Vitamin B12 Deficiency: Difference between revisions

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== Introduction ==
== Introduction ==
Vitamin B12 deficiency is one of the most prevalent nutritional deficiencies. It causes a range of symptoms, such as fatigue, forgetfulness, and tingling of the hands and feet. The reason for the wide variety of symptoms is that vitamin B12 plays a principal role in numerous body functions.[[File:Vitamin_B12.jpeg|right|frameless|A vial of Vitamin B12 with syringe]]
[[File:Vitamin_B12.jpeg|A vial of Vitamin B12|alt=|thumb]]
Vitamin B12 is a water-soluble vitamin that is essential for DNA synthesis. Vitamin B12 deficiency is an often overlooked deficiency and was at one time thought to be mainly found in vegetarians<ref name=":0" /><ref name=":1">Stabler SP. Vitamin B12 deficiency. New England Journal of Medicine. 2013 Jan 10;368(2):149-60.</ref>. However, studies have found it is much more common in young people throughout their lifespan in developing countries and poorer populations whereas in wealthier nations it is seen more commonly in the elderly, or HIV-infected patients<ref name=":0">Allen LH. How common is vitamin B-12 deficiency?. The American journal of clinical nutrition. 2009 Feb 1;89(2):693S-6S.</ref>. Common sources of this vitamin can be found in many of the foods we eat such as fish, meat, eggs, and dairy products. It is recommended that adults receive 2.4 micrograms of vitamin B12 daily. In order for vitamin B12 to be absorbed by the body, the body has to have proper amounts of intrinsic factor (IF). Intrinsic Factor helps to absorb vitamin B12 in digestion. When there is a decline in IF, vitamin B12 cannot be absorbed and this causes pernicious anaemia.&nbsp;<ref name="Mayoclinic">Mayoclinic [https://www.mayoclinic.org/drugs-supplements-vitamin-b12/art-20363663 Drugs and Supplements:Vitamin B12 Deficiency.]  Available from:<nowiki>http://www.mayoclinic.org/drugs-supplements/vitamin-b12/background/hrb-20060243</nowiki>. (last accessed 16.5.2019)</ref>
Vitamin B12 deficiency is one of the most prevalent nutritional deficiencies. It causes a range of symptoms, eg fatigue, forgetfulness, and tingling of the hands and feet.  


Vitamin B12 deficiency, also known as Cobalamin deficiency is&nbsp;difficult to define. There is some debate on appropriate metabolic levels that should classify vitamin B12 deficiency. Previously, the cutoff metabolic levels were anything less than 200 pg/mL.<ref name="CDC">Center of Disease control [http://www.cdc.gov/ncbddd/b12/intro.html. Vitamin B12 Deficiency .] Available at:http://www.cdc.gov/ncbddd/b12/intro.html. (last accessed 16.5.2019)</ref> However, levels have been raised to anything less than 250-300 pg/mL.<ref name="Berg">Berg R, Shaw G. Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing. Clinical and Medical Research. 2013; 11(1): 7-15.</ref><ref name="Leishear">Leishear K et al. The Relationship of Vitamin B12 and Sensory and Motor Peripheral Nerve Function in Older Adults. J Am Geriatr Soc. 2012 June;60(6): 1057–1063.</ref>
The reason for the wide variety of symptoms is that vitamin B12 plays a principal role in numerous body functions eg
== Prevalence  ==


Clinical prevalence of vitamin B12 deficiency is very hard to determine. This is mostly due to the lack of agreement of what metabolic level actually defines vitamin B12 deficiency. Also, deficiency in this vitamin is assumed to be caused by inadequate intake. This may cause the prevalence to be underestimated because even those who get B12 in their diet can still have malabsorption issues. It is common to have mild or subclinical vitamin B12 deficiency and less common to have severe or clinical vitamin B12 deficiency. The National Health and Nutrition Examination Survey estimated that between the years of 2001 and 2004, 1 out of 31 adutls that were older than 51 years was deficient in vitamin B12. The most at risk populations are elderly adults and adults of Northern European or African American Decent. This study based their cutoff metabolic levels at 200 pg/mL. Some studies use higher cutoff levels, and therefore may see a higher incidence of deficiency. <ref name="CDC" />  
# Essential for DNA synthesis. DNA (central information storage system of most animals, plants, and even some [[Viral Infections|virus]]<nowiki/>es), directs proper formation of every part of the body. <ref>Allen LH. Vitamin b-12. Advances in Nutrition. 2012 Jan;3(1):54-5. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262614/]</ref>
# Vitamin B12 deficiency increases homocysteine levels (normally degraded by vitimain B 12) which causes inflammation and toxic damage to the body. Elevated homocysteine increases your risks for [[dementia]], heart disease and [[stroke]], as it .<ref name=":0">Very well health How Vitamin B12 Deficiency Affects the Body Available: https://www.verywellfit.com/causes-and-effects-of-vitamin-b12-deficiency-4126428<nowiki/>(accessed 12.4.2022)</ref>
== Vitamin B12 Uptake ==
[[File:What is Crohn's disease.jpg|right|frameless]]
Vitamin B12 is bound to [[Proteins|protein]] in food and must be released before it is absorbed. The process starts in the mouth when food is mixed with saliva. The freed vitamin B12 then binds with haptocorrin (protects acid sensitive B12 as it moves through the stomach). In the duodenum, digestive [[enzymes]] free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic factor, a transport and delivery binding protein secreted by the stomach’s parietal (lining) cells. The resulting complex is absorbed in the distal ileum by receptor-mediated endocytosis. If vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and therefore does not require the separation step<ref name=":1">NIH Vit B 12 Available:https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ (accessed 12.4.2022)</ref>.
 
== Etiology ==
Causes of vitamin B12 deficiency include:
 
* Difficulty absorbing vitamin B12 from food, eg any patient with a history of gastric bypass surgery may be at risk; surgical resection terminal ileum due to eg [[Crohn's Disease|Crohn's disease]]; damage to the small intestine, eg inflammation from [[Celiac Disease|celiac disease]] or infection with the tapeworm.
* Autoimmune: Pernicious [[Anaemia|anemia]] is an [[Autoimmune Disorders|autoimmune condition]] in which [[Immunoglobulins (Ig)|antibodies]] to intrinsic factor are produced. Anti-intrinsic factor antibodies bind to and inhibit the effects of intrinsic factor, resulting in an inability of B12 to be absorbed by the terminal ileum.
* Prolonged use of certain medications e.g. [[metformin]], proton pump inhibitors.
* Dietary Insufficiency: Vitamin B12 is stored in excess in the liver; however, patients who have followed a strict vegan diet for approximately three years may develop a B12 deficiency from a lack of dietary intake<ref name=":1" />.
 
== Risk Factors ==
The following groups are among those most likely to be vitamin B12 deficient.
 
* [[Older People - An Introduction|Older adults]]: Between 3% and 43% of community-dwelling older adults, especially those with atrophic gastritis (an autoimmune condition) have vitamin B12 deficiency.
* Conditions associated with vitamin B12 inadequacy include: pernicious anemia; Atrophic gastritis,  affects 8–9% of adults aged 65 and older; Helicobacter pylori infection, inflammation leads to malabsorption of vitamin B12 from food.
* Individuals with gastrointestinal disorders or who have had gastrointestinal surgery
* Vegetarians and Infants of vegan women


The below video gives a good summary of the condition
The below video gives a good summary of the condition
{{#ev:youtube|https://www.youtube.com/watch?v=i3A7PLhrDck|width}}<ref>Healthline 5 signs and symptoms of vitamin B 12 deficiency. Available from: https://www.youtube.com/watch?v=i3A7PLhrDck (last accessed 15.5.2019)</ref>  
{{#ev:youtube|https://www.youtube.com/watch?v=i3A7PLhrDck|width}}<ref>Healthline 5 signs and symptoms of vitamin B 12 deficiency. Available from: https://www.youtube.com/watch?v=i3A7PLhrDck (last accessed 15.5.2019)</ref>  
== Characteristics/Clinical Presentation  ==
== Characteristics/Clinical Presentation  ==
 
[[File:Fatigue2.jpeg|thumb|Fatigue a common sign in many diseases]]
The most common sign of vitamin B12 deficiency is Fatigue. This is caused by the lack of red blood cells to carry oxygen to body tissue.  
The most common sign of vitamin B12 deficiency is Fatigue. This is caused by the lack of red blood cells to carry oxygen to body tissue.<br>Lack of red [[blood]] cells may also cause:  
 
<br>Lack of red [[blood]] cells may also cause:  
* Weakness
* Weakness
* Shortness of breath
* Shortness of breath
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* Soreness of mouth <ref name="Pernicious Anemia">Nation Institutes of Health [http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/. Pernicious Anemia]  Available at:http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/.</ref><ref name="NIH">National Institutes of Health [http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h5. Vitamin B12] Available at http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h5.</ref>
* Soreness of mouth <ref name="Pernicious Anemia">Nation Institutes of Health [http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/. Pernicious Anemia]  Available at:http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/.</ref><ref name="NIH">National Institutes of Health [http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h5. Vitamin B12] Available at http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h5.</ref>


== Associated Co-morbidities  ==
== Treatment ==
 
Vitamin B12 deficiency can be managed with supplemental B12. This could be an oral supplement or an injection. If B12 deficiency is caused by a problem with absorption, an injection of B12 will help the vitamin to be absorbed directly into the body.
Vitamin B12 deficiency typically is a co-morbidity of several conditions. Although each patient presents very differently with associated co-morbidities, there are five major conditions that are most commonly seen with Vitamin B12 deficiency.  
 
'''Comorbidities include:'''<ref name="C Def" /><ref name="DD" />
* Gastrointestinal Disorders
* [[Diabetes]]<ref name=":1" />
* Pernicious Anaemia
* [[Depression]]
* Liver or Kidney Disease
 
==  Medications ==
There are several different medications that are thought to affect the absorption of vitamin B12.&nbsp; Although evidence suggests that medications could have an effect on absorption, there is not sufficient evidence to prove that they do.&nbsp; However, patients that use these medications should keep track of their vitamin B12 levels.&nbsp;
 
Medications that can interfere with the absorption of vitamin B12 include:


-Chloramphenicol (antibiotic) May interfere with the RBC response to Vit. B12<br>-Proton Pump Inhibitors (Prilosec) These medications slow down the absorption of Vit. B12.&nbsp; They do this because they slowly release acid into the stomach. <br><br>-H2 Receptor Antagonist (Pepcid, Zantac) These medications slow down the absorption of Vit. B12 by releasing hydrochloric acid into the stomach.<br>-Metformin (Hypoglycemic used for diabetes) May alter the mobility and bacteria in the intestines or may alter the intrinsic factor needed to absorb Vit. B12. <ref name="NIH" /><br>
Some patients need lifelong B12 supplementation. This usually depends on the cause of the deficiency, possibly with the need to continue taking B12 supplements even after symptoms have improved.


== Diagnostic Tests/Lab Tests/Lab Values  ==
Recovery from vitamin B12 deficiency takes time. Improvement may be gradual and may continue for up to six to 12 months<ref name=":0" />.
 
There are a few diagnostic tests used to diagnose a Vitamin B12 deficiency. The most common tests used include:
 
*Study of Gastric function: includes an examination of the acid contents found in gastric juices and the presence of gastric intrinsic factor (IF). This study will help differentiate between Imerslund-Grasbeck Syndrome, juvenile pernicious anaemia, and Vitamin B12 deficiency. The acidity of gastric juices is high and IF is present in Imerslund-Grasbeck Syndrome. In juvenile pernicious anaemia, both factors are decreased, and in Vitamin B12 deficiency the IF is absent or below normal values.<ref name="C Def">Adami F, Binotto G, Briani C et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847746/ Cobalamin Deficiency: Clinical Picture and Radiological Findings.] Nutrients. 2013 Nov 15 . Available from PubMed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847746/</ref>&nbsp; <ref name="Berg" />
*Elevated Methylmalonic Acid (MMA) &gt;0.30 umol/L. MMA is useful to identify vitamin B12 metabolism activity. Kidney disorders should be identified before a Vitamin B12 diagnosis is made.<ref name="C Def" />&nbsp; <ref name="Berg" /><ref name="O'Leary">O’Leary F, Samman S. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257642/pdf/nutrients-02-00299.pdf Vitamin B12 in Health and Disease.] Nutrients. 2010 Feb 2 ;2:299-316. Available from PubMed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257642/pdf/nutrients-02-00299.pdf</ref>
*Elevated Hemocysteine (tHccy) &gt;13mmol/L in females and &gt; 15 mmol/L in males. Any folate deficiencies must be ruled out.<ref name="O'Leary" />
*Decreased serum Vitamin B12 (cobalamin) levels &lt;148-258 pmol/L.&nbsp;<ref name="C Def" />&nbsp;<ref name="Berg" /><ref name="O'Leary" />
*Schilling Test is less commonly used clinically. It is performed by giving the patient an oral medication and collecting a urine sample 24hrs after administration.<ref name="C Def" /> <ref name="Berg" /><br>
 
In current research, there is a great deal of variability in which diagnostic tests hold the greatest value in diagnosing Vitamin B12 deficiency. There is also a great deal of disagreement in the cut-off values for each lab test performed. <ref name="C Def" /> <ref name="Berg" /><ref name="O'Leary" />
 
== Aetiology/Causes  ==
 
<br>There are many things that can cause a vitamin B12 deficiency:<br>Lack of Intrinsic Factor:<br>A lack of intrinsic factor (IF) may cause a vitamin B12 deficiency.&nbsp; This is an essential protein in the small intestine that allows vitamin B12 to be absorbed.&nbsp; Decreased production of IF can occur during middle age, leaving many elderly adults at risk. Atrophic gastritis can lead to decreased IF production.&nbsp; This is caused by ageing, iron or folate deficiency, autoimmune disorders, endocrine disorders or infections. <ref name="Goodman">Goodman CC, Fuller KS, Boissonnault WG. Pathology: Implications for the Physical Therapist.2nd ed. Philadelphia: Saunders Elsevier;2003</ref>
 
=== Malabsorption in the Small Intestine ===
<br>There are several reasons why the small intestine may not be able to absorb vitamin B12:<br>The small intestine can have too much bacteria in it.&nbsp; The bacteria will take up space and&nbsp;not allow vitamin B12 to be absorbed. Certain diseases of the small intestine may decrease absorption of Vitamin B12 such as celiac disease, Chron’s disease, and HIV.&nbsp; <br>Surgery to the small intestine may interfere with absorption of vitamin B12.<br>A tapeworm in the small intestines would cause a decrease in absorption of vitamin B12 into the body.
 
=== Diet Lacking Vitamin B12 ===
<br>Many people can develop vitamin B12 deficiencies by not eating enough foods that contain B12.&nbsp;<ref name="Pernicious Anemia" />  


== Systemic Involvement  ==
== Systemic Involvement  ==
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* Haematologic - Hematologic pathology may cause the following symptoms: skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.
* Haematologic - Hematologic pathology may cause the following symptoms: skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.


* Neurological - The most common neurological symptom is tingling in the hands and feet.&nbsp; Other possible neurological symptoms that could occur: paresthesia, weakness, motor deficits, loss of vision, behavioural changes, and cognitive changes.
* Neurological - The most common neurological symptom is tingling in the hands and feet.&nbsp; Other possible neurological symptoms that could occur: paresthesia, weakness, motor deficits, loss of vision, behavioural changes, and [[Cognitive Impairments|cognitive changes]].


* Gastrointestinal - Gastrointestinal dysfunction can cause symptoms such as anorexia, flatulence, diarrhoea, and constipation.
* Gastrointestinal - Gastrointestinal dysfunction can cause symptoms such as anorexia, flatulence, diarrhoea, and constipation.


* Cardiovascular - Vitamin B12 deficiency can lead to increased risk of coronary artery disease and stroke.&nbsp; Vitamin B12 deficiency causes hyperhomocysteinemia which can increase occlusions in the vascular system.&nbsp; There is not a lot of evidence to prove that vitamin B12 will cause vascular issues, but the evidence does link the two together.&nbsp; <ref name="CDC" /><br>
* Cardiovascular - Vitamin B12 deficiency can lead to increased risk of [[Coronary Artery Disease (CAD)|coronary artery disease]] and stroke.&nbsp; Vitamin B12 deficiency causes hyperhomocysteinemia which can increase occlusions in the vascular system.&nbsp; There is not a lot of evidence to prove that vitamin B12 will cause vascular issues, but the evidence does link the two together.&nbsp; <ref name="CDC">Center of Disease control [http://www.cdc.gov/ncbddd/b12/intro.html. Vitamin B12 Deficiency .] Available at:http://www.cdc.gov/ncbddd/b12/intro.html. (last accessed 16.5.2019)</ref><br>


== Medical Management ==
== Physical Therapy Management ==


=== Treatment ===
An individual with a confirmed or suspected Vitamin B12 deficiency is typically treated by a primary physician with mediation that includes intramuscular injection, oral Vitamin B12 supplements, or through a change in nutritional habits. Treating or diagnosing a patient with a vitamin deficiency typically falls outside of the Physical Therapist Scope of Practice, however physical therapists should be aware of the presenting sign and symptoms of Vitamin B12 deficiency and refer to proper medical personnel with any unusual findings. Physical Therapists should be particularly familiar with the role Vitamin B12 on the nervous system. 
The most common treatment is vitamin B12 supplements.&nbsp; Patients can also get vitamin B12 shots, sublingual tablets, and nasal injections.<br>Recommended dietary amounts (RDAs) for Vitamin B12


{| class="wikitable"
* If a physical therapist suspects that a Vitamin B12 deficiency may be present they should refer to MD. 
!Age
* Early diagnosis of the deficiency is extremely important because the effect of treatments is believed to be linked to the time of diagnosis<ref name="C Def">Adami F, Binotto G, Briani C et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847746/ Cobalamin Deficiency: Clinical Picture and Radiological Findings.] Nutrients. 2013 Nov 15 . Available from PubMed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847746/</ref>.  
!Male
!Female
|-
|0-6 months
|0.4 mcg
|0.4 mcg
|-
|7-12 months
|0.5 mcg
|0.5 mcg
|-
|1-3 years
|0.9 mcg
|0.9 mcg
|-
|4-8 years
|1.2 mcg
|1.2 mcg
|-
|9-13 years
|1.8 mcg
|1.8 mcg
|-
|14 and older
|2.4 mcg
|2.4 mcg
|-
|Pregnancy
|n/a
|2.6 mcg
|-
|Breastfeeding
|n/a
|2.8 mcg
|}


=== Recommended Supplements ===
== Vitamin B12 and the Nervous System ==
{| class="wikitable"
[[File:VitB12 CT.jpeg|thumb|Deficit of B12; Spinal cord MRI degeneration posterior columns. ]]
!Patient
Vitamin B12 acts as a co-enzyme that facilitates [[Axons|myelin]] synthesis. A defect in the myelin synthesis can lead to both central and peripheral nerve function abnormalities. Some conditions seen with this dysfunction include: myelopathy, [[Neuropathies|neuropathy]] and optic nerve atrophy. Roughly 25% of individuals suffering from a vitamin B12 deficiency experience peripheral neuropathy.
!Male
!Female
|-
|>50 years old
|25-100 mcg
|25-100 mcg
|-
|Vitamin B12 Deficiency
|125-2000 mcg
|125-2000 mcg
|-
|Preventing Anemia
|2-10 mcg
|2-10 mcg <ref name="Mayoclinic" /><ref name="NIH" />
|}


== Physical Therapy Management  ==
The spinal cord can become involved in severe deficiency and a syndrome often seen with this is '''sub-acute combined degeneration (SCD)'''. [[MRI Scans|MRI]] findings may reveal an inflammation of the spinal cord, most commonly reported at the T2 level. <ref name="C Def" />Clinical presentations of SCD include<ref name="C Def" /> <ref name="Leishear">Leishear K et al. The Relationship of Vitamin B12 and Sensory and Motor Peripheral Nerve Function in Older Adults. J Am Geriatr Soc. 2012 June;60(6): 1057–1063.</ref>
 
An individual with a confirmed or suspected Vitamin B12 deficiency is typically treated by a primary physician with mediation that includes intramuscular injection, oral Vitamin B12 supplements, or through a change in nutritional habits. Treating or diagnosing a patient with a vitamin deficiency typically falls outside of the Physical Therapist Scope of Practice, however physical therapists should be aware of the presenting sign and symptoms of Vitamin B12 deficiency and refer to proper medical personnel with any unusual findings. Physical Therapists should be particularly familiar with the role Vitamin B12 on the nervous system. If a physical therapist suspects that a Vitamin B12 deficiency may be present they should refer to MD. Early diagnosis of the deficiency is extremely important because the effect of treatments is believed to be linked to the time of diagnosis<ref name="C Def" />.
 
=== Vitamin B12 and the Nervous System ===
<br>Vitamin B12 acts as a co-enzyme that facilitates [[Axons|myelin]] synthesis. A defect in the myelin synthesis can lead to both central and peripheral nerve function abnormalities. Some conditions seen with this dysfunction include: myelopathy, [[Neuropathies|neuropathy]] and optic nerve atrophy. Roughly 25% of individuals suffering from a vitamin B12 deficiency experience peripheral neuropathy.
 
The spinal cord can become involved in severe deficiency and a syndrome often seen with this is '''sub-acute combined degeneration (SCD)'''. [[MRI Scans|MRI]] findings may reveal an inflammation of the spinal cord, most commonly reported at the T2 level. <ref name="C Def" />Clinical presentations of SCD include<ref name="C Def" /> <ref name="Leishear" />
*Bilateral sensory deficits most commonly affecting bilateral lower extremities&nbsp;  
*Bilateral sensory deficits most commonly affecting bilateral lower extremities&nbsp;  
*Bilateral lower extremity weakness  
*Bilateral lower extremity weakness  
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The most common way to treat vitamin B12 deficiency alternatively is through increasing dietary intake.  
The most common way to treat vitamin B12 deficiency alternatively is through increasing dietary intake.  
Vitamin B12 is a nutrient that is only found in animal products such as meat, chicken, fish, eggs, and dairy. Therefore vegans are at especially high risk of low nutritional vitamin B12, as are non-vegan individuals who do not eat enough of these vitamin B12 rich foods.
Some foods are fortified with vitamin B12, vegans have to make an effort to seek out those types of foods.<ref name=":0" />


<br>'''Food Sources containing vitamin B12, in descending order'''
<br>'''Food Sources containing vitamin B12, in descending order'''
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0.3/ 5 <ref name="NIH" />
0.3/ 5 <ref name="NIH" />
|}
|}  
 
== Differential Diagnosis  ==
 
Vitamin B12 may cause many disorders to occur, however there are many disorders that may present similar to Vitamin B12 deficiency without having the actual deficiency. Some potential differential diagnoses include:<ref name="DD">Epocrates [https://online.epocrates.com/noFrame/showPage.do?method=diseases&MonographId=822&ActiveSectionId=35 Vitamin B12 deficiency] Available from: https://online.epocrates.com/noFrame/showPage.do?method=diseases&amp;MonographId=822&amp;ActiveSectionId=35</ref><br>
 
*Vitamin B6 Deficiency (Folic Acid)
*[[Hypothyroidism]] <ref name="C Def" />
*Liver Disease <ref name="C Def" />
*[[Neuropathies|Peripheral Neuropathy]](due to DM or thyroid involvement) <ref name="C Def" />
*[[Diabetic Neuropathy]]
*[[Dementia]] <ref name="C Def" /><ref name="O'Leary" />
*[[Depression]]
*Pernicious Anaemia <ref name="C Def" />
*[[Crohn's Disease|Crohns Disease]]
*Gastrointestinal Disorders <ref name="C Def" />
*Ciliac Disease
*Peptic Ulcer
*Panceratistis (chronic)
*Bacterial infection of small intestines
*[[Multiple Sclerosis (MS)|Multiple Sclerosis]] (MS)
*[[Syphilis]]
*[[Human Immunodeficiency Virus (HIV)|HIV]]
*Toxicity due to drugs
*[[Addison's Disease|Addison's]] Disease
*[[Graves' Disease|Graves Disease]]
*[[Hashimoto Thyroiditis|Hashimoto]] Disease
*Imerslund-Grasbeck Syndrome<ref name="C Def" />
*[[Multiple Myeloma|Multiple Myelomas]]
*Kidney Disease<ref name="C Def" />
 
== Case Reports/ Case Studies  ==
 
'''Title:'''<br>Vitamin B12 deficiency associated with symptoms of frontotemporal dementia <ref name="Case Study">Blundo C, Marin D, Ricci M. [http://www.ncbi.nlm.nih.gov/pubmed/20927562 Vitamin B12 deficiency associated with symptoms of frontotemporal dementia.] Neurol Sci 2011 [cited 2014 Mar 25];32(1):101-5. Available from PubMed: http://www.ncbi.nlm.nih.gov/pubmed/20927562</ref><br>'''Authors:'''<br>C. Blundo, D Marin, and M Ricci<br>'''Abstract:'''<br>C. Blundo, D Marin, and M Ricci presented a case report of a 72 year old male patient who was believed to have Alzheimer’s disease. He suffered a change in mental activity, along with behavioral and functional decline. Upon further investigation, researchers revealed that changes in patient’s symptoms were due to Vitamin B12 deficiency. The patient was treated with Vitamin B12 supplements. A 7 year follow up study revealed that frontotemporal dementia, due to Vitamin B12 deficiency, can be reversible if proper treatment is implemented. <br>'''Patient Characteristics:'''<br>Demographics- Patient is a 72 Year old retired male physician, with no past medical or psychiatric history.<br>Patient History of Symptoms- Patient’s family reported that he was currently showing apathy, irritability, decreased attention span and memory deficits. The family also reports that one year after the onset of initial symptoms, the patient began to display psychotic episodes. These “psychotic episodes” included paranoia, jealousy, and delusional thoughts. The patient was diagnosed with psychosis in an outpatient psychiatric unit. In 2001 the patient’s symptoms began to decline and the patient was placed on Donepezil and was diagnosed with [[Alzheimer's Disease|Alzheimer’s Disease]]. In November 2001 the patient began to show signs of cognitive impairment and peripheral neuropathy and was hospitalized. <br>The patient has no known co-morbidities and no known previous treatment.
 
'''Examination:''' The patient was awake, but was not oriented. Impairments noted:<br>• long term memory was impeded<br>• speech was reduced<br>• ADL initiation was limited<br>• Insidious onset<br>• Gradual prognosis<br>• Early loss of ability to control behavior<br>• Easily distracted<br>• Decreased proprioception<br>• Flexor plantar response bilaterally<br>• + Rhombergs test<br>• Ataxic gait<br>'''Lab Values:'''<br>• Serum Vitamin B12 below normal range of 200-1200pg/ml with his lab value of 54 pg/ml<br>• Folate Serum level higher than normal at 18.0ng/ml<br>• RBC 2.52, HGB 9.3g/dl, MCV 104.8 fl<br>• Hemocysteine elevated 18 ng/ml<br>• MMA not examined<br>• Normal thyroid hormone level<br>• Biopsy by gastroscopy showed gastric atrophy
 
'''Results:'''<br>The patient was diagnosed with Alzhiemers Disease; however the patient had frontotemporal dementia that was caused by Vitamin B12 deficiency. A table is presented below identifying the areas studied before and after vitamin B12 supplements were taken. In conclusion the patient was able to reverse all of the damage that was caused by the deficiency, and maintained the changes 7 years later<ref>Blundo C, Marin D, Ricci M. [https://www.ncbi.nlm.nih.gov/pubmed/20927562 Vitamin B12 deficiency associated with symptoms of frontotemporal dementia.] Neurological Sciences. 2011 Feb 1;32(1):101-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20927562 (last accessed 16.5.2019)</ref>
 
Additional Case of optic involvement see reference 14:<ref name="Optic case">Kowing D, Kester E. Patient’s B12 Deficiency Causes Chiasmal Lesion. Review of Optometry [Internet]. 2007 Feb 15 [cited 2014 Mar 22];144(2):122-6. Available from: Health Source: Nursing/Academic Edition:http://eds.a.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=3&amp;sid=fd074f5f-ec93-4793-9443-b18513a59ce8%40sessionmgr4001&amp;hid=4102</ref>
 
== Resources    ==
 
http://www.healthaliciousness.com/articles/foods-high-in-vitamin-B12.php


http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/<br>
== References  ==  
== References  ==  



Latest revision as of 15:22, 13 October 2023

Introduction[edit | edit source]

A vial of Vitamin B12

Vitamin B12 deficiency is one of the most prevalent nutritional deficiencies. It causes a range of symptoms, eg fatigue, forgetfulness, and tingling of the hands and feet.

The reason for the wide variety of symptoms is that vitamin B12 plays a principal role in numerous body functions eg

  1. Essential for DNA synthesis. DNA (central information storage system of most animals, plants, and even some viruses), directs proper formation of every part of the body. [1]
  2. Vitamin B12 deficiency increases homocysteine levels (normally degraded by vitimain B 12) which causes inflammation and toxic damage to the body. Elevated homocysteine increases your risks for dementia, heart disease and stroke, as it .[2]

Vitamin B12 Uptake[edit | edit source]

What is Crohn's disease.jpg

Vitamin B12 is bound to protein in food and must be released before it is absorbed. The process starts in the mouth when food is mixed with saliva. The freed vitamin B12 then binds with haptocorrin (protects acid sensitive B12 as it moves through the stomach). In the duodenum, digestive enzymes free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic factor, a transport and delivery binding protein secreted by the stomach’s parietal (lining) cells. The resulting complex is absorbed in the distal ileum by receptor-mediated endocytosis. If vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and therefore does not require the separation step[3].

Etiology[edit | edit source]

Causes of vitamin B12 deficiency include:

  • Difficulty absorbing vitamin B12 from food, eg any patient with a history of gastric bypass surgery may be at risk; surgical resection terminal ileum due to eg Crohn's disease; damage to the small intestine, eg inflammation from celiac disease or infection with the tapeworm.
  • Autoimmune: Pernicious anemia is an autoimmune condition in which antibodies to intrinsic factor are produced. Anti-intrinsic factor antibodies bind to and inhibit the effects of intrinsic factor, resulting in an inability of B12 to be absorbed by the terminal ileum.
  • Prolonged use of certain medications e.g. metformin, proton pump inhibitors.
  • Dietary Insufficiency: Vitamin B12 is stored in excess in the liver; however, patients who have followed a strict vegan diet for approximately three years may develop a B12 deficiency from a lack of dietary intake[3].

Risk Factors[edit | edit source]

The following groups are among those most likely to be vitamin B12 deficient.

  • Older adults: Between 3% and 43% of community-dwelling older adults, especially those with atrophic gastritis (an autoimmune condition) have vitamin B12 deficiency.
  • Conditions associated with vitamin B12 inadequacy include: pernicious anemia; Atrophic gastritis, affects 8–9% of adults aged 65 and older; Helicobacter pylori infection, inflammation leads to malabsorption of vitamin B12 from food.
  • Individuals with gastrointestinal disorders or who have had gastrointestinal surgery
  • Vegetarians and Infants of vegan women

The below video gives a good summary of the condition

[4]

Characteristics/Clinical Presentation[edit | edit source]

Fatigue a common sign in many diseases

The most common sign of vitamin B12 deficiency is Fatigue. This is caused by the lack of red blood cells to carry oxygen to body tissue.
Lack of red blood cells may also cause:

  • Weakness
  • Shortness of breath
  • Dizziness
  • Headache
  • Coldness in your hands and feet,
  • Pale or yellowish skin
  • Chest pain
  • Sensory and Motor Impairments
  • Loss of appetite and Weight loss
  • Loss of Balance
  • Depression and Confusion
  • Poor Memory
  • Dementia or Cognitive changes
  • Soreness of mouth [5][6]

Treatment[edit | edit source]

Vitamin B12 deficiency can be managed with supplemental B12. This could be an oral supplement or an injection. If B12 deficiency is caused by a problem with absorption, an injection of B12 will help the vitamin to be absorbed directly into the body.

Some patients need lifelong B12 supplementation. This usually depends on the cause of the deficiency, possibly with the need to continue taking B12 supplements even after symptoms have improved.

Recovery from vitamin B12 deficiency takes time. Improvement may be gradual and may continue for up to six to 12 months[2].

Systemic Involvement[edit | edit source]

Vitamin B12 deficiency can cause haematologic, neurologic, gastrointestinal, and cardiovascular symptoms.

  • Haematologic - Hematologic pathology may cause the following symptoms: skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.
  • Neurological - The most common neurological symptom is tingling in the hands and feet.  Other possible neurological symptoms that could occur: paresthesia, weakness, motor deficits, loss of vision, behavioural changes, and cognitive changes.
  • Gastrointestinal - Gastrointestinal dysfunction can cause symptoms such as anorexia, flatulence, diarrhoea, and constipation.
  • Cardiovascular - Vitamin B12 deficiency can lead to increased risk of coronary artery disease and stroke.  Vitamin B12 deficiency causes hyperhomocysteinemia which can increase occlusions in the vascular system.  There is not a lot of evidence to prove that vitamin B12 will cause vascular issues, but the evidence does link the two together.  [7]

Physical Therapy Management[edit | edit source]

An individual with a confirmed or suspected Vitamin B12 deficiency is typically treated by a primary physician with mediation that includes intramuscular injection, oral Vitamin B12 supplements, or through a change in nutritional habits. Treating or diagnosing a patient with a vitamin deficiency typically falls outside of the Physical Therapist Scope of Practice, however physical therapists should be aware of the presenting sign and symptoms of Vitamin B12 deficiency and refer to proper medical personnel with any unusual findings. Physical Therapists should be particularly familiar with the role Vitamin B12 on the nervous system.

  • If a physical therapist suspects that a Vitamin B12 deficiency may be present they should refer to MD.
  • Early diagnosis of the deficiency is extremely important because the effect of treatments is believed to be linked to the time of diagnosis[8].

Vitamin B12 and the Nervous System[edit | edit source]

Deficit of B12; Spinal cord MRI degeneration posterior columns.

Vitamin B12 acts as a co-enzyme that facilitates myelin synthesis. A defect in the myelin synthesis can lead to both central and peripheral nerve function abnormalities. Some conditions seen with this dysfunction include: myelopathy, neuropathy and optic nerve atrophy. Roughly 25% of individuals suffering from a vitamin B12 deficiency experience peripheral neuropathy.

The spinal cord can become involved in severe deficiency and a syndrome often seen with this is sub-acute combined degeneration (SCD). MRI findings may reveal an inflammation of the spinal cord, most commonly reported at the T2 level. [8]Clinical presentations of SCD include[8] [9]

  • Bilateral sensory deficits most commonly affecting bilateral lower extremities 
  • Bilateral lower extremity weakness
  • Ataxia 
  • Decreased proprioception and vibration sensation 
  • Positive Rombergs Sign
  • Abnormal reflexes
  • Spastic paresis                                              

For an image of MRI showing image of see SCD

Dietary Management [edit | edit source]

The most common way to treat vitamin B12 deficiency alternatively is through increasing dietary intake.

Vitamin B12 is a nutrient that is only found in animal products such as meat, chicken, fish, eggs, and dairy. Therefore vegans are at especially high risk of low nutritional vitamin B12, as are non-vegan individuals who do not eat enough of these vitamin B12 rich foods.

Some foods are fortified with vitamin B12, vegans have to make an effort to seek out those types of foods.[2]


Food Sources containing vitamin B12, in descending order

Food and Serving Size Micrograms (mcg)

Per Serving/Percent of Daily Values

Clams, cooked, 3 ounces

Liver, beef, cooked, 3 ounces 

Breakfast cereals, fortified with 100% of the DV for vitamin B12, 1 serving

Trout, rainbow, wild, cooked, 3 ounces

Salmon, sockeye, cooked, 3 ounces

Trout, rainbow, farmed, cooked, 3 ounces

Tuna fish, light, canned in water, 3 ounces  

Cheeseburger, double patty and bun, 1 sandwich 

Haddock, cooked, 3 ounces

Breakfast cereals, fortified with 25% of the DV for vitamin B12, 1 serving  

Beef, top sirloin, broiled, 3 ounces

Yogurt, fruit, low-fat, 8 ounces 

Cheese, Swiss, 1 ounce

Beef taco, 1 soft taco

Ham, cured, roasted, 3 ounces

Egg, whole, hard boiled, 1 large

Chicken, breast meat, roasted, 3 ounces

84.1/ 1,40

70.7 /1,178
6.0 /100
5.4 /90
4.8 /80
3.5/ 58

2.5/ 42

2.1 /35
1.8/ 30

1.5 /25

1.4 /23

1.2/ 18

1.1 /18

0.9 /15

0.9/ 15

0.6 /10

0.6 /10

0.3/ 5 [6]

References[edit | edit source]

  1. Allen LH. Vitamin b-12. Advances in Nutrition. 2012 Jan;3(1):54-5. [1]
  2. 2.0 2.1 2.2 Very well health How Vitamin B12 Deficiency Affects the Body Available: https://www.verywellfit.com/causes-and-effects-of-vitamin-b12-deficiency-4126428(accessed 12.4.2022)
  3. 3.0 3.1 NIH Vit B 12 Available:https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ (accessed 12.4.2022)
  4. Healthline 5 signs and symptoms of vitamin B 12 deficiency. Available from: https://www.youtube.com/watch?v=i3A7PLhrDck (last accessed 15.5.2019)
  5. Nation Institutes of Health Pernicious Anemia Available at:http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/.
  6. 6.0 6.1 National Institutes of Health Vitamin B12 Available at http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h5.
  7. Center of Disease control Vitamin B12 Deficiency . Available at:http://www.cdc.gov/ncbddd/b12/intro.html. (last accessed 16.5.2019)
  8. 8.0 8.1 8.2 Adami F, Binotto G, Briani C et al. Cobalamin Deficiency: Clinical Picture and Radiological Findings. Nutrients. 2013 Nov 15 . Available from PubMed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847746/
  9. Leishear K et al. The Relationship of Vitamin B12 and Sensory and Motor Peripheral Nerve Function in Older Adults. J Am Geriatr Soc. 2012 June;60(6): 1057–1063.