As always, my blog is a resource for me to have an easy way to retrieve my medical studies. But I hope that others find the post and the blog useful. The resources below are a quick and, I think, comprehensive review of vitamin b12 and vitamin b12 deficiency.
Tired? Forgetful? Tingling hands and feet? It could be Vitamin B12 deficiency!
Posted on October 10, 2011 by Tom Wade MD
Vitamin B12 as Protection for the Aging Brain Personal Health
By JANE E. BRODY SEPT. 6, 2016 New York Times
Vitamin B12 Dietary Supplement Fact Sheet from the National Institutes of Health Office of Dietary Supplements: Strengthening Knowledge and Understanding of Dietary Supplements
What percentage of patients with vitamin b12 deficiency will have a normal serum vitamin b12 level?: Search results from asking Google on 9-7-2016
Vitamin B-12 Associated Neurological Diseases Workup (Laboratory Studies)
Author: Niranjan N Singh, MD, DM; Chief Editor: Selim R Benbadis, MD more…
The following is from the emedicine.medscape.com article directly above:
Clinical evidence of vitamin B-12 deficiency
- Serum cobalamin levels are the initial test.
- Two assays exist: radioassay and the nonradioisotopic assay, chemiluminescence, which is becoming more popular because of improved automation, safety, and cost. Chemiluminescence has a higher reference range value, from 250-1100 pg/mL versus 170-900 pg/mL for radioassay. Using the radioassay and elevated homocysteine (HC) and methylmalonic acid (MMA) as criterion standards, levels are less than 200 pg/mL in 90-95% of patients, 200-300 pg/mL in 5-10%, and greater than 300 pg/mL in 0.1-1%. Be aware of the assay used and how the reference range was determined. A serum cobalamin level that is within the reference range does not exclude cobalamin deficiency.
Abnormally low vitamin B-12 levels: Test for PA by measuring antibodies against IF.
- Antiparietal cell antibodies are present in 90% of PA cases. In patients older than 70 years, 10% have false-positive abnormal antibody levels.
- IF antibodies are present in 60% of patients. These are more specific but less sensitive.
- If either antibody is positive, the diagnosis of PA is confirmed and further testing is not required.
- If antibodies are negative, obtain a serum gastrin level to test for achlorhydria, which is associated with PA. If these are elevated, the diagnosis is likely PA. If these results are normal, perform a Schilling test.
Borderline vitamin B-12 level and clinical features of vitamin B-12 deficiency: Measure methylmalonic acid (MMA) and homocysteine (HC).
- Both folate and vitamin B-12 deficiency can lead to metabolite elevation.
- In vitamin B-12 deficiency, MMA and HC are elevated, although HC elevation occurs by itself. MMA is more sensitive than HC.
- In folate deficiency, MMA is within the reference range and HC is elevated.
- MMA and HC are considered abnormal when greater than 3 standard deviations above the mean. Reference range values are not age dependent for MMA and are 70-350 nM/L. For patients younger than 60 years, reference range values are 5-15 µM/L for HC. In people older than 60 years, the cutoff for HC is 20 µM/L.
- If both metabolites are within the reference range, vitamin B-12 deficiency is effectively ruled out. Only 0.2% of 400 patients with low serum vitamin B-12 had normal metabolite levels, and 10% of 98 patients with folate deficiency had metabolite levels within the reference range. False-positive elevations in MMA and HC occur in inborn errors of metabolism, renal disease, and deficiencies of folate. If either metabolite is elevated, test for PA or use the Schilling test.
Schilling test: The Schilling test is used to determine the etiology of vitamin B-12 deficiency in patients with normal IF antibodies.
- Stage 1: Administer radiolabeled cobalamin 0.5-2.0 mCi PO to fasted patients. One to 6 hours later, administer unlabeled cobalamin 1000 mcg IM to saturate transcobalamin and flush hepatic storage. Measure the percentage of radiolabeled cobalamin in a 24-hour urine specimen. Urinary excretion within the reference range is 10-35% over 24 hours. Reduced urinary excretion of cobalamin, ie, less than 7-9% based on individual laboratory reference range values, in persons with normal renal function supports decreased absorption of oral cobalamin. If excretion is low, proceed to stage 2.
- Stage 2: Stage 1 is repeated with coadministration of porcine IF 60 mg. If the absorption of cobalamin is normalized, the presumptive diagnosis is PA. If poor absorption persists after administration, proceed to stage 3.
- Stage 3: Tetracycline is administered for 5 days prior to reperformance of stage 1 to exclude blind loop as the etiology.
- Stage 4: Pancreatic enzymes are administered with repetition of stage 1 to test for pancreatic disease.
- Caveats: If vitamin B-12 is administered 48 hours before the Schilling test, dilution of the radiolabeled cobalamin and spuriously low apparent urinary excretion and false-positive results occur. False-negative values occur in food-bound malabsorption due to achlorhydria. True negative results are from dietary deficiencies (vegan) and cobalamin binding–protein abnormalities.
Routine hematologic and chemistry tests
- Hematologic abnormalities may be absent at the time of neurologic presentation.
- Vitamin B-12 deficiency produces the classic picture of macrocytic anemia, with a mean corpuscular value (MCV) greater than 100 fL. The MCV correlates with estimated vitamin B-12 level:
- MCV of 80-100 fL (normal) indicates less than 25% probability of vitamin B-12 deficiency.
- MCV of 115-129 fL indicates a 50% probability.
- MCV greater than 130 fL indicates a 100% probability.
- Peripheral blood smear shows macro-ovalocytosis, anisocytosis, and poikilocytosis, as well as basophilic stippling of the erythrocytes and Howell-Jolly bodies. Reticulocyte count can be within the reference range or low. Hypersegmentation (>5% of neutrophils with > 5 lobes or 1% with > 6 lobes) of polymorphonuclear cells may occur without anemia. Thrombocytopenia is observed in approximately 50% of patients, and platelets often have bizarre size and shape.
- Serum indirect bilirubin and lactate dehydrogenase (LDH) may be elevated because PA can have a hemolytic component.
- Achlorhydria is present in many patients with PA.
Laboratory parameters after administration of vitamin B-12
- Anemic patients
- Reticulocytosis starts in 3-4 days and peaks at 1 week.
- Hemoglobin concentration rises in 10 days and returns to the reference range in 8 weeks.
- LDH falls within 2 days.
- Hypersegmented neutrophils disappear in 1-2 weeks.
- Patients with severe anemia and borderline-to-low iron stores
- Serum iron level falls within 24 hours because of increased erythropoiesis.
- Hypokalemia may develop because of increased potassium utilization in hematopoiesis.