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:

• Fatigue
• Weight loss
• Palpitations
• Development of sore in the mouth and tongue
• Diarrhea
• Problems with menstrual cycle
• Increased susceptibility to infections
• Development of yellowish coloration of skin

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]:

• Generalized muscular weakness
• Development of tingling and numbness in the hands and feet
• Calf muscle become tender
• Bouts of confusion, irritability and forgetfulness
• Experiencing grave difficulty in walking properly 

• 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]

  It’s as easy as that. Vitamin B12 can be our friend for life. What is Vitamin B12? Vitamin B12 is one of the vitamins belonging to the B complex group of vitamins. [stylecraze.com]

• Anemia

  She was found to have megaloblastic anemia and subacute combined degeneration secondary to B12 deficiency caused by pernicious anemia. [ncbi.nlm.nih.gov]

  Pernicious anemia is often used synonymously with vitamin B 12 deficiency. [merckmanuals.com]

  The main type of vitamin B 12 deficiency anemia is pernicious anemia. It is characterized by a triad of symptoms: Anemia with bone marrow promegaloblastosis (megaloblastic anemia). [en.wikipedia.org]

  Other dietary vitamin B12 deficiency anemia D51.8 Other vitamin B12 deficiency anemias D51.9 Vitamin B12 deficiency anemia, unspecified D52 Folate deficiency anemia D52.0 Dietary folate deficiency anemia D52.1 Drug-induced folate deficiency anemia D52.8 [icd10data.com]

• Weakness

  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]

  It manifests with failure to thrive and symptoms of anemia (e.g. asthenia, weakness, headache, infections). If untreated, neurological damage may occur such as peripheral neuropathy, subacute combined degeneration of the spinal cord and/or ataxia. [orpha.net]

  In Urdu Fefol Vit Capsules /Benefits Uses Side effects/آئرن اور خون کی کمی کو دور اور چھائیاں ختم کرے Multivitamin Multibionta-M Capsule Is Use for General Weakness & Mascular Weakness|Stamina&Anemia Vidaylint 30 tablets multivitamin tablets for teens [tweb.live]

  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]

  Anemia develops, causing paleness, weakness, fatigue, and, if severe, shortness of breath and dizziness. [merckmanuals.com]

• Fatigue

  The clinical symptoms are weakness, fatigue, shortness of breath and neurologic abnormalities. [ncbi.nlm.nih.gov]

  Consequences of vitamin B12 deficiency can include fatigue and weakness, as well as hematological, neurological, psychiatric and cardiovascular symptoms. [kidsnewtocanada.ca]

  When fatigue, often the first symptom of PA, is present, a qualified healthcare practitioner should be consulted. Symptoms of PA can be caused by other conditions, none of which would respond to vitamin B12 supplementation. [uofmhealth.org]

  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]

• 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]

  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]

  Surprisingly, two of them are practices often undertaken to improve health: a vegetarian diet and weight-loss surgery. Plants don’t make vitamin B12. [health.harvard.edu]

• Malnutrition

  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]

  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]

  If accompanied by severe protein or calorie malnutrition, iron deficiency anemia and other nutrient deficiencies, such as those caused by gastrointestinal disorders and poor digestion or absorption of nutrients, hair loss could occur as a result of a [livestrong.com]

• Diarrhea

  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]

  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]

  Consequences Vitamin B12 deficiency can have a range of clinical manifestations: 2 General symptoms (e.g., fatigue, weakness, stomatitis, diarrhea, constipation, loss of appetite, weight loss), Hematological symptoms (e.g., megaloblastic anemia, pancytopenia [kidsnewtocanada.ca]

  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]

  This is due to the inhibition of DNA synthesis (specifically purines and thymidine) Gastrointestinal symptoms: alteration in bowel motility, such as mild diarrhea or constipation, and loss of bladder or bowel control. [en.wikipedia.org]

• Dyspepsia

  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]

• Regurgitation

  Finally, progressive scarring with entrapment of chordae tendineae, mitral and/or tricuspid valve regurgitation, and endomyocardial fibrosis leads to a restrictive cardiomyopathy. [nature.com]

• Jaundice

  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]

  Jaundice Jaundice is a condition in which the skin and white of the eyes turn yellow. This can occur in the case of a lack of B12 and its affect on the body’s red blood cell production. [urdunewsreport.com]

  Summary: If you have a B12 deficiency, your skin may appear pale or jaundiced. Weakness and fatigue are common symptoms of vitamin B12 deficiency. [healthline.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]

• Cheilitis

  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]

  Cracked Corners of Mouth, Lips, Causes, Angular Cheilitis, Vitamin Deficiency, Pregnancy, Remedies, Treatment The lips might become much chapped and then dry when they’ re much exposed to the sun, wind or even cold air. [duqoboyuhac.tk]

• Hyperpigmentation

  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]

• Delusion

  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]

  A 27-year-old gentleman presented with 6 months of progressive behavior changes characterized by wandering tendencies, persecutory delusions, apathy, mutism, irritability, crying spells, disturbed sleep, and a decline in bio-socio-occupational functioning [doi.org]

  Symptoms can include: Confusion Short-term memory loss Depression Loss of balance Numbness and tingling in the hands and feet Problems concentrating Irritability Hallucinations Delusions Optic nerve atrophy The goal of treatment is to increase your vitamin [nlm.nih.gov]

  It could have been worse—a severe vitamin B12 deficiency can lead to deep depression, paranoia and delusions, memory loss, incontinence, loss of taste and smell, and more. [health.harvard.edu]

• Peripheral Neuropathy

  Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. [ncbi.nlm.nih.gov]

  Additionally, a clear link has been established between a lack of vitamin B12 and peripheral neuropathy. [foundationforpn.org]

  […] due to folic acid deficiency Neuropathy due to vitamin B12 deficiency Optic neuropathy due to vitamin B12 deficiency Pantothenic acid deficiency Peripheral nerve disorder due to vit B12 deficiency Peripheral neuropathy due to B12 deficiency Peripheral [icd9data.com]

• Ataxia

  We describe a previously healthy adolescent girl who presented with emotional lability, mental status changes, hyperreflexia, and ataxia. [ncbi.nlm.nih.gov]

• Paresthesia

  […] a range of clinical manifestations: 2 General symptoms (e.g., fatigue, weakness, stomatitis, diarrhea, constipation, loss of appetite, weight loss), Hematological symptoms (e.g., megaloblastic anemia, pancytopenia), Neurological complications (e.g., paresthesia [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]

  In 1986, Schilling described 2 patients with unrecognized vitamin B-12 deficiency who developed paresthesias and poor manual dexterity 1-3 months after brief N 2 O exposure. [17] In 1995, Kinsella and Green described a 70-year-old man with paresthesias [emedicine.medscape.com]

• Seizure

  […] an obvious cause for psychosis, seizures or hypertension. [ncbi.nlm.nih.gov]

• Personality Change

  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]

  Psychiatric Vitamin B12 deficiency can cause poor memory, cognitive loss, irritability and personality changes, depression, and dementia. Psychosis is rare but has been known to occur. [news-medical.net]

  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

  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

  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]

  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].

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].

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.