Vitamin B12 Deficiency and Anesthesia

B12 Operations 

Vitamin B12 Deficiency and Anesthesia

Local and general anesthetic via laughing gas for operations requires large quantities of vitamin B12 and can lead to a severe B12 deficiency.


  • Why can a vitamin B12 deficiency result from an anesthesia with nitrous oxide?
  • What are the consequences?
  • What measures should be taken before and after a nitrous oxide anesthesia?

General and Local Anesthesia Require Vitamin B12

General and local anesthetic are essential for many operations and medical interventions. One of the most commonly used tools for this is so-called laughing gas (nitrous oxide, N2O). This anesthetic unfortunately has the side effect of using up to 60 percent of the vitamin B12 stored in the body

Despite being so necessary for operations and interventions, laughing gas is seen by the body as a toxin, that must be rendered harmless. This process happens when methylcobalamin or reduced cobalamin reacts with the nitrous oxide.

Through this, laughing gas molders into water and non-reactive nitrogen, and the central cobalt atom in vitamin B12 is oxidized.The resulting oxidized form of vitamin B12 is however biologically inactive and thus cannot fulfill its important enzyme functions in methionine synthesis and the reactivation of folic acid. This deactivation is irreversible: the oxidized cobalamin is converted into ineffective B12 analogs and thereafter excreted. 

Laughing gas requires so much vitamin B12, that it can provide a genuine health risk in many instances. Anesthetics can lead to a vitamin B12 deficiency, often with severe symptoms. 

Use of Laughing Gas in Anesthesia

This is problematic particularly in view of current developments, as laughing gas was the clinical standard for anesthetics for decades at various levels. Today the use of nitrous oxide for general anesthesia has declined slightly, but is still used widely in dental practices and in maternity care.Laughing gas is also commonplace in dermatologyand more problematically in children’s dentistry.In minor surgery and treatment of injuries, laughing gas remains the standard.

Over many years, laughing gas has developed into a party drug as a legal high too, which is also known to cause a vitamin B12 deficiency.5

Vitamin B12 Deficiency Through Laughing Gas

Vitamin B12 deficiency can occur very easily through an increased requirement of cobalamin. This can consequentially lead to very severe symptoms of deficiency, ranging from depression over the destruction of nerves in limbs and the spinal cord to severe amnesia. 

Nerve damage is particularly common, because vitamin B12 is responsible for the development of the protective coating for nerves (the myelin sheath). Typical symptoms to indicate the beginnings of nerve damage are numbness or tingling sensations in the limbs. These typically occur a few days after anesthesia, if the myelin sheath isn’t fully repaired due to deficiency. 

Upon the occurrence of B12 deficiency symptoms after surgery with anesthesia, there is an urgent need to prevent permanent damage.

More information on symptoms can be found here: Vitamin B12 deficiency symptoms.

Anesthesia and Vitamin B12 Deficiency

The effect of laughing gas is heavily criticized when used on people who show signs of a potential vitamin B12 deficiency before the operation. 

“Patients with vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration becomes irreversible and may result in death.”

The above quotation is taken from the findings of one study in 1993.This assessment has been repeatedly confirmed through numerous examples and studies.7-11

The situation involving children is equally critical; as a result of their shorter lifespan, many children haven’t built up an adequate vitamin B12 store meaning that an anesthetic can cause significant damage. The consequences on the development of the brain and the nervous system seem to be particularly severe, which is why some researchers advise against use of nitrous oxide in pediatrics altogether.12,13

Despite these very real and serious dangers, this information is only shared with a small number of patients today and appropriate countermeasures are almost never introduced. 


  • Anesthesia requires large quantities of vitamin B12
  • This can lead to a severe B12 deficiency
  • Before undergoing anesthesia, the body’s B12 store should be sufficiently topped up
  • After anesthetics, a vitamin B12 treatment should be used
  • The active ingredients should be either methylcobalamin or hydroxocobalamin


B12 Before a General or Local Anesthetic

For many high risk groups, it is advisable to top up the body’s B12 storage before an operation, in order to limit the chances of a deficiency occurring as a result of the anesthesia. The effectiveness of the anesthesia will not be affected by this. 

Amongst others, this is particularly relevant for:

A good quantity to take here would be a daily oral dose of 500 µg, starting 4 weeks before the surgery. 

The high risk groups listed above should also be sure to enquire with their dentist during their next visit, regarding the use of laughing gas in their surgery. 

Vitamin B12 – a Must After an Operation

As a result of the dangers of a severe vitamin B12 deficiency, it is a matter of urgency to complete a course of vitamin B12 after an anesthetic with laughing gas. 

This can be pursued through either injections or through oral supplements.


1000 µg per week
2 – 4 weeks

Oral Supplements

500 µg in the morning and evening
4 – 6 months
Methylcobalamin or hydroxo-/methylcobalamin

Injections are necessary for treating very severe symptoms, as they represent the quickest way of refilling the body’s B12 store. After operations in the stomach or intestine, injections can be particularly necessary, as oral supplements may be too difficult to absorb. 

In most other cases, an oral supplement should be sufficient for prevention of a deficiency.

Consequences of Anesthesia for B12 Storage

As a result of the disastrous potential consequences, the effect of laughing gas on the body’s B12 store has thus far only been tested on animals. This testing provided the following results:14,15

  1. Laughing gas destroys methylcobalamin and thus deactivates the enzyme methionine synthase
  2. 20 to 60 percent of the methylcobalamin in the blood plasma, cells and liver store are destroyed
  3. This leads to an increased number of inactive B12 analogs
  4. A vitamin B12 deficiency occurs

The worst finding in these results is certainly that not only is the vitamin B12 in the serum destroyed, but also the B12 in the cells and in the liver store. Up to 60 percent of the B12 in the body’s storage was destroyed in animal testing. This is a dramatic loss, which can take years to replenish on a normal diet.

Risk of a Vitamin B12 Deficiency After Anesthesia

Whether or not a vitamin B12 deficiency occurs after anesthesia, and how severe it is, is dependent upon the vitamin B12 status of the patient before the surgery. 

With a high and healthy vitamin B12 level, vitamin B12 content in the body will drop but not to a critical low, before slowly replenishing itself over a long period of time, assuming that the patient does not have to undergo surgery again. The non-specific symptoms of slight deficiency are understandably often seen as consequences of medical intervention.

With moderate to low B12 levels, there is a big danger of an acute deficiency and very severe symptoms can develop. 

In all cases, it is advisable to top up the body’s B12 store after surgery. An oral product is the most common method, except in instances where there is a severe deficiency or oral supplements are not possible due to the type of operation.


The danger of a vitamin B12 deficiency through anesthesia is high and the consequences are real. A balancing supplement is recommended after surgery, as the high loss of vitamin B12 cannot be easily replaced through diet. 

Since methylcobalamin is most affected out of all the vitamin B12 forms, it is particularly important to ensure a supplement with either methylcobalamin as an active ingredient, or the sustainable hydroxocobalamin. Cyanocobalamin should not be chosen, as there are too many metabolic conversion steps needed here. 


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2Mohr, B. Lachgasanwendung in der Zahnheilkunde. Zahnmedizin up2date 2014; 8(1): 15-32
3Drosner, Michael. Lachgas-Sauerstoff-Inhalation. ästhetische dermatologie & kosmetologie, 2014, 6. Jg., Nr. 3, S. 1-7.
4Jeglitsch, A., F. G. Mathers, Bürkle V. Lachgassedierung in der Kinderzahnheilkunde. Stomatologie, 2014, 111. Jg., Nr. 4-5, S. 182-187.
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6Flippo TS, Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency. Arch Surg. 1993 Dec;128(12):1391-5. Review. PubMed PMID: 8250714.
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8Kathryn L. Holloway, M.D., and Anthony M. Alberico, M.D. Postoperative myeloneuropathy: a preventable complication in patients with B12 deficiency. Journal of Neurosurgery. May 1990, Vol. 72, No. 5, Pages 732-736
9Pema PJ, Horak HA, Wyatt RH. Myelopathy caused by nitrous oxide toxicity. AJNR Am J Neuroradiol. 1998 May;19(5):894-6. PubMed PMID: 9613506.
10Jameson, M et al. Nitrous oxide-induced vitamin B12 deficiency. Journal of Clinical Neuroscience, Volume 6, Issue 2, 164 – 166
11Hadzic A, Glab K, Sanborn KV, Thys DM. Severe neurologic deficit after nitrous oxide anesthesia. Anesthesiology 1995, 83(4):863-866
12Schmitt EL, Baum VC. Nitrous oxide in pediatric anesthesia: friend or foe? Curr Opin Anaesthesiol. 2008 Jun;21(3):356-9.
13Baum, V. C. (2007), When nitrous oxide is no laughing matter: nitrous oxide and pediatric anesthesia. Pediatric Anesthesia, 17: 824–830. doi: 10.1111/j.1460-9592.2007.02264.x
14Kondo H, Osborne ML, Kolhouse JF, et al. Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats. Journal of Clinical Investigation. 1981;67(5):1270-1283.
15Muir, M. and Chanarin, I. (1984), Conversion of endogenous cobalamins into microbiologically-inactive cobalamin analogues in rats by exposure to nitrous oxide. British Journal of Haematology, 58: 517–523. doi: 10.1111/j.1365-2141.1984.tb03999.x

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