Vitamin-b12, the way it used to be

Mrs X came to see me a couple of days before Christmas in 1983. She got a vitamin-b12 shot, which really improved her festive season that year.

Her story went that she had a hiatal hernia for 15 years and couldn't tolerate raw food nor roasts. She had terrible heartburn, and everything had tasted bitter for months.
Her sense of balance had been getting worse for years, but a month earlier it had suddenly got really poor.

1mg of cyanocobalamin in her arm and the next day she reported "Not so shaky, had a good nights sleep and feels better all over." This improvement was sustained and she subsequently had vitamin-b12 injections regularly.

She later had a Schillings test, in those days the way to prove she couldn't absorb vitamin b12 from her food. She excreted 18.8% of the dose of radioactive b12, which was normal (>10%.)

The clinical response was clear, but the pathology test then available was unable to establish why.

Doctors often gave this treatment on spec, and as a "tonic." Balance, energy or sleep disorders⁴ on a background of indigestion would make one suspect vitamin b12 deficiency.

Another person illustrates this type of scenario.
Mrs R, aged 50, was "tired, sleepless, sore in her bones and tense." She suffered from indigestion.
After a B12 shot she "slept 11 hours straight and felt good next morning." This benefit wore off over the next two days.

At her next visit, on hearing this, I gave her a zinc taste test . She was unable to taste 1/1000 zinc sulphate solution, and was given 40mg of ZnSO4 intravenously. She reported the following visit that she felt "fit, not tired" after the zinc injection.

Zinc is needed for the mechanism by which vitamin B12 is transported past our blood-brain barrier¹, into our central nervous system.

She was certainly short of zinc, but no test was available to establish whether she was generally short of B12 as well ( as distinct from short of it in her brain.)

Some years later, a Miss L aged 21 was stressed to the point of feeling run down and tired, unable to think straight. She had headaches, had lost weight and was bumping into things and dropping things.

These last two symptoms mentioned raised suspicions re B12.

A blood test for vitamin B12 was by then available. Her level was 195, at the bottom of the reference range of 170 to 740.

This was still not conclusive proof that she was deficient.

Homocysteine has made all the difference

We are now able to measure the vitamin-B12 level⁸ in the blood stream, and if this is low in the reference range combined with a homocysteine level⁷ high in its reference range, we are on much safer ground.

Elevated homocysteine can be caused by low B12, folate, vitamin B6 or betaine - often combined with genetic propensity to it.

I give a couple of shots of B12 and repeat the homocysteine level, to see if it drops more than could be explained by chance³. This confirms b12 deficiency provided that nothing else has been done which could have influenced the homocysteine level.

Dosage for vitamin B12 treatment

People may need treatment because they cannot absorb vitamin B12 from their food, because they cannot efficiently transport it into their brain or because they destroy it rapidly in their brain.

If one has cerebral allergy the production of a chemical messenger called nitric oxide (NO) may be increased in the brain , and this destroys vitamin B12⁶.

If a person is taking certain drugs (PPI's, metformin) or has autoimmune or Helicobactor gastritis , they may not be able to take the vitamin in.

As mentioned above, if one is zinc deficient, the transport of vitamin-b12 into ones' brain is impaired.

The result of all this diversity means that different people need quite different dosages. Most people tolerate 1mg⁵ as an intramuscular injection, and I've people who need this twice a week, once a year and all points between.

Occasional people can only tolerate say 200mcg (0.2mg) doses.

The response to the first injection is very helpful in this regard. If you feel better in any way, note exactly what symptoms improved or disappeared.

We want to keep your chemistry good enough so that you do not get these symptoms back again. If this does happen, work out how long it was from the last injection. If it was say 3 months, have the next injection after two months.

The improvement is usually obvious after the first dose, and mostly within 24 hours

As always, there are exceptions. Mrs. M had felt "generally awful" and looked tired. My notes read..."suddenly better a few minutes after 2nd B12 (quite spectacular!)" Three months later she also reported that her "sore shoulder (was) better too."

Ms. F, 35, reported "Half an hour after (the first injection) she was more alert and 4 days later had "more energy, tearing around doing things, couldn't stop and (was) sleeping better." Her serum B 12 level had been 369 (ref range 170-670.)

Anecdotes don't prove anything, but I don't suggest to people how they may react and the stories are often very similar.

Autoimmune gastritis and pernicious anaemia

Here something allows susceptible people to develop an immune damage to their own stomach². This isn't found until it has caused a lot of damage and the person has run out of the body's quite large reserve of vitamin-b12.

Vitamin-b12 is very important if you're planning pregnancy.

Vitamin-b12, folate and methionine are all needed for the earliest stages of developement of the foetus. Sheep deliberately given diets short of these from 8 weeks before to 6 days after conception, had lambs which grew up fatter and had insulin resistance⁹.

The nutrients were lowish, still within what 95% of sheep normally eat. The ewes themselves showed no obvious ill effects, but their offspring did!

The perspective of a vegan

This page on 50 ways to develop B12 deficiency should stimulate a lot of thought and probably a lot of further reading.

Michelle Bosmier has an article on this at as well...

Other manifestations of vit B 12 deficiency

Paresthesia (pins and needles,) sensory loss (numbness), ataxia (wobbly walking,) mental decline10 and psychiatric disorders11 including obsessive compulsive disorder12 can occur.

Dr. Cees J . M. van Tiggelen found low vitamin B 12 levels in the cerebrospinal fluid around the brain¹³, despite normal levels in the blood, in Alzheimer and alcoholic dementia but not in multi-infarct dementia (caused by repeated strokes.)

Modern work with non-invasive tests is giving more detail¹⁴.

One man's VTE (venous thrombo-embolism) was very likely from vitamin B 12 deficiency. His homocysteine had dropped on B 12 treatment from a peak of 24.3 down to a pretty healthy 9.8. He then had no injection for 8 months prior to the pulmonary embolus and it had risen to 19.6

The future - nutrigenomics

Testing for variants of your FUT2 gene can help predict the need for supplemental vitamin B 12.

Notes and references for vitamin-b12 page

1. We have "barriers" which protect our central nervous system and our genital organs, from poisons circulating around in our blood.

Our bowel, liver and lungs process toxins, in a 2 stage chemical conversion, in preparation for elimination in our urine or bile. The poisons circulate in the blood waiting for excretion by the kidneys.

Karlsson, F. al Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach. J. Clin. Invest. 81: 475-479.1988.

Gleeson, P. A., et al Molecular targets in pernicious anaemia. Immunol. Today 12: 233-238. 1991

D'Elios, M. M., et al H+,K+-ATPase (proton pump) is the target autoantigen of Th1-type cytotoxic T cells in autoimmune gastritis. Gastroenterology 120: 377-386. 2001.

3. The day to day variation in homocysteine levels is about 7.5%. The standard error of the blood test is about 5%. The greatest variation in the blood test which could be attributed to error and chance is therefore 12.5%. If the second homocysteine has dropped more than this, I interpret that as a genuine treatment effect - that is that the level has dropped because of the vitamin-b12 injections.

4. From Dr. Reza Samvat...

"Vitamin-b12 causes an earlier release of melatonin at night which resets the sleep-wake cycle. B12 acts directly on the pineal gland to provoke a faster release of melatonin. At the tail end, B12 causes melatonin to drop off faster. B12 helps you get to sleep earlier, and may help you wake up earlier if you leave a curtain open to the morning sun. B12 sensitizes you to morning light, which helps you wake up."

His book for professionals is very comprehensive.

• Reza Samvat, Henry Oseicki. Sleep, Health & Consciousness: A Physicians Guide. Bioconcepts Publishing, 2009

5. These days I don't give this 1000mcg the first time, following experiences as with Mr.V, who had a serum B12 of 262 and had the above dose first. The next day he was worse ("no get up and go, pale') before he was "good and OK since."
I always start with 500mcg vitamin-b12 now.

6. The valency of the cobalt atom is changed, inactivating the vitamin. The inactivated vitamin will still be read as normal by a blood test however.

7. Homocysteine is an amino acid, formed when another called methionine donates a methyl (-CH3) molecule for use in our metabolism. Methyl (one carbon) units are used for inactivating genes etc.
Homocysteine is then recycled back to methionine by folate with the help of vitamin B12, but builds up if these are deficient.

A 3gm dose of methionine given 4 hours before, will pick up more people with difficulties in this process, but we usually measure homocysteine in a fasting state.

8. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative, but this study found it not much different to the total B12.

9. Kevin D. Sinclair et al DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status Proceedings of National Academy of Sciences PNAS December 4, 2007 vol. 104 no. 49 19351-19356


11. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. Lindenbaum J



14. C.C. Tangney, et al Vitamin B12, cognition, and brain MRI measures, a cross-sectional examination.
Neurology. 2011 September 27; 77(13): 1276–1282.

15. Latent_pernicious_anaemia:_a_preliminary_report_(1975)

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