06/11/2025
Credits to Stichting B12 Tekort for the folowing information...
Out of fear of overdosing vitamin B12, treatment is often reduced to below the frequency that is needed by the patient, or, even worse, treatment is stopped completely.
As a result, symptoms can reoccur again and again and even become irreversible.
It is very clear this fear of overdosing is based on a misunderstanding. For over 60 years high dose vitamin B12 treatment has been used without any signs of the danger of an overdose.
The Dutch National Health Counsel and the Regional Disciplinary Medical Board of Eindhoven have stated clearly that vitamin B12 is non-toxic.
Clinical research and the treatment for cyanide poisoning have shown that even extremely high doses of vitamin B12 and the serum values that go with it are harmless.
A decennia long history of safe treatment
In 1926 it was discovered that patients with pernicious anaemia could be saved from a certain death by eating a pound of raw liver a day. More than 20 years later the substance that was responsible for that was isolated from liver extract: vitamin B12 or cobalamin. Since then numerous patients have been treated with high dose vitamin B12 worldwide. Usually per injection and often lifelong, as a deficiency is mostly caused by an irreversible absorption disorder. In all that time harmful effects have never been shown from overdose. No single case has been found in medical literature in the past 60 years.
No maximum dose
The Dutch National Health Council therefore decided not to determine a safe upper intake level for vitamin B12. In their report from 2003 “Voedingsnormen: vitamine B6, foliumzuur en vitamine B12” the council joined expert commissions from the American Institute of Medicine and the Scientific Committee for Human Food from the European Union, who had already reported 3 years earlier that toxicity from high dose vitamin B12 poses no real danger.1
Of course, like with any medical treatment, side effects can occur. Acne, eczema and itching seldom occur and very rarely anaphylactic shock. Changing brands of vitamin B12, forms of B12 (cyanocobalamin vs hydroxocobalamin), or switching from injections to tablets can be a solution in those (rare) cases.
Misunderstandings about blood and reference values
Yet often physicians reduce injections or even stop treatment altogether out of fear of overdosing B12. The result is that many patients are left with recurring or lasting symptoms, which could be relieved by more frequent injections. After an injection the serum B12 value rises quickly, well above the upper reference value (on average 150-700 pmol/L), followed by a slow decrease. Apparently the underlying thought is that it is necessary to keep the value between the (upper and lower) reference values. However the blood level of serum B12 rises regardless of therapeutic effectiveness.2
A high serum B12 value does not mean that symptoms are treated sufficiently. This presumption can have damaging effects for patients with neurological symptoms, which can become irreversible with insufficient treatment.
Treatment based on symptoms instead of blood values
The recommended treatment in the Netherlands consists of a hydroxocobalamin injection of 1mg every two months, after an initial loading dose of 10 injections in 5 to 10 weeks.3
No reference is made to the serum value or a danger of overdosing, unlike for instance in case of a vitamin D or A deficiency. The lack of danger of an overdose is further underlined by the advice to treat patients with neurological involvement with two injections a week for up to two years, if necessary. This also emphasizes that symptoms and not blood values should be used as a guideline. If serum values were decisive, even patients with neurological involvement could suffice with the maintenance dose of one injection every two months after the initial loading dose.
Elevated serum B12 values in serious conditions
Maybe the concern for a possible overdose is caused by the knowledge that some life-threatening diseases can be accompanied by a strong increase in the B12 blood value, in some cases to even 30 times the upper reference value.4
In blood diseases like leukemia, polycythemia vera and hypereosinophylic syndrome, the cause is often an enhanced production of the transport protein haptocorrin, to which most of the circulating B12 in blood is bound.
In liver diseases such as acute hepatitis, live cirrhosis and liver cancer, elevated B12 values are often found because the liver is no longer capable of storing vitamin B12.
Elevated B12 values are always cause for further testing, but of course, to the contrary, it cannot be concluded that elevated levels after B12 injections leads to serious disease.
Scientific research
Scientific literature offers numerous examples from which it can be concluded that treatment with high dose B12 up to very high serum values is no cause for concern.
In the treatment of children with an inborn error in the production of transcobalamin II, the binding protein that transports B12 to the cells, serum values are kept at levels of 10 000 pg/ml (about 7 400 pmol/L) without any side-effects.5
Japanese research from 1994 into the effects of B12 therapy in patients with multiple sclerosis shows that a daily tablet with 60 mg methylcobalamin during six months is non-toxic. Half of the patients even started with two weeks of daily 5 mg B12 injections straight into the blood. 6
In the fifties, when chemotherapy wasn’t available yet, children with neuroblastoma (a tumour of the autonomous nervous-system) received 1 mg B12 injections every other day during 2 to 3 years in a London children’s hospital. From 1957 the dose was adjusted to 1 mg per 7 kilograms of body-weight. In the majority of patients the tumour disappeared wholly or partially and the chance of survival was considerably increased.7
In 1999 in Japan, kidney dialysis patients with polyneuropathy, received 0.5 mg methylcobalamin 3 times a week intravenously for 6 months. Because of lack of renal clearance, serum values rose to more than a hundredfold from 422 pmol/L on average to 54 000 pmol/L, with 67 000 pmol/L as highest value, without side-effects. 8
Also in Japan, in 2007, patients with the incurable neurodegenerative disease ALS (Lou Gehrig’s disease) received daily injections with 25 mg methylcobalamin for 4 weeks, followed by daily injections of 50 mg intravenously, followed by 50 mg a week. In the long term, treated patients survived for longer because of this, than did untreated patients.9
Megadoses B12 as lifesaving antidote
The safety of vitamin B12 treatment is further illustrated by the decennia long use of hydroxocobalamin as an antidote for cyanide poisoning, often caused by smoke inhalation. In the Netherlands ambulances, fire departments and emergency rooms have the Cyanokit at their disposal. In life threatening situations 5 g hydroxocobalamin is given intravenously within 15 minutes, an amount that corresponds with 5 000 injections of 1 mg B12.10 Hydroxocobalamin reacts in the body with cyanide, and forms cyanocobalamin, which is excreted in urine.
The serum value of B12 can rise to an average of 560 000 000 pmol/L within 50 minutes.11 If necessary this treatment is repeated within several hours, making the total dose 10 grams. The side effects that occur, like reddening of the skin and urine and changes in heart rate and blood pressure are temporary and harmless. In short: 10 000 injections a day are still not enough for an overdose of vitamin B12.
Regional Disciplinary Medical Board: vitamin B12 cannot be overdosed
In 2009, the Regional Disciplinary Medical Board in Eindhoven stated very clearly that an overdose is not possible: “There can be no question of an overdose of hydroxocobalamin, as the excess is excreted in urine by the kidneys and therefore cannot accumulate in the body.12 The Medical Board ruled against a patient who claimed his deteriorating health was due to the continued treatment with B12 injections. The patient received monthly injections for 10 years. The physician was not rebuked because the patient was treated according to guidelines.
Conclusion
A vitamin B12 deficiency can cause many different symptoms, among which are serious neurological problems. The treatment with high dose B12 injections is not only completely safe but fortunately also very effective. With the right treatment patients can recover completely. Starting straight away with treatment is essential, as is the continuing treatment in order to give the body enough B12 to fully recover. Therefore it is essential that patients are no longer exposed to the real danger of irreversible symptoms because of the imaginary fear of overdosing.
