Nitrous Oxide

Vitamin B12 and Folate - Supplementation Possibly Helpful

Nitrous oxide gas is used primarily as a local anesthetic in dentistry as well as in certain phases of cardiac bypass surgery.

FolateVitamin B12 Nitrous oxide can occasionally cause significant vitamin B 12 deficiency especially in people who are already borderline deficient in the vitamin (total vegetarians, for example) or those who are frequently exposed to the gas such as dentists and anesthesiologists. 1–4 The effect on B 12 impacts folate, too. 5,6,7 Taking folate and B 12 supplements at the U.S. Dietary Reference Intake (formerly known as the Recommended Dietary Allowance) levels should prevent any problems from developing.


Ermens AA, Refsum H, Rupreht J, et al. Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate plasma and urine. Clin Pharmacol Ther 49: 385–393, 1991.

Flippo TS and Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B 12 deficiency. Arch Surg 128: 1391–1395, 1993.

Amos RJ, Amess JAL, Hinds CJ, and Mollin DL. Incidence and pathogenesis of acute megaloblastic bone-marrow change in patients receiving intensive care. Lancet 2: 835–839, 1982.

Shils M, et al. (eds.). Modern nutrition in health and disease, 9th ed. Baltimore: Williams and Wilkins, 1999: 1635.

Nunn JF, Chanarin I, Tanner AG, and Owen ER. Megaloblastic bone marrow changes after repeated nitrous oxide anesthesia. Reversal with folic acid. Br J Anaesth 58: 1469–1470, 1986.

Amos RJ, Amess JA, Hinds CJ, and Mollin DL. Investigations into the effect of nitrous oxide anesthesia on folate metabolism in patient receiving intensive care. Chemioterapia 4: 393–399, 1985.

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