VITAMIN B12 (COBALAMIN): BRAIN FOOD FOR AUTISTIC CHILDREN

Many autistic children have a deficiency of Vitamin B12, which is vital for the proper functioning of the brain and nervous system. This article examines the functions and benefits of vitamin B12 and discusses how to diagnose and correct any deficiencies.

Group B vitamins can act individually or in combination with the cellular enzymes to form vitamin B co-enzymes. These vitamin B co-enzymes are crucial to the metabolic pathways that generate the energy from carbohydrates, fat and protein, needed by every cell in the body

Because they are co-dependent in their metabolic activities, a deficiency of one B vitamin can affect optimal functioning of organ systems throughout the body. Therefore, B vitamins are best taken in combination as vitamin B complex.

However certain B vitamins like B12 and folic acid are more crucial, and these may be needed at higher doses.

Benefits of Vitamin B12

The most important role of vitamin B12 is it works synergistically with B vitamin folate in the common metabolic pathway supplying essential methyl groups for DNA, RNA and protein synthesis. This is crucial for neurons regeneration and growth in the treatment of autism.

The next most important role is it maintains a healthy nervous system and it greatly improves cognitive function.

Vitamin B12 other benefits are:

• It acts as a co-factor for methionine synthase, the enzyme that re-methylates homocysteine to methionine by using 5-methyltetrahydrofolate as a methyl donor. Vitamins B12 and folic acid are essential for maintaining a healthy physiological level of homocysteine in the circulation. Therefore a deficiency of either will result in increased serum total homocysteine.
• It is necessary for the formation and regeneration of red blood cells. Because B12 converts folate to its active form, a physical or dietary deficiency of B12 can lead to anemia caused by folate deficiency. Inactive folate, due to a B12 deficiency, will slow DNA synthesis resulting in large immature red blood cells that are incapable of carrying oxygen or dividing. This is megaloblastic anemia.
• It promotes growth and therefore increases appetite in children.
• It promotes the metabolic pathways for energy release from fat and carbohydrates. This increases the energy level.

The most common form of dietary B12 is cyanocobalamin. This is mainly found in meat products. This variety is found only in certain vegetable sources like spirulina. Therefore, vegetarians are more susceptible to a dietary deficiency of B12.

While cyanocobalamin form of vitamin B12 works well to prevent anemia, it is the methylcobalamin form that is required to maintain neurological health.

Methylcobalamin is the active co-enzyme form of B12 and is the only type present in the brain and central nervous system required for transporting the vitally important methyl groups to proteins in the myelin sheath surrounding nerves.

The liver naturally converts a small amount of cyanocobalamin into methylcobalamin, but to regenerate neurons and the myelin sheath that protects axons and peripheral nerves, higher doses of methylcobalamin are necessary. Therefore, for healthy nervous system development additional methylcobalamin is advocated.

Most vitamin B12 (cyanocobalamin and methylcobalamin) are derived from meat products, and meat eaters are rarely lack of dietary B12.

Methylcobalamin form is crucial in the treatment of autism. Higher dosages may be required and be given by injection. There is no known toxicity effect.

Vitamin B12 is the largest vitamin known. Being a very large molecule, it is not easily absorbed. Our body developed a sophisticated system to absorb B12 requiring the production of intrinsic factor in the stomach that attaches to the B12 and allows the complex to be absorbed in the end of the small intestine.

This intrinsic factor is produced through a very sophisticated and complex biochemical pathway requiring about 30 enzyme-mediated steps for its synthesis.

Vitamin B12 deficiency can occur in the following situations:

• Reduced intrinsic factor production due to damaged stomach mucosal lining as seen in stomach ulceration, Helicobacter infection and stomach surgery (stomach stapling bariatric surgery)
• Low gastric hydrochloric production as seen in those on antacids or proton pump inhibitors and in old people.
• Impaired small intestine absorption (malabsorption) as seen in people with imbalanced intestinal flora (dysbiosis) commonly found in autism, and small intestine removal commonly done in Crohn’s disease.
• Poor dietary intake as seen among vegetarian and vegans who do not supplement their diet with B12 or use B12 fortified food. This is especially important in infants born to strict vegetarian mothers.
• Exposed to nitrous oxide (laughing gas anesthesia) as seen in dental offices and hospital operating room, and elderly undergoing surgery. Nitrous oxide inhibits the action of B12 when the tissue stores are low.

Methylcobalamin B12 is commonly deficient among autistic children. Its deficient state contributes to the severity of autism, and often renders the treatment of autism rather difficult. Or, it even gives the impression of resistance to treatment.

Why are autistic children “deficient” in methylcobalamin? Poor bio-availability of B12 is caused by the following.

• Picky eating habits leading to poor dietary B12 intake.
• Dysbiosis in the gut leading to poor and mal-absorption of B12. This may be associated to low intrinsic factor production.
• Neurodegenerative damage of the neurons as caused by autoimmune antibodies, neurotoxins, and heavy metals poisoning. This renders the neurons unresponsive to the standard B12 dose. Massive pharmacological dosing may be necessarily to produce any significant benefits.
• The capacity of transsulfuration, transmethylation and antioxidation are severely abnormal in autism. B12 is intricately involved in these metabolic pathways.

The clinical presentation of vitamin B12 deficiency varies considerably and rarely includes all the classic features, such as megaloblastic anemia, peripheral neuropathy, and subacute combined degeneration of the spinal cord.

More typically, vitamin B12 deficiency presents as nonspecific symptoms of fatigue, lassitude, malaise, vertigo, and cognitive impairment. Moreover, the clinical severity of vitamin B12 deficiency is unrelated to vitamin B12 concentrations, reflecting the limitations of standard vitamin B12 assays.

Accurate identification of vitamin B12 deficiency is important because inappropriate treatment with folic acid will correct the hematologic signs of vitamin B12 deficiency but leave the neurologic symptoms unaltered.

Serum total homocysteine (tHcy) concentrations.
Normal <15umol/L

Rationale: Vitamin B12 acts as a co-factor for methionine synthase, the enzyme that remethylates homocysteine to methionine by using 5-methyltetrahydrofolate as a methyl donor. Deficiency of either folate or vitamin B12 results in increased serum tHcy concentrations. Therefore, a raised tHcy implicates the presence of folate or vitamin B12 deficiency.

Serum methylmalonic acid (MMA) concentrations.
Normal < 0.35umol/L

Rationale: Vitamin B12 acts as a cofactor for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA; hence, deficiency of vitamin B12 results in elevated serum concentrations of methylmalonic acid (MMA). Therefore, elevated concentrations of MMA indicate vitamin B12 deficiency.

Cerebral spinal fluid methylcobalamin concentrations.

Rationale: Only the methylcobalamin form of vitamin B12 is beneficial for the brain and central nervous system. It is found only in the cerebral spinal fluid (CSF) where it acts as the crucial co-enzyme for the synthesis of the methyl group for the DNA, RNA and proteins production in neuron and myelin sheath regeneration, growth and maintenance. However, there is no other simpler way to estimate the CSF methylcobalamin concentrations. An autistic child may have impaired methylcobalamin metabolism without the increased MMA in serum or urine.

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Conclusion

Vitamin B12, together with B1, B6 and Folic acid; calcium with magnesium; vitamins C with E, and omega 3 fatty acids, are crucial for the regeneration, growth and proper function of the brain. This is particularly relevant in the treatment of autism.

Since only the methylcobalamin form the vitamin B12 is beneficial to the central nervous system, a trial of injection methylcobalamin might be justified. Vitamin B12 supplements are not well absorbed orally.

Dr. Ang Poon Liat
MBBS, M.Med (Paediatric), MRCP (UK Paediatric), FAMS, MD
Senior Consultant Pediatrician