Vitamin B12 loading of the brain happens predominantly in the womb, with little
other vitamin B12 loading of the brain for the rest of life
Vitamin B12 loading of the brain increases progressively as the foetus matures.
Premature babies have lower brain vitamin B12.
Vitamin B12
deficiency during pregnancy leads to vitamin B12 deficiency in the neonate
Vitamin B12 deficiency during pregnancy increases the risk for preterm labour,
low birth weight and increased infant mortality.
The
brains of children with autism have been found to have greatly reduced levels of
vitamin B12.
Vitamin B12
deficiency leads to lower production of creatine, and that alone can give most
of the symptoms of autism
All
children with ASD have been found to be functionally deficient in vitamin B12
at time of assessment
Vitamin B12 deficiency in the neonate is associated with delayed physical and
mental development.
Vitamin B12 deficiency in the mothers during pregnancy is known to cause severe
retardation of myelination of the nervous system of the foetus.
Vitamin B12 deficiency during development is associated with delay in the
development of speech
Inadequate myelination in the various regions of the brain is common in children
with autism
Vitamin B12 deficiency reduces the production of melatonin in the child and is
associated with sleep disorders in ASD
Vitamin B12 deficiency has been associated with epilepsy in children with ASD
Paradoxical B12 deficiency is common in children with ASD
Infants born
with cobalamin (vitamin B12) deficiency are at significant risk of lasting
brain damage. Further, the deficiency can cause developmental and intellectual
delay, hypotonia, tremor, seizure, and failure to thrive. In addition the
children may have speech, linguistics and social impairments, as well as
behavioural disorders, and problems with fine and gross motor movement. Without
therapy, there can be irreversible intellectual impairment, as well as cognitive
and developmental delay Hasbaoui
etal, 2021.
Of these the concurrence of hypotonia with developmental and intellectual delay,
especially with premature birth, low birth weight, difficulties feeding, and
problems sleeping are all "Red
Flags" for
Vitamin B12 deficiency. They are also all associated with autism.
It is almost unbelievable that despite countless publications on the effects of
vitamin B12 deficiency in the neonate that this association with autism is
missed by the medical profession, who do not test for metabolic makers of
vitamin B12 deficiency, such as homocysteine, and MMA (. Identification of
hypotonia in neonates is a strong indication of potential vitamin B12 deficiency
(either absolute or paradoxical) Chalouhi
et al, 2008; Demir et al, 2013;
Bousselamti et al, 2018;Acıpayam
et al, 2020;
Akcaboy etal, 2015; Serin et al, 2019;
Incecik et al, 2010; Honzik et al, 2010; Bicakci 2015; Smolka etal,
2001;Taskesen et al, 2011; Gupta et al, 2019; Benbir etal, 2007; Vieira etal,
2020;
Ma etal, 2011;
Borkowska etal 2007; Wagnon etal, 2005; Kamoun etal, 2017; Tosun
etal, 2011; Kose etal, 2020; Lövblad etal, 1997; Lücke etal,
2007; Hall 1990; Vieira etal, 2020; Taskesen etal, 2011; Serin
etal, 2015; Bicakci 2015; Serin HM, Arslan , 2019; Aguirre etal,
2019; Casella etal, 2005; Acıpayam etal, 020; Bousselamti etal,
2018;Hasbaoui etal, 2021
Hypotonia, is very common in autism, and early diagnosis of autism should be
suspected in children with hypotonia, as "Hypotonia is a recognizable marker of ASD and should serve as a "red flag" to
prompt earlier recognition and neurodevelopmental evaluation toward an autism
diagnosis." (Gabis etal 2021;
Lopez-Espejo, etal, 2021). Hypotonia is associated with decreased language
development and IQ in autism (Osljeskova etal, 2007;
Fillano etal, 2002).
Not surprisingly hypotonia is a common symptom in those with autism (Badescu et
al, 2016; Oslejskova et al, 2007; Lopez-Espejo et al, 2021; Gabis et al, 2021).
Whilst the authors of the aforementioned papers did not come to any conclusion
about the reason for vitamin B12 deficiency and hypotonia, clearly in methyl B12
deficiency there is reduced production of creatine, due to the reduced activity
of GNMT (Longo etal, 2011; Pacheva etal, 2016;
Stöckler et al, 1994;
Mercimek-Mahmutoglu et al, 2006; Stockler-Ipsiroglu et al, 2014;
Mercimek-Mahmutoglu et al 2014; O'Rourke et al, 2009; Araújo et al, 2005;
Lion-François et al, 2006; Mercimek-Mahmutoglu et al, 2009; Leuzzi
et al, 2013 Schulze et al, 2006;Verbruggen et al 2007; Morris et al,
2007; Item etal, 2004), and reduced production of CoQ10, both of which
would lead to poor muscle tone. Several studies have shown a link between
creatine deficiency and hypothonia (Longo etal, 2011), including studies on
deficiency of the creatine producing enzyme Guanidoacetate-N-methyl transferase
(Nasrallah
et al, 2012); and the creatine
transporter (Yıldız
etal, 2020;
It is known that the majority of vitamin B12 loading of the brain occurs during
foetal development where as much as 17% of transplacentally derived vitamin B12
enters the foetal brain. Loading is maximal during the last trimester of foetal
life, and continues until the time of birth and
thereafter very, very little enters the brain (Roed
etal, 2008: Agarwal and Nathani, 2009
In addition, there is increased homocysteine, and reduced levels of methionine,
SAM and lower thiol reducing activity with lower Cysteine, and GSH. Of
particular note is the lower level of cystathionine, the initial product of CBS
through its reduced action on homocysteine, suggesting a block methylation and
in conversion of Hcy to Cystathioinine.
Over 40% of all
methylation within the brain goes to the production of creatine, an essential
energy transporter in muscles and brain. As the level of methyl B12 decreases,
so too does the formation of creatine. Creatine deficiency has been associated
with severe neurodevelopmental delay, intellectual disability, behavioral
abnormalities, poorly developed muscle mass and muscle weakness (Stockebrand
etal, 2018; Braissant etal, 2011). Creatine deficiency has also been associated
with epilepsy and aphasia (difficulty reading, speaking and writing - a
common problem in children with autism)(Perna etal, 2016), and with mental
retardation, autism, hypotonia, and seizures (Longo etal, 2011). Creatine
deficiency has been shown to reduce energy transfer from the electron transport
chain (in the mitochondria) to energy available within the cytoplasm of the
cell. (Nabuurs etal, 2013). Creatine deficiency has also been shown to affect
spatial and object learning (Udobi etal, 2019), Creatine deficiency has also
been associated with conditions such as Huntington's, ALS, Parkinson's disease,
and Chronic Fatigue Syndrome (Riesberg etal, 2016). Creatine plays an essential
role in myelination of neuronal cells by the oligodendrocytes, which use them
for energy. In low creatine, there is poor myelination and developmental delay
results (Rosko et al 2021). Creatine also has an important role in remyelination,
and as such deficiency in creatine, or functional B2/B12 will result in poor
remyelination and ultimately lead to myelin breakdown.
For over 60 years it has been known that
Vitamin B12 sufficiency is crucial for the development of myelination of the
central nervous system, and poor vitamin B12 status is linked to poor growth and
neurodevelopment (Gutierrez-Diaz, 1959; Schrimshaw etal, 1959; Agrawal and Nathani
2009;
Sheng etal, 2019
Melatonin, together with vitamin D, stimulates neuronal stem
cells to differentiate into oligodendrocytes, which are the cells in the brain
that are responsible for myelination of the nerves in the brain. Production of
melatonin gradually increases during pregnancy, peaking in the third trimester.
After birth, the newborn child initially relies on melatonin in the mother's
milk, as it gradually turns on its own production of melatonin, which in
neurotypically normal children peaks at around 5 years of age, and starts to
decline after puberty. It has been known for over 60 years, that the production
of melatonin involves the O-methylation of N-acetyl serotonin, by the action of
enzyme hydroxyindole-O-methyl transferase, using S-Adenosylmethionine (SAM), as
the methyl donor (Axelrod and Weissbach 1960, Weissbach and Axelrod 1960). As
such production of melatonin, ultimately relies on methyl cobalamin as the
initial methyl donor for the production of SAM, and so in mothers that are low
in vitamin B12, foetal melatonin will be lower, as too will neonatal melatonin,
thereby resulting in the delayed myelination typical of ASD. Despite the obvious
correlation between low functional vitamin B12 resulting in a reduced ability to
produce melatonin, we could find very little evidence that this association has
been made in the literature. This is despite countless publications, finding an
association between lower melatonin production in the mother, the fetus, or in
the neonate, and the severity of symptoms in autism (Wiebe etal, 2018; Yunho
etal, 2018;
Gagnon and Godbout, 2018; Rossignol and Frye, 2011; 2014,
Sanchez-Barcelo et al, 2017;
Haidar etal 2016). Further, rather than to measure and address the vitamin B12
deficiency in such children, melatonin is the more common treatment (Blackmer
and Feinstein, 2016). Further, the association was
still not made in studies showing the elevated melatonin precursor, N-acetylserotonin,
and reduced melatonin in ASD (Pagan etal, 2014).
Melatonin levels in mothers in the 1st, 2nd, and 3rd Trimester
Voiculescu etal, 2014
Melatonin levels during developmentr
Grivas and Savvidou, 2007
The final step in production of Melatonin is the methylation of
N-Acetyl-Serotonin (NAcSer) by the enzyme HydroxyIndole-O-methyltransferase (HIOMT),
which has an absolute requirement for S-Adenosylmethionine (SAM), a product of
the methylation cycle
(Axelrod and Weissbach 1960, Weissbach and Axelrod 1960).
Melatonin synthesis and SAM
In Methyl B12 deficiency, there is a greatly reduced production of SAM, and
breakdown products of tryptophan, Kynurenic acid (KA) and Quinolinic acid (QA),
as well as the breakdown product of Serotonin, 5-Hydroxyindoleacetic acid
(5HIAA) start to accumulate and can be detected as elevated levels in urine.
Metabolites increased in SAM deficiency
In functional B2 deficiency due to lack of Iodine
and/or Selenium, riboflavin is not converted to FMN and then levels of serotonin
and KA are reduced.
The typical symptoms of vitamin B12 deficiency in the neonate are very similar
to those observed in autism and include megaloblastic anemia, feeding
difficulties, developmental delay (Casella etal, 2005; Honzik etal, 2010;
Hall 1990),
microcephaly (Honzik etal, 2010; Hall 1990), failure to thrive, hypotonia (Aquirre etal,
2019; Casella etal, 2005; Kanra etal, 2005;
Chandra etal,
2006; Lucke etal, 2007; Schlapbach etal, 2007; Borkowska etal, 2007;
Honzik etal, 2010; Hall 1990), and cerebral atrophy with symptoms of lethargy
(Hall 1990; Shevell and Rosenblat 1992), and
occasionally seizures (
A deficiency in the Adenosyl-form of vitamin B12 has
been linked to tiredness, vomiting, weak muscle tone, developmental delay,
intellectual disability, and frequent illnesses. In functional B2 deficiency,
the child has reduced capacity to gain energy from fats, as the reductase is
FAD-dependent, or to gain energy from sugar, due to the need of pyruvate
decarboxylase for TPP, lipoate and FAD. Hence the body turns to the metabolism
of protein for energy. The break-down of proteins results in increased levels of
the 9 essential amino acids lysine, tyrosine, phenylalanine, tryptophan,
methionine, and the branched chain amino acids leucine, isoleucine, and valine.
Of these lysine, tyrosine, phenylalanine and tryptophan cannot be processed for
energy as their break-down products enter the glycolysis pathway and so cannot
be used, thus energy must be obtained from methionine, and the branched chain
amino acids (BCA acids). Processing of the later requires MMA-CoA mutase an
Adenosyl-B12 dependent enzyme. In Adenosyl-B12 deficiency, levels of urinary
methyl malonic acid are elevated. Elevated BCA acids are found in autism (Gao et
al, 2024)
Other markers of Adenosyl B12 deficiency include ethyl malonic
acid, and methyl succinic acid. Methylsuccinate is a by-product of the
metabolism of methionine and threonine. Ethylmalonic acid and methylsuccinic
acid are altered metabolites of isoleucine (Nowaczyk
et al, 1998). Elevated ethylmalonicacid and methylsuccinic acid have been
associated with developmental delay, hypotonia, and vascular instability
associated with lactic acidemia (Nowaczyk et al, 1998). Functional vitamin B2
deficiency, also results in the catabolism of hydroxyproline, leading to
elevated oxalate, pyruvate, hippuric acid, glycolate, and glyoxylate. Elevated
levels of MMA, EMA, MSA, oxalate, hippuric acid, glycolate and glyoxylate are
common in autism. Conversely, levels of methionine, leucine, cysteine, threonine
are lower in ASD (Bala etal, 2016; Li et al, 2018).
Methyl malonic acid in urine of children with autism.
Children
born of vegan and vegetarian mothers often have moderate to severe vitamin B12
deficiency
Accompanying the vitamin B12 deficiency of the vegan and vegetarian diets are
deficiencies in protein, calcium, iron, zinc, and omega-3 fatty acids (97-98-99),
so much so that the German Nutrition Society does NOT recommend such diets
during pregnancy, lactation, and childhood (99).
Maternal serum B12 levels are closely correlated with the vitamin B12 levels in
the mother's milk. In the years 2009 to 2017, there was an increase in the rate
of veganism in the US from 0.1% to 6%, and in increase in the rate of autism
from 1:200 to 1:35 over the same period.
Myelination of Brocca's region in the brain precedes the development of speech,
and as such delayed myelination would be expected to cause the delay in speech
which is so characteristic of many children with autism. Depression is a
common side-effect of vitamin B12 deficiency, and can lead to thoughts of, and
commitment of, suicide in children with
autism
Vitamin B12 deficiency and Nitrous oxide and anaesthetics.
Use of Nitrous
oxide either as an anaesthetic or though inhalation from a "Nang" can have
disastrous affects on the function of vitamin B12.
During the methylation reaction of MethylCo(III)B12 +
Homocysteine, 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.. Higher levels of Co(I)B12 are present in functional B2
deficiency, due to lack of activity of MTHFR, particularly with 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.
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.
Nitrous
oxide was commonly used as an anaesthetic gas, yet as long ago as 1956 (Lassen
et al, 1956) it was realized that it the activity of vitamin B12 was destroyed
by nitrous oxide 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-CoB12 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, clinicains 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 etal, 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.They
do, though, express concerns about the potential effect on Global warming, which
is of greater concern that 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 to now 35=45% of births in 2024, has paralleled the rise in the
rate of autism from <0.1% to now ~ 3%. Simplistically one
would assume that simply measuring vitamin B12 levels in serum would determine
if a person was sufficient or insufficient, and to a large extent this is what
is done. Most Pathology labs simply measure the amount of B12 in serum and using
an arbitrary cut-off value (generally 150 pmol/L) assign values above this as being
sufficient. Unfortunately it is nowhere near that simple. Even in common dietary
insufficiency, signs of biochemical deficiency of vitamin B12 can be observed
when vitamin B12 levels drop below 250 pmol/L. Measurement of
biochemical deficiency has uncovered a huge range of serum B12 levels even as
high as 2000 pmol/L in which biochemical deficiency of vitamin B12 can be
measured. This, then is paradoxical and the term "Paradoxical vitamin B12
deficiency" has been used to describe this condition. It appears that in
"paradoxical B12 deficiency", the form of B12 that is in serum is an inactive
form of B12 (most likely to be Co(II)B12). If this form of B12 was present in the
mother during pregnancy it would be this form of B12 (the inactive Co(II)B12)
that would have stocked the brain, with the result that the child would be born
with what seems to be adequate vitamin B12 levels, however, the child would be
functionally deficient in vitamin B12. Further, the B12 in breast milk from the
mother would also be inactive. Paradoxical B12 deficiency is common in children
with ASD (Hope etal, 2020). Studies by
Dr Russell-Jones have
shown that every child with ASD was functionally deficient in vitamin B12, with
the majority also having
Paradoxical B12
deficiency. Thus, the only way
to tell if the vitamin B12 in serum is active or inactive is to measure
metabolic by-products of B12 metabolism and see if they are raised. The two most
commonly raised markers in vitamin B12 deficiency are homocysteine and methyl
malonic acid (MMA). There are a number of others that are readily identified if
an assessment of urinary Organic Acids is performed. Interpretation of such data
should though only be attempted by those sufficiently trained in such
assessment, which the general medical profession are not. Elevated homocysteine
is common in children with autism (Kałużna-Czaplińska,
etal, 2011;
Altun etal, 2018) SAM:SAH ratio
As vitamin B12 deficiency increases lack of methyl transferase activity leads to
elevations in Homocysteine, and a decrease in the ratio of SAM:SAH GSH:GSSG
ratio. Reduced methylation causes a reduction in the transfer of the sulphur
from homocysteine into the sulphation cycle, leading to lower intracellular
cysteine, and reduced production of glutathione. Lack of cysteine then causes an
increase in Pyroglutamic acid, one of the surrogate markers for vitamin B12
deficiency. Reduced GSH works in combination with thiosulfate sulphur
transferase in the formation of SeCystRNA, and the efficacy of thereaction drops
in functional B12 deficiency. In addition levels of toxic intracellular sulphite
increase (ASD 107 nmol/ml, NT 2.1 nmol/ml) as well as thiosulfate (ASD 131 nmol/ml,
NT 19 nmol/ml) (Kruithof et al, 2020). This can then result in a metabolic
spiral, as lack of production of SeCystRNA, will reduce the production of
Selenoproteins, such as the deiodinases that are responsible for conversion of
T4 to T3. This in turn leads to lower production of ribofavin kinase, with a
reduced activity of MTHFR and MTRR, which are critical for maintaining the
activity of MethylB12.
Mothers should ensure vitamin B12 sufficiency before they are pregnant, however,
if this is not possible, urinary Organic Acids Testing should be carried out to
establish sufficiency, and cases of deficiency mothers should supplement not
only with vitamin B12, but also with Iodine, Selenium, Molybdenum and vitamin B2
if there is reason to believe that these may also be deficient. Warning signs in
the mothers can be fatigue, obesity, gestational diabetes, insufficient dietary
intake such as occurs in vegetarian or vegan diets. Correcting of
deficiency cannot be achieved by large oral doses of vitamin B12 due to both the
very limited uptake of vitamin B12 from the gut, as well as the extensive
denaturation of the majority of the orally administered dose of vitamin B12, by
gastric acid. Instead vitamin B12 should be given by injection or via the TransdermoilTM delivery route.
Any person on antidepressant medication going into or during pregnancy should
suspect vitamin B12 or iron deficiency, and get checked via OAT. Vitamin B12
deficiency has been shown to occur in all children with ASD and this needs to be addressed if the
child is going to have any chance of normal development. Several studies on
children who were vitamin B12 deficient have shown significant increase in
growth and cognitive scores when supplemented with vitamin B12 (Sheng etal,
2019; Strand etal, 2015). Given that
co-deficiency in functional vitamin B2 is universal in autistic children this
deficiency must be fixed first, and then the active forms of vitamin B12,
adenosyl B12 and methyl B12 must be given either by injection of via the
TransdermoilTM delivery route
Other signs of vitamin B12 deficiency in the neonate include megalobastic
anaemia, feeding difficulties (difficulties in suckling), developmental delay,
microcephaly, hyptonia, lethargy, irritability, involuntary movements, seizures
and cerebral atrophy" (Benbir etal, 2007).
The majority of studies looking at vitamin B12 deficiency in children and in autism
have now addressed the likely co-deficiency of iron, however, one could
assume that a diet low in vitamin B12 would also be a diet low in iron.
Every child that we have data for who has autism is also deficient in active
vitamin B2 (FMN and FAD) and is deficient in active vitamin B12 (Adenosyl and
Methyl B12), these deficiencies also have to be addressed or the child will not
progress developmentally. Accompanying these deficiencies, deficiencies of
Iodine, Selenium and/or Molybdenum are very common.
Transport of vitamin B12 into the brain happens primarily during the last
trimester of pregnancy. Once this has occurred, the brain becomes almost
recalcitrant to further uptake of vitamin B12, and seems to have to survive on
what was in the brain at the time of birth. This can be seen in levels of
vitamin B12 detected in the brains of subjects with normal serum B12 levels as
they age (Zhang et al, 2016). Of particularly note is the huge drop in both
Methyl and Adenosyl B12 in the Frontal Cortex in those over 61..
Attempts to resolve this deficiency
through intravenous administration are hindered by the very limited amount of
vitamin B12 taken into the brain following even intravenous administration, as
can be seen in numerous imaging studies.
As can be seen in the study by
Flodh (1967), the brain of the mouse seems to have virtually no uptake of
131-I-cobalamin.
Calculation of
89Zr-Cobalamin PET Tracer (Workinger, et al, 2017),
confirmed these findings, and showed almost no detectable uptake into the brain.
The corollary to
this is that if, the brain is loaded with "dud" B12 in utero, or if the brain is
exposed to vitamin B12 modifying agents such as Nitrous Oxide, it will be almost
impossible to displace the alterred vitamin B12.
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.
Black
2011 Effects of vitamin B12 and folate deficiency on brain development in
children
PMC3137939
Jain
etal 2015 Vitamin B12 deficiency in children: a treatable cause of developmental
delay
24453156
Hall CA. Function of vitamin B12 in the central nervous system as revealed by
congenital defects. Am J Hematol. 1990 Jun;34(2):121-7. doi:
10.1002/ajh.2830340208. PMID: 1692663.
Dubaj C,
Czyż K, Furmaga-Jabłońska W. Vitamin B12 deficiency as a cause of
severe neurological symptoms in breast fed infant - a case report. Ital J
Pediatr. 2020 Mar 30;46(1):40. doi: 10.1186/s13052-020-0804-x. PMID: 32228659;
PMCID: PMC7106665.
Blom H.
Methylmalonic acid values in healthy Dutch children. Eur J Nutr. 2008
Feb;47(1):26-31. doi: 10.1007/s00394-007-0692-5. Epub 2007 Dec 18. PMID:
18092123.
Mariani
A, Chalies S, Jeziorski E, Ludwig C, Lalande M, Rodière M. Conséquences de
l'allaitement maternel exclusif chez le nouveau-né de mère végétalienne--A
propos d'un cas [Consequences of exclusive breast-feeding in vegan mother
newborn--case report]. Arch Pediatr. 2009 Nov;16(11):1461-3. French. doi:
10.1016/j.arcped.2009.07.027. Epub 2009 Sep 11. PMID: 19748244.
Baatenburg de Jong A, Bekhof J, Zwart P, Langenhorst VJ, Roorda RJ.
Ontwikkelingsachterstand bij borstgevoede kinderen door ontoereikend dieet van
de moeder [Developmental delay in breastfed children due to inadequate diet of
the mother]. Ned Tijdschr Geneeskd. 2006 Mar 4;150(9):465-9. Dutch. PMID:
16553042.
Dorsvik
I, Ueland PM, Markestad T, Bjørke-Monsen AL. Cobalamin supplementation improves
motor development and regurgitations in infants: results from a randomized
intervention study. Am J Clin Nutr. 2013 Nov;98(5):1233-40. doi:
10.3945/ajcn.113.061549. Epub 2013 Sep 11. PMID: 24025626.
Öztürk
Z, Arhan E, Aydin K, Hirfanoğlu T, Tümer L, Okur I, Serdaroğlu A, Akbaş Y,
Karaoğlu B. COBALAMIN C DEFICIENCY WITH INFANTILE SPASM AND CUTANEOUS FINDINGS:
A UNIQUE CASE. Genet Couns. 2016;27(3):399-403. PMID: 30204970.
Wang F,
Han L, Yang Y, Gu X, Ye J, Qiu W, Zhang H, Zhang Y, Gao X, Wang Y. Clinical,
biochemical, and molecular analysis of combined methylmalonic acidemia and
hyperhomocysteinemia (cblC type) in China. J Inherit Metab Dis. 2010 Dec;33
Suppl 3:S435-42. doi: 10.1007/s10545-010-9217-0. Epub 2010 Oct 6. PMID:
20924684.
Gowda
VK, Srinivasan VM. A Treatable Cause of Global Developmental Delay with Autism
Spectrum Disorder Due to Cobalamin Related Remethylation Disorder. Indian J
Pediatr. 2022 Aug;89(8):832. doi: 10.1007/s12098-022-04221-0. Epub 2022 May 23.
PMID: 35604587.
Zengin
E, Sarper N, Caki Kiliç S. Clinical manifestations of infants with nutritional
vitamin B deficiency due to maternal dietary deficiency. Acta Paediatr. 2009
Jan;98(1):98-102. doi: 10.1111/j.1651-2227.2008.01059.x. Epub 2008 Oct 6. PMID:
18945280.
El Din
EMS, Rabah TM, Metwally AM, Nassar MS, Elabd MA, Shalaan A, Kandeel W, El Etreby
LA, Shaaban SY. Potential Risk Factors of Developmental Cognitive Delay in the
First Two Years of Life. Open Access Maced J Med Sci. 2019 Jun
30;7(12):2024-2030. doi: 10.3889/oamjms.2019.566. PMID: 31406549; PMCID:
PMC6684437.
Tanc C,
Yildiz I. Evaluation of Neurodevelopmental Screening Test Scores in Children
with Vitamin B12 Deficiency. Neuropediatrics. 2024 Apr;55(2):97-103. doi:
10.1055/s-0043-1777125. Epub 2023 Dec 20. PMID: 38122810.
Bravo J
P, Ibarra C J, Paredes M M. Compromiso neurológico y hematológico por déficit de
vitamina B12 en lactante hijo de madre vegetariana: caso clínico [Hematological
and neurological compromise due to vitamin B12 deficit in infant of a vegetarian
mother: case report]. Rev Chil Pediatr. 2014 Jun;85(3):337-43. Spanish. doi:
10.4067/S0370-41062014000300010. PMID: 25697251.
Blom H.
Methylmalonic acid values in healthy Dutch children. Eur J Nutr. 2008
Feb;47(1):26-31. doi: 10.1007/s00394-007-0692-5. Epub 2007 Dec 18. PMID:
18092123.
Bousselamti A, El Hasbaoui B, Echahdi H, Krouile Y. Psychomotor regression due
to vitamin B12 deficiency. Pan Afr Med J. 2018 Jun 20;30:152. doi:
10.11604/pamj.2018.30.152.12046. PMID: 30374398; PMCID: PMC6201603.
Acıpayam
C, Güneş H, Güngör O, İpek S, Sarışık N, Demir NŞ. Cerebral atrophy in 21
hypotonic infants with severe vitamin B12 deficiency. J Paediatr Child Health.
2020 May;56(5):751-756. doi: 10.1111/jpc.14733. Epub 2019 Dec 23. PMID:
31868292.
Chalouhi
C, Faesch S, Anthoine-Milhomme MC, Fulla Y, Dulac O, Chéron G. Neurological
consequences of vitamin B12 deficiency and its treatment. Pediatr Emerg Care.
2008 Aug;24(8):538-41. doi: 10.1097/PEC.0b013e318180ff32. PMID: 18708898.
Bjørke-Monsen AL, Ueland PM. Cobalamin status in children. J Inherit Metab Dis.
2011 Feb;34(1):111-9. doi: 10.1007/s10545-010-9119-1. Epub 2010 May 27. PMID:
20508991.
JADHAV
M, WEBB JK, VAISHNAVA S, BAKER SJ. Vitamin B12 deficiency in Indian infants. A
clinical syndrome. Lancet. 1962 Nov 3;2(7262):903-7. doi:
10.1016/s0140-6736(62)90682-7. PMID: 13964414.
Doyle JJ,
Langevin AM, Zipursky A. Nutritional vitamin B12 deficiency in infancy: three
case reports and a review of the literature. Pediatr Hematol Oncol.
1989;6(2):161-72. doi: 10.3109/08880018909034282. PMID: 2702070.
Graham
SM, Arvela OM, Wise GA. Long-term neurologic consequences of nutritional vitamin
B12 deficiency in infants. J Pediatr. 1992 Nov;121(5 Pt 1):710-4. doi:
10.1016/s0022-3476(05)81897-9. PMID: 1432418.
Dror DK,
Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants:
current knowledge and possible mechanisms. Nutr Rev. 2008 May;66(5):250-5. doi:
10.1111/j.1753-4887.2008.00031.x. PMID: 18454811.
Honzik
T, Adamovicova M, Smolka V, Magner M, Hruba E, Zeman J. Clinical presentation
and metabolic consequences in 40 breastfed infants with nutritional vitamin B12
deficiency--what have we learned? Eur J Paediatr Neurol. 2010 Nov;14(6):488-95.
doi: 10.1016/j.ejpn.2009.12.003. Epub 2010 Jan 20. PMID: 20089427.
Ganesan
S, Thanawala N, Hussain N. Vitamin B12 deficiency: a treatable cause of
developmental delay in infancy. J Paediatr Child Health. 2013 Apr;49(4):E348-9.
doi: 10.1111/jpc.12158. PMID: 23574564.
Hawes D,
Shute PE, Dicke O, Paul SP. Vitamin B12 deficiency presenting with solid food
aversion and global developmental delay in a child. Br J Hosp Med (Lond). 2014
Jun;75(6):352-3. doi: 10.12968/hmed.2014.75.6.352. PMID: 25040415.
Akcaboy
M, Malbora B, Zorlu P, Altınel E, Oguz MM, Senel S. Vitamin B12 Deficiency in
Infants. Indian J Pediatr. 2015 Jul;82(7):619-24. doi:
10.1007/s12098-015-1725-3. Epub 2015 Apr 5. PMID: 25840526.
Azad C,
Jat KR, Kaur J, Guglani V, Palta A, Tiwari A, Bansal D. Vitamin B12 status
and neurodevelopmental delay in Indian infants: a hospital-based cross-sectional
study. Paediatr Int Child Health. 2020 May;40(2):78-84. doi:
10.1080/20469047.2019.1638130. Epub 2019 Jul 3. PMID: 31267850.
Lin YC,
Chung CJ, Huang YL, Hsieh RL, Huang PT, Wu MY, Ao PL, Shiue HS, Huang SR, Su CT,
Lin MI, Mu SC, Hsueh YM. Association of plasma folate, vitamin B12 levels, and
arsenic methylation capacity with developmental delay in preschool children in
Taiwan. Arch Toxicol. 2019 Sep;93(9):2535-2544. doi: 10.1007/s00204-019-02540-4.
Epub 2019 Aug 31. PMID: 31473767.
Warghat
PA, Sharath HV, Raghuveer R. The Effect of Early Pediatric Rehabilitation in an
Infant With Vitamin B12 Deficiency Associated With Developmental Delay: A Case
Report. Cureus. 2024 Jun 18;16(6):e62648. doi: 10.7759/cureus.62648. PMID:
39036156; PMCID: PMC11258930.
Dupuy G,
Roux CJ, Barrois R, Imbard A, Pontoizeau C, Dangles MT, Aubart M, Arnoux JB,
Margoses D, Brassier A, Marbach C, Bérat CM, Sarda E, Gitiaux C, de Lonlay P,
Boddaert N, Schiff M, Desguerre I. Vitamin deficiencies in children: Lessons
from clinical and neuroimaging findings. Eur J Paediatr Neurol. 2024
May;50:6-15. doi: 10.1016/j.ejpn.2024.02.013. Epub 2024 Feb 26. PMID: 38520815.
Mütze U,
Gleich F, Haas D, Urschitz MS, Röschinger W, Janzen N, Hoffmann GF, Garbade SF,
Syrbe S, Kölker S. Vitamin B12 Deficiency Newborn Screening. Pediatrics. 2024
Aug 1;154(2):e2023064809. doi: 10.1542/peds.2023-064809. PMID: 39040028.
Jain
etal 2015 Vitamin B12 deficiency in children: a treatable cause of developmental
delay
24453156
Rasmussen etal, 2001 Vitamin B12 deficiency in children and adolescents
S0022
Sukumar
etal, 2016 Vitamin B12 status among pregnant women in the UK and its association
with obesity and gestational diabetes. PMID 27916927
Knight
etal 2015 Lower circulating B12 is associated with higher obesity and insulin
resistance during pregnancy in a non-diabetic white British Population. PMID
Low-Beer, etal, 1968 Serum vitamin B12 levels and vitamin B12 binding capacity
in pregnant and non-pregnant Europeans and West Indians
Krishnaveni etal, 2009 Low plasma vitamin B12 in pregnancy is associated with
gestational 'diabeity' and later diabetes. PMID
19707742
Lai etal,
2017 High folate and low vitamin B12 status during pregnancy is associated with
gestational diabetes PMID: 28381340
Zhang
etal, 2016 Decreased levels of vitamin B12 in aging, autism and schizophrenia. PMID: 26799654
Chu etal,
2016 Effects of melatonin and its analogues on neural stem cells. PMID 26499359
Rudnitskaya etal, 2015 Melatonin Attenuates Memory Impairment, Amyloid-β
Accumulation, and Neurodegeneration in a Rat Model of Sporadic Alzheimer's
Disease.
Shen
etal, 2016 Effect of Melatonin and Resveratrol against Memory Impairment and
Hippocampal Damage in a Rat Model of Vascular Dementia. PMID 28419991
Li etal,
2017 Effect of Melatonin on renewal of chick small intestinal mucosa PMID
28431176
Whiton
etal, 1979 Brain damage in infancy and dietary B12 deficiency PMID
502936
Smolka
etal, 2001 Metabolic complications and neurological manifestations of vitamin
B12 deficiency in children of vegetarian mothers. PMID
11787236
Zengin
etal, 2008 Clinical manifestations of infants with nutritional vitamin B
deficiency due to maternal dietary deficiency PMID
18945280
Halicioglu etal, 2011 Nutritional deficiency in infants of vitamin B12 deficient
mothers PMID
99429203
Demir
etal, 2013 Clinical and neurological findings of severe vitamin B12
deficiency... PMID
23781950
Kvestad
etal Vitamin B12 status in infancy is positively associated with development and
cognitive functioning 5 y later in Nepalese children. Am. J. Clin Nut. 2017
105(5):1122-1131
Strand
etal, The effect of vitamin B12 supplementation in Nepalese infants...Trials,
2017: 187
Strand
etal, Maternal and infant vitamin B12 status during infancy predict linear
growth at 5 yrs, Ped Res 2018
https://doi.org/10.1038/s41390-018-0072-2
Smith,
AD 2018 Maternal and infant vitamin B12 status and development. Ped Res.
https://doi.org/10.1038/s41390-018-0110-0
Guez
etal, 2012 Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old
Italian infant born to a mother receiving multivitamin supplementation during
pregnancy PMC
Roed
etal, 2008 Severe vitamin B12 deficiency in infants breastfed by vegans (Ugesr
Laeger, 171: 3099-101
Agrawal
and Nathani, 2009 Neruo-regression in vitamin B12 deficiency MBJ 2009
Gutierrez-Diaz, 1959 Effect of magnesium, molybdate, vitamin B12 and vitamin T
complex, alone and combined, on development in children. Act Ped Esp. 17; 125-53
Riesberg
LA, Weed SA, McDonald TL, Eckerson JM, Drescher KM. Beyond muscles: The untapped
potential of creatine. Int Immunopharmacol. 2016 Aug;37:31-42. doi:
10.1016/j.intimp.2015.12.034. Epub 2016 Jan 8. PMID: 26778152; PMCID:
PMC4915971.
Rosko L,
Gentile T, Smith V, Huang JK. 86583 The role of creatine in developmental
myelination and remyelination. J Clin Transl Sci. 2021 Mar 30;5(Suppl 1):99. doi:
10.1017/cts.2021.655. PMCID:
PMC8827867.
Schimshaw etal, 1959 Growth and development of Central American children. II The
effect of oral administration of vitamin B12 to rural children of preschool and
school age. Am J. Clin Nutr. 7: 180-4
Chalouhi
et al, 2008 Neurological consequences of vitamin B12 deficiency and its
treatment. Ped Emerg Care, 24: 538-41
Sheng
etal, 2019 Effects of dietary intervention on vitamin B12 status and cognitive
level of 18 month-old toddlers in high poverty areas...BMC Pert 19:334
Smolka
etal 2001 Metabolic complications and neurological manifestations of vitamin B12
deficiency in children of vegetarian mothers. Cas Lek Cesk 140: 732-5
Lucke et
al, 2007 Maternal vitamin B12 deficiency: cause for neurological symptoms in
infancy. Z Geburtshilfe Neonatol, 211: 157-161
Obeid
etal, 2017 Cobalamin status from pregnancy to early childhood.... Adv Nutr 8:
971-979
Lovblad
etal 1997 Retardation of myelination due to dietary vitamin B12 deficiency:
cranial MRI findings Pediatr Radiol 27: 155-8
Horstemann etal 2003 Infantile cobalamin deficiency with cerebral lactate
accumulation and sustained choline depletion. Neuroped 34; 261-4
Rosenblatt etal, 1985 Prenatal vitamin B12 therapy of a fetus with
methylcobalamin deficiency. Lancet, 18: 1127-9
Graham
etal, 1992 Long-term neurologic consequences of nutritional vitamin B12
deficiency in infants. J Ped. 121:710-4
Stockebrand etal, 2018 A mouse model of creatine transporter deficiency reveals
impaired motor function and muscle energy metabolism. Front Physiol 9, 773
Braissant etal. Creatine deficiency syndromes and the importance of creatine
synthesis in the brain. Amion Acids, 2011 40; 1315-24
Perna
etal Creatine transporter deficiency leads to increased whole body and cellular
metabolism. Amino Aicds 2016 48; 2057-65
Udobi
eatl, Deletion of the creatine transporter gene in neonatal, but not adult, mice
leads to cognitive defects J Inherit Metab Dis. 2019; 42; 966-974
Renault
etal 1999 Neuropathy in two cobalamin-deficient breast-fed infants of vegetarian
mothers. Muscle Nerv 22:252-4
Nabuurs
etal, Disturbed energy metabolism and muscular dystrophy caused by pure creatine
deficiency are reversible by creatine intake. J Physiol. 2013 591;571-92
Longo
etal. Disorders of creatine transport and metabolism. Am J Med Genet C Semin Med
Genet 2011 157; 72-8
Hall CA
1990 Function of vitamin B12 in the central nervous system as revealed by
congenital defects. Am J Hematol. 34:121-7
Kosenen
and Pihko 1994 Development regression in a child caused by vitamin B12
deficiency. Duodecim. 110: 588-91
Monfort-Gouraud et al. 1993 Severe megaloblastic anemia in a child breast fed by
a vegetarian mother. Ann Pediatr 40,:28-31
von
Schenck etal, 1997 Persistence of neurological damage induced by dietary vitamin
B12 deficiency in infancy. Arch Dis. Child, 77: 137-9
Tashiro
etal, 1983 Phosphatidylethanolamine methyltransferase activity in developing,
demyelinating, and diabetic mouse brains. Tohuku. J. Exp. Med 141 S485-90
Axelrod and Weissbach 1960 Science, 131, 1312
Weissbach and Axelrod 1960 J. Fed Proc. 19, 50
Weibe etal. Low maternal melatonin level increases Autism Spectrum Disorder Risk
in children. Res Deve Disabil 2018 92, 79-89
Yunho et al. The relationship between autism spectrum disorder and melatonin
during fetal development. Molecules 2018, 23,
Gagnon and Godbout Melatonin and comorbidities in children with autism spectrum
disorder. Curr Dev Disord Rep 2018, 5, 197-206
Rossignol and Frye Melatonin in Autism Spectrum Disorders: a
systematic review and meta-analysis. Dev Med Child Neurol, 2011, 53, 783-792
Rossignol and Frye Melatonin in Autism Spectrum Disorders. Curr
Clin Pharmacol 2014 9, 326-34
Sanchez-Barcelo et al. Clinical uses of Melatonin in neurological
diseases and mental and behavioural disorders Curr Med Chem, 2017 24, 3851-3878
Haidar etal. Low oxytocin and melatonin levels and their possible role in the
diagnosis and prognosis in Iraqi Autistic children. Saudi Med J. 2016 37, 29-36
Blackmer and Feinstein Management of sleep disorders in children
with neurodevelopmental disorders: A review Pharmacotherapy. 2016, 36, 84-98
Pagan, et al. The serotonin-N-acetylserotonin-melatonin pathway as a biomarker
for Autism Spectrum Disorders. Trans Psychiatry, 2014 4, e479
Voiculescu et al. Role of melatonin in embryo fetal development. J Med Life.
2014;7(4):488–492
Grivas and Savvidou Melatonin the "light of night"...Scoliosis
2007; 2, 6
Hasbaoui BE, Mebrouk N, Saghir S, Yajouri AE, Abilkassem R, Agadr A. Vitamin B12
deficiency: case report and review of literature. Pan Afr Med J. 2021 Mar
4;38:237. doi: 10.11604/pamj.2021.38.237.20967. PMID: 34046142; PMCID:
PMC8140678.
Bousselamti A, El Hasbaoui B, Echahdi H, Krouile Y. Psychomotor regression due
to vitamin B12 deficiency. Pan Afr Med J. 2018 Jun 20;30:152. doi:
10.11604/pamj.2018.30.152.12046. PMID: 30374398; PMCID: PMC6201603.
Acıpayam C, Güneş H, Güngör O, İpek S, Sarışık N, Demir NŞ. Cerebral atrophy in
21 hypotonic infants with severe vitamin B12 deficiency. J Paediatr Child
Health. 2020 May;56(5):751-756. doi: 10.1111/jpc.14733. Epub 2019 Dec 23. PMID:
31868292.
Casella EB, Valente M, de Navarro JM, Kok F. Vitamin B12 deficiency in infancy
as a cause of developmental regression. Brain Dev. 2005 Dec;27(8):592-4. doi:
10.1016/j.braindev.2005.02.005. PMID: 16310594.
Aguirre JA, Donato ML, Buscio M,
Ceballos V, Armeno M, Aizpurúa L, Arpí L. Compromiso neurológico grave por
déficit de vitamina B12 en lactantes hijos de madres veganas y vegetarianas
[Serious neurological compromise due to vitamin B12 deficiency in infants of
vegan and vegetarian mothers]. Arch Argent Pediatr. 2019 Aug 1;117(4):e420-e424.
Spanish. doi: 10.5546/aap.2019.e420. PMID: 31339288.
Serin HM, Arslan EA. Neurological symptoms of vitamin B12 deficiency: analysis
of pediatric patients. Acta Clin Croat. 2019 Jun;58(2):295-302. doi:
10.20471/acc.2019.58.02.13. PMID: 31819326; PMCID: PMC6884369.
Bicakci Z. Growth retardation, general hypotonia, and loss of acquired
neuromotor skills in the infants of mothers with cobalamin deficiency and the
possible role of succinyl-CoA and glycine in the pathogenesis. Medicine
(Baltimore). 2015 Mar;94(9):e584. doi: 10.1097/MD.0000000000000584. PMID:
25738478; PMCID: PMC4553967.
Serin HM, Kara AO, Oğuz B. West syndrome due to vitamin B12 deficiency. Turk
Pediatri Ars. 2015 Dec 1;50(4):251-3.
Taskesen M, Yaramis A, Pirinccioglu AG, Ekici F. Cranial magnetic resonance
imaging findings of nutritional vitamin B12 deficiency in 15 hypotonic infants.
Eur J Paediatr Neurol. 2012 May;16(3):266-70. doi: 10.1016/j.ejpn.2011.08.005.
Epub 2011 Sep 7. PMID: 21903432.
Vieira D, Florindo C, Tavares de Almeida I, Macário MC. Adult-onset
methylenetetrahydrofolate reductase deficiency. BMJ Case Rep. 2020 Mar
10;13(3):e232241. doi: 10.1136/bcr-2019-232241. PMID: 32161077; PMCID:
PMC7066602.
Casella EB, Valente M, de Navarro JM, Kok F. Vitamin B12 deficiency in infancy
as a cause of developmental regression. Brain Dev. 2005 Dec;27(8):592-4. doi:
10.1016/j.braindev.2005.02.005. PMID: 16310594.
Hall CA. Function of vitamin B12 in the central nervous system as revealed by
congenital defects. Am J Hematol. 1990 Jun;34(2):121-7. doi:
10.1002/ajh.2830340208. PMID: 1692663.
Lücke T, Korenke GC, Poggenburg I, Bentele KH, Das AM, Hartmann H. Mütterlicher
Vitamin-B12-Mangel: Ursache neurologischer Symptomatik im Säuglingsalter
[Maternal vitamin B12 deficiency: cause for neurological symptoms in infancy]. Z
Geburtshilfe Neonatol. 2007 Aug;211(4):157-61. German. doi:
10.1055/s-2007-981249. PMID: 17729202.
Lövblad K, Ramelli G, Remonda L, Nirkko AC, Ozdoba C, Schroth G. Retardation of
myelination due to dietary vitamin B12 deficiency: cranial MRI findings. Pediatr
Radiol. 1997 Feb;27(2):155-8. doi: 10.1007/s002470050090. PMID: 9028851.
Tosun A, Aral YZ, Çeçen E, Aydoğdu A, Çetinkaya Çakmak B. Involuntary movement
in infants during vitamin B12 treatment. Turk J Haematol. 2011 Dec
5;28(4):317-22. English. doi: 10.5152/tjh.2011.18. PMID: 27264590.
Kamoun F, Guirat R, Megdich F, Ben Ameur S, Kallel C, Hachicha M. Frequent
Infections, Hypotonia, and Anemia in a Breastfed Infant. J Pediatr Hematol Oncol.
2017 Mar;39(2):141-142. doi: 10.1097/MPH.0000000000000725. PMID: 28060111.
Borkowska A, Plata-Nazar K, Łuczak G, Matheisel A. Niedobór witaminy B12 u
rocznego dziecka karmionego wyłacznie piersia [Vitamin B12 deficiency in a
one-year-old, exclusively breast fed child]. Med Wieku Rozwoj. 2007
Oct-Dec;11(4):435-8. Polish. PMID: 18605198.
Longo N, Ardon O, Vanzo R, Schwartz E, Pasquali M. Disorders of creatine
transport and metabolism. Am J Med Genet C Semin Med Genet. 2011 Feb
15;157C(1):72-8. doi: 10.1002/ajmg.c.30292. Epub 2011 Feb 9. PMID: 21308988
Nasrallah F, Kraoua I, Joncquel-Chevalier Curt M, Bout MA, Taieb SH, Feki M,
Khouja N, Briand G, Kaabachi N. Guanidinoacetate methyltransferase (GAMT)
deficiency in two Tunisian siblings: clinical and biochemical features. Clin
Lab. 2012;58(5-6):427-32. PMID: 22783571.
Yıldız Y, Göçmen R, Yaramış A, Coşkun T, Haliloğlu G. Creatine Transporter
Deficiency Presenting as Autism Spectrum Disorder. Pediatrics. 2020
Nov;146(5):e20193460. doi: 10.1542/peds.2019-3460. PMID: 33093139.
Pacheva I, Ivanov I, Penkov M, Kancheva D, Jordanova A, Ivanova M. Creatine
Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate
Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures,
and Behavioral Changes, but Normal Structural MRI. Ann Clin Lab Sci. 2016
Sep;46(5):557-61. PMID: 27650626.
Morris AA, Appleton RE, Power B, Isherwood DM, Abernethy LJ, Taylor RW, Turnbull
DM, Verhoeven NM, Salomons GS, Jakobs C. Guanidinoacetate methyltransferase
deficiency masquerading as a mitochondrial encephalopathy. J Inherit Metab Dis.
2007 Feb;30(1):100. doi: 10.1007/s10545-006-0478-2. Epub 2006 Dec 14. PMID:
17171576.
Schulze A. Creatine deficiency syndromes. Handb Clin Neurol. 2013;113:1837-43.
doi: 10.1016/B978-0-444-59565-2.00053-8. PMID: 23622406
Casella
etal, 2005 Vitamin B12 deficiency in infancy as a cause of developmental
reqression. Brain Dev. 27: 592-4
Aquirre
etal, 2019 Serious neurological compromise due to vitamin B12 deficiency in
infants of vegan and vegetarian mothers. Arch Argent Pediatr 117
Ars etal
2019 Prenatal folate, homocysteine and vitamin B12 levels and child brain
volumes. Br J. Nutr. 122: S1-S9
Black
2008 Effects of vitamin B12 and folate deficiency on brain development in
children. Food Nutr. Bull. 29: S126-31
Renault
etal, 1999 Neuropathy in two coblamin-deficient breast-fed infants of vegetarian
mothers. Muscle Nerve. 22: 252-4
Kanra
etal, 2005 Answer to hypotonia: a simple hemogram. J Child Neurol 20: 930-1
Stollhoff and Schulte 1987 Vitamin B12 and brain development. Eur J. Pediatr
146: 201-5
von
Schenck etal 1997 Persistence of neurological damage induced by dietary vitamin
B12 deficiency in infancy. Arch Dis Chil 77: 137-9
Chandra
etal, 2006 Tremors and thrombocytosis during treatment of megaloblastic anaemia.
Ann Trop Paediatr 26: 101-5
Lucke
etal, 2007 Maternal vitamin B12 deficiency: cause for neurological symptoms in
infancy. Z Gebrurtshilfe Neonatoal 211: 157-61
Schlapbach etal, 2007 Floppy baby with macrocytic anemia and vegan mother.
Praxis 29: 1309-14
Borkowska etal 2007 Vitamin B12 deficiency in a one-year-old, exclusively breast
fed child. Med Wieku Rozwoj 11:435-8
Chalouhi
etal, 2008 Neurological consequences of vitamin B12 deficiency and its
treatment. Pediatr Emerg Care 24:538-41
Honzik
etal, 2010 Clinical presentation and metabolic consequences of 40 breastfed
infants with nutritional vitamin B12 deficiency - what have we learned? Eur J
Paediatr Neurol 14:488-95
Hall
1990 Function of vitamin B12 in the central nevous system as revealed by
congenital defects. Am J. Hematol. 34; 121-7
Shevell
and Rosenblatt 1992 The neurology of cobalamin. Can J Neurol Sci 19: 472-86
Strucinska 2002 Vegetarian diets of breastfeeding women in the light of dietary
recommendations. Rocz Panstw Zakl Hig 53: 65-79
Rendle-Short
et al 1979 Vegan mothers with vitamin B12 deficiency. Med J Aust 3:483
Michaud
et al, 1992 Nutritional vitamin B12 deficiency: two cases detected by routine
newborn urinary screening. Eur J Pediatr. 151;218-20
Specker
1994 Nutritional concerns of lactating women consuming vegetarian diets. Am J
Clin Nutr. 59: 1182S
Renault
et al 1999 Neuropathy in two cobalamin-deficient breast-fed infants of
vegetarian mother. Muscle Nerv 22:252-4
Ueland
and Monsen 2003 Hyperhomocysteinemia and B-vitamin deficiences in infants and
children. Clin Chem Lab Med. 41:1418-26
Weiss et
al, 2004 Severe vitamin B12 deficiency in an infant associated with maternal
deficiency and a strict vegetarian diet. J Ped Hem Oncol. 26:270-1
Jarosz
et al, 2004 Vitamin B12 deficiency anaemia in a 7.5 months old girl. Med Wieku
Rozwoj 8:283-8
Baatenburg et al 2006 Developmental delay in breastfed children due to
inadequate diet of the mother. Ned Tijdshr Geneeskd 150: 465-9
Kollee
2006 Vitamin deficiencies in breastfed children due to maternal dietary
deficiency. Ned Tijdschr Geneeskd. 150:473-6
Yajnik
2006 Nutritional control of fetal growth. Nutr Rev. 64: S50-1
Cetinkaya etal, 2007 Nutritional vitamin B12 deficiency in hospitalized young
children. Ped. Hem. Onco. 24:15-21
Fadyl
and Inoue 2007 Combined B12 and iron deficiency in a child breast-fed by a
vegetarian mother. J Ped Hemato Oncol. 29:74
Mathey
et al, 2007 Failure to thrive and psychomotor regression revealing vitamin B12
deficiency in 3 infants. Arch Ped 14: 467-71
Dror and
Allen, 2008 Effect of vitamin B12 deficiency on neurodevelopment in infants...
Nutr Rev. 66:250-5
Honzik
et al, 2010 Clinical presentation and metabolic consequences in 40 breastfed
infants... Eur J Paed Neurol. 14:488-95
Kocaoglu
et al, 2014 Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian
mother. J Health Pop Nutr 32:367-71
Bousselamati et al. 2018 Psychomotor regression due to vitamin B12 deficiency.
Pan Afr MEd J 20:30
Bravo
etal, 2014 Haematological and neurological compromise due to vitamin B12
deficient in infant of a vegetarian mother.... PMID
25697251
Schroder
etal 2017 Pregnant women of South Asian Ethnicity in Canada have substantially
lower vitamin B12 status compared with pregnant woemen of European ethnicity
PMID
28920568
Chandyo
etal, 2017 The effects of vitamin B12 supplementation during pregnancy PMID
28851784
Woods
etal, 1960 Vitamin B12Co-60 readily passes the placenta into fetal organs and
nursing provides B12 from mother to pup... PMC
2137236
Graber
etal, 1971 Placental transport of vitamin B12 in the pregnant rat PMID
5552402
Michelson etal, 1999 Urinary organic acid screening in children with
developmental language delay
Specker
et al. 1990 Vitamin B12: Low milk concentrations are related to low serum
concentrations in vegetarian women.....Am J Clin Nutr 52:1073-6
Specker
et al. 1994 Vegetarian diets during lactation. Am J. Clin Nutr 59:1182S-6S
Davis
and Melina 2014 Becoming vegan: comprehensive addition.
Strand
etal, 2015 Vitamin B12, folic acid, and growth in 6- to 30-month-old children...
Pediatrics 135;918-26
Benbir
etal, 2007 Seizures during treatment of vitamin B12 deficiency. Seizure. 2007
Jan;16(1):69-73. Epub 2006 Dec 5
Gao Q,
Bi D, Li B, Ni M, Pang D, Li X, Zhang X, Xu Y, Zhao Q, Zhu C. The Association
Between Branched-Chain Amino Acid Concentrations and the Risk of Autism Spectrum
Disorder in Preschool-Aged Children. Mol Neurobiol. 2024 Aug;61(8):6031-6044.
doi: 10.1007/s12035-024-03965-4. Epub 2024 Jan 24. PMID: 38265552; PMCID:
PMC11249470.
Nowaczyk MJ, Lehotay DC, Platt BA, Fisher L, Tan R, Phillips H, Clarke JT.
Ethylmalonic and methylsuccinic aciduria in ethylmalonic encephalopathy arise
from abnormal isoleucine metabolism. Metabolism. 1998 Jul;47(7):836-9. doi:
10.1016/s0026-0495(98)90122-6. PMID: 9667231.
Kałużna-Czaplińska, J., Michalska, M., & Rynkowski, J. (2011). Homocysteine
level in urine of autistic and healthy children.
Altun, H., Kurutaş, E. B., Şahin, N., Güngör, O., & Fındıklı, E. (2018). The
Levels of Vitamin D, Vitamin D Receptor, Homocysteine and Complex B Vitamin in
Children with Autism Spectrum Disorders.
Nitrous Oxide and Vitamin B12 deficiency
Flodh H, Ullberg S. Accumulation of labelled vitamin B12 in some transplanted
tumours. Int J Cancer. 1968 Sep 15;3(5):694-9. doi: 10.1002/ijc.2910030518. PMID:
5724527.
ANW,
Workinger JL, Nexo E, Doyle RP, Viola-Villegas N. 89Zr-Cobalamin
PET Tracer: Synthesis, Cellular Uptake, and Use for Tumor Imaging. ACS Omega.
2017 Oct 31;2(10):6314-6320. doi: 10.1021/acsomega.7b01180. Epub 2017 Oct 2.
PMID: 29104950; PMCID: PMC5664145.
Copyright © 2014 B12 Oils. All Rights Reserved.
Vitamin B12 Deficiency in Autism
Vitamin B12
Deficiency in Neonates
Vitamin B12 Deficiency and Hypotonia
Vitamin B12 Loading of the Foetal
Brain
Vitamin B12 Deficiency and Creatine deficiency
Vitamin B12 Deficiency and Developmental Delay
Vitamin B12
and the Production of Melatonin
Adenosyl Vitamin B12 Deficiency
Vitamin B12 Deficiency in Vegetarian Mothers
Vitamin B12 and the Development of Speech
Vitamin B12 deficiency and
Depression
Determination of vitamin B12
Deficiency
Markers associated with Vitamin B12
Deficiency
Resolving Vitamin B12
Deficiency in Pregnant mothers
Resolving Vitamin B12
Deficiency in Autism
Other signs of
Vitamin B12 Deficiency in Neonates
Associated
Deficiencies in Autism
Resolving Vitamin B12 Deficiency in
the Brain
References
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.
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