Vitamin B12 Deficiency
Original Editors - Aneta Petri & Katie Wilson from Bellarmine University's Pathophysiology of Complex Patient Problems project.
- 1 Definition/Description
- 2 Prevalence
- 3 Characteristics/Clinical Presentation
- 4 Associated Co-morbidities
- 5 Medications
- 6 Diagnostic Tests/Lab Tests/Lab Values
- 7 Etiology/Causes
- 8 Systemic Involvement
- 9 Medical Management
- 10 Physical Therapy Management
- 11 Dietary Management
- 12 Differential Diagnosis
- 13 Case Reports/ Case Studies
- 14 Resources
- 15 References
Vitamin B12 is a water-soluble vitamin that is essential for DNA synthesis. Vitamin B12 deficiency is rare, but is most likely found in vegetarians, the elderly, or HIV-infected patients. 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 anemia. 
Vitamin B12 deficiency, also known as Cobalamin deficiency is 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. However, levels have been raised to anything less than 250-300 pg/mL.
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 were 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 higher incidence of deficiency. 
The below video gives a good summary of the condition
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 RBC may also cause:
- Shortness of breath
- 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 
Vitamin B12 deficiency typically is a co-morbidity of several conditions. Although each patient present very differently with associated co-morbidities, there are five major conditions that are most commonly seen with Vitamin B12 deficiency.
- Gastrointestinal Disorders
- Pernicious Anemia
- Liver or Kidney Disease
There are several different medications that are thought to affect the absorption of vitamin B12. Although evidence suggest that medications could have an effect on absorbtion, there is not sufficient evidence to prove that they do. However, patients that use these medications should keep tract of their vitamin B12 levels.
Medications that can interfere with the absorption of vitamin B12 include:
-Chloramphenicol (antibiotic) May interfere with the RBC response to Vit. B12
-Proton Pump Inhibitors (Prilosec) These medications slow down the absorption of Vit. B12. They do this because they slowly release acid into the stomach.
-H2 Receptor Antagonist (Pepcid, Zantac) These medications slow down the absorbtion of Vit. B12 by releasing hydrochloric acid into the stomach.
-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. 
Diagnostic Tests/Lab Tests/Lab Values
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 anemia, and Vitamin B12 deficiency. The acidity of gastric juices is high and IF is present in Imerslund-Grasbeck Syndrome. In juvenile pernicious anemia both factors are decreased, and in Vitamin B12 deficiency the IF is absent or below normal values. 
- Elevated Methylmalonic Acid (MMA) >0.30 umol/L. MMA is useful to identify the vitamin B12 metabolism activity. Kidney disorders should be identified before a Vitamin B12 diagnosis is made. 
- Elevated Hemocysteine (tHccy) >13mmol/L in females and > 15 mmol/L in males. Any folate deficiencies must be ruled out.
- Decreased serum Vitamin B12 (cobalamin) levels <148-258 pmol/L.  
- Schilling Test is less commonly used clincally. It is performed by giving the patient an oral medication and collecting a urine sample 24hrs after administration. 
In current research there is great deal of variability in which diagnostic tests holds 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.  
There are many things that can cause a vitamin B12 deficiency:
Lack of Intrinsic Factor:
A lack of intrinsic factor (IF) may cause a vitamin B12 deficiency. This is an essential protein in the small intestine that allows vitamin B12 to be absorbed. Decreased production of IF can occur during middle age, leaving many elderly adults at risk. Atrophic gastritis can lead to decreased IF production. This is caused by aging, iron or folate deficiency, autoimmune disorders, endocrine disorders or infections. 
Malabsorption in the Small Intestine
There are several reasons why the small intestine may not be able to absorb vitamin B12:
The small intestine can have too much bacteria in it. The bacteria will take up space and 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.
Surgery to the small intestine may interfere with absorption of vitamin B12.
A tape worm in the small intestines would cause a decrease in absorption of vitamin B12 into the body.
Diet Lacking vitamin B12
Many people can develop vitamin B12 deficiencies by not eating enough foods that contain B12. 
Vitamin B12 deficiency can cause hemotalogic, neurologic, gastrointestinal, and cardiovascular symptoms.
Hematologic pathology may cause the following symtoms: skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.
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, behavioral changes, and cognitive changes.
Gastrointestinal dysfunction can cause symptoms such as anorexia, flatulence, diarrhea, and constipation.
Vitamin B12 deficiency can lead to increased risk of coronary artery disease and stroke. Vitamin B12 deficiency causes hyperomocysteinemia 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 evidence does link the two together. 
The most common treatment is vitamin B12 supplements. Patients can also get vitamin B12 shots, sublingual tablets, and nasal injections.
Recommended dietary amounts (RDAs) for Vitamin B12
|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|
|>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 |
Physical Therapy Management
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 maybe 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.
Vitamin B12 and the Nervous System
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. 
- bilateral sensory deficits most commonly affecting bilateral lower extremities
- bilateral lower extremity weakness
- decreased proprioception and vibration sensation
- positive Rombergs Sign
- abnormal reflexes
- spastic paresis
For an image of MRI showing image of see SCD:
The most common way to treat vitamin B12 deficiency alternatively is through increasing dietary intake.
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
0.3/ 5 
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:
- Vitamin B6 Deficiency (Folic Acid)
- Hypothyroidism 
- Liver Disease 
- Peripheral Neuropathy(due to DM or thyroid involvement) 
- Diabetic Neuropathy
- Dementia 
- Pernicious Anemia 
- Crohns Disease
- Gastrointestinal Disorders 
- Ciliac Disease
- Peptic Ulcer
- Panceratistis (chronic)
- Bacterial infection of small intestines
- Multiple Sclerosis
- Toxicity due to drugs
- Addison's Disease
- Graves Disease
- Hashimoto Disease
- Imerslund-Grasbeck Syndrome
- Multiple Myelomas
- Kidney Disease
Case Reports/ Case Studies
Vitamin B12 deficiency associated with symptoms of frontotemporal dementia 
C. Blundo, D Marin, and M Ricci
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.
Demographics- Patient is a 72 Year old retired male physician, with no past medical or psychiatric history.
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. In November 2001 the patient began to show signs of cognitive impairment and peripheral neuropathy and was hospitalized.
The patient has no known co-morbidities and no known previous treatment.
Examination: The patient was awake, but was not oriented. Impairments noted:
• long term memory was impeded
• speech was reduced
• ADL initiation was limited
• Insidious onset
• Gradual prognosis
• Early loss of ability to control behavior
• Easily distracted
• Decreased proprioception
• Flexor plantar response bilaterally
• + Rhombergs test
• Ataxic gait
• Serum Vitamin B12 below normal range of 200-1200pg/ml with his lab value of 54 pg/ml
• Folate Serum level higher than normal at 18.0ng/ml
• RBC 2.52, HGB 9.3g/dl, MCV 104.8 fl
• Hemocysteine elevated 18 ng/ml
• MMA not examined
• Normal thyroid hormone level
• Biopsy by gastroscopy showed gastric atrophy
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
Additional Case of optic involvement see reference 14:
- Mayoclinic Drugs and Supplements:Vitamin B12 Deficiency. Available from:http://www.mayoclinic.org/drugs-supplements/vitamin-b12/background/hrb-20060243. (last accessed 16.5.2019)
- Center of Disease control Vitamin B12 Deficiency . Available at:http://www.cdc.gov/ncbddd/b12/intro.html. (last accessed 16.5.2019)
- Berg R, Shaw G. Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing. Clinical and Medical Research. 2013; 11(1): 7-15.
- 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.
- Healthline 5 signs and symptoms of vitamin B 12 deficiency. Available from: https://www.youtube.com/watch?v=i3A7PLhrDck (last accessed 15.5.2019)
- Nation Institutes of Health Pernicious Anemia Available at:http://www.nhlbi.nih.gov/health/health-topics/topics/prnanmia/.
- National Institutes of Health Vitamin B12 Available at http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h5.
- 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/
- Epocrates Vitamin B12 deficiency Available from: https://online.epocrates.com/noFrame/showPage.do?method=diseases&MonographId=822&ActiveSectionId=35
- O’Leary F, Samman S. 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
- Goodman CC, Fuller KS, Boissonnault WG. Pathology: Implications for the Physical Therapist.2nd ed. Philadelphia: Saunders Elsevier;2003
- Blundo C, Marin D, Ricci M. 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
- Blundo C, Marin D, Ricci M. 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)
- 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&sid=fd074f5f-ec93-4793-9443-b18513a59ce8%40sessionmgr4001&hid=4102