Vitamin B12 deficiency - wikipedia Vitamin B deficiency Vitamin B deficiency Synonyms Hypocobalaminemia Cyanocobalamin Specialty Neurology Symptoms Decreased ability to think, depression, irritability, abnormal sensations, changes in reflexes Complications Megaloblastic anemia Causes Poor absorption, decreased intake, increased requirements Diagnostic method Blood levels below 120 -- 180 picomol / L ( 170 -- 250 pg / mL ) in adults Prevention Supplementation in those at high risk Treatment Supplementation by mouth or injection Frequency 6 % ( < 60 years old ), 20 % ( > 60 years old ) ( edit on Wikidata ) Vitamin B deficiency is the medical condition of low blood levels of vitamin B. A wide variety of signs and symptoms may occur including a decreased ability to think and behavioural and emotional changes such as depression, irritability, and psychosis. Abnormal sensations, changes in reflexes, and poor muscle function can also occur as may inflammation of the tongue, decreased taste, low red blood cells, reduced heart function, and decreased fertility. In young children symptoms include poor growth, poor development, and difficulties with movement. Without early treatment some of the changes may be permanent. Common causes include poor absorption from the stomach or intestines, decreased intake, and increased requirements. Decreased absorption may be due to pernicious anemia, surgical removal of the stomach, chronic inflammation of the pancreas, intestinal parasites, certain medications, and some genetic disorders. Decreased intake may occur in those who eat a vegan diet or are malnourished. Increased requirements occur in HIV / AIDS and in those with rapid red blood cell breakdown. Diagnosis is typically based on vitamin B blood levels below 120 -- 180 picomol / L ( 170 -- 250 pg / mL ) in adults. Elevated methylmalonic acid levels ( values > 0.4 micromol / L ) may also indicate a deficiency. A type of low red blood cells known as megaloblastic anemia is often but not always present. Supplementation is recommended to prevent deficiency in vegetarians who are pregnant. Once identified it is easily treated with supplementation by mouth or injection. Excess vitamin B among those who are otherwise healthy is thought to be safe. Some cases may also be helped by treating the underlying cause. Other cases may require ongoing supplementation as the underlying cause is not curable. Vitamin B deficiency is common. It is estimated to occur in about 6 % of those under the age of 60 and 20 % of those over the age of 60. Rates may be as high as 80 % in parts of Africa and Asia. Contents 1 Signs and symptoms 1.1 Psychological 2 Causes 3 Mechanism 3.1 Metabolic 3.2 Pathomorphology 4 Diagnosis 4.1 Effect of folic acid 5 Treatment 6 Epidemiology 7 Veterinary medicine 8 See also 9 References 10 Further reading 11 External links Signs and symptoms Vitamin B deficiency can lead to anemia and neurologic dysfunction. A mild deficiency may not cause any discernible symptoms, but as the deficiency becomes more significant, symptoms of anemia may result, such as weakness, fatigue, light - headedness, rapid heartbeat, rapid breathing and pale color to the skin. It may also cause easy bruising or bleeding, including bleeding gums. GI side effects including sore tongue, stomach upset, weight loss, and diarrhea or constipation. If the deficiency is not corrected, nerve cell damage can result. If this happens, vitamin B deficiency may result in tingling or numbness to the fingers and toes, difficulty walking, mood changes, depression, memory loss, disorientation and, in severe cases, dementia. The main syndrome of vitamin B deficiency is pernicious anemia. It is characterized by a triad of symptoms : Anemia with bone marrow promegaloblastosis ( megaloblastic anemia ). 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. These are thought to be due to defective DNA synthesis inhibiting replication in a site with a high turnover of cells. This may also be due to the autoimmune attack on the parietal cells of the stomach in pernicious anemia. There is an association with GAVE syndrome ( commonly called watermelon stomach ) and pernicious anemia. Neurological symptoms : Sensory or motor deficiencies ( absent reflexes, diminished vibration or soft touch sensation ), subacute combined degeneration of spinal cord, seizures, or even symptoms of dementia and or other psychiatric symptoms may be present. Deficiency symptoms in children include developmental delay, regression, irritability, involuntary movements and hypotonia. The presence of peripheral sensory - motor symptoms or subacute combined degeneration of spinal cord strongly suggests the presence of a B deficiency instead of folate deficiency. Methylmalonic acid, if not properly handled by B, remains in the myelin sheath, causing fragility. Dementia and depression have been associated with this deficiency as well, possibly from the under - production of methionine because of the inability to convert homocysteine into this product. Methionine is a necessary cofactor in the production of several neurotransmitters. Each of those symptoms can occur either alone or along with others. The neurological complex, defined as myelosis funicularis, consists of the following symptoms : Impaired perception of deep touch, pressure and vibration, loss of sense of touch, very annoying and persistent paresthesias Ataxia of dorsal chord type Decrease or loss of deep muscle - tendon reflexes Pathological reflexes -- Babinski, Rossolimo and others, also severe paresis Vitamin B deficiency can cause severe and irreversible damage, especially to the brain and nervous system. These symptoms of neuronal damage may not reverse after correction of hematological abnormalities, and the chance of complete reversal decreases with the length of time the neurological symptoms have been present. Tinnitus may be associated with vitamin B deficiency. Psychological Vitamin B deficiency can also cause symptoms of mania and psychosis, fatigue, memory impairment, irritability, depression, ataxia, and personality changes. In infants symptoms include irritability, failure to thrive, apathy, anorexia, and developmental regression. Causes Inadequate dietary intake of vitamin B. Vitamin B occurs in animal products ( eggs, meat, milk ) and recent research indicates it may also occur in some algae, such as Chlorella and Susabi - nori ( Porphyra yezoensis ). B isolated from bacterial cultures is also added to many fortified foods, and available as a dietary supplement. Vegans, and also vegetarians but to a lesser degree, may be at risk for B deficiency due to inadequate dietary intake of B, if they do not supplement. However, B deficiency can occur even in people who consume meat, poultry, and fish. Children are at a higher risk for B deficiency due to inadequate dietary intake, as they have fewer vitamin stores and a relatively larger vitamin need per calorie of food intake. Selective impaired absorption of vitamin B due to intrinsic factor deficiency. This may be caused by the loss of gastric parietal cells in chronic atrophic gastritis ( in which case, the resulting megaloblastic anemia takes the name of `` pernicious anemia '' ), or may result from wide surgical resection of stomach ( for any reason ), or from rare hereditary causes of impaired synthesis of intrinsic factor. Impaired absorption of vitamin B in the setting of a more generalized malabsorption or maldigestion syndrome. This includes any form of structural damage or wide surgical resection of the terminal ileum ( the principal site of vitamin B absorption ). Forms of achlorhydria ( including that artificially induced by drugs such as proton pump inhibitors and histamine 2 receptor antagonists ) can cause B malabsorption from foods, since acid is needed to split B from food proteins and salivary binding proteins. This process is thought to be the most common cause of low B in the elderly, who often have some degree of achlorhydria without being formally low in intrinsic factor. This process does not affect absorption of small amounts of B in supplements such as multivitamins, since it is not bound to proteins, as is the B in foods. Surgical removal of the small bowel ( for example in Crohn 's disease ) such that the patient presents with short bowel syndrome and is unable to absorb vitamin B. This can be treated with regular injections of vitamin B. Long - term use of ranitidine hydrochloride may contribute to deficiency of vitamin B. Untreated celiac disease may also cause impaired absorption of this vitamin, probably due to damage to the small bowel mucosa. In some people, vitamin B12 deficiency may persist despite treatment with a gluten - free diet and require supplementation. Some bariatric surgical procedures, especially those that involve removal of part of the stomach, such as Roux - en - Y gastric bypass surgery. ( Procedures such as the adjustable gastric band type do not appear to affect B metabolism significantly ). Bacterial overgrowth in parts of the small bowel are thought to be able to absorb B. An example occurs in so - called blind loop syndrome. The diabetes medication metformin may interfere with B dietary absorption. Hereditary causes such as severe MTHFR deficiency, homocystinuria, and transcobalamin deficiency. Malnutrition of alcoholism. Nitrous oxide abuse. Infection with the Diphyllobothrium latum tapeworm Mechanism The total amount of vitamin B stored in the body is between two and five milligrams in adults. Approximately 50 % is stored in the liver, but approximately 0.1 % is lost each day, due to secretions into the gut -- not all of the vitamin in the gut is reabsorbed. While bile is the main vehicle for B excretion, most of the B secreted in bile is recycled via enterohepatic circulation. Due to the extreme efficiency of this mechanism, the liver can store three to five years worth of vitamin B under normal conditions and functioning. However, the rate at which B levels may change when dietary intake is low depends on the balance between several variables. Metabolic Vitamin B deficiency causes particular changes to the metabolism of 2 clinically relevant substances in humans : Homocysteine ( homocysteine to methionine, catalysed by methionine synthase ) leading to hyperhomocysteinemia may lead to varicose veins Methylmalonic acid ( methylmalonyl - CoA to succinyl - CoA, of which methylmalonyl - CoA is made from methylmalonic acid in a preceding reaction ) Methionine is activated to S - adenosyl methionine, which aids in purine and thymidine synthesis, myelin production, protein / neurotransmitters / fatty acid / phospholipid production and DNA methylation. 5 - Methyl tetrahydrofolate provides a methyl group, which is released to the reaction with homocysteine, resulting in methionine. This reaction requires cobalamin as a cofactor. The creation of 5 - methyl tetrahydrofolate is an irreversible reaction. If B is absent, the forward reaction of homocysteine to methionine does not occur, and the replenishment of tetrahydrofolate stops. Because B and folate are involved in the metabolism of homocysteine, hyperhomocysteinuria is a non-specific marker of deficiency. Methylmalonic acid is used as a more specific test of B deficiency. Pathomorphology A spongiform state of neural tissue along with edema of fibers and deficiency of tissue. The myelin decays, along with axial fiber. In later phases, fibric sclerosis of nervous tissues occurs. Those changes apply to dorsal parts of the spinal cord and to pyramidal tracts in lateral cords. The pathophysiologic state of the spinal cord is called subacute combined degeneration of spinal cord. In the brain itself, changes are less severe : They occur as small sources of nervous fibers decay and accumulation of astrocytes, usually subcortically located, and also round hemorrhages with a torus of glial cells. Pathological changes can be noticed as well in the posterior roots of the cord and, to lesser extent, in peripheral nerves. Abnormalities might be observed in MRI. Diagnosis MRI image of the brain in an axial view showing the `` precontrast FLAIR image ''. Note the abnormal lesions ( circled ) in the per ventricular area suggesting white matter pathology in someone with vitamin B12 deficiency. Serum B levels are often low in B deficiency, but if other features of B deficiency are present with normal B then further investigation is warranted. One possible explanation for normal B levels in B deficiency is antibody interference in people with high titres of intrinsic factor antibody. Some researchers propose that the current standard norms of vitamin B levels are too low. One Japanese study states the normal limits as 500 -- 1,300 pg / mL. Range of vitamin B12 levels in humans is considered as normal : > 300 pg / mL ; moderate deficiency : 201 -- 300 pg / mL ; and severe deficiency : < 201 pg / mL. Serum vitamin B tests results are in pg / mL ( picograms / milliliter ) or pmol / L ( pico moles / liter ). The laboratory reference ranges for these units are similar, since the molecular weight of B is approximately 1000, the difference between mL and L. Thus : 550 pg / mL = 400 pmol / L. Serum homocysteine and methylmalonic acid levels are considered more reliable indicators of B deficiency than the concentration of B in blood. The levels of these substances are high in B deficiency and can be helpful if the diagnosis is unclear. Routine monitoring of methylmalonic acid levels in urine is an option for people who may not be getting enough dietary B, as a rise in methylmalonic acid levels may be an early indication of deficiency. If nervous system damage is suspected, B analysis in cerebrospinal fluid is possible, though such an invasive test should be considered only if blood testing is inconclusive. The Schilling test has been largely supplanted by tests for antiparietal cell and intrinsic factor antibodies. Effect of folic acid The National Institutes of Health has found that `` Large amounts of folic acid can mask the damaging effects of vitamin B deficiency by correcting the megaloblastic anemia caused by vitamin B deficiency without correcting the neurological damage that also occurs '', there are also indications that `` high serum folate levels might not only mask vitamin B deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B deficiency ''. Due to the fact that in the United States legislation has required enriched flour to contain folic acid to reduce cases of fetal neural - tube defects, consumers may be ingesting more than they realize. To counter the masking effect of B deficiency the NIH recommends `` folic acid intake from fortified food and supplements should not exceed 1,000 μg daily in healthy adults. '' Most importantly, B deficiency needs to be treated with B repletion. Limiting folic acid will not counter the irrevocable neurological damage that is caused by untreated B deficiency. Treatment Hydroxocobalamin injection is a clear red liquid solution of hydroxocobalamin. B can be supplemented by pill or injection and appear to be equally effective in those with low levels due to absorption problems. When large doses are given by mouth its absorption does not rely on the presence of intrinsic factor or an intact ileum. Generally 1 to 2 mg daily is required as a large dose. Even pernicious anemia can be treated entirely by the oral route. These supplements carry such large doses of the vitamin that 1 % to 5 % of high oral doses of free crystalline B is absorbed along the entire intestine by passive diffusion. Very high doses of B over many years has been linked to an increase in lung cancer risk in male smokers. Epidemiology In the developing world the deficiency is very widespread, with significant levels of deficiency in Africa, India, and South and Central America. This is theorized to be due to low intakes of animal products, particularly among the poor. B deficiency is more common in the elderly. This is because B absorption decreases greatly in the presence of atrophic gastritis, which is common in the elderly. The 2000 Tufts University study found no correlation between eating meat and differences in B serum levels, likely due to a combination of fortified foods and B absorption disorders. Veterinary Medicine Ruminants, such as cows and sheep, absorb B produced by bacteria in their guts. For gut bacteria of ruminants to produce B the animal must consume sufficient amounts of cobalt in order for B to be synthesized. In the early 20th century during the development for farming of the North Island Volcanic Plateau of New Zealand, cattle suffered from what was termed `` bush sickness ''. It was discovered that the volcanic soils lacked the cobalt salts essential for the cattle food chain. The `` coast disease '' of sheep in the Ninety Mile Desert of the Southeast of South Australia in the 1930s was found to originate in nutritional deficiencies of the trace elements, cobalt and copper. The cobalt deficiency was overcome by the development of `` cobalt bullets '', dense pellets of cobalt oxide mixed with clay given orally for lodging in the animal 's rumen. See also Beriberi ( caused by Vitamin B1 deficiency ) References ^ Jump up to : Hunt, A ; Harrington, D ; Robinson, S ( 4 September 2014 ). `` Vitamin B12 deficiency. '' ( PDF ). BMJ ( Clinical research ed. ). 349 : g5226. PMID 25189324. doi : 10.1136 / bmj. g5226. Archived ( PDF ) from the original on 12 March 2017. ^ Jump up to : `` Dietary Supplement Fact Sheet : Vitamin B12 -- Health Professional Fact Sheet ''. National Institutes of Health : Office of Dietary Supplements. 2016 - 02 - 11. 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Annual Review of Nutrition. 19 : 357 -- 77. PMID 10448529. doi : 10.1146 / annurev. nutr. 19.1. 357. Jump up ^ Gille, D ; Schmid, A ( February 2015 ). `` Vitamin B12 in meat and dairy products. ''. Nutrition Reviews. 73 ( 2 ) : 106 -- 15. PMID 26024497. doi : 10.1093 / nutrit / nuu011. ^ Jump up to : McDowell, Lee Russell ( 2008 ). Vitamins in Animal and Human Nutrition. ( 2nd ed. ). Hoboken : John Wiley & Sons. p. 525. ISBN 9780470376683. Archived from the original on 2017 - 09 - 08. Jump up ^ `` Soils ''. Waikato University. Archived from the original on 2012 - 01 - 25. Retrieved 2012 - 01 - 16. Jump up ^ Australian Academy of Science > Deceased Fellows > Hedley Ralph Marston 1900 -- 1965 Archived 2006 - 12 - 06 at the Wayback Machine. Accessed 12 May 2013. Further reading Pacholok SM, Stuart JJ ( 2011 ). Could It Be B12 ? : An Epidemic of Misdiagnoses. Fresno, CA : Linden Publishing. ISBN 978 - 1 - 61035 - 065 - 5. Hooper M ( 2012 ). Pernicious Anaemia : The Forgotten Disease - the causes and consequences of Vitamin B12 Deficiency. London : Hammersmith Press. ISBN 978 - 1 - 78161 - 004 - 6. External links Classification V T D ICD - 10 : E53. 8 ICD - 9 - CM : 266.2 DiseasesDB : 13905 External resources MedlinePlus : 000574 Patient UK : Vitamin B12 deficiency http://www.webmd.com/a-to-z-guides/vitamin-b12-deficiency-anemia-topic-overview WebMD overview Vitamin B12 and Folate at Lab Tests Online Malnutrition or nutrition disorders ( E40 -- E68, 260 -- 269 ) Malnutrition Protein - energy malnutrition Kwashiorkor Marasmus Catabolysis Vitamin deficiency B vitamins B : Beriberi / Wernicke -- Korsakoff syndrome ( Wernicke 's encephalopathy Korsakoff 's syndrome ) B : Riboflavin deficiency B : Pellagra ( Niacin deficiency ) B : Pyridoxine deficiency B : Biotin deficiency B : Folate deficiency B : Vitamin B deficiency Other vitamins A : Vitamin A deficiency / Bitot 's spots C : Scurvy D: Vitamin D deficiency / Rickets / Osteomalacia E : Vitamin E deficiency K : Vitamin K deficiency Mineral deficiency Sodium Potassium Magnesium Calcium Iron Zinc Manganese Copper Iodine Chromium Molybdenum Selenium ( Keshan disease ) Overnutrition Overweight Obesity Childhood obesity Obesity hypoventilation syndrome Abdominal obesity Vitamin poisoning Hypervitaminosis A Hypervitaminosis D Hypervitaminosis E Mineral overload see inborn errors of metal metabolism, toxicity Retrieved from `` https://en.wikipedia.org/w/index.php?title=Vitamin_B12_deficiency&oldid=808101934 '' Categories : Vitamin deficiencies Biology of bipolar disorder Vitamin B12 Hidden categories : CS1 maint : Extra text : authors list Webarchive template wayback links All articles with unsourced statements Articles with unsourced statements from April 2012 Articles with unsourced statements from July 2016 Articles with unsourced statements from May 2017 Articles with unsourced statements from December 2012 RTT RTTEM Talk Contents About Wikipedia Català Deutsch فارسی עברית Lingála 日本 語 ଓଡ଼ିଆ Polski Português Slovenščina Svenska ไทย 中文 Edit links This page was last edited on 31 October 2017, at 22 : 05. 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Question: a severe vitamin b12 deficiency results in what form of anemia
Answer: pernicious