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Vitamin B12 Deficiency

Cobalamin Deficiency

Vitamin B12 deficiency occurs when the blood levels of vitamin B 12 drop below normal. Vitamin B 12 is essential for the development of red blood cells (RBC), and is also important for the appropriate functioning of nerve tissues.


Deficiency of vitamin B12 significantly affects the functioning of the nerves associated neurological functioning. The following are the signs and symptoms of vitamin B12 deficiency:

In more advanced stages, when the deficiency continues for a prolonged duration, then the nervous system can get affected, and would showcase the following symptoms [6]:

Easy Bruising
  • The symptoms of B12 deficiency include tiredness, light-headedness , rapid heart rate , easy bruising and bleeding, weight loss, bowel upset and sore tongue.[healthdirect.gov.au]
  • Tingling or numbness in fingers and toes Difficulty in walking Mood swings and depression Psychosis and hallucinations in advanced stages of deficiency Weight loss and stomach upset Rapid heartbeat and breathing Pale skin Swollen and inflamed tongue Easy[stylecraze.com]
  • It may also cause easy bruising or bleeding, including bleeding gums, gastrointestinal side effects including sore tongue, stomach upset, weight loss, and diarrhea or constipation. If the deficiency is not corrected, nerve cell damage can result.[en.wikipedia.org]
  • As a subset of microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura can present with a constellation of symptoms similar to the hemolytic anemia attributed to severe vitamin B12 deficiency.[ncbi.nlm.nih.gov]
  • Megaloblastic anemias are a subgroup of macrocytic anemias, in which distinctive morphologic abnormalities occur in red cell precursors in bone marrow, namely megaloblastic erythropoiesis.[ncbi.nlm.nih.gov]
  • She was found to have megaloblastic anemia and subacute combined degeneration secondary to B12 deficiency caused by pernicious anemia.[ncbi.nlm.nih.gov]
  • On examination, he had physical signs of megaloblastic anemia, mood swings with intermittent hallucinations, and features of cerebellar impairment. Blood investigations revealed megaloblastic anemia, and pernicious anemia was ruled out.[ncbi.nlm.nih.gov]
  • Deficiency of vitamin B12 is a well known cause of megaloblastic anemia and pancytopenia. Splenomegaly and leukoerythroblastosis are much less well known manifestations of B12 deficiency.[ncbi.nlm.nih.gov]
  • The clinical symptoms are weakness, fatigue, shortness of breath and neurologic abnormalities.[ncbi.nlm.nih.gov]
  • The most common symptoms of the patients were; infections in 30 %, pallor in 25 %, hypotonia and neuro-developmental delay in 25 %, refusal to solid food or to suck in 20 %, failure to thrive in 15 %, fatigue in 10 %.[ncbi.nlm.nih.gov]
  • Symptoms: In the initial stages, vitamin B12 deficiency manifests with signs of fatigue, weight loss, diarrhea, sores in the mouth and tongue, menstrual disorders and increased susceptibility to infections.[symptoma.com]
  • Weakness and Fatigue One of the most common B12 deficiency signs is muscle weakness and generalized fatigue.[vitamins.lovetoknow.com]
  • People often naturally think whatever fatigue or weakness they feel is the result of not enough time and rest, but symptoms could well be due to a Vitamin B12 deficiency.[worldhealth.net]
  • We report a case of a 66-year-old non-vegetarian man presenting with generalised weakness for 1 month and misdiagnosed on bone marrow biopsy as MDS. However, laboratory investigations revealed severe deficiency of vitamin B12.[ncbi.nlm.nih.gov]
  • The clinical symptoms are weakness, fatigue, shortness of breath and neurologic abnormalities.[ncbi.nlm.nih.gov]
  • A 23-year-old man presented with weakness in the lower limbs, numbness in hands and feet over past 6 months.[ncbi.nlm.nih.gov]
  • We describe a 61-year-old man who was admitted to Emergency Department (ED) with trouble to walk independently, suffering from weakness and a long history of dyspepsia that had worsened in the last four weeks.[ncbi.nlm.nih.gov]
  • He presented with weakness and numbness of the distal limbs and absent deep tendon reflex in all four extremities. Nerve conduction study (NCS) showed an axonal type sensori-motor polyneuropathy.[ncbi.nlm.nih.gov]
  • When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect.[ncbi.nlm.nih.gov]
  • This case presentation serves as a reminder about the prevalence of vitamin B12 deficiency and malnutrition in elderly individuals in our community.[ncbi.nlm.nih.gov]
  • In developing countries like India, nutritional deficiencies are prevalent and hyperpigmentation due to protein energy malnutrition, zinc deficiency and pellagra are common. Indian women, especially vegetarian are prone to vitamin B12 deficiency.[ncbi.nlm.nih.gov]
  • Alcoholism: Alcohol drinkers suffer from malnutrition, due to poor absorption of nutrients from food. The exact prevalence of vitamin B12 deficiency is unknown.[symptoma.com]
  • Peripheral neuropathy may occur as a result of malnutrition, for which there are many causes including poor nutrition caused by an unbalanced diet and/or alcoholism.[foundationforpn.org]
  • Vitamin B12 deficiency is rare in children, with nonspecific symptoms including failure to thrive, vomiting, anorexia, and neurologic changes with or without hematologic disturbances. The neuropathy can be severe and irreversible.[ncbi.nlm.nih.gov]
  • B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa.[ncbi.nlm.nih.gov]
  • In patients with bulimia or anorexia nervosa, vitamin B12 deficiency also can be related to diet. However, your liver can store vitamin B12 for up to five years, so it's rare for diet to cause this anemia.[drugs.com]
  • Symptoms: In the initial stages, vitamin B12 deficiency manifests with signs of fatigue, weight loss, diarrhea, sores in the mouth and tongue, menstrual disorders and increased susceptibility to infections.[symptoma.com]
  • Symptoms of Vitamin B12 Deficiency Some don't show any symptoms of a vitamin B12 deficiency, while others may experience: Diarrhea Constipation Tiredness Light-headedness Loss of appetite Pale skin Lack of focus Shortness of breath Swollen, red tongue[everydayhealth.com]
  • As the condition worsens, common symptoms include: Weakness and fatigue Light-headedness and dizziness Palpitations and rapid heartbeat Shortness of breath A sore tongue that has a red, beefy appearance Nausea or poor appetite Weight loss Diarrhea Yellowish[blogs.naturalnews.com]
  • ., fatigue, weakness, stomatitis, diarrhea, constipation, loss of appetite, weight loss), Hematological symptoms (e.g., megaloblastic anemia, pancytopenia), Neurological complications (e.g., paresthesia, peripheral neuropathy, spinal cord degeneration[kidsnewtocanada.ca]
Heart Disease
  • There was no history of hypertension, diabetes or ischemic heart disease. He had low serum vitamin B12 and elevated serum homocystine levels. He improved dramatically following B12 replacement therapy.[ncbi.nlm.nih.gov]
  • Deficiencies of B12, folate, or vitamin B6 can block important pathways, causing high levels of homocysteine, which is a 15 times greater predictor of heart disease than high cholesterol. 7.[laurapower.com]
  • Poultry is relatively low in fat and cholesterol, so it is safer for those who are at risk for heart disease.[worldhealth.net]
  • Also, homocysteine levels will be high (risk factor for heart disease, stroke and complications during pregnancy) long before any of the early vitamin B12 deficiency symptoms show up.[heathernicholds.com]
  • There’s also some evidence that vitamin B12 may help prevent heart disease and possibly even Alzheimer disease (the jury is still out on this one).[diabetesselfmanagement.com]
  • Hyperpigmentation as the first presentation of Vitamin B12 deficiency is rare. Our patient, a 45 year-old Hindu vegetarian female presented to us with generalized hyperpigmentation. Examination revealed associated anaemia and peripheral neuropathy.[ncbi.nlm.nih.gov]
  • Cases of generalized hyperpigmentation associated with vitamin B12 deficiency have rarely been reported. Localized hyperpigmentation is less frequently described, affecting palms, soles, and flexural areas.[ncbi.nlm.nih.gov]
  • We hereby are presenting an interesting case of a 4 year old boy who was being treated for Vitamin B 12 deficiency on the basis of history of delayed milestone, abdominal pain and hyperpigmentation of skin which was diagnosed as homocystinuria.[ncbi.nlm.nih.gov]
  • A 9-year-old boy presented with knuckle hyperpigmentation and oral ulcers for 3 years, pallor and easy fatigability for 6 months, gait abnormalities for 3 months, and abnormal speech and behavioral abnormalities for 3 days.[ncbi.nlm.nih.gov]
  • Developmental delay or regression, pallor, skin hyperpigmentation, and sparse brown hair were present in all. Majority were hypotonic and involuntary movements were encountered in 18.[ncbi.nlm.nih.gov]
Peripheral Neuropathy
  • Those with NTSS-6 scores 6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms.[ncbi.nlm.nih.gov]
  • Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different.[ncbi.nlm.nih.gov]
  • Vitamin B12 deficiency leads to abnormal myelination or demyelination, resulting in sub-acute combined degeneration, peripheral neuropathy, and psychiatric problems, including delusions, hallucinations, cognitive changes, depression, and dementia.[ncbi.nlm.nih.gov]
  • Examination revealed associated anaemia and peripheral neuropathy. Laboratory investigation confirmed vitamin B12 deficiency. Clinical features along with hyperpigmentation improved with vitamin B12 supplementation.[ncbi.nlm.nih.gov]
  • Being a very commonly seen disorder in the general population, B12 deficiency should be born in mind as a probable diagnosis in patients with peripheral neuropathy and no clear underlying cause presenting to the ED.[ncbi.nlm.nih.gov]
  • We describe an elderly patient with vitamin B12 deficiency who presented cognitive dysfunction, peripheral polyneuropathy and sensory ataxia, and whose first clinical manifestation was the presence of Lhermitte's sign.[ncbi.nlm.nih.gov]
  • We describe a patient who manifested with acute onset of language dysfunction, chorea and ataxia. There was no history of hypertension, diabetes or ischemic heart disease. He had low serum vitamin B12 and elevated serum homocystine levels.[ncbi.nlm.nih.gov]
  • We highlighted a case of Chiari type I malformation, who presented with posterolateral ataxia associated with significant vitamin B(12) deficiency.[ncbi.nlm.nih.gov]
  • We describe a previously healthy adolescent girl who presented with emotional lability, mental status changes, hyperreflexia, and ataxia.[ncbi.nlm.nih.gov]
  • A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass.[ncbi.nlm.nih.gov]
  • This study aimed to determine the relationship between serum vitamin B12 level and tension-type headache.[ncbi.nlm.nih.gov]
  • The symptomatology of Arnold-Chiari malformations may mimic multiple sclerosis, primary headache syndromes, spinal tumours and benign intracranial hypertension.[ncbi.nlm.nih.gov]
  • General symptoms of anaemia may include: extreme tiredness (fatigue) lack of energy (lethargy) breathlessness feeling faint headaches pale skin noticeable heartbeats (palpitations) hearing sounds coming from inside the body, rather than from an outside[nhs.uk]
  • . * Headache. * Smooth or sore tongue. * Unusual neurological symptoms, including numbness, visual disturbance, sensory changes (especially in the hands and feet, a condition known as peripheral neuropathy). * Psychiatric symptoms including depression[stuff.co.nz]
  • Less common symptoms include headaches, a 'thumping heart' (palpitations), altered taste, loss of appetite, and ringing in the ears (tinnitus). You may look pale.[patient.info]
  • ., paresthesia, peripheral neuropathy, spinal cord degeneration), Psychiatric symptoms (irritability, personality change, depression), Cardiovascular problems (e.g., myocardial infarction and stroke).[kidsnewtocanada.ca]
  • Neurologic sequelae from vitamin B 12 deficiency include paresthesias, peripheral neuropathy, and demyelination of the corticospinal tract and dorsal columns (subacute combined systems disease).[aafp.org]
  • Paresthesia (tingling sensation in hands, feet, limbs). Spinal cord/myelin sheath degeneration. Insomnia. Bowel/urinary incontinence.[globalhealingcenter.com]
Personality Change
  • ., paresthesia, peripheral neuropathy, spinal cord degeneration), Psychiatric symptoms (irritability, personality change, depression), Cardiovascular problems (e.g., myocardial infarction and stroke).[kidsnewtocanada.ca]
  • Difficulty ambulating Dizziness Tremor Restless legs Visual disturbances Forgetfulness, memory loss Dementia Impotence Urinary or fecal incontinence Psychiatric symptoms: Depression Irritability Paranoia Mania Hallucinations Psychosis Violent behavior Personality[b12awareness.org]
  • changes Depression Macrocytosis Anaemia Hypersegmented neutrophils (type of white blood cells) Leukopenia (low white blood cell count) Thrombocytopenia (low blood platelet count) Glossitis Hyperpigmentation of the skin Vomiting Diarrhea and/or intestinal[stichtingb12tekort.nl]
  • , thrombocytopenia) Neurologic Paresthesias Peripheral neuropathy Combined systems disease (demyelination of dorsal columns and corticospinal tract) Psychiatric Irritability, personality change Mild memory impairment, dementia Depression Psychosis Cardiovascular[aafp.org]


A preliminary physical examination will be done, to study for the signs of vitamin B12 deficiency. In addition, the following tests would also be carried out to diagnose the condition [7]:

  • Blood tests: This is done to analyze the levels of vitamin B12 and RBCs. The shape of the red blood cells would also be taken note of, in order to check for other accompanying disorders. Blood tests also furnish information, on whether the individual is suffering from pernicious anemia or not.
  • Biopsy of bone marrow: This is done to rule out any possibility of development of anemia, and other abnormalities concerning the red cells.
  • Breath test: This is one of the new tests, to determine vitamin B12 deficiency. It is one of the simpler and cheaper techniques to diagnose the deficiency, which would also help in early diagnosis of the condition, thereby preventing onset of other complications [8].
  • Macrocytosis was found in 24.2% of vitamin B12 deficient residents. A significant increase in macrocytosis was associated with a decrease in serum vitamin B12 below 100pmol/L. Macrocytosis was most common in those with vitamin B12 69pmol/L (50.9%).[ncbi.nlm.nih.gov]
  • There were no clinical or biological signs of maternal anaemia or macrocytosis. Treatment with oral vitamin B12 rapidly improved the biological findings of the child.[ncbi.nlm.nih.gov]
  • Significant investigation results included a low serum vitamin B12 concentration, mild macrocytosis and raised serum homocysteine concentration.[ncbi.nlm.nih.gov]
  • Anemia and macrocytosis was found in 83% and 71% infants, respectively. Low serum vitamin B12 was present in 12 of 21 infants. Seven of the 9 infants with normal serum vitamin B12 had received vitamin B12 before referral.[ncbi.nlm.nih.gov]
  • Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems.[ncbi.nlm.nih.gov]
Macrocytic Anemia
  • Megaloblastic anemias are a subgroup of macrocytic anemias, in which distinctive morphologic abnormalities occur in red cell precursors in bone marrow, namely megaloblastic erythropoiesis.[ncbi.nlm.nih.gov]
  • Vitamin B12 deficiency is classically encountered in the adult Caucasian population and manifests as a subacute combined degeneration in the presence or absence of macrocytic anemia.[ncbi.nlm.nih.gov]
  • Deficiency signs in infants include: failure to thrive, movement disorders, delayed development, and macrocytic anemia.[laurapower.com]
  • Megaloblastic macrocytic anemia Antony AC. Megaloblastic anemias. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice . 7th ed. Philadelphia, PA: Elsevier; 2018:chap 39. Bunn HF. Approach to the anemias.[medlineplus.gov]


Supplementation of vitamin B12, either orally or intravenously, is employed for correcting its deficiency. The vitamin supplement is available either as a single component, or in combination with other nutrients. Complete repletion of liver stores with vitamin B12 requires about 20 injections, along with injections given on monthly basis for maintenance of the stores [9].

Vitamin B12 injections are either given through the subcutaneous route, or intramuscularly. These injections contain hydroxycobalamin, cyanocobalamin or methycobalamin. Administration of vitamin B12 through the parenteral route, has been shown to enhance the absorption of this vitamin [10].

Hypokalemia is a common occurrence in patients, who are given supplements of vitamin B12. This is so because potassium is excessively used by the new hematopoietic cells for the process of growth and division.


Individuals with vitamin B12 deficiency have a good prognosis, if the treatment is initiated within 6 months of experiencing the symptoms. Failure to do so can cause permanent damage to the nerves, and other associated problems.


The following are the various factors responsible for causing vitamin B12 deficiency:

  • Diet: Consuming a diet deficient in vitamin B12 can cause deficiency to set in. It has been stated that vegans and vegetarians are at an increased risk to develop deficiency of this vitamin, because the human body cannot absorb the form of vitamin B12 that is present in the plant sources.
  • Disease: Certain underlying disease conditions such as celiac disease, Crohn disease, and megaloblastic anemia, can interfere with the absorption of vitamin B12, causing its deficiency to set in [2].
  • Alcoholism: Alcohol drinkers suffer from malnutrition, due to poor absorption of nutrients from food.


The exact prevalence of vitamin B12 deficiency is unknown. However, it has been estimated that about 300,000 – 3 million individuals can get affected by its deficiency. It was also reported that about, 3 to 16% of the population had a vitamin B12 level less than 200 pg/mL (using the cut offs of radioassay techniques). Using cut off value of 300 pb/mL for elderly population, vitamin B12 deficiency was found in 21% of population. In European countries, vitamin B12 deficiency is found in approximately 1.6 to 10% individuals [3].

Sex distribution
Age distribution


After ingestion of foods containing vitamin B12, the low pH of the stomach cleaves cobalamine from dietary protein. This then binds to gastric R binder, and reaches the duodenum and jejunum, where the enzymes present in pancreas digest the complex, and release cobalamin. Following this event, free cobalamin binds with the gastric intrinsic factor (IF). The secretion of IF is dependent on secretion with hydrochloric acid. Therefore, during conditions of achlorhydria, when the secretion of IF is reduced, lead to deficiency of vitamin B12 [4] [5].


Vegans and vegetarians, who do not consume eggs, are at an increased risk for developing vitamin B12 deficiency. Such individuals should consider consuming several breakfast cereals, which are fortified with vitamin B12. In addition, certain types of soy milk are also fortified with the vitamin, which if consumed, can help maintain the blood levels of vitamin B12. Individuals can also consider popping in multivitamin, which contain about 6 micrograms of vitamin B12, which is sufficient to cover an individual’s daily requirement.


Deficiency of this vitamin, can therefore lead to anemia, and can also cause serious damage to the nerve and brain functioning. Vitamin B12 deficiency occurs at all age groups, and often goes undiagnosed due to its complex etiology. According to the research conducted by the Framingham Offspring Study, it was postulated that deficiency of vitamin B12 primarily occurs due to its improper absorption, rather than its poor consumption [1].

Patient Information

Definition: Vitamin B12 deficiency is characterized by low levels of vitamin B12 in the body. It is an essential vitamin required for optimal functioning of nervous tissues. Therefore, deficiency of the vitamin can have serious consequences on the neurological functioning.

Cause: A diet deficient in vitamin B12, and all those factors that interfere with the absorption of the vitamin, causes its deficiency to set in. In addition, various other underlying disease conditions, such as pernicious anemia, and condition of chronic alcoholism, can cause deficiency of vitamin B12 to develop.

Symptoms: In the initial stages, vitamin B12 deficiency manifests with signs of fatigue, weight loss, diarrhea, sores in the mouth and tongue, menstrual disorders and increased susceptibility to infections. In advanced stages, when neurological problems set in, individuals experience confusion, irritability, forgetfulness, tingling sensation in the hands and feet, and difficulty in walking properly.

Diagnosis: Vitamin B12 deficiency is diagnosed through blood tests and bone marrow biopsy. These tests also help determine the shape of the red blood cells, and presence of pernicious anemia. A new test known as breath test is also used for diagnosis of vitamin B12 deficiency.

Treatment: The condition is treated with supplements, administered either through the oral or intravenous route. Parenteral administration of vitamin B12 has been shown to enhance the absorption of this vitamin.



  1. Nielsen MJ, Rasmussen MR, Andersen CB, Nexø E, Moestrup SK. Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway. Nat Rev Gastroenterol Hepatol. May 1 2012;9(6):345-54.
  2. Antony AC. Megaloblastic anemias. In: Hematology: Basic principles and practice, 4th ed, Hoffman R, Benz EJ, Shattil SJ, et al. (Eds), Churchill Livingstone, New York 2005. p.519.
  3. Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Topolski R. The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study. J Am Board Fam Med. Sep-Oct 2009;22(5):528-34.
  4. Scalabrino G, Peracchi M. New insights into the pathophysiology of cobalamin deficiency. Trends Mol Med 2006; 12:247.
  5. Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM 2013; 106:505.
  6. Healton EB, Savage DG, Brust JC. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore). Jul 1991;70(4):229-45.
  7. Balducci L. Epidemiology of anemia in the elderly: information on diagnostic evaluation. J Am Geriatr Soc. Mar 2003;51(3 Suppl):S2-9.
  8. Green R, Kinsella LJ. Current concepts in the diagnosis of cobalamin deficiency. Neurology 1995; 45:1435.
  9. Hathcock JN, Troendle GJ. Oral cobalamin for treatment of pernicious anemia? JAMA 1991; 265:96.
  10. Butler CC, Vidal-Alaball J, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 2006; 23:279.

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Last updated: 2018-06-22 00:03