Vitamin B12 (cobalamin) deficiency diseases

   ›      ›   Vitamin B12 (cobalamin) deficiency diseases.

What is vitamin B12?

Vitamin B12, also known as cobalamin, is an essential micronutrient. Cobalamin deficiency is known as hypocobalaminemia.
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Vitamin B9 is one of the water-soluble B-complex group of vitamins. Cobalamin is essential for DNA synthesis and regulation. Cobalamin is also involved in fatty acid, phospholipid and amino acid metabolism. The normal function of brain and nervous system and also the formation of blood cells depend upon cobalamin.
Hypocobalaminemia is becoming a common nutritional disease, especially in elderly. Hypocobalaminemia manifestations can become serious when not properly treated. Cobalamin is present only in animal sources of food.
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Primary hypocobalaminemia occurs when the diet is very low in cobalamin food sources. The vegans and vegetarians are under the risk of developing primary insufficiency in the blood serum.

The common initial symptoms of cobalamin include lesions in the oral cavity, poor muscle function, anemia, neuropathy, depression and decreased fertility. Animals and plants are not capable of producing cobalamin as they lack enzymes required for its synthesis. Only bacteria, including gut bacteria can synthesize this vitamin.

Cobalamin food sources

Animals must obtain their cobalamin requirements directly or indirectly from bacteria inhabiting the rumen or distal section of the gut. In human beings small quantities of cobalamin is synthesized by the gut bacteria. Cobalamin is present in most of the animal sources of food, including shellfish (clams), organ meat (liver, heart and brain), yeast, fish, poultry, eggs, milk, yogurt and cheese.

Cobalamin absorption and excretion

The protein-bound cobalamin in the food has to be released from the proteins by the action of digestive protease enzymes. Then, in the stomach, the cobalamin is bound to R-proteins produced in the salivary glands to form Haptocorrin-Vitamin B12 complex. It protects vitamin B12 from degradation in the acidic environment.

In the duodenum, proteases digest R-proteins and release cobalamin from Haptocorrin-Vitamin B12 complex. Then cobalamin binds to a protein synthesized by gastric parietal cells, intrinsic factor (IF), to form vitamin B12-IF complex. The receptors on the enterocytes in the terminal ileum of the small bowel can only recognize the B12-IF complex for uptake.

Then the B12-IF complex is degraded and the transcobalamin II (TCN2), a carrier protein, binds cobalamin to form TCII-Vitamin B12 complex. The TCII-Vit B12 complex enters portal circulation and is processed in the liver to active cobalamin form. Studies have indicated that about 1.5 µg is assimilated from a single dose of cobalamin. For better absorption of cobalamin, the supplemental dose must be spread over the day.

Cobalamin is excreted in bile, but is recycled via enterohepatic circulation. Excesses of cobalamin in blood circulation are excreted in urine. The body can store about 2 to 5 mg of vitamin B12 in adults out of which 50% is stored in the liver. About 0.1% of cobalamin store is lost daily in secretions.

Daily requirements of vitamin B12

The Center for Food Safety and Applied Nutrition (CFSAN), a product-oriented center of Food and Drug Administration (FDA), USA, recommends a daily value of 6 µg of vitamin B12, based on a caloric intake of 2,000 calories, for adults and children four or more years of age.

Cobalamin deficiency causes

  • The primary dietary insufficiency of cobalamin is very rare, except in vegans. The secondary inadequacy arises in to several situations.
  • Severe malnutrition due to poverty or eating only foods of plant origin may cause low levels of the vitamin B12 in the plasma.
  • Infants born to vegan mothers are likely to suffer from hypocobalaminemia.
  • Elderly people with limited resources and source of animal food are at the risk of developing deficiency.
  • Malabsorption diseases including, short bowel syndrome, coeliac disease, Crohn's disease, chronic diarrhea and ulcerative colitis can cause inadequacy of vitamin B12 and hypocobalaminemia.
  • Medications like aminosalicylic acid may affect absorption of the vitamin.
  • The diabetes medication such as metformin may interfere with cobalamin absorption.
  • Prolonged total parenteral nutrition without supplementation of vitamin B12 can lead to low cobalamin blood levels.
  • Alcoholism and related malnutrition may cause dietary inadequacy and/or poor absorption of micronutrients.
  • Conditions affecting secretion of intrinsic factor such as autoimmunity to gastric parietal cells and chronic infections of gastrointestinal system may lead to deficiency of cobalamin.
  • Surgical resection of the terminal ileum which is the main site of cobalamin absorption can cause its deficiency in the body.
  • Poor secretion of gastric acids and use of antacids can impair breakdown of protein-bound cobalamin causing the vitamin deficiency.
  • Heavy bacterial growth in the gut can cause cobalamin insufficiency by consuming much of the available B12 for their metabolic activities.

Cobalamin deficiency signs and symptoms

The initial symptoms of cobalamin deficiency may be subtle and may go unnoticed. With the progress of vitamin B12 insufficiency several severe symptoms affecting most of the organ systems may appear. Graells J. et al. in their study published in 2009, reported that "We believe that glossitis with linear lesions is an early clinical sign of vitamin B12 deficiency". They described the condition of four patients with low serum levels of cobalamin. These patients had oral linear lesions, but were free of neurologic symptoms and anemia.
Some of the signs and symptoms of inadequate vitamin cobalamin are:
  • weakness,
  • lethargy,
  • easy bruising,
  • ulcers of the oral cavity,
  • bleeding gums,
  • glossitis,
  • peptic ulcers,
  • breathlessness,
  • depression,
  • polyneuropathy,
  • lack of coordination,
  • learning disabilities,
  • hallucination,
  • ataxia,
  • paresis,
  • behavioral problems,
  • seborrhoeic dermatitis,
  • hair loss,
  • mental confusion,
  • cognitive deficits,
  • reduced immune function,
  • heart palpitations,
  • pernicious anemia and
  • hyperhomocisteinemia (homocysteine accumulation).

Diagnosis of cobalamin deficiency disease

Accelerated pulse, pale skin, oral lesions and abnormal sensations are some of the indicators of deficiency of cobalamin. Blood test is done to measure the level of hemoglobin and to check the number of red blood cells and their appearance. Low serum levels of cobalamin indicate its insufficiency. High serum homocysteine and methylmalonic acid levels are considered more reliable indicators of vitamin B12 deficiency than the concentration of cobalamin in blood. Sometimes high folic acid levels may mask the symptoms of low cobalamin disease.

Vitamin B12 deficiency diseases

Low levels of vitamin B12 in the blood causes several disorders including, pernicious anemia, increased homocysteine level in the blood and associated cardiovascular ramifications, mucocutaneous lesions and severe neuropsychiatric manifestations.

Pernicious anemia

Pernicious anemia is one of the many types of megaloblastic anemias. It is caused by atrophic gastritis, parietal cell loss and lack of intrinsic factor. Atrophic gastritis is a chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells, caused by persistent infection with Helicobacter pylori. It can also be caused by autoimmune destruction of gastric parietal cells and autoimmunity to intrinsic factor (IF). The loss of gastric glandular cells results in loss of secretion of IF. Without IF, food bound cobalamin cannot be absorbed.

Hyperhomocysteinemia

Hyperhomocysteinemia is a disease wherein an abnormally high level of homocysteine is present in the blood. The deficiency of B-complex vitamins, especially folic acid and cobalamin involved in the biochemical reactions of homocysteine causes this disorder. High levels of homocysteine is a risk factor for cardiovascular disease, thrombosis, renal dysfunction, Alzheimer's disease, schizophrenia and increased fractures. Supplementation with pyridoxine, folic acid or cobalamin reduces the concentration of homocysteine in the bloodstream.

Neuropsychiatric manifestations

Durand C et al. reported a case study of neuropsychiatric manifestations of due to inadequate levels of vitamin B12. The patient had presented severe depression with delusion, time disorientation, memory and attention impairment, guilt complex, incurability and devaluation impressions and sleep disorders. The researchers recommended consideration of vitamin B12 deficiency and serum cobalamin determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology."

Treatment of vitamin B12 deficiency

The treatment is by vitamin B12 replacement therapy. Initially vitamin B12 injections are given. Later 1-2 mg doses of cobalamin supplement is given till the symptoms resolve.
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References:
1.Durand C, Mary S, Brazo P, Dollfus S. [Psychiatric manifestations of vitamin B12 deficiency: a case report]. [Article in French]. Encephale. 2003 Nov-Dec;29(6):560-5.
2.Kumar J, Garg G, Sundaramoorthy E, Prasad PV, Karthikeyan G, Ramakrishnan L, Ghosh S, Sengupta S. Vitamin B12 deficiency is associated with coronary artery disease in an Indian population. Clin Chem Lab Med. 2009;47(3):334-8.
3.Osimani A, Berger A, Friedman J, Porat-Katz BS, Abarbanel JM. Neuropsychology of vitamin B12 deficiency in elderly dementia patients and control subjects. J Geriatr Psychiatry Neurol. 2005 Mar;18(1):33-8.
4.Susan Hanna, MD, Leonard Lachover, MD, and R. P. Rajarethinam, MD. Vitamin B12 Deficiency and Depression in the Elderly: Review and Case Report. Prim Care Companion J Clin Psychiatry. 2009; 11(5): 269–270.
5.Rajendran Kannan. Cutaneous lesions and vitamin B12 deficiency. An often-forgotten link. Can Fam Physician. 2008 Apr; 54(4): 529–532.
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