, though I've heard that people do. I've got enough problems that I'd rather use a chemical compound where I don't have to worry about one more thing.
Great. Thanks.
 
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Update:

I've gone through some interesting changes since I last posted. First, I have no luck on this protocol when I eat anything besides beef and honey (small amounts). Repeatedly eating something different, such as apples, which are the second least reactive whole food for me, brings me right back to stiffness, lethargy, mental lethargy, and digestive problems. So I dabble from time to time but only in small quantities and spaced out.

I've been able to up my methylcobalamin intake to 1.5-3grams/day sublingually. This is a change from it causing debilitating headaches previously in the left side of my head, which I believe now was due to things turning back on in that area of my brain. I do get energy and strength from the B12, but it can be a type of nervous energy and sometimes I have to move/exercise after I take it, and it's helping with exercise/therapy strength.

Something else I've discovered during this ramp up process where I've had periods of feeling excellent, I hit a point where I needed to take methylfolate otherwise the methylb12 would stop working. So I started out with my crumbs and increased to 200mcg MTHFL. Then I ran into a problem again, a feeling where I hit a wall. I backed off, took a few days off, tried again, and again, but this wall is pretty solid, leading me to think I'm missing another cofactor. It's possible that it's donut hole insufficiency, but it doesn't feel that way. My symptoms are feeling extreme weakness and lethargy. I backed off again to crumbs, every other day or so, which is keeping me functioning without long down times. It would take 3 days after I hit the wall to want to get back to functioning and be able to take MB12 again.

Something else that's very interesting, and Freddd has reported something similar but not with riboflavin. I've always felt like I wasn't absorbing vitamins, in particular they would come out a bright yellow in my urine if I'd taken them, or my urine would be near clear. Now, if I don't take MTHFL with B12, I get pretty much the same response. However, if I take MTHFL with the MB12, even if I don't take riboflavin, it delays urine output and my urine coloration becomes a darker yellow, indicating to me additional processes happened, plus I feel like it's gotten into my cells.

I've been able to take some potassium on an empty stomach with a lot of water, 100mcg doses at a time. This fatigues me while it's in my stomach, but it does help with the overall fatigue and tooth/gum sensitivity. So it feels like it's going in the right area.

So right now I've got a few things to try next, I'll probably do them in this order:

Up methylfolate to try to get out of donut hole insufficiency, if that is indeed what I have​
Try adenosylcobalamin again. 100mcg once every 3 days was too much, so maybe I'll try to figure out how to cut the dose down to 20% of that and see how I react.​
Try Sam-E again. The first time i tried 50mcg I did feel better, kinda anti-depressant better, but became genuinely depressed the following day, which is not something I'm familiar with and really disliked. i'd appreciate other's input here as its billed as improving mood and joints, not as something you gain immediate dependence on. What are the risks?​

Any advice appreciated. After rereading my post again, I do think in my case digestion is really screwed up, as my my energy first collapsed concurrently with digestion completely stopping. I suspect that eating carnivore (only meat) bypasses the impaired pancreas and is allowing this treatment to work on some level. Intend to keep Mb12 at this level if I can while working these other things in.

[EDIT: I wanted to include the link to a prior post I made documenting my troubles with Mb12. I think the carnivore diet was the key to my now being able to consume Mb12 and it having a positive effect: https://forums.phoenixrising.me/thr...urological-brightening-hydroxy-engergy.39221/ ]
 
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BeADocToGoTo1

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Hi wookielove,

Please check out my thread on exocrine pancreatic insufficiency (EPI). It flies under the radar of many sufferers and doctors. Most docs have no idea how to recognize the many, many symptoms, how to properly test for it, and forget about comprehensive treatment. It is also a little understood cause of ME/CFS and not to be taken lightly in terms of impact on nutrient deficiencies, metabolic pathways and mitochondrial functioning.

https://forums.phoenixrising.me/thr...y-epi-and-chronic-fatigue-syndrome-cfs.62997/
 
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BeADocToGoTo1

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Just in case you have not looked into this, have you tested for nutrient deficiencies or any form of malabsorption or microbiome dysbiosis which can cause nutrient deficiencies?

Some tests to consider:

1. Genova Diagnostics - FMV - Gives a great overall picture of nutrient deficiencies, neurotransmitter metabolites, microbiome dysbiosis, pancreatic enzyme issues, and many more. Biochemistry and metabolomics in practice. This test should be standard for all primary care and family practice doctors as a regular preventative maintenance test, and for anything chronic or hard to diagnose. Great Plains Laboratories has similar tests.

2. Genova Diagnostics - Comprehensive Digestive Stool Analysis 2.0 with Parasitology (microbiome dysbiosis indicators), Fecal Fat Distribution (checks if you have issues with different types of fat intake and digestion), Elastase (for EPI, pancreas enzyme marker)and Chymotrypsin (for EPI, pancreas enzyme marker). Doctor's Data has similar tests.

3. Small intestinal bacterial overgrowth (SIBO) breath test, for example, Commonwealth Diagnostics International. But the first one will also provide you with SIBO indicators.

But also look at HbA1c as a quick, standard indicator of excess sugar intake which impacts your microbiome, pancreas functioning amongst many other things. 5.2% or lower is what I strive for.

There are many reasons for malabsorption and nutrient deficiencies often overlooked by doctors, so it would be good to rule out things like exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO), Candida yeast overgrowth, food sensitivities or allergies, gluten sensititivity, Chrohn's etc.
 
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Every time I restart on methylfolate, my skin gets dry and irritated. I I have eczema, but I get a lot of what appears to be dermatitis and very dry skin.

Anyone have a solution for this? It seems I need more omega 3, but the fish capsules or sardines I try to work in seem to just cause digestive issues and worsen the problem. Seems like this problem should be solved by potassium or something, but it's not.

@matt3n Tried copper, seems to wipe out my digestive system. I need to get a better baseline, it's too damaging to supplement.

Regarding the other processes, I temporarily gave up on doctors and naturopaths a few years ago. Nothing, and I mean nothing, they provide has helped anything more that what I've found in resources like this forum.
 

Kathevans

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I see that I’ve chimed in before, but quite a while ago... Yet, with many similar symptoms, I have recently met with some success. For me, the symptoms have been low folate (despite taking 5-7mg/day of Fred’s favorite, Methyl Pro, very dry skin, muscle wasting to the point where my arms were very sore and painful.

Methylation block, indeed. I think that’s it. I’ve spent more time at the “Understanding B-12 Deficiency” site on fb than here, and the essential thing I learned is that to have recycling B12, you need to have functioning, which is to say, active B2. This requires a functioning thyroid, which in turn requires adequate iodine, molybdenum and selenium. But for me, the past few years have been a bit of a fiasco—and a painful and frustrating one—in getting the right forms of these minerals, and taking them in the right way to help with absorption. That is, avoiding a gut with questionable absorption! So I don’t have to repeat myself, I will refer you to an earlier post of mine, and to the recent posts I’ve made on this issue.

I am still in early days, still titrating up on iodide, my last of the three minerals (I was taking another kind, which apparently wasn’t working well, if at all) still making my way through adrenaline reactions that come from not having methylation working, and suddenly being turned on, and having my hard little muscle knots relax and begin to once again grow (I find myself with a frequent desire to stretch...and I am taking Fred’s daily recommendation of L-carnitine fumarate ...though I have been on it all along and I have never felt this so strongly).

Also...from earlier in this thread, my opinions on Boron: I take it all back. Once I began to take selenite, my body didn’t care at all about boron. I now take the usual boron, 3 mags, to avoid osteoporosis.

The Post, from @Pyrrus’s thread on Dr. Gregory Russell-Jones’ B12 oils:
What I'm puzzled about is how can people miss out on that; selenium, iodine, molybdenum and B2 are fairly common supps for 'us' sufferers, you'd think this isn't overlooked.
Note that in earlier posts I talk about the forms of these minerals and how they are taken. This is essential - at least it has been for me--a person with gut issues and an oral infection I've had for as long as I've had Fibro/chronic fatigue. No citric acid (including taking at the same time as Vit C), or taking with lemon juice. In fact, best taken on an empty stomach a.m. and p.m. The forms that work best--or at all--are SELENITE (I took selenATE for years to no avail; this was after I ate 3 Brazil Nuts /day, recommended by Greg back in 2015 or 16); MOLYBDATE (again, make sure if you titrate up drops as I did, that they don't have citric acid as a preservative!); and IODIDE.

This last has been tricky for me because I had been using BodyBio's Potassium Iodide for YEARS, and was taking up to 450 mcg/day. But my TSH was still over 3, and Greg has said it must be somewhere between .5 and 1.5. Adding the correct form of SELENITE made inroads to my thryroid number over a 6 month period last year when the TSH dropped below 2 for the first time in a decade or more. But I still wasn't making enough T4-- Greg says T4 under 7 means you probably need more iodide. So, I switched from bodyBio to Genestra and had much stronger start-up reactions (the Genestra is a natural form of IODIDE made from Kelp). I am still on my way up to 300mcg, after which I will wait another 4 weeks or so and re-do my thyroid tests. With each quarter drop increase, I find my sleep improves a bit and becomes more consolidated, though whether this will last, I have no idea. My view is that all of this, for me, is in service to ultimately activating B2 (which btw, is not so easy to utilize, no matter how much you take!) into FMN and FAD, the levels for which I have been 'HIGH NEED' on NutrEval since the first time I took the test back in 2014. If you cannot activate B2 into FMN and FAD, you are just flushing it down the toilet...

Another thing. Back in December I began to exhibit re-feeding symptoms that only Selenite would quench. Though Greg recommends taking no more than 200mcg of Selenite, I tried raising it with success, or an alleviation of the symptoms, then followed the symptoms till they resolved at 300mcg/day of selenite. I am hoping that with a hair-mineral analysis - which Greg has ideal numbers for apparently--I can then lower the selenite. Concerned over taking too much, I also got on PR and searched the threads and found that there was at least one person--I think it was @Hip who took higher doses without negative affect.
 

Eastman

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Every time I restart on methylfolate, my skin gets dry and irritated. I I have eczema, but I get a lot of what appears to be dermatitis and very dry skin.
There are suggestions that eczema and other skin problems can be treated with biotin. For example, from the University of Rochester Medical Center website:
There may be benefits that have not yet been proven through research.

Biotin may help treat hair loss (alopecia). It may also treat skin issues. These can include acne, seborrhea, and eczema.
The Dr. Schweikart Publisher website says that vitamin B12 and biotin work together in feeding the citric acid cycle.
Biotin and B12 – in the B12 form of adenosylcobalamin – work as a coenzyme in two directly successive metabolic steps: the biotin-dependent reaction provides the starting substance for the B12-dependent reaction.

Without a sufficient supply of biotin, adenosylcobalamin cannot take effect.

... B12 cannot function when there is a biotin deficiency, since the starting substance required by B12 for its relevant reaction, methylmalonyl-CoA, is missing.

Biotin deficiency can thus lead to a functional B12 deficiency, even if sufficient adenosylcobalamin is present.

The other way around, a biotin deficiency can also arise due to a sudden, large influx of B12 – as in high-dose initial therapy. This is because, through correcting the B12 level, the metabolic steps that were previously blocked are suddenly increasingly carried out. As a result, correspondingly larger amounts of biotin are consumed. If the biotin level is already in the lower range before B12 therapy begins, the biotin supply can be impaired.