We have got together some of the interdependencies of the vitamins and minerals that are required for maintenance of vitamin B12 function.

Sequentially we have tried to demonstrate what happens under different deficiencies.

Hence the basic methylation pathway, absolute B12 deficiency, functional B12 deficiency due to Molybdenum deficiency, and functional B12 deficiency due to Iodine/and/or Selenium deficiency.

Modification of Methylation pathway in absolute B12 deficiency

Methylation is required for the formation of S-Adenosylmethionine (SAMe), which is used by over 200 methylation enzymes.

Lack of activity of the enzyme Guanidinoacetate-N-Methyl-transferase, which is the enzyme that is involved in the formation of creatine, can by itself result in many of the symptoms of autism . Mental fatigue, reduced cognitive function and muscle hypotonia are common in those with creatine deficiency. Prolonged creatine deficiency leads to conditions such as Chronic Fatigue syndrome, and  other cerebral deficiency syndromes..

Methylation is also required for the formation of Melatonin, and in absolute B12 deficiency, there is developmental delay, poor myelination, leading to slower conduction speed, delays in potty training, speech delay, and poorly developed motor skills. In addition, there is lack of maturation of the gut, and over-production of serotonin, leading to serotonin syndrome, IBS-like symptoms, food intolerance/hypersensitivity, poor sleep, etc. Poor sleep is characteristic of other B12 deficiency associated conditions such as CFS, dementia, and Parkinson's disease.

Vitamin B12 deficiency also is causative for many of the neurotransmitter disorders associated with autism.

Methylation is required for the conversion of phosphatidylethanolamine to phosphatidylchoine, the precursor for the production of choline. Choline is reacted with acety-CoA to form the neurotransmitter acetyl-choline. Acetylcholine is used in arousal, attention, memory and motivation. Low levels of acetylcholine are common in autism.

Overproduction of serotonin, due to the methyl B12 deficiency, can also lead to depression in conditions associated with vitamin B12 deficiency, such as autism, CFS, Alzheimer's disease, Parkinson's disease (Richdale etal, 2023; Russell-Jones, 2022)

Methylation is also required for the production of Adrenalin

 

In absolute B12 deficiency, there is reduced production of adrenalin, with over-production of dopamine and nor-adrenalin. The over-production of dopamine can lead to symptoms such as anxiety, which is very common in many children with autism (Richdale etal, 2023), and has been termed social anxiety disorder. It is also common in conditions associated with vitamin B12 deficiency, such as CFS, Alzheimer's disease and Parkinson's disease.

 

Lack of methylation leads to lower activity in the sulfation cycle, and lower production of milk thiols, which then can result in difficulty feeding. Feeding difficulties are common in those who later have developmental delay. There is reduced production of glutathione with an increase in pyroglutamate in OAT (Russell-Jones 2022C)

Lack of methylation leads to deficiency in CoQ10, with resultant drop in mitochondrial energy. There is an elevation in 3-HMG in OAT (Russell-Jones 2022C). This in turn increases the degree of cholesterol biosynthesis.

Lack of methylation leads to greater sensitivity to allergens as the methylating enzyme Histamine-N-Methyl transferase is required for inactivation of histamine.

Lack of vitamin B12, also affects the cycling of dietary folate, especially 5MTHF and in part explains the known disorders of cerebral folate metabolism seen in autism (Zigman etal, 2021).

Functional B12 deficiency leads to elevated MMA, homocysteine, and branched chain amino acids, and odd chain fatty acids all characteristic of disorders such as autism, CFS, and dementia (Russell-Jones 2022B, C; Zigman etal, 2021)..

Neurotransmitter Abnormalities in vitamin B12 deficiency

Melatonin deficiency