Nitrous Home Vitamin B2 B12 Iron Vitamin D Treatment Development Paradoxical Prevention Nexus Contact ☰

Nitrous Oxide and Autism

  • Use of Nitrous Oxide during pregnancy can result in the formation of toxic, and inactive NO-Cobalamin

  • Serum levels of vitamin B12 will be normal or elevated - Paradoxical B12 deficiency

  • Children with Pardoxical B12 deficiency due to Nitrous intoxication, will not respond to MethylCo(III)B12 until there is new synthesis of methionine synthase.

Vitamin B12 deficiency and Nitrous oxide and anaesthetics. 

Methionine synthase binds to MethylCo(III)B12 which subsequently acts as a Methyl Donor to convert Homocysteine to Methionine, and the resultant Co(I)B12 can act as an acceptor for incoming methyl groups such as those on 5-methyltetrahydrofolate.

MethylCo(III)B12 + Homocysteine [Methionine Synthase] <=> Co(I)B12 + Methionine

Co(I)B12 + 5MTHF [Methionine Synthase] <=> MethylCo(III)B12 + THF

This donor/acceptor function can be dramatically reduced through exposure to Nitrous oxide either as an anaesthetic or though inhalation from a "Nang" which can then have disastrous affects on the function of vitamin B12, and its role in methylation. During the methylation reaction of MethylCo(III)B12 + Homocysteine [Methionine Synthase], the product, Co(I)B12 + Methionine is formed. In the absence of 5MTHF, free Co(I)B12 can readily reacts with nitrous oxide to form NO-Co(III)B12, which is inactive, yet will “clog up” methylation by Methionine synthase, and irreversibly inactivate the enzyme, hence explaining the toxicity of Nitrous oxide.

Co(I)B12 + Nitrous Oxide <=> NO-Co(III)B12

The NO-Co(III)cobalamin has an extremely long half-life and is resistant to loss of the NO moiety, meaning that the child may be "stuck" with it for life time. Normally, in the absence of incoming folate, Co(I)B12 is oxidized to Co(II)B12 and MethylCo(III)B12 is formed by the action of MTRR and SAM. If this does not occur, methionine synthase releases Co(II)B12 and thereby frees up the binding site for MethylCo(III)B12. The Co(II)B12 then is secreted into serum and so contributes to the elevated serum B12 levels. Unless functional B12 markers, such as MMA and homocysteine are measured it is not possible to tell if the vitamin B12 is functionally active or inactive. Hence Paradoxical B12 deficiency will result. Thus, poisoning with nitrous oxide is very different to functional B12 deficiency due to folate, or functional B2 deficiency, in that whilst Co(II)B12 or Co(I)B12 can be converted to MethylCo(III)B12, thereby restoring activity of the [MethylCo(III)B12-methionine synthase] complex, NO-Co(III)B12 cannot be displaced and thereby regenerate the activity of the enzyme.

Higher levels of Co(I)B12 are present in functional B2 deficiency, such as occurs in Iodine, Selenium and/or Molybdenum deficiency, due to lack of activity of the FAD/NADH-dependent MTHFR enzyme, particularly in those mutations in the MTHFR protein, or in those with a diet low in folate, thereby making those individuals more susceptible to the action of Nitrous oxide. The inactive NO-Co(III)B12 would be indistinguishable from inactive Co(II)B12, and when measured in the current total serum B12 and the inappropriately named active B12 tests, as they do not distinguish which analogue of cobalamin is being measured, cyanocobalamin, hydroxycobalamin, methylcobalamin, adenosylcobalamin, Co(II)cobalamin, Co(I)cobalamin, glutathionyl-Co(III)cobalamin or NO-Co(III)cobalamin, to name but a few. in indication of the extent of damage that nitrous can do to the nervous system can be gleaned from those who use Nangs, and their devastating neurological consequences. Reports of side-effects include “subacute-onset, progressive distal lower limb sensory symptoms and unsteadiness”, “subacute combined degeneration of the cord”” ataxia and progressive paresis”, depression, development of diseases of the brain, spine and nerves. The severity of these reactions has led the UK government to consider criminalizing the use of Nitrous Oxide. Genetically, Nitrous oxide sensitivity should be higher in those with MTRR +/+ mutations, as is found for the following SNPs, MTRRG12099A, MTRRA66G, and in MTHFR mutations A1298C, and rs13306571

Nitrous oxide was commonly used as an anaesthetic gas, yet as long ago as 1956 (Lassen et al, 1956) it was realized that the activity of vitamin B12 was destroyed by nitrous oxide use and could cause megaloblastic anemia. In 1968, Banks and co-workers demonstrated that nitrous oxide could react with the cobalt in vitamin B12 and lead to the inactive NO-Co(III)B12 complex. The destruction of the activity of vitamin B12 is dependent upon the time and dose of administration of nitrous, with over 50% of individuals producing signs of megaloblastic depression of bone marrow function (Nunn and Chanarin, 1978). As early as 1978 (Amess et al, 1987) the use of nitrous oxide for anaesthesia was found to be contra-indicated, yet to this day it is still used, and many individuals report signs of B12 deficiency following use. Unbelievably, despite numerous publications showing poor outcomes of nitrous oxide use in pregnancy, and several demonstrating an association between nitrous and autism, and over 200 publications, demonstrating inactivation of vitamin B12 with subsequent sequelae, clinicians in the US, UK and Australia claim "“ Initiation and management of nitrous oxide by registered nurses is a safe and cost-effective option for labor pain.”. (See PDF).  One of the problems with Nitrous inactivation of vitamin B12 activity is that the levels of B12 in serum still remain high, yet paradoxically the B12 is inactive - as per the discussion on paradoxical vitamin B12 deficiency. Unbelievably, nitrous oxide is still used as an anaesthetic to this day in the USA and Australia, both on mothers during pregnancy, and also on young children. Evidence suggests that this alone is responsible for many cases of autism (Xin et al, 2024). It has been known for over 40 years that the use of nitrous oxide in anaesthesia (laughing gas) or in recreational abuse, can cause vitamin B12 deficiency (Shah and Murphy, 2019: Tani etal, 2019; Oussalah etal, 2019; Chi, 2018; Stockton etal, 2017; Massey etal, 2016: Garakani etal, 2014; Safari etal, 2013; Chiang etal, 2013; Krajewski etal, 2007; Cohen etal, 2007; Jameson etal, 1999; Smith, 2001: Deleu etal, 2001; Mayall, 1999; Horne and Holloway, 1997: Kinsella and Green 1995; Carmel etal, 1993; Koblin etal,1990; O'Leary etal, 1985; van der Westhuyzen and Metz, 1984; 1982; Lumb etal, 1982; Kondo etal, 1981: Seteinberg etal, 1981; McKenna etal, 1980; Linnell  etal, 1978; Deacon  etal, 1978). Post surgical complications of the use of Nitrous include peripheral neuropathy  (Neuveu etal, 2019: Egan, 2018: Kaski etal, 2017; Richardson 2010),  metabolic encephalopathy (Vive etal, 2019), myeloneuropathy (Edigin etal, 2019; Friedlander and Davies, 2018; Alt etal, 2011; Waklawik etal, 2003; Sesso etal, 1999: Nestor and Stark, 1996), neuropathy (Gullestrup etal, 2019; Conaerts etal, 2017:Middleton and Roffers, 2018), pancytopenia (Norris and Mallia, 2019), Myopathy  (Williamson etal, 2019), myelopathy (Dong etal, 2019; Mancke etal, 2016;  Probasco etal, 2011: Hathout and El-Saden, 2011; Pema et al, 1998), severe neuropsychiatric symptoms (Lundin etal, 2019), combined degeneration of the spinal chord (Lan etal, 2019; Patel etal, 2018; Anderson etal, 2018; Antonucci, 2018; Keddie etal, 2018; El-sadawi etal, 2018; Yuan etal 2017: Buizert etal, 2017; Chen and Huang, 2016; Pugliese etal, 2015: Chaugny etal, 2014; Cheng  etal, 2013; Lin etal, 2011; Wijesekera, etal, 2009; Renaud etal, 2009: Wu etal, 2007; Ahn and Brown, 2005 Ilniczky etal, 2003: Beltramello etal, 1998: Rosener and DIchgans, 1996), neurotoxicity (Johnsonn etal, 2018), neuronopathy  (Morris etal, 2015), polyneuropathy (Alarcia etal, 1999), psychosis (Sethi et, al, 2006), dementia (El Otmani etal, 2007), ataxia (Miller etal, 2004), megaloblastic anemia (Barbosa etal, 2000), neurological impairment (McNeeely etal, 2000), neurologic decompensation (Felmet etal, 2000), neurologic degeneration (Flippo and Holder, 1993), spastic paraparesis (Lee etal, 1999). Curiously, Nitrous is still recommended by the American Association of Anesthesiologists, NSW Department of Health, and the Association of Anesthesiologists, the New Zealand College of Midwives..  In fact, several countries with high standards of healthcare, such as Canada, Sweden, Australia, Finland, and the United Kingdom, use a blend of 50% oxygen and 50% nitrous oxide to treat pain during labor. Whilst they do not express concerns about potential damage to the newborn, they do, however, express concerns about the potential effect on Global warming, which is of greater concern than the effect on the neonatal brain!!  The rational appears to be due to the replacement of epidural medication, with its risk on the spine, with the nitrous oxide. This attitude typifies the medical profession, treat the problem now, worry about the side effects later. We have contacted numerous hospitals, the Royal Children's Hospital Melbourne, Mayo Clinic Kopabirth, NZ College of Midwives, midwife associations, The America Pregnancy Association, Queensland Government, Doctors for the Environment and anaesthesiologists expressing our concerns yet not one has "returned our call". Atrocious!! Interestingly, the increase in the use of Nitrous from around 1% of births in 1980,  in 2011-2014 is was 12% to now 35=55% of births in 2024, has paralleled the rise in the rate of autism from <0.1% to now ~ 3%. In response to concerns about health, Dr Vitoria Eley of Queensland Department of Health "Great to see you engaging with the anaesthesia literature"..Queensland Government "Nitrous Oxide : Gas is safe for your baby..." Estimates suggest that if a woman chooses nitrous oxide, she has an 8-10% chance of having a baby who subsequently is diagnosed with autism, and a 25% chance of the child having ADHD or OCD. The Ameridcan Association of Obstetrics and Gynecology "Nitrous oxide is safe for you and your baby. You may feel dizzy or nauseous while inhaling nitrous oxide, but these sensations go away within a few minutes".

There are several groups who have shown the deleterious effects of nitrous on the brain. Thus Selzer (2003) demonstrated increased susceptibly of those with MTHFR mutations to Nitrous Oxide, and Kalikiri and co-workers (2004) found a dramatic change in MMA and homocysteine levels in nitrous, as too Baum (2007). The study findings of a mechanistic link between nitric oxide levels and  are significant (Jackson, 2023). 

Potential signs of deficiency in folate, or functional B12 would be any orofacial defects such as Cleft palate, tongue tie, difficulty feeding.

The extent of damage to the brain will be dependent upon how long the child was exposed to nitrous oxide, and at what stage their development was at. Hence areas of the brain that were most active at the time of exposure are most likely to be affected the most. At time of birth this would be cerebellum, followed after birth by the subcortical areas and then the cerebral cortex.

Treatment of Nitrous oxide intoxication 

Treatment of Nitrous oxide inhalation is possible if it is done early, however, treatment has to be quick, or permanent damage is done. This, though, is not what happens following exposure during labour, and so the potential for treatment is lost, particularly given that diagnosis of neurological damage is not done until many months or even years later. There is hope though, but it depends upon making sure that you get any deficiencies such as functional B2 and B12 deficiencies right first, and then slowly let nature take its course.

Prevention of Nitrous oxide intoxication 

Obviously prevention involves total avoidance of nitrous oxide during pregnancy.

Copyright.

The descriptions and findings on vitamin B12 and autism, is the property of B12 Oils Pty Ltd. Reproduction in whole or in part constitutes an infringement in the Copyright law. Copyright infringement carries serious penalties.

References

    • Nitrous Oxide and Vitamin B12 deficiency
     Vive MGD, Anguelova GV, Duim S, Hofstee HMA. Metabolic encephalopathy caused by nitrous oxide ('laughing gas') induced hyperammonaemia. BMJ Case Rep. 2019 Nov 25;12(11). pii: e232163. doi: 10.1136/bcr-2019-232163. PubMed PMID: 31772134.
     Neveu J, Perelman S, Suisse G, Monpoux F. Severe hyperhomocysteinemia and peripheral neuropathy as side effects of nitrous oxide in two patients with
     sickle cell disease. Arch Pediatr. 2019 Oct;26(7):419-421. doi: 10.1016/j.arcped.2019.09.006. Epub 2019 Oct 17. PubMed PMID: 31630905.
     Edigin E, Ajiboye O, Nathani A. Nitrous Oxide-induced B12 Deficiency Presenting With Myeloneuropathy. Cureus. 2019 Aug 6;11(8):e5331. doi:10.7759/cureus.5331. PubMed PMID: 31598438; PubMed Central PMCID: PMC6777927.
     Tani J, Weng HY, Chen HJ, Chang TS, Sung JY, Lin CS. Elucidating Unique Axonal Dysfunction Between Nitrous Oxide Abuse and Vitamin B12 Deficiency. Front Neurol. 2019 Jul 9;10:704. doi: 10.3389/fneur.2019.00704. eCollection 2019. PubMed PMID: 31354607; PubMed Central PMCID: PMC6633399.
     Nouri A, Patel K, Montejo J, Nasser R, Gimbel DA, Sciubba DM, Cheng JS. The Role of Vitamin B(12) in the Management and Optimization of Treatment in Patients With Degenerative Cervical Myelopathy. Global Spine J. 2019 May;9(3):331-337. doi: 10.1177/2192568218758633. Epub 2018 May 17. Review. PubMed PMID: 31192102; PubMed Central PMCID: PMC6542160.
     Gullestrup A, Jensen RB, Bøgevig S, Nilsson PM. [Acute neuropathy and liver injury following the abuse of nitrous oxide]. Ugeskr Laeger. 2019 May 13;181(20).
     pii: V12180890. Danish. PubMed PMID: 31124452.
     Norris F, Mallia P. Lesson of the month 2: A case of nitrous oxide-induced pancytopenia. Clin Med (Lond). 2019 Mar;19(2):129-130. doi: 10.7861/clinmedicine.19-2-129. PubMed PMID: 30872294; PubMed Central PMCID:
     PMC6454366.
     Williamson J, Huda S, Damodaran D. Nitrous oxide myelopathy with functional vitamin B (12) deficiency. BMJ Case Rep. 2019 Feb 13;12(2). pii: e227439. doi:
     10.1136/bcr-2018-227439. PubMed PMID: 30765444.
     Lundin MS, Cherian J, Andrew MN, Tikaria R. One month of nitrous oxide abuse causing acute vitamin B (12) deficiency with severe neuropsychiatric symptoms.
     BMJ Case Rep. 2019 Feb 7;12(2). pii: bcr-2018-228001. doi: 10.1136/bcr-2018-228001. PubMed PMID: 30737329.
     Lan SY, Kuo CY, Chou CC, Kong SS, Hung PC, Tsai HY, Chen YC, Lin JJ, Chou IJ, Lin KL; PCHAN Study Group. Recreational nitrous oxide abuse related subacute combined degeneration of the spinal cord in adolescents - A case series and literature review. Brain Dev. 2019 May;41(5):428-435. doi: 10.1016/j.braindev.2018.12.003. Epub 2019 Jan 2. Review. PubMed PMID: 30611595.
     Dong X, Ba F, Wang R, Zheng D. Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report and review of the literature. Int J Neurosci.
     2019 Mar;129(3):225-229. doi: 10.1080/00207454.2018.1526801. Epub 2018 Dec 4.Review. PubMed PMID: 30234413.
     Patel KK, Mejia Munne JC, Gunness VRN, Hersey D, Alshafai N, Sciubba D, Nasser R, Gimbel D, Cheng J, Nouri A. Subacute combined degeneration of the
     spinal cord following nitrous oxide anesthesia: A systematic review of cases. Clin Neurol Neurosurg. 2018 Oct;173:163-168. doi: 10.1016/j.clineuro.2018.08.016.
     Epub 2018 Aug 9. Erratum in: Clin Neurol Neurosurg. 2019 Feb;177:123-124. Abstract corrected. PubMed PMID: 30144777.
     Jolobe OMP. Other aspects of nitrous oxide-related neuromyelopathy. Am J Emerg Med. 2019 Feb;37(2):350-351. doi: 10.1016/j.ajem.2018.05.076. Epub 2018 May 30. PubMed PMID: 29866413.
     Egan W, Steinberg E, Rose J. Vitamin B(12) deficiency-induced neuropathy secondary to prolonged recreational use of nitrous oxide. Am J Emerg Med. 2018
     Sep;36(9):1717.e1-1717.e2. doi: 10.1016/j.ajem.2018.05.029. Epub 2018 May 24. PubMed PMID: 29859645.
     Anderson D, Beecher G, van Dijk R, Hussain M, Siddiqi Z, Ba F. Subacute Combined Degeneration from Nitrous Oxide Abuse in a Patient with Pernicious
     Anemia. Can J Neurol Sci. 2018 May;45(3):334-335. doi: 10.1017/cjn.2018.15. PubMed PMID: 29756593.
     Antonucci MU. Subacute Combined Degeneration from Recreational Nitrous Oxide Inhalation. J Emerg Med. 2018 May;54(5):e105-e107. doi: 10.1016/j.jemermed.2018.01.045. Epub 2018 Mar 27. PubMed PMID: 29602528.
     Keddie S, Adams A, Kelso ARC, Turner B, Schmierer K, Gnanapavan S, Malaspina A, Giovannoni G, Basnett I, Noyce AJ. No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation. J Neurol. 2018 May;265(5):1089-1095. doi: 10.1007/s00415-018-8801-3. Epub 2018 Mar 3. PubMed
     PMID: 29502317; PubMed Central PMCID: PMC5937900.
     Johnson K, Mikhail P, Kim MG, Bosco A, Huynh W. Recreational nitrous oxide-associated neurotoxicity. J Neurol Neurosurg Psychiatry. 2018 Aug;89(8):897-898. doi: 10.1136/jnnp-2017-317768. Epub 2018 Jan 24. PubMed PMID: 29367261.
     Al-Sadawi M, Claris H, Archie C, Jayarangaiah A, Oluya M, McFarlane SI. Inhaled Nitrous Oxide 'Whip-Its!' Causing Subacute Combined Degeneration of
     Spinal Cord. Am J Med Case Rep. 2018;6(12):237-240. doi: 10.12691/ajmcr-6-12-3. Epub 2018 Dec 26. PubMed PMID: 31058215; PubMed Central PMCID: PMC6499494.
     Friedlander G, Davies T. The Last Laugh - Reversible myeloneuropathy induced by chronic nitrous oxide use. Acute Med. 2018;17(4):232-235. PubMed PMID:
     30882108.
     Yuan JL, Wang SK, Jiang T, Hu WL. Nitrous oxide induced subacute combined degeneration with longitudinally extensive myelopathy with inverted V-sign on
     spinal MRI: a case report and literature review. BMC Neurol. 2017 Dec 28;17(1):222. doi: 10.1186/s12883-017-0990-3. PubMed PMID: 29282001; PubMed
     Central PMCID: PMC5745895.
     Conjaerts SHP, Bruijnes JE, Beerhorst K, Beekman R. [Nitrous oxide-induced polyneuropathy]. Ned Tijdschr Geneeskd. 2017;161:D2044. Dutch. PubMed PMID:
     29192578.
     Kaski D, Kumar P, Murphy E, Warner TT. Iatrogenic B12-deficient peripheral neuropathy following nitrous oxide administration for functional tonic leg spasm:
     A case report. Clin Neurol Neurosurg. 2017 Sep;160:108-110. doi:10.1016/j.clineuro.2017.07.006. Epub 2017 Jul 6. PubMed PMID: 28709008.
     Stockton L, Simonsen C, Seago S. Nitrous oxide-induced vitamin B12 deficiency. Proc (Bayl Univ Med Cent). 2017 Apr;30(2):171-172. PubMed PMID: 28405070; PubMed Central PMCID: PMC5349816.
     Buizert A, Sharma R, Koppen H. When the Laughing Stops: Subacute Combined Spinal Cord Degeneration Caused by Laughing Gas Use. J Addict Med. 2017
     May/Jun;11(3):235-236. doi: 10.1097/ADM.0000000000000295. PubMed PMID: 28166085.
     40: Chen HJ, Huang CS. Nitrous Oxide-induced Subacute Combined Degeneration Presenting with Dystonia and Pseudoathetosis: A Case Report. Acta Neurol Taiwan. 2016 Jun 15;25(2):50-55. PubMed PMID: 27854092.
     Mancke F, Kaklauskaitė G, Kollmer J, Weiler M. Psychiatric comorbidities in a young man with subacute myelopathy induced by abusive nitrous oxide consumption: a case report. Subst Abuse Rehabil. 2016 Sep 29;7:155-159. eCollection 2016.PubMed PMID: 27729826; PubMed Central PMCID: PMC5047713.
     Massey TH, Pickersgill TT, J Peall K. Nitrous oxide misuse and vitamin B12 deficiency. BMJ Case Rep. 2016 May 31;2016. pii: bcr2016215728. doi:10.1136/bcr-2016-215728. PubMed PMID: 27247211; PubMed Central PMCID: PMC4904416.
     Duque MA, Kresak JL, Falchook A, Harris NS. Nitrous Oxide Abuse and Vitamin B12 Action in a 20-Year-Old Woman: A Case Report. Lab Med. 2015 Fall;46(4):312-5. doi: 10.1309/LM0L9HAVXCHF1UQM. PubMed PMID: 26489675.
     Pugliese RS, Slagle EJ, Oettinger GR, Neuburger KJ, Ambrose TM. Subacute combined degeneration of the spinal cord in a patient abusing nitrous oxide and
     self-medicating with cyanocobalamin. Am J Health Syst Pharm. 2015 Jun 1;72(11):952-7. doi: 10.2146/ajhp140583. PubMed PMID: 25987690.
     Morris N, Lynch K, Greenberg SA. Severe motor neuropathy or neuronopathy due to nitrous oxide toxicity after correction of vitamin B12 deficiency. Muscle
     Nerve. 2015 Apr;51(4):614-6. doi: 10.1002/mus.24482. Epub 2015 Feb 24. PubMedPMID: 25297001.
     Garakani A, Welch AK, Jaffe RJ, Protin CA, McDowell DM. Psychosis and low cyanocobalamin in a patient abusing nitrous oxide and cannabis. Psychosomatics.
     2014 Nov-Dec;55(6):715-9. doi: 10.1016/j.psym.2013.11.001. Epub 2013 Nov 5.PubMed PMID: 24367897.
     Safari A, Emadi F, Jamali E, Borhani-Haghighi A. Clinical and MRI manifestations of nitrous oxide induced vitamin B12 deficiency: A case report. Iran J Neurol. 2013;12(3):111-3. PubMed PMID: 24250916; PubMed Central PMCID: PMC3829298.
     Chiang TT, Hung CT, Wang WM, Lee JT, Yang FC. Recreational nitrous oxide abuse-induced vitamin B12 deficiency in a patient presenting with
     hyperpigmentation of the skin. Case Rep Dermatol. 2013 Jun 29;5(2):186-91. doi: 10.1159/000353623. Print 2013 May. PubMed PMID: 23898268; PubMed Central PMCID: PMC3724136.
     Chaugny C, Simon J, Collin-Masson H, De Beauchêne M, Cabral D, Fagniez O, Veyssier-Belot C. [Vitamin B12 deficiency due to nitrous oxide use: unrecognized
     cause of combined spinal cord degeneration]. Rev Med Interne. 2014 May;35(5):328-32. doi: 10.1016/j.revmed.2013.04.018. Epub 2013 Jun 14. French. PubMed PMID: 23773901.
     Cheng HM, Park JH, Hernstadt D. Subacute combined degeneration of the spinal cord following recreational nitrous oxide use. BMJ Case Rep. 2013 Mar 8;2013.
     pii: bcr2012008509. doi: 10.1136/bcr-2012-008509. PubMed PMID: 23476009; PubMed Central PMCID: PMC3618752.
     Ghobrial GM, Dalyai R, Flanders AE, Harrop J. Nitrous oxide myelopathy posing as spinal cord injury. J Neurosurg Spine. 2012 May;16(5):489-91. doi:10.3171/2012.2.SPINE11532. Epub 2012 Mar 2. PubMed PMID: 22385084.
     Probasco JC, Felling RJ, Carson JT, Dorsey ER, Niessen TM. Teaching NeuroImages: myelopathy due to B₁₂ deficiency in long-term colchicine treatment
     and nitrous oxide misuse. Neurology. 2011 Aug 30;77(9):e51. doi:10.1212/WNL.0b013e31822c910f. PubMed PMID: 21876193.
     Lin RJ, Chen HF, Chang YC, Su JJ. Subacute combined degeneration caused by nitrous oxide intoxication: case reports. Acta Neurol Taiwan. 2011 Jun;20(2):129-37. Review. PubMed PMID: 21739392.
     Hathout L, El-Saden S. Nitrous oxide-induced B12 deficiency myelopathy: Perspectives on the clinical biochemistry of vitamin B12. J Neurol Sci. 2011 Feb
     15;301(1-2):1-8. doi: 10.1016/j.jns.2010.10.033. Epub 2010 Nov 26. Review. PubMed PMID: 21112598.
     Alt RS, Morrissey RP, Gang MA, Hoffman RS, Schaumburg HH. Severe myeloneuropathy from acute high-dose nitrous oxide (N2O) abuse. J Emerg Med. 2011
     Oct;41(4):378-80. doi: 10.1016/j.jemermed.2010.04.020. Epub 2010 Jun 7. PubMed PMID: 20605391.
     Richardson PG. Peripheral neuropathy following nitrous oxide abuse. Emerg Med Australas. 2010 Feb;22(1):88-90. doi: 10.1111/j.1742-6723.2009.01262.x. PubMedPMID: 20152009.
     Wijesekera NT, Davagnanam I, Miszkiel K. Subacute combined cord degeneration: a rare complication of nitrous oxide misuse. A case report. Neuroradiol J. 2009
     May 15;22(2):194-7. Epub 2009 May 15. PubMed PMID: 24207040.
     Renard D, Dutray A, Remy A, Castelnovo G, Labauge P. Subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia. Neurol Sci.
     2009 Feb;30(1):75-6. doi: 10.1007/s10072-009-0013-2. Epub 2009 Jan 24. PubMed PMID: 19169627.
     Jameson M, Roberts S, Anderson NE, Thompson P. Nitrous oxide-induced vitamin B(12) deficiency. J Clin Neurosci. 1999 Mar;6(2):164-6. PubMed PMID: 18639144.
     Sethi NK, Mullin P, Torgovnick J, Capasso G. Nitrous oxide "whippit" abuse presenting with cobalamin responsive psychosis. J Med Toxicol. 2006 Jun;2(2):71-4. Review. PubMed PMID: 18072118; PubMed Central PMCID: PMC3550053.
     Krajewski W, Kucharska M, Pilacik B, Fobker M, Stetkiewicz J, Nofer JR, Wronska-Nofer T. Impaired vitamin B12 metabolic status in healthcare workers
     occupationally exposed to nitrous oxide. Br J Anaesth. 2007 Dec;99(6):812-8. Epub 2007 Oct 20. PubMed PMID: 17951609.
     Wu MS, Hsu YD, Lin JC, Chen SC, Lee JT. Spinal myoclonus in subacute combined degeneration caused by nitrous oxide intoxication. Acta Neurol Taiwan. 2007
     Jun;16(2):102-5. PubMed PMID: 17685135.
     Singer MA, Lazaridis C, Nations SP, Wolfe GI. Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: case report and literature review. Muscle Nerve. 2008 Jan;37(1):125-9. PubMed PMID: 17623854.
     Cohen Aubart F, Sedel F, Vicart S, Lyon-Caen O, Fontaine B. [Nitric-oxide triggered neurological disorders in subjects with vitamin B12 deficiency]. Rev Neurol (Paris). 2007 Mar;163(3):362-4. French. PubMed PMID: 17404524.
     Ahn SC, Brown AW. Cobalamin deficiency and subacute combined degeneration after nitrous oxide anesthesia: a case report. Arch Phys Med Rehabil. 2005 Jan;86(1):150-3. PubMed PMID: 15641006.
     Miller MA, Martinez V, McCarthy R, Patel MM. Nitrous oxide "whippit" abuse presenting as clinical B12 deficiency and ataxia. Am J Emerg Med. 2004 Mar;22(2):124. PubMed PMID: 15011232.
     Waclawik AJ, Luzzio CC, Juhasz-Pocsine K, Hamilton V. Myeloneuropathy from nitrous oxide abuse: unusually high methylmalonic acid and homocysteine levels.
     WMJ. 2003;102(4):43-5. Erratum in: WMJ. 2003;102(6):5. PubMed PMID: 12967021.
     Ilniczky S, Jelencsik I, Kenéz J, Szirmai I. MR findings in subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia--two cases.
     Eur J Neurol. 2002 Jan;9(1):101-4. PubMed PMID: 11784385.
     Barbosa L, Leal I, Timóteo AT, Matias T. [Acute megaloblastic anemia caused by inhalation of nitrous oxide in a patient with multiple autoimmune pathology]. Acta Med Port. 2000 Sep-Dec;13(5-6):309-12. Portuguese. PubMed PMID: 11234497.
     Deleu D, Hanssens Y, Louon A. Nitrous oxide-induced cobalamin deficiency. Arch Neurol. 2001 Jan;58(1):134-5. PubMed PMID: 11176951.
     McNeely JK, Buczulinski B, Rosner DR. Severe neurological impairment in an infant after nitrous oxide anesthesia. Anesthesiology. 2000 Dec;93(6):1549-50.
     PubMed PMID: 11149458.
     Felmet K, Robins B, Tilford D, Hayflick SJ. Acute neurologic decompensation in an infant with cobalamin deficiency exposed to nitrous oxide. J Pediatr. 2000 Sep;137(3):427-8. PubMed PMID: 10969273.
     Marié RM, Le Biez E, Busson P, Schaeffer S, Boiteau L, Dupuy B, Viader F. Nitrous oxide anesthesia-associated myelopathy. Arch Neurol. 2000 Mar;57(3):380-2. PubMed PMID: 10714665.
     Göthe CJ, Petersson G. [Nitrous oxide and cobalamin deficiency]. Lakartidningen. 1999 Dec 15;96(50):5609. Swedish. PubMed PMID: 10643221.
     Lindstedt G. [Nitrous oxide can cause cobalamin deficiency. Vitamin B12 is a simple and cheap remedy]. Lakartidningen. 1999 Nov 3;96(44):4801-5. Review.
     Swedish. PubMed PMID: 10584542.
     Alarcia R, Ara JR, Serrano M, García M, Latorre AM, Capablo JL. [Severe polyneuropathy after using nitrous oxide as an anesthetic. A preventable disease?]. Rev Neurol. 1999 Jul 1-15;29(1):36-8. Spanish. PubMed PMID: 10528308.
     Sesso RM, Iunes Y, Melo AC. Myeloneuropathy following nitrous oxide anesthaesia in a patient with macrocytic anaemia. Neuroradiology. 1999 Aug;41(8):588-90. PubMed PMID: 10447571.
     Mayall M. Vitamin B12 deficiency and nitrous oxide. Lancet. 1999 May 1;353(9163):1529. PubMed PMID: 10232347.
     Pema PJ, Horak HA, Wyatt RH. Myelopathy caused by nitrous oxide toxicity. AJNR Am J Neuroradiol. 1998 May;19(5):894-6. PubMed PMID: 9613506.
     Beltramello A, Puppini G, Cerini R, El-Dalati G, Manfredi M, Roncolato G, Idone D, De Togni L, Turazzini M. Subacute combined degeneration of the spinal
     cord after nitrous oxide anaesthesia: role of magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):563-4. PubMed PMID: 9576560; PubMed
     Central PMCID: PMC2170040.
     Horne DW, Holloway RS. Compartmentation of folate metabolism in rat pancreas: nitrous oxide inactivation of methionine synthase leads to accumulation of 5-methyltetrahydrofolate in cytosol. J Nutr. 1997 Sep;127(9):1772-5. PubMed PMID: 9278558.
     Takács J. [N2O-induced acute funicular myelosis in latent vitamin B 12 deficiency]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1996 Oct;31(8):525-8. German. PubMed PMID: 9019188.
     Nestor PJ, Stark RJ. Vitamin B12 myeloneuropathy precipitated by nitrous oxide anaesthesia. Med J Aust. 1996 Aug 5;165(3):174. PubMed PMID: 8709889.
     Rösener M, Dichgans J. Severe combined degeneration of the spinal cord after nitrous oxide anaesthesia in a vegetarian. J Neurol Neurosurg Psychiatry. 1996
     Mar;60(3):354. PubMed PMID: 8609528; PubMed Central PMCID: PMC1073874.
     Hadzic A, Glab K, Sanborn KV, Thys DM. Severe neurologic deficit after nitrous oxide anesthesia. Anesthesiology. 1995 Oct;83(4):863-6. Review. PubMed PMID: 7574068.
     King M, Coulter C, Boyle RS, Whitby RM. Neurotoxicity from overuse of nitrous oxide. Med J Aust. 1995 Jul 3;163(1):50-1. PubMed PMID: 7609693.
     Young PB, Kennedy S, Molloy AM, Scott JM, Weir DG, Kennedy DG. Effect of N2O treatment/vitamin B12 deficiency in pigs on tissue concentrations of odd-numbered, branched-chain fatty acids. Int J Vitam Nutr Res.1995;65(4):255-60. PubMed PMID: 8789622.
     Louis-Ferdinand RT. Myelotoxic, neurotoxic and reproductive adverse effects of nitrous oxide. Adverse Drug React Toxicol Rev. 1994 Winter;13(4):193-206.Review. PubMed PMID: 7734639.
     Flippo 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.
     Carmel R, Rabinowitz AP, Mazumder A. Metabolic evidence of cobalamin deficiency in bone marrow cells harvested for transplantation from donors given nitrous oxide. Eur J Haematol. 1993 Apr;50(4):228-33. PubMed PMID: 8500605.
     Koblin DD, Tomerson BW, Waldman FM, Lampe GH, Wauk LZ, Eger EI 2nd. Effect of nitrous oxide on folate and vitamin B12 metabolism in patients. Anesth Analg. 1990 Dec;71(6):610-7. PubMed PMID: 2240633.
     Koblin DD, Tomerson BW, Waldman FM. Disruption of folate and vitamin B12 metabolism in aged rats following exposure to nitrous oxide. Anesthesiology. 1990 Sep;73(3):506-12. PubMed PMID: 2393136.
     van Achterbergh SM, Vorster BJ, Heyns AD. The effect of sepsis and short-term exposure to nitrous oxide on the bone marrow and the metabolism of vitamin B12 and folate. S Afr Med J. 1990 Sep 1;78(5):260-3. PubMed PMID: 2392722.
      van der Westhuyzen J, Davis RE, Icke GC, Metz J. Tissue folates in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency and neurological impairment. Br J Nutr. 1987 Nov;58(3):485-91. PubMed PMID:3120768.
     Van de List C, Combs M, Schilling RF. Nitrous oxide and vitamin B12 deficiency interact adversely on rat growth. J Lab Clin Med. 1986 Oct;108(4):346-8. PubMed PMID: 3760674.
     Koblin DD, Biebuyck JF. Is nitrous oxide a dangerous anesthetic for vitamin  B12-deficient subjects? JAMA. 1986 Aug 8;256(6):716. PubMed PMID: 3723770.
     Schilling RF. Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects? JAMA. 1986 Mar 28;255(12):1605-6. PubMed PMID: 3951096.
     McLoughlin JL, Cantrill RC. Nitrous oxide induced vitamin B12 deficiency: measurement of methylation reactions in the fruit bat (Rousettus aegyptiacus).
     Int J Biochem. 1986;18(2):199-202. PubMed PMID: 3949064.
     Wilson SD, Horne DW. Effect of nitrous oxide inactivation of vitamin B12 on the levels of folate coenzymes in rat bone marrow, kidney, brain, and liver. Arch Biochem Biophys. 1986 Jan;244(1):248-53. PubMed PMID: 3947060.
     van Tonder SV, Ruck A, van der Westhuyzen J, Fernandes-Costa F, Metz J. Dissociation of methionine synthetase (EC 2.1.1.13) activity and impairment of
     DNA synthesis in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency. Br J Nutr. 1986 Jan;55(1):187-92. PubMed PMID: 3663573.
     van der Westhuyzen J, van Tonder SV, Gibson JE, Kilroe-Smith TA, Metz J.Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency. Br J Nutr. 1985 May;53(3):657-62. PubMed PMID: 4063293.
     O'Leary PW, Combs MJ, Schilling RF. Synergistic deleterious effects of nitrous oxide exposure and vitamin B12 deficiency. J Lab Clin Med. 1985 Apr;105(4):428-31. PubMed PMID: 3981056.
     van der Westhuyzen J, Metz J. Betaine delays the onset of neurological impairment in nitrous oxide-induced vitamin B-12 deficiency in fruit bats. J Nutr. 1984 Jun;114(6):1106-11. PubMed PMID: 6726473.
      van der Westhuyzen J, Fernandes-Costa F, Metz J. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates. Life Sci. 1982 Nov 1;31(18):2001-10. PubMed PMID: 7176808.
     Lumb M, Perry J, Deacon R, Chanarin I. Urinary folate loss following inactivation of vitamin B12 by nitrous oxide in rats. Br J Haematol. 1982 Jun;51(2):235-42. PubMed PMID: 7082582.
     Kondo H, Osborne ML, Kolhouse JF, Binder MJ, Podell ER, Utley CS, Abrams RS, Allen RH. Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats. J Clin Invest. 1981 May;67(5):1270-83. PubMed PMID: 6112240; PubMed Central PMCID: PMC370693.
     Steinberg SE, Campbell C, Hillman RS. The effect of nitrous oxide-induced vitamin B12 deficiency on in vivo folate metabolism. Biochem Biophys Res Commun.
     1981 Feb 27;98(4):983-9. PubMed PMID: 6164371.
     McKenna B, Weir DG, Scott JM. The induction of functional vitamin B-12 deficiency in rats by exposure to nitrous oxide. Biochim Biophys Acta. 1980 Mar 20;628(3):314-21. PubMed PMID: 7370297.
     Lumb M, Deacon R, Perry J, Chanarin I, Minty B, Halsey MJ, Nunn JF. The effect of nitrous oxide inactivation of vitamin B12 on rat hepatic folate.Implications for the methylfolate-trap hypothesis. Biochem J. 1980 Mar 15;186(3):933-6. PubMed PMID: 7396845; PubMed Central PMCID: PMC1161731.
     Adornato BT. Nitrous oxide and vitamin B12. Lancet. 1978 Dec 16;2(8103):1318. PubMed PMID: 82831.
     Deacon R, Lumb M, Perry J, Chanarin I, Minty B, Halsey MJ, Nunn JF. Selective inactivation of vitamin B12 in rats by nitrous oxide. Lancet. 1978 Nov
     11;2(8098):1023-4. PubMed PMID: 82036.
     Amess JA, Burman JF, Rees GM, Nancekievill DG, Mollin DL. Megaloblastic haemopoiesis in patients receiving nitrous oxide. Lancet. 1978 Aug12;2(8085):339-42. PubMed PMID: 79709.
    Selzer, RR, Rosenblatt, DS, Laxova, R, Hogan, K. Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. New England Journal of Medicine, July 2003; 349: 45–50.
    Kalikiri, PC, Sachan Gajraj Singh Sachan, R. Nitrous oxide induced elevation of plasma homocysteine and methylmalonic acid levels and their clinical implications. The Internet Journal of Anesthesiology, 2004; Vol. 8 (2).
    Baum, VC. When nitrous oxide is no laughing matter: Nitrous oxide and pediatric anesthesia. Paediatric Anaesthesia, Sept. 2007; 17(9):824-30.     https://www.apsf.org/wp-content/uploads/presentations/2018-stoelting/Nitrous-Oxide-Vitamin-B12-Destruction-and-Myeloneuropathy-Kirk-Hogan.pdf https://www.haveyoursay.nsw.gov.au/nitrous-oxide-reform


     

 

 

 

Copyright © 2014 B12 Oils. All Rights Reserved. 
Reproduction in whole or in part in any form or medium without express written permission is prohibited