Edit concept Question Editor Create issue ticket

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]
  • 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]
  • 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]
  • 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]
  • Present status of treatment of pernicious anemia: Ninth announcement of USP Anti-Anemia Preparations Advisory Board. JAMA 1959 ;171: 2092 – 4. Google Scholar Crossref Medline 3. Lederle, FA. Oral cobalamin for pernicious anemia.[doi.org]
  • When you don't have enough, you have a type of vitamin B12 deficiency anemia called “pernicious anemia.”[webmd.com]
  • 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]
  • Your muscles feel weak. You often have mood changes. You're confused or forgetful. Because these can also be symptoms of other conditions, see your doctor for a diagnosis.[webmd.com]
  • The clinical symptoms are weakness, fatigue, shortness of breath and neurologic abnormalities.[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]
Weight Loss
  • By intervening early with parenteral vitamin B12 and nutritional assessment prior to onset of weight loss in at risk individuals, clinicians will be able to improve their patients' quality of life.[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]
  • Surprisingly, two of them are practices often undertaken to improve health: a vegetarian diet and weight-loss surgery. Plants don’t make vitamin B 12 .[health.harvard.edu]
  • 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]
  • 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]
  • These tests may be ordered on a regular basis for individuals being treated for malnutrition or a B12 or folate deficiency to evaluate the effectiveness of their treatments.[labtestsonline.org]
  • 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]
  • 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]
  • Prevalences of endoscopic and histological findings in subjects with and without dyspepsia. Br Med J . 1991;302:749-752. Suter PM, Golner BB, Goldin BR, Morrow FD, Russell RM.[pharmacytimes.com]
  • Patients with evidence of vitamin B 12 deficiency and chronic gastrointestinal symptoms such as dyspepsia, recurrent peptic ulcer disease, or diarrhea may warrant evaluation for such entities as Whipple's disease (a rare bacterial infection that impairs[aafp.org]
Abdominal Pain
  • 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]
  • This is a serious condition where the placenta starts to come away from the inside of the womb wall, causing tummy (abdominal) pain and bleeding from the vagina.[nhs.uk]
  • Symptoms Symptoms of severe vitamin B12 deficiency (regardless of the cause) may include burning of the tongue, fatigue, weakness, loss of appetite, intermittent constipation and diarrhea, abdominal pain, weight loss, menstrual symptoms, psychological[uofmhealth.org]
  • Various GI symptoms, including weight loss and poorly localized abdominal pain, may occur. Glossitis, usually described as burning of the tongue, is uncommon.[merckmanuals.com]
  • We report an adolescent girl who presented with jaundice and weight loss for 6 months secondary to vitamin B12 deficiency, leading to megaloblastic anaemia.[ncbi.nlm.nih.gov]
  • Jaundice Most of us have only heard of jaundice in reference to newborn babies, who are occasionally born with this condition, in which skin and eyes may take on a yellow tone. Jaundice occurs when bilirubin builds up in the bloodstream.[healthyway.com]
  • Indian researchers also found that jaundice can be one of the vitamin B12 deficiency symptoms that indicated a severe lack of vitamin B12.[rd.com]
  • Paranoia and hallucinations Anemia Jaundiced skin An inflamed and swollen tongue Many people are not very well educated about their nutritional needs and the problems they may experience from various deficiencies.[worldhealth.net]
  • You may even notice a slight yellow tinge in the white of your eyes, not unlike in jaundice. When the B12 levels in your body dip, red blood cells become fragile and start breaking down into bilirubin.[curejoy.com]
  • The presence of oral signs and symptoms, including glossitis, angular cheilitis, recurrent oral ulcer, oral candidiasis, diffuse erythematous mucositis and pale oral mucosa offer the dentist an opportunity to participate in the diagnosis of this condition[ncbi.nlm.nih.gov]
Recurrent Oral Ulceration
  • The presence of oral signs and symptoms, including glossitis, angular cheilitis, recurrent oral ulcer, oral candidiasis, diffuse erythematous mucositis and pale oral mucosa offer the dentist an opportunity to participate in the diagnosis of this condition[ncbi.nlm.nih.gov]
  • 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]
Peripheral Neuropathy
  • The prevalence of vitamin B12 deficiency (defined by concentrations 6 were considered to have peripheral neuropathy.[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]
  • ., paresthesia, peripheral neuropathy, spinal cord degeneration), Psychiatric symptoms (irritability, personality change, depression), Cardiovascular problems (e.g., myocardial infarction and stroke).[kidsnewtocanada.ca]
  • Baron, Case 5-2019: A 48-Year-Old Woman with Delusional Thinking and Paresthesia of the Right Hand, New England Journal of Medicine, 10.1056/NEJMcpc1807495, 380, 7, (665-674), (2019). T. R. Elliott and A. L.[doi.org]
  • 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]
  • KEYWORDS: Anxiety; Children; Depression; Headache; Vitamin B12 deficiency[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]


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].
  • 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]
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]
  • Macrocytic anemias are generally classified into megaloblastic or nonmegaloblastic anemia.[doi.org]
Megaloblastic Bone Marrow
  • The finding of a macrocytic peripheral blood picture with a megaloblastic bone marrow usually indicates either vitamin B12 deficiency or float deficiency.[lifesave.org]


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.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 20:47