B12 newbie: Injection frequency? - Pernicious Anaemi...

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B12 newbie: Injection frequency?

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First, as a newly (self-diagnosed) B-12 deficient, I'm so grateful to have discovered this site! For some background, a year and a half ago my blood tests showed signs of macrocytic anemia (high MCV, high MCH, high lactate dehydrogenase). My doctor dismissed it as "probably nothing" and ordered no follow-up testing. After my exhaustion escalated to unbearable levels, I finally ordered my own labs to discover low B12 (folate was fine). Several weeks of sublingual B12 did nothing, so I got my first B12 injection 4 days ago. I've been feeling quite good these past few days, but I'm not sure how long to expect this to last. Since I'm now directing my own treatment (I don't trust my doctor any more), I'm wondering if you all could advise on how frequently I should be getting injections. I see recommendations ranging from every other day to every 3 months, so I'm somewhat confused. Do I wait until I start to feel tired again, or is it important to keep them up more frequently, before symptoms return?

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clivealiveForum Support

Hi etreas good morning and welcome. As I'm not a medically trained person I can only make suggestions from my own experience not give definitive answers.

Firstly it would be good to try and establish why you are B12 Deficient. Look at the below and see if you identify with any of the "people".

Who’s at greatest risk for B12 Deficiency?

Anyone at any age, can become B12 deficient. However, certain people are at an elevated risk. They include the following:

Vegetarians, vegans and people eating macrobiotic diets.

People aged sixty and over

People who’ve undergone any gastric and/or intestinal surgery, including bariatric surgery for weight loss purposes (Gastric bypass).

People who regularly use proton-pump- inhibitors. H2 blockers, antacids, Metformin, and related diabetes drugs, or other medications that can interfere with B12 absorption.

People who undergo surgeries or dental procedures involving nitrous oxide, or who use the drug recreationally.

People with a history of eating disorders (anorexia or bulimia).

People with a history of alcoholism.

People with a family history of pernicious anaemia.

People diagnosed with anaemia (including iron deficiency anaemia, sickle cell anaemia and thalassaemia).

People with Crohn’s disease, irritable bowel syndrome, gluten enteropathy (celiac disease), or any other disease that cause malabsorption of nutrients.

People with autoimmune disorders (especially thyroid disorders such as Hashimoto’s thyroiditis and Grave’s disease) Type 1 diabetes, vitiligo, lupus, Addison’s disease, ulcerative colitis, infertility, acquired agammaglobulinemia, or a family history of these disorders.

Women with a history of infertility or multiple miscarriages.

Infants born to and/or breast fed by women who are symptomatic or are at risk for B12 deficiency.

Are there areas in your lifestyle that can be altered, e.g. diet, medications, alcohol consumption etc that can improve your natural uptake of B12 from your food?

If there is a history of Pernicious Anaemia in your family you may need to be tested for it.

As to frequency of B12 injections - how long is a piece of string?

The figures you have read about "recommendations ranging from every other day to every 3 months" are used as a yardstick when treatment for B12 Deficiency or P.A. starts depending whether or not there are neurological symptoms. The "every other day until there is no further improvement" relates to the start of treatment after which "without neurological symptoms" injections every three months or "with neurological symptoms" injections every two months.

You have had one injection so far and have "been feeling quite good these past few days" well that's good and it would be brilliant if that was enough but you don't say what symptoms remain that will need further injections.

Sadly it is not likely to be an overnight instant "fix" and it is not uncommon for symptoms to appear to get worse and even new ones arise as the B12 starts repairing the damage done to your nervous system.

A lot will depend on the longevity and severity of the deficiency and if you are diagnosed with Pernicious Anaemia then the B12 injections are for the rest of your life.

I get the impression that you are getting treatment "privately" so there is a cost implication there.

You mention (folate was fine) - that will need to be kept fine as it gets used up processing the B12.


Hi I'm Patricia Nutritionist. In my Nutrition and Metabolic text is states every month for Pernicious Anemia. I was misdiagnosed for MS.

Do you know anyone else?

clivealiveForum Support
in reply to OConnor1964

Hi OConnor1964 I'm guessing that you are not in the U.K. perhaps in America/Canada?

Your reference to "every month for Pernicious Anemia." suggests that the B12 treatment being prescribed in your "Nutrition and Metabolic text" was cyanocobamalin and it is true that that needs to be administered every four weeks for life.

There are alternatives to cyano - namely methylcobamalin and hydroxocobamalin (the latter prescribed in the U.K.) which are supposed to last between eight and twelve weeks.

Sadly some people with P.A. are misdiagnosed with M.S (as well as other things) but I do not know any personally.

Remember I am not a medically trained person but I've had P.A. (a form of B12 deficiency) for more than 45 years, treated with cyanocobamalin since 1972 and still "clivealive" and over 75.

I wish you well


HiddenThis reply has been deleted
in reply to Hidden


@fbirder response to one of your earlier replies:

Re cobalamin and light sensitivity: only the energetic, short-wavelength, light that does any serious amount of phwotodegradation. And amber glass cuts out almost all of that. It's why photographer's dark rooms have red lights - they don't degrade the emulsion in B&W film.

Hydroxocobalamin and cyanocobalamin are much more resistant to thermal degradation. That's why they can be stored up to 25ºC. Methylcobalamin, OTOH, is more thermally labile and many manufacturers recommend storing it in the fridge.

Your idea that Hydroxocobalamin is 'not very active' due to light and storage issues is wrong.

Hydroxocobalamin is more stable than methylcobalamin and is not a 'cheap non-bio' alternative. Most people can easily convert Hydroxocobalamin to methylcobalamin and adenosylcobalamin.

Different cobalamins suit different individuals.

Please stop posting in accurate and misleading information.

HiddenThis reply has been deleted
in reply to Hidden

I'm in a hospital waiting room so I've not read all of this. What I have read leaves me confused. What does the thermal stability of the MMACHC protein have to do with the stability of B12 in solution?

in reply to fbirder

I am also confused. There are a lot of studies out there of hydroxocobalamin, cyanocobalamin and methylcobalamin absorption and retention in the sort of doses that are used for treating B12 deficiency. To rely upon a study that relates to abnormally high doses which are rarely administered - 5000x the amounts used for treament of deficiency, seems totally unbalanced and ridiculous.

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in reply to Gambit62

Add me to the confused list too!

The paper you quoted was on about the thermostability of the protein MMACHC when it binds to various hydroxo /cyano /methyl / adeno cobalamin. This is NOT the thermostability of the cobalamins themselves!! This paper also mentions hydroxo as being considered a naturally occurring form.

The "Pharmacokinetics of hydroxocobalamin in smoke inhalation victims" is not available online in its entirety currently so I cannot look into this paper - only the abstract ( tandfonline.com/doi/abs/10.... ). In your "EXPLANATION section" you appear to have misunderstood the term half-life. (See this link for more info en.wikipedia.org/wiki/Biolo... )

Your statement "On the 6th day after taking 5grams (5000mcg) no human had any trace of hydroxocobalamin or its metabolites in their body." is also incorrect.

5g = 5000mg = 5,000,000mcg (also written as µg) so you are a power of a 1000 out.

Half-life means that with each 26.2hrs ( +/- 2.7hrs) that passes half of the starting amount is left, eg

0hrs = 5,000,000mcg

26.2hrs = 2,500,000mcg

52.4hrs = 1,250,000mcg

78.6hrs = 625,000mcg

104.8hrs = 312,500mcg

131rs = 156,250mcg

157.2hrs (6 and a half days ) = 78,125mcg

Half life is logarithmic. This is ignoring the +/- 2.7hrs for illustration purposes. At 6 days there'd still be a heck of a lot still around!!

As for MTHFR polymorphisms - for the 2 most researched snps, people with 1 or 2 copies of the appropriate snp have a loss of function of the enzyme not a complete abolition of its functions. As far as I can tell the consequences of this are still being examined and what is currently known makes for a confusing picture as to what is actually means for people.

People are free to do as they wish. No one here is a medic as far as I know. This is merely a collection of people all trying to make the best of having PA, learning more about it and trying to make sure they have appropriate treatment!

I hope your father has made a good recovery from his heart attacks and surgery.

in reply to taka

Well said Taka 👍

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in reply to Hidden

In contrary, hydroxocobalamin is not more stable,


and how do you or anyone know "Most people can easily convert Hydroxocobalamin to methylcobalamin and adenosylcobalamin"?

Well, for a start there's the simple fact that the vast majority of people with B12 deficiencies experience releif of symptoms with injections of cyanocobalamin or hydroxocobalamin.

From ncbi.nlm.nih.gov/pubmed/258...

Currently, we do not have sufficient evidence to suggest that the benefits of using MeCbl or AdoCbl override that of using CNCbl or HOCbl in terms of bioavailability, biochemical effects, or clinical efficacy. There is uncertainty regarding the claimed superior role of [B12] coenzyme forms for prevention and treatment of [B12] deficiency. However, HOCbl may be an advantageous precursor of the cofactors, particularly in the inherited disorders of metabolic Cbl processing. CNCbl is a more stable and inexpensive form that appears to be best suited for oral supplementation and parenteral [intravenous] treatment as well.

For a supposed medical professional you have a limited understanding of half life. After 4 half lives there will still be 8% of the original dose in the blood. Note that last bit - 'in the blood'. Cobalamins are also stored in the body.

If a patient has inherited the very common MTHFR polymorphisms then it would be unethical not to advise taking methylcobalamin.

Yes, some of those polymorphisms are very common. Indeed, so common that one would expect most of the world to be having problems. In fact, the only evidence is for a decreased stability of the MTHFR enzyme when the C677>T mutation is present. If one is heterozygous (one copy) then the enzyme has about 80% of normal stability. Two copies (homozygous) means it's about 30% stability.

But the body can just replace the enzyme faster - so no problems at all for those heterozygous people. Homozygotes (like me) may have problems.

But there's no need to take methylcobalamin. Indeed, it's pointless because the first thing that happens to methylcobalamin when it enters the cell is that MMACHC (your favourite enzyme) removes the methyl group!

What can help is supplementation with the product of the reaction catalysed by MTHFR - methylfolate. Easier to obtain that methylcobalamin and much more likely to be helpful in C677>T homozygotes.

But it's better for the naturopaths to sell books if they recommend methylcobalamin. Pills just aren't sexy enough. Besides, it requires an understanding of the chemistry that is far beyond their capabilities.

And that's as far as I'm going. I've had a long day going up to London to see a neurologist at the University College National Hospital for Neurology and Neurosurgery.

Besides I was just looking for the half-life of methylcobalamin when I remembered looking it up before, for a similarly poorly argued piece of balderdash. Very similar in fact. Posted by some troll who, I believe, was banned. I'll go looking for it tomorrow.


different countries use different protocols and different formats of B12

assuming that you are using hydroxocobalamin the BCSH recommendations are

a) no neurological involvement: 3x weekly loading shots for 2 weeks followed by 3 monthly maintenance shots

b) neurological involvement: 3x weekly loading shots until symptoms stop improving (review at 3 weeks) followed by 2 monthly maintenance shots.

In Germany the loading regime is similar - but maintenance would be monthly regardless (and you can get B12 over the counter, without prescription)

In US they use cyanocobalamin and maintenance tends to be monthly - though loading regimes seem to vary (possibly by state) and may be weekly

3x weekly is basically every other day.

The above are all guidelines. There are a lot of factors that can actually affect how much you need for loading and how much you need for maintenance. A key step would be to make a full list of your symptoms and monitor these - particularly true if you are talking about working out how frequently you need to do maintenance.

I find that my symptoms return within 24 hours of maintenance shot so for me none of the maintenance regimes above work. I'm at the extreme end but a lot of people find that even 1 month is too long for them so listen to your symptoms rather than worrying about what it says on the tin.

The other thing to bear in mind is your folate (B9) levels - as B9 is needed to fully absorb and process B12 and if your levels are low they can be depleted. The best form of B9 is from food but if you have an absorption problem leading to a B12 deficiency then this can mean that you also have problems absorbing other nutrients from your food so you may find it useful to take some folic acid.

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The B12 Deficiency charity b12d.org suggests a loading dose of injections every other day for 14 days, which I believe is how I came to get my levels high enough to sort out my tinnitus and some other stuff I had not connected w b12. It took some time (better part of a year maybe) but it actually worked whereas oral b12 never helped anything.

After the loading dose I injected once a month but that didn't prevent my symptoms from returning, so I am going to try twice a month and see if that helps.

I am not a medical pro and am undiagnosed, so my only professional contact re b12 has been w the helpful admin at that website but my understanding is that ideally you'll keep your symptoms at bay to avoid allowing further neuro damage to take place.


Hi etreas

Things are getting a bit too technical. Keep it simple.

Take 1 injection a week for 6 weeks.

Then take 1 injection every 2 weeks(2 injections in 4 weeks).

Then reduce to 1 injection every 4 weeks for 3 months.(so 3 in 3 months).

Then reduce to 1 every 3 months.

You will also need to take folate(usual dose 400ug once daily).

Hydroxocobalamin is good.(if you're using any other form then try and see, over 6 weeks you'll know)

The most common side effect of hydroxocobalamin is rash/spots mainly around your forehead. If they get very bad you will need to stop and try another form, but with time they usually do get much less, enough not to bother you.

This way your B12 slowly increases weekly over 6 wks. That's like a loading dose. Then you gradually reduce like I said.

By the time you reach your 3 monthly injections your B12 would be high and you should feeling much better, and you're gradually reducing your dose so you don't suddenly stop.

I tried and tested before I got to this way of dosing. It works GOOD !

When you come to 1 every 3 months according to your symptoms it's up to you how long you want to carry on.

Please note that I'm not a professional and am just trying to give you the best advice as people have gone off topic and is very confusing.

My method is simple and effective. If you have any unusual symptoms whilst taking the B12 please talk to your doctor.

This way you can't really overdose or overthink and confuse yourself. Also because it's weekly you will notice the difference especially after 6 weekly injections.

Keep it simple and results will show especially after about 10 weeks there should be a lot of change.

I've tried to keep it simple.

Hope it helps and wish you well.

If you would like to ask me anything, I'm more than happy to help.

There's a lot of people on here who know much more than me but this is a simple routine as you can see and I don't think anyone would disagree.

Hope it helps and wish you well.


Thanks for all the helpful feedback! I think I somewhat sorted it out through some trial and error. Over the first couple weeks I received weekly shots of 1mg methylcobalamin, and felt fantastic until roughly 5 days post-injection ... then the fatigue returned full-strength. I just started on self-injections of methylcobalamin this week, and plan to keep them up at a loading dose of every 5 days (boy was that scary to self-inject!). If all goes well I'll drop down to weekly then monthly. I've also been taking 400ug folate daily, so I don't think that's much of an issue.


I'm a B12 💉 newbie too and suspect my GP has prescribed a dose that's far too low !

My bloods are below low and he says one injection every two weeks for 2 months !!!

I've also got ongoing serious Neuro history and after reading all this I now KNOW this isn't going to be enough 😱

Where do I go from here ? What's my line of defence ...the combat is heavy out there 😏

I'm due my first 💉 this afternoon.

So many thanks to you all for so much great info, I was really beginning to loose my pragmatism 😁


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