„Vitamin-B12-Mangel“ – Versionsunterschied

aus Wikipedia, der freien Enzyklopädie
Zur Navigation springen Zur Suche springen
Versionsgeschichte interaktiv durchsuchen
[ungesichtete Version][ungesichtete Version]
← Zum vorherigen VersionsunterschiedZum nächsten Versionsunterschied →
Inhalt gelöscht Inhalt hinzugefügt
VisuellWikitext
imported>Biomed author
reference
imported>Biomed author
references
Zeile 18: Zeile 18:


<!-- Cause and diagnosis -->
<!-- Cause and diagnosis -->
Common causes include poor absorption from the stomach or intestines, decreased intake, and increased requirements.<!-- <ref name=BMJ2014/> --> Decreased absorption may be due to [[pernicious anemia]], surgical removal of the stomach, chronic [[pancreatitis|inflammation of the pancreas]], [[intestinal parasite]]s, certain medications, and some [[genetic disorder]]s.<!-- <ref name=BMJ2014/> --> Decreased intake may occur in those who eat a [[vegan diet]] or have [[malnutrition]].<!-- <ref name=BMJ2014/> --> Increased requirements occur in [[HIV/AIDS]] and in those with [[hemolysis|rapid red blood cell breakdown]].<ref name=BMJ2014/> Diagnosis is typically based on vitamin B<sub>12</sub> blood levels below 120–180 picomol/L (170–250 pg/mL) in adults.<!-- <ref name=Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood (2005) 105(3):978–85> --> Elevated [[methylmalonic acid]] levels (values >0.4 micromol/L) may also indicated deficiency.<!-- <ref name=NIH2011/> --> A type of low red blood cells known as [[megaloblastic anemia]] is often but not always present.<ref name=NIH2011/>
Common causes include poor absorption from the stomach or intestines, decreased intake, and increased requirements.<!-- <ref name=BMJ2014/> --> Decreased absorption may be due to [[pernicious anemia]], surgical removal of the stomach, chronic [[pancreatitis|inflammation of the pancreas]], [[intestinal parasite]]s, certain medications, and some [[genetic disorder]]s.<!-- <ref name=BMJ2014/> --> Decreased intake may occur in those who eat a [[vegan diet]] or have [[malnutrition]].<!-- <ref name=BMJ2014/> --> Increased requirements occur in [[HIV/AIDS]] and in those with [[hemolysis|rapid red blood cell breakdown]].<ref name=BMJ2014/> Diagnosis is typically based on vitamin B<sub>12</sub> blood levels below 120–180 picomol/L (170–250 pg/mL) in adults <ref>{{Cite journal|title = Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing|url = http://www.bloodjournal.org/content/105/3/978|journal = Blood|date = 2005-02-01|issn = 0006-4971|pmid = 15466926|pages = 978–985|volume = 105|issue = 3|doi = 10.1182/blood-2004-04-1641|language = en|first = Lawrence R.|last = Solomon}}</ref><ref>{{Cite journal|title = Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice|url = http://journal.frontiersin.org/article/10.3389/fnut.2016.00001/full|journal = Animal Nutrition and Metabolism|date = 2016-01-01|pmc = 4722109|pages = 1|doi = 10.3389/fnut.2016.00001|first = Shampa|last = Ghosh|first2 = Jitendra Kumar|last2 = Sinha|first3 = Uday Kumar|last3 = Putcha|first4 = Manchala|last4 = Raghunath}}</ref>.<!-- <ref name=Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood (2005) 105(3):978–85> --> Elevated [[methylmalonic acid]] levels (values >0.4 micromol/L) may also indicated deficiency.<!-- <ref name=NIH2011/> --> A type of low red blood cells known as [[megaloblastic anemia]] is often but not always present.<ref name=NIH2011/>


<!-- Prevention, treatment, and epidemiology -->
<!-- Prevention, treatment, and epidemiology -->
Zeile 38: Zeile 38:
# Pathological reflexes &mdash; [[Babinski]], [[Rossolimo's sign|Rossolimo]] and others, also severe [[paresis]]
# Pathological reflexes &mdash; [[Babinski]], [[Rossolimo's sign|Rossolimo]] and others, also severe [[paresis]]


Vitamin B<sub>12</sub> 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.
Vitamin B<sub>12</sub> deficiency can cause severe and irreversible damage, especially to the brain and nervous system <ref>{{Cite journal|title = Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes|url = http://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&Cmd=ShowDetailView&TermToSearch=19707742|journal = Diabetologia|date = 2009-11-01|issn = 1432-0428|pmc = 3541499|pmid = 19707742|pages = 2350–2358|volume = 52|issue = 11|doi = 10.1007/s00125-009-1499-0|first = G. V.|last = Krishnaveni|first2 = J. C.|last2 = Hill|first3 = S. R.|last3 = Veena|first4 = D. S.|last4 = Bhat|first5 = A. K.|last5 = Wills|first6 = C. L. S.|last6 = Karat|first7 = C. S.|last7 = Yajnik|first8 = C. H. D.|last8 = Fall}}</ref>. 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.


Vitamin B<sub>12</sub> deficiency symptoms also include shortness of breath and increased pallor.
Vitamin B<sub>12</sub> deficiency symptoms also include shortness of breath and increased pallor.
Zeile 105: Zeile 105:
A study in the year 2000 indicates that B<sub>12</sub> deficiency is far more widespread than formerly believed. The study found that 39 percent of studied group of 3,000 had low values.<ref name="2000 study"/> This [[Tufts University]] study used the B<sub>12</sub> concentration 258 pmol/l (= 350 pg/mL) as a criterion of "low level". However, recent research<ref>{{cite book |last=Thomas |first=Donald |title=New Jump Swing Healthy Aging and Athletic Nutrition Program |publisher=Xlibris |isbn=978-1-4628-8427-8 |page=41 |url=http://books.google.com/?id=1nsURahqYWAC&lpg=PA19&pg=PA40#v=onepage&q&f=false |date=2011-06-22}}</ref> has found that B<sub>12</sub> deficiency may occur at a much higher B<sub>12</sub> concentration (500–600 pg/mL). Against this background, there are reasons to believe that B<sub>12</sub> deficiency is present in a far greater proportion of the population than 39% as reported by Tufts University.
A study in the year 2000 indicates that B<sub>12</sub> deficiency is far more widespread than formerly believed. The study found that 39 percent of studied group of 3,000 had low values.<ref name="2000 study"/> This [[Tufts University]] study used the B<sub>12</sub> concentration 258 pmol/l (= 350 pg/mL) as a criterion of "low level". However, recent research<ref>{{cite book |last=Thomas |first=Donald |title=New Jump Swing Healthy Aging and Athletic Nutrition Program |publisher=Xlibris |isbn=978-1-4628-8427-8 |page=41 |url=http://books.google.com/?id=1nsURahqYWAC&lpg=PA19&pg=PA40#v=onepage&q&f=false |date=2011-06-22}}</ref> has found that B<sub>12</sub> deficiency may occur at a much higher B<sub>12</sub> concentration (500–600 pg/mL). Against this background, there are reasons to believe that B<sub>12</sub> deficiency is present in a far greater proportion of the population than 39% as reported by Tufts University.


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.<ref name="Baik HW, Russell RM 1999 357–77">{{cite journal | vauthors = Baik HW, Russell RM | title = Vitamin B12 deficiency in the elderly | journal = Annual Review of Nutrition | volume = 19 | issue = | pages = 357–77 | year = 1999 | pmid = 10448529 | doi = 10.1146/annurev.nutr.19.1.357 }}</ref>
In the developing world the deficiency is very widespread <ref>{{Cite journal|title = Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice|url = http://journal.frontiersin.org/article/10.3389/fnut.2016.00001/full|journal = Animal Nutrition and Metabolism|date = 2016-01-01|pmc = 4722109|pages = 1|doi = 10.3389/fnut.2016.00001|first = Shampa|last = Ghosh|first2 = Jitendra Kumar|last2 = Sinha|first3 = Uday Kumar|last3 = Putcha|first4 = Manchala|last4 = Raghunath}}</ref>, 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.<ref name="Baik HW, Russell RM 1999 357–77">{{cite journal | vauthors = Baik HW, Russell RM | title = Vitamin B12 deficiency in the elderly | journal = Annual Review of Nutrition | volume = 19 | issue = | pages = 357–77 | year = 1999 | pmid = 10448529 | doi = 10.1146/annurev.nutr.19.1.357 }}</ref>


B<sub>12</sub> deficiency is more common in the elderly.<ref name="Baik HW, Russell RM 1999 357–77"/> This is because B<sub>12</sub> absorption decreases greatly in the presence of [[atrophic gastritis]], which is common in the elderly.
B<sub>12</sub> deficiency is more common in the elderly.<ref name="Baik HW, Russell RM 1999 357–77"/> This is because B<sub>12</sub> absorption decreases greatly in the presence of [[atrophic gastritis]], which is common in the elderly.

Version vom 3. Februar 2016, 19:20 Uhr

Vorlage:Infobox disease Vitamin B12 deficiency, also known as hypocobalaminemia, refers to low blood levels of vitamin B12.[1] A wide variety of signs and symptoms may occur including a decreased ability to think and changes in personality 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.[2] In young children symptoms include poor growth, poor development, and difficulties with movement.[3] Without early treatment some of the changes may be permanent.[4]

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 have malnutrition. Increased requirements occur in HIV/AIDS and in those with rapid red blood cell breakdown.[2] Diagnosis is typically based on vitamin B12 blood levels below 120–180 picomol/L (170–250 pg/mL) in adults [5][6]. Elevated methylmalonic acid levels (values >0.4 micromol/L) may also indicated deficiency. A type of low red blood cells known as megaloblastic anemia is often but not always present.[3]

Supplementation is recommended to prevent deficiency in vegetarians who are pregnant.[3] Once identified it is easily treated with supplementation by mouth or injection.[7] There are no concerns from excess vitamin B12 among those who are otherwise healthy.[3] Some cases may also be helped by treating the underlying cause.[8] Other cases may require ongoing supplementation as the underlying cause is not curable.[9] Vitamin B12 deficiency is common.[2] 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.[2]

Signs and symptoms

Vitamin B12 deficiency can lead to vitamin B12 deficiency 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 B12 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 B12 deficiency is pernicious anemia. It is characterized by a triad of symptoms:

  1. Anemia with bone marrow promegaloblastosis (megaloblastic anemia). This is due to the inhibition of DNA synthesis (specifically purines and thymidine)
  2. Gastrointestinal symptoms: alteration in bowel motility, such as mild diarrhea or constipation, and loss of bladder or bowel control.[10] 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.[11]
  3. Neurological symptoms: Sensory or motor deficiencies (absent reflexes, diminished vibration or soft touch sensation), subacute combined degeneration of spinal cord, seizures,[12][13][14][15] or even symptoms of dementia [16] and or other psychiatric symptoms may be present. The presence of peripheral sensory-motor symptoms or subacute combined degeneration of spinal cord strongly suggests the presence of a B12 deficiency instead of folate deficiency. Methylmalonic acid, if not properly handled by B12, 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:

  1. Impaired perception of deep touch, pressure and vibration, loss of sense of touch, very annoying and persistent paresthesias
  2. Ataxia of dorsal chord type
  3. Decrease or loss of deep muscle-tendon reflexes
  4. Pathological reflexes — Babinski, Rossolimo and others, also severe paresis

Vitamin B12 deficiency can cause severe and irreversible damage, especially to the brain and nervous system [17]. 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.

Vitamin B12 deficiency symptoms also include shortness of breath and increased pallor.

Psychological

Vitamin B12 deficiency can also cause symptoms of mania and psychosis, fatigue, memory impairment, irritability, depression, ataxia, and personality changes.[18][19][20] In infants symptoms include irritability, failure to thrive, apathy, anorexia, and developmental regression.[21][22]

Causes

  • Inadequate dietary intake of vitamin B12. Vitamin B12 occurs in animal products (eggs, meat, milk) and recent research indicates it may also occur in some algae, such as Chlorella[23][24][25] and Susabi-nori (Porphyra yezoensis).[26][27] B12 isolated from bacterial cultures is also added to many fortified foods, and available as a dietary supplement [28] Vegans, and also vegetarians but to a lesser degree, may be at risk for B12 deficiency due to inadequate dietary intake of B12, if they do not supplement. However, B12 deficiency can occur even in people who consume meat, poultry, and fish.[29] Children are at a higher risk for B12 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 B12 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 B12 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 B12 absorption).
  • Forms of achlorhydria (including that artificially induced by drugs such as proton pump inhibitors and histamine 2 receptor antagonists) can cause B12 malabsorption from foods, since acid is needed to split B12 from food proteins and salivary binding proteins.[30] This process is thought to be the most common cause of low B12 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 B12 in supplements such as multivitamins, since it is not bound to proteins, as is the B12 in foods.Vorlage:Citation needed
  • 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 B12. This can be treated with regular injections of vitamin B12.
  • Long-term use of ranitidine hydrochloride may contribute to deficiency of vitamin B12.[31]
  • Celiac disease may also cause impaired absorption of this vitamin, though this is due not to loss of intrinsic factor, but rather damage to the small bowel.Vorlage:Citation needed
  • 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 B12 metabolism significantly).Vorlage:Citation needed
  • Bacterial overgrowth in parts of the small bowel are thought to be able to absorb B12. An example occurs in so-called blind loop syndrome.Vorlage:Citation needed
  • The diabetes medication metformin may interfere with B12 dietary absorption.[32]
  • Hereditary causes such as severe MTHFR deficiency, homocystinuria, and transcobalamin deficiency.Vorlage:Citation needed
  • One anecdotal study has shown that giardiasis may be a cause of vitamin B12 deficiency,[33] but larger studies have shown no correlation.[34]
  • Malnutrition of alcoholism.
  • Nitrous oxide abuse.[35]

Mechanism

The total amount of vitamin B12 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 B12 excretion, most of the B12 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 B12 under normal conditions and functioning.[36] However, the rate at which B12 levels may change when dietary intake is low depends on the balance between several variables.[37]

Metabolic

Vitamin B12 deficiency causes particular changes to the metabolism of 2 clinically relevant substances in humans:

  1. Homocysteine (homocysteine to methionine, catalysed by methionine synthase) leading to hyperhomocysteinemia may lead to varicose veins
  2. 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 B12 is absent, the forward reaction of homocysteine to methionine does not occur, and the replenishment of tetrahydrofolate stops.[38]

Because B12 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 B12 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.[39]

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.[40]

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 B12 levels are often low in B12 deficiency, but if other features of B12 deficiency are present with normal B12 then further investigation is warranted. One possible explanation for normal B12 levels in B12 deficiency is antibody interference in people with high titres of intrinsic factor antibody.[41] Some researchers propose that the current standard norms of vitamin B12 levels are too low.[42] One Japanese study states the normal limits as 500–1,300 pg/mL.[43]

Serum vitamin B12 tests results are in pg/mL (picograms/milliliter) or pmol/L (picomoles/liter). The laboratory reference ranges for these units are similar, since the molecular weight of B12 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 B12 deficiency than the concentration of B12 in blood.[44] The levels of these substances are high in B12 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 B12, as a rise in methylmalonic acid levels may be an early indication of deficiency.[45]

If nervous system damage is suspected, B12 analysis in cerebrospinal fluid is possible, though such an invasive test should be considered only if blood testing is inconclusive.[46]

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 B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency without correcting the neurological damage that also occurs", there are also indications that "high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency".[47] 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.[48] To counter the masking effect of B12 deficiency the NIH recommends "folic acid intake from fortified food and supplements should not exceed 1,000 μg daily in healthy adults."[47] Most importantly, B12 deficiency needs to be treated with B12 repletion. Limiting folic acid will not counter the irrevocable neurological damage that is caused by untreated B12 deficiency.Vorlage:Citation needed

Treatment

Hydroxocobalamin injection is a clear red liquid solution of hydroxocobalamin.

B12 can be supplemented by pill or injection and appear to be equally effective in those with low levels.[7]

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.[49]

Epidemiology

A study in the year 2000 indicates that B12 deficiency is far more widespread than formerly believed. The study found that 39 percent of studied group of 3,000 had low values.[29] This Tufts University study used the B12 concentration 258 pmol/l (= 350 pg/mL) as a criterion of "low level". However, recent research[50] has found that B12 deficiency may occur at a much higher B12 concentration (500–600 pg/mL). Against this background, there are reasons to believe that B12 deficiency is present in a far greater proportion of the population than 39% as reported by Tufts University.

In the developing world the deficiency is very widespread [51], 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.[52]

B12 deficiency is more common in the elderly.[52] This is because B12 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 B12 serum levels.[29]

See also

  • Beriberi (caused by Vitamin B1 deficiency)

References

Vorlage:Reflist

Further reading

  • Sally M. Pacholok, Jeffrey J. Stuart: Could It Be B12?: An Epidemic of Misdiagnoses. Linden Publishing, 2011, ISBN 978-1-61035-065-5.
  • M. Hooper: Pernicious Anaemia: The Forgotten Disease - the causes and consequences of Vitamin B12 Deficiency. Hammersmith Press, 2012, ISBN 978-1-78161-004-6.

External links

Vorlage:Nutritional pathology

  1. ↑ Wolfgang Herrmann: Vitamins in the prevention of human diseases. Walter de Gruyter, Berlin 2011, ISBN 978-3-11-021448-2, S. 245 (google.it).
  2. ↑ a b c d A Hunt, D Harrington, S Robinson: Vitamin B12 deficiency. In: BMJ (Clinical research ed.). 349. Jahrgang, 4. September 2014, S. g5226, doi:10.1136/bmj.g5226, PMID 25189324.
  3. ↑ a b c d Vitamin B12 Dietary Supplement Fact Sheet. 24. Juni 2011, abgerufen am 21. April 2015.
  4. ↑ C Lachner, NI Steinle, WT Regenold: The neuropsychiatry of vitamin B12 deficiency in elderly patients. In: The Journal of neuropsychiatry and clinical neurosciences. 24. Jahrgang, Nr. 1, 2012, S. 5–15, doi:10.1176/appi.neuropsych.11020052, PMID 22450609.
  5. ↑ Lawrence R. Solomon: Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. In: Blood. 105. Jahrgang, Nr. 3, 1. Februar 2005, ISSN 0006-4971, S. 978–985, doi:10.1182/blood-2004-04-1641, PMID 15466926 (englisch, bloodjournal.org).
  6. ↑ Shampa Ghosh, Jitendra Kumar Sinha, Uday Kumar Putcha, Manchala Raghunath: Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice. In: Animal Nutrition and Metabolism. 1. Januar 2016, S. 1, doi:10.3389/fnut.2016.00001, PMC 4722109 (freier Volltext) – (frontiersin.org).
  7. ↑ a b J Vidal-Alaball, CC Butler, R Cannings-John, A Goringe, K Hood, A McCaddon, I McDowell, A Papaioannou: Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. In: The Cochrane database of systematic reviews. Nr. 3, 20. Juli 2005, S. CD004655, doi:10.1002/14651858.CD004655.pub2, PMID 16034940.
  8. ↑ Graeme J. Hankey, Joanna M. Wardlaw: Clinical neurology. Manson, London 2008, ISBN 978-1-84076-518-2, S. 466 (google.it).
  9. ↑ William Schwartz: The 5-minute pediatric consult. 6th Auflage. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia 2012, ISBN 978-1-4511-1656-4, S. 535 (google.it).
  10. ↑ Chiara Briani, Chiara Torre, Valentina Citton, Renzo Manara, Sara Pompanin, Gianni Binotto, Fausto Adami: Cobalamin Deficiency: Clinical Picture and Radiological Findings. In: Nutrients. 5. Jahrgang, Nr. 11, 2013, ISSN 2072-6643, S. 4521–4539, doi:10.3390/nu5114521, PMID 24248213, PMC 3847746 (freier Volltext).
  11. ↑ DN Amarapurka MD, ND Patel MD: Gastric Antral Vascular Ectasia Syndrome. In: Journal of The Association of Physcians of India. 52. Jahrgang, September 2004, S. 757.
  12. ↑ Matsumoto A, Shiga Y, Shimizu H, Kimura I, Hisanaga K: [Encephalomyelopathy due to vitamin B12 deficiency with seizures as a predominant symptom]. In: Rinshō Shinkeigaku = Clinical Neurology. 49. Jahrgang, Nr. 4, April 2009, S. 179–85, doi:10.5692/clinicalneurol.49.179, PMID 19462816 (jst.go.jp).
  13. ↑ Kumar S: Recurrent seizures: an unusual manifestation of vitamin B12 deficiency. In: Neurology India. 52. Jahrgang, Nr. 1. Neurologyindia.com, März 2004, S. 122–123, PMID 15069260 (neurologyindia.com).
  14. ↑ Mustafa TAŞKESEN, Ahmet YARAMIŞ, Selahattin KATAR, Ayfer GÖZÜ PİRİNÇÇİOĞLU, Murat SÖKER: Neurological presentations of nutritional vitamin B12 deficiency in 42 breastfed infants in Southeast Turkey. In: Turk J Med Sci. 41. Jahrgang, Nr. 6, S. 1091–1096 (gov.tr [PDF; abgerufen am 29. Dezember 2013]).
  15. ↑ Yavuz H: 'Vitamin B12 deficiency and seizures'. In: Developmental Medicine and Child Neurology. 50. Jahrgang, Nr. 9, September 2008, S. 720, doi:10.1111/j.1469-8749.2008.03083.x, PMID 18754925 (wiley.com).
  16. ↑ Reversible dementia in young persons due to cobalamin deficiency. Kumar S, Narasimha A, Holla B, Viswanath B, Narayanaswamy JC, Math SB, Chandrashekar CR. The Journal of Neuropsychiatry and Clinical Neurosciences 2013;25:E62-E63. doi:10.1176/appi.neuropsych.12040083 http://journals.psychiatryonline.org/article.aspx?articleid=1660553
  17. ↑ G. V. Krishnaveni, J. C. Hill, S. R. Veena, D. S. Bhat, A. K. Wills, C. L. S. Karat, C. S. Yajnik, C. H. D. Fall: Low plasma vitamin B12 in pregnancy is associated with gestational 'diabesity' and later diabetes. In: Diabetologia. 52. Jahrgang, Nr. 11, 1. November 2009, ISSN 1432-0428, S. 2350–2358, doi:10.1007/s00125-009-1499-0, PMID 19707742, PMC 3541499 (freier Volltext) – (nih.gov).
  18. ↑ Sethi NK, Robilotti E, Sadan Y: Neurological Manifestations Of Vitamin B-12 Deficiency. In: The Internet Journal of Nutrition and Wellness. 2. Jahrgang, Nr. 1, 2005, doi:10.5580/5a9 (ispub.com).
  19. ↑ Masalha R, Chudakov B, Muhamad M, Rudoy I, Volkov I, Wirguin I: Cobalamin-responsive psychosis as the sole manifestation of vitamin B12 deficiency. In: The Israel Medical Association Journal. 3. Jahrgang, Nr. 9, September 2001, S. 701–703, PMID 11574992 (org.il).
  20. ↑ Pernicious anemia: MedlinePlus Medical Encyclopedia. Nlm.nih.gov, abgerufen am 29. Dezember 2013.
  21. ↑ Dror DK, Allen LH: Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. In: Nutrition Reviews. 66. Jahrgang, Nr. 5, Mai 2008, S. 250–5, doi:10.1111/j.1753-4887.2008.00031.x, PMID 18454811 (doi.org).
  22. ↑ Black MM: Effects of vitamin B12 and folate deficiency on brain development in children. In: Food and Nutrition Bulletin. 29. Jahrgang, 2 Suppl, Juni 2008, S. S126–31, PMID 18709887, PMC 3137939 (freier Volltext).
  23. ↑ Kittaka-Katsura H, Fujita T, Watanabe F, Nakano Y: Purification and characterization of a corrinoid compound from Chlorella tablets as an algal health food. In: Journal of Agricultural and Food Chemistry. 50. Jahrgang, Nr. 17, August 2002, S. 4994–7, doi:10.1021/jf020345w, PMID 12166996.
  24. ↑ Watanabe F, Takenaka S, Kittaka-Katsura H, Ebara S, Miyamoto E: Characterization and bioavailability of vitamin B12-compounds from edible algae. In: Journal of Nutritional Science and Vitaminology. 48. Jahrgang, Nr. 5, Oktober 2002, S. 325–31, doi:10.3177/jnsv.48.325, PMID 12656203.
  25. ↑ Nakano S, Takekoshi H, Nakano M: Chlorella pyrenoidosa supplementation reduces the risk of anemia, proteinuria and edema in pregnant women. In: Plant Foods for Human Nutrition. 65. Jahrgang, Nr. 1, März 2010, S. 25–30, doi:10.1007/s11130-009-0145-9, PMID 20013055.
  26. ↑ Watanabe F, Takenaka S, Katsura H, Miyamoto E, Abe K, Tamura Y, Nakatsuka T, Nakano Y: Characterization of a vitamin B12 compound in the edible purple laver, Porphyra yezoensis. In: Bioscience, Biotechnology, and Biochemistry. 64. Jahrgang, Nr. 12, Dezember 2000, S. 2712–5, doi:10.1271/bbb.64.2712, PMID 11210144.
  27. ↑ Croft MT, Lawrence AD, Raux-Deery E, Warren MJ, Smith AG: Algae acquire vitamin B12 through a symbiotic relationship with bacteria. In: Nature. 438. Jahrgang, Nr. 7064, November 2005, S. 90–3, doi:10.1038/nature04056, PMID 16267554.
  28. ↑ Martens JH, Barg H, Warren MJ, Jahn D: Microbial production of vitamin B12. In: Applied Microbiology and Biotechnology. 58. Jahrgang, Nr. 3, März 2002, S. 275–85, doi:10.1007/s00253-001-0902-7, PMID 11935176.
  29. ↑ a b c Judy McBride: B12 Deficiency May Be More Widespread Than Thought. In: Agricultural Research Service. United States Department of Agriculture, 2. August 2000, abgerufen am 2. Juli 2012.
  30. ↑ Lam JR, Schneider JL, Zhao W, Corley DA: Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. In: Jama. 310. Jahrgang, Nr. 22, Dezember 2013, S. 2435–2442, doi:10.1001/jama.2013.280490, PMID 24327038.
  31. ↑ Yeomans ND, Hanson RG, Smallwood RA, Mihaly GW, Louis WJ: Effect of chronic ranitidine treatment on secretion of intrinsic factor. In: Br Med J (Clin Res Ed). 285. Jahrgang, Nr. 6337, 1982, S. 264, doi:10.1136/bmj.285.6337.264, PMID 6124297, PMC 1499627 (freier Volltext).
  32. ↑ Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM: Risk factors of vitamin B(12) deficiency in patients receiving metformin. In: Archives of Internal Medicine. 166. Jahrgang, Nr. 18, Oktober 2006, S. 1975–9, doi:10.1001/archinte.166.18.1975, PMID 17030830.
  33. ↑ Cordingley FT, Crawford GP: Giardia infection causes vitamin B12 deficiency. In: Australian and New Zealand Journal of Medicine. 16. Jahrgang, Nr. 1, Februar 1986, S. 78–9, doi:10.1111/j.1445-5994.1986.tb01127.x, PMID 3458451.
  34. ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640781/pdf/ijph-41-47.pdf
  35. ↑ Kondo H, Osborne ML, Kolhouse JF, Binder MJ, Podell ER, Utley CS, Abrams RS, Allen RH: Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats. In: The Journal of Clinical Investigation. 67. Jahrgang, Nr. 5. The American Society For Clinical Investigation, Mai 1981, S. 1270–1283, doi:10.1172/JCI110155, PMID 6112240, PMC 370693 (freier Volltext).
  36. ↑ Voet, Donald, Voet, Judith G.: Biochemistry. J. Wiley & Sons, New York 2010, ISBN 978-0-470-57095-1, S. 957.
  37. ↑ Kazuhiro Yamada: Interrelations between Essential Metal Ions and Human Diseases. Hrsg.: Astrid Sigel, Helmut Sigel and Roland K. O. Sigel (= Metal Ions in Life Sciences. Band 13). Springer, 2013, Chapter 9. Cobalt: Its Role in Health and Disease, S. 295–320, doi:10.1007/978-94-007-7500-8_9.
  38. ↑ Shane B, Stokstad EL: Vitamin B12-folate interrelationships. In: Annual Review of Nutrition. 5. Jahrgang, 1985, S. 115–41, doi:10.1146/annurev.nu.05.070185.000555, PMID 3927946.
  39. ↑ Vitamin B12 / Pathophysiology Text. LifeSave.org, S. 215, abgerufen am 31. Dezember 2013.
  40. ↑ Guez S, Chiarelli G, Menni F, Salera S, Principi N, Esposito S: Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy. In: BMC Pediatrics. 12. Jahrgang. Biomedcentral.com, 2012, S. 85, doi:10.1186/1471-2431-12-85, PMID 22726312 (biomedcentral.com).
  41. ↑ Hamilton MS, Blackmore S, Lee A: Possible cause of false normal B-12 assays. In: Bmj. 333. Jahrgang, Nr. 7569, September 2006, S. 654–5, doi:10.1136/bmj.333.7569.654-c, PMID 16990334, PMC 1570871 (freier Volltext).
  42. ↑ Goodman M, Chen XH, Darwish D: Are U.S. lower normal B12 limits too low? In: Journal of the American Geriatrics Society. 44. Jahrgang, Nr. 10, Oktober 1996, S. 1274–5, doi:10.1111/j.1532-5415.1996.tb01389.x, PMID 8856015.
  43. ↑ Mitsuyama Y, Kogoh H: Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment--preliminary study. In: The Japanese Journal of Psychiatry and Neurology. 42. Jahrgang, Nr. 1, März 1988, S. 65–71, doi:10.1111/j.1440-1819.1988.tb01957.x, PMID 3398357.
  44. ↑ Test used to diagnose B12 deficiency may be inadequate, news-medical.net, October 28, 2004. Abgerufen am 4. Dezember 2007 
  45. ↑ Donaldson MS: Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. In: Annals of Nutrition & Metabolism. 44. Jahrgang, Nr. 5-6, 2000, S. 229–34, doi:10.1159/000046689, PMID 11146329 (karger.com).
  46. ↑ Devalia V: Diagnosing vitamin B-12 deficiency on the basis of serum B-12 assay. In: Bmj. 333. Jahrgang, Nr. 7564, August 2006, S. 385–6, doi:10.1136/bmj.333.7564.385, PMID 16916826, PMC 1550477 (freier Volltext).
  47. ↑ a b Dietary Supplement Fact Sheet:Vitamin B12. National Institutes of Health;
  48. ↑ Melinda Beck: Sluggish? Confused? Vitamin B12 May Be Low, Wall Street Journal, January 18, 2011 
  49. ↑ Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J: Effective treatment of cobalamin deficiency with oral cobalamin. In: Blood. 92. Jahrgang, Nr. 4, August 1998, S. 1191–1198, PMID 9694707 (bloodjournal.org).
  50. ↑ Donald Thomas: New Jump Swing Healthy Aging and Athletic Nutrition Program. Xlibris, 2011, ISBN 978-1-4628-8427-8, S. 41 (google.com).
  51. ↑ Shampa Ghosh, Jitendra Kumar Sinha, Uday Kumar Putcha, Manchala Raghunath: Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice. In: Animal Nutrition and Metabolism. 1. Januar 2016, S. 1, doi:10.3389/fnut.2016.00001, PMC 4722109 (freier Volltext) – (frontiersin.org).
  52. ↑ a b Baik HW, Russell RM: Vitamin B12 deficiency in the elderly. In: Annual Review of Nutrition. 19. Jahrgang, 1999, S. 357–77, doi:10.1146/annurev.nutr.19.1.357, PMID 10448529.
Abgerufen von „https://de.wikipedia.org/w/index.php?title=Vitamin-B12-Mangel&oldid=152177115“