• Dr. Lena Fernandez

Symptoms of B12 Deficiency You Might Not Be Aware Of!



Vitamin B12 is essential for DNA synthesis and for cellular energy production within your body. It does so by regulating the formation of red blood cells and helps in the utilization of iron, preventing anemia and low energy. It is an important component of the body system because it is required for proper digestion, absorption, and synthesis of foods, protein synthesis, and the metabolism of carbohydrates and fats. Vitamin B12 is also necessary for a healthy nervous system.


It is known that roughly 50% of the population in America suffers from low levels of vitamin B12 mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at a higher risk of vitamin B12 deficiency as are other groups with low intake of animal foods or those with restrictive dietary patterns.


Several types of B12 exist, the important question to keep in mind is, are you getting sufficient amounts of the right kind of B12?

What Are the Four Types of Vitamin B12?

Vitamin B12 also known as cobalamin, and comprises a number of forms including cyano-, methyl-, deoxyadenosyl- and hydroxy-cobalamin.

  1. Cyanocobalamin is a synthetic compound formed in the lab, used in many nutritional supplements and injectables involving vitamin B12 preparation. It is usually found at most in trace amounts in human plasma, although people exposed to cigarette smoke (which contains cyanide) often have higher plasma cyanocobalamin levels. Cyanocobalamin must be converted to other cobalamins to become active, so this form is not the best type of B12 to ingest via supplementation or intramuscularly.

  2. Methylcobalamin and 5-deoxyadenosylcobalamin (also known as adenosyl-cobalamin) are the coenzyme forms of vitamin B12 that play a role in human metabolism. Methylcobalamin is the most readily absorbable form of vitamin B12. It is also most bioavailable because your body requires little effort to convert to the stable form since methylcobalamin already acquires methyl group. Hence, methylation is an important process, in which your body utilizes the methyl groups to stabilize free radicals and remove toxins. This essential step protects your brain from degeneration by decreasing the glutamate, a non-essential protein that causes neural damage.

  3. Hydroxycobalamin is also found in the human body; it is a stable form of vitamin B12 that can be converted to active coenzyme forms. Hydroxycobalamin is given intravenously or intramuscularly for vitamin B12 deficiency and for the treatment of cyanide poisoning.

  4. Adenosylcobalamin is the least stable form outside of the body and is not the best choice for oral supplementation.

The last three types of cobalamin can be converted to the methyl- or 5-deoxyadenosyl forms that are required as cofactors for methionine synthase and L-methyl-malonyl-CoA mutase.


The body does not make methionine, it must get it from foods such as sesame seeds or brazil nuts. Methionine is an important amino acid to make melatonin, an essential hormone released by the pineal gland at night. Melatonin is known to improve sleep quality, support heart health, reduce histamine levels, break down fats in the liver (lipotropic), lower cholesterol, and is crucial for the brain to function effectively.

What Are the Signs and Symptoms of Vitamin B12 Deficiency?

The neurological manifestations of vitamin B12 deficiency may become irreversible if not treated in a timely manner.


The long-term consequences of sub-clinical deficiency may include the following:

  • Chronic fatigue

  • Low energy

  • Depression

  • Confusion

  • Delirium

  • Paranoia

  • Loss of memory

  • Numbness and tingling in hands and feet

  • Permanent nerve and brain damage

  • Constipation

  • Inability to maintain balance

  • Tremors in adults

  • Infants: feeding difficulties, irritation, slow growth, and tremors

  • Low blood pressure


How is B12 absorbed and secreted?

Vitamin B12 in food is usually bound to protein. It is related to the protein by the combined action of gastric hydrochloric acid and pepsin and then binds to an intrinsic factor, which is secreted by the stomach. The B12 intrinsic factor complex is absorbed into the bloodstream in the ileum part of the small intestine.


Pernicious anemia is a condition in which vitamin B12 malabsorption occurs secondary to autoimmune destruction of the gastric parietal cells (the cells that produce intrinsic factor).


Some patients with chronic fatigue syndrome or various neuropsychiatric disorders (such as dementia, depression, or neurasthenia) have been found to have normal serum B12 concentrations and normal hematological parameters. However, they showed subnormal or undetected levels of the vitamin in their cerebrospinal fluid (CSF), suggesting that they had a defect in the transport of vitamin B12 across the blood-brain barrier or accelerated breakdown of the vitamin in brain tissue. In this case, B12 IM injections can improve symptoms, whereas oral supplementation is ineffective.

Who is at risk for Vitamin B12 deficiency?

Malabsorption of vitamin B12 is most commonly seen in the elderly, second to gastric achlorhydria (low or absent hydrochloric acid). The symptoms of subclinical deficiency are subtle and often not recognized. Also, long-term use of certain medications causes vitamin B12 deficiency due to interaction with vitamin B12.


The following most common medications prescribed are known to cause B12 deficiency and the symptoms of low B12.

Acid-suppressive therapy: Histamine-2 (H2) blockers and proton pump inhibitors (PPI) have been reported to inhibit the absorption of vitamin B12.

  • H2 blocker drugs include:

  • Ranitidine (Zantac)

  • Nizatidine (Axid)

  • Famotidine (Pepcid)

  • Cimetidine (Tagament)

  • PPI drugs include:

  • Omperazole (Prilosec, Prilosec OTC, Zegerid)

  • Lansoprazole (Prevacid)

  • Pantoprazole (Protonic)

  • Rebeprazole (Aciphex)

  • Esomeprazole (Nexium)

  • Dexlansoprazole (Dexilant)

Aspirin: The prevalence of vitamin B12 deficiency was significantly higher by 75% among aspirin users than among non-users, after adjustment for potential confounding variables.


Colchicine: a medication most commonly used to treat gout. It would be prudent to give a vitamin B12 supplement to patients receiving long-term treatment with colchicine.


Contraceptives, oral medications


Gentamicin: Intramuscular administration of B12 (methylcobalamin) protects against the development of gentamicin-induced ototoxicity in guinea pigs.


Glucocorticoids: This group of synthetic steroid drugs is commonly used to treat pain, inflammation, and low adrenal reserve.

Examples of glucocorticoids drugs include:

  • Beclomethasone

  • Betamethasone

  • Budesonide

  • Cortisone

  • Dexamethasone

  • Hydrocortisone

  • Methylprednisolone

  • Prednisolone

  • Prednisone

  • Triamcinolone

Metformin: Metformin, most commonly used to treat type 2 diabetes, has been reported to inhibit the absorption of vitamin B12. All my patients who have been on Metformin for longer than three months are vitamin B12 deficient. Our long-term goal with this group of patients is to reverse type 2 diabetes, so there would be no long-term need for Metformin use, and hence prevent vitamin B12 deficiency.


Nitrous oxide: Also known as laughing gas used in the dental office as a sedative agent. Administration of nitrous oxide to vitamin B12-deficient patients can precipitate significant neurological dysfunction.


Potassium citrate or potassium chloride: Treatment of humans with potassium citrate or potassium chloride resulted in a modest decrease in vitamin B12 absorption. Decreased B12 absorption appeared to be due to drug-induced. Treatment of heart patients with potassium chloride for 6-24 months was not associated with decreased serum vitamin B12 levels. However, research studies indicate that it may take longer than 5 years to completely deplete vitamin B12 stores, but one cannot rule out the possibility that a shorter duration of treatment would result in vitamin B12 deficiency.


Zidovudine: Vitamin B12 deficiency may increase the hematologic toxicity of zidovudine used in acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV).

What Are Common Natural Food Sources of Vitamin B12?

  • Fish (haddock, and tuna)

  • Meat (beef, poultry, and lamb)

  • Eggs

  • Milk

  • Cheese

  • Yogurt

Note some of these natural food sources carry the risk of a toxic burden, which is why the oral B12 supplement is prescribed. While vegetarians can get vitamin B12 through dairy, it is not the best source and supplementation becomes essential for them.

Vitamin B12 is particularly important vitamin for women of childbearing age and for older people, however, adequate vitamin B12 status over the whole of the lifecycle is needed for optimal health.

There has been renewed interest in vitamin B12 since the reporting of associations between homocysteine and chronic disease, particularly vascular disease. The effects of subclinical deficiency are not fully known and many aspects of vitamin B12 absorption, bioavailability and metabolism are yet to be determined.

The identification of sensitive biomarkers of vitamin B12 status will help elucidate the relationships between vitamin B12 and chronic disease and help to identify those at risk of clinical and subclinical deficiency.

A final note, do not supplement or inject with Cyanocobalamin, a common form of vitamin B12 found in poor quality supplements. Cyanide is poisonous to the liver in large doses and can cause long term harm to your health. If you do get intramuscular (IM) vitamin B12, be aware of the form of vitamin B12 you are injecting with.


Resources:

1. Dr. D’Souza, Jonathan. The 4 Types Of Vitamin B12 Supplements & Which One You Should Be taking. Bit.ly/whymethylcobalamin. Accessed July 2, 2017.

2. Gaby, Alan R. 2011. Nutritional Medicine. Concord, N.H: Fritz Perlberg Publishing.

3. O’Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2(3):299-316


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