Professional Documents
Culture Documents
Deficiency in the
Older Adult
C. Christine Orton, PhD, FNP-BC
ABSTRACT
Vitamin B12 (cobalamin) deficiency in the older adult occurs frequently and has the
potential for serious neurological and hematological complications. Because of a myriad of
discreet clinical manifestations, this disorder is often unrecognized by providers. The pur-
pose of this article is to increase awareness of cobalamin deficiency, its causes, clinical mani-
festations, diagnostic work-up, and management. As primary providers, nurse practitioners
should have a high degree of suspicion for at-risk populations. With early identification and
treatment, cobalamin anemia has an excellent prognosis with a normal lifespan.
548 The Journal for Nurse Practitioners - JNP Volume 8, Issue 7, July/August 2012
vitamin C may inhibit absorption and lead to a deficiency
of cobalamin. 14 Increased risk of developing either cobal- Box 1. Etiologies of Vitamin B12 Deficiency
amin deficiency or folic acid anemia is seen in certain Malabsorption of Vitamin B12
populations; these include adults older than 50, elderly, • Pernicious anemiaa
alcoholics, and those with malabsorption/malnutrition • Atrophic gastritis
disorders. • Pancreatic insufficiency
Prevalence of cobalamin deficiency is difficult to • Partial or total gastrectomy
ascertain because of the diverse etiologies and different • Ileal resection
assays used to determine serum levels.6 However, using a • Bacterial overgrowth
serum radioassay cutoff level of 200 pg/mL, the preva- • Helicobacter pyloris
lence rate for the older (⬎ 51 years) population was • Intestinal disorders
reported to be 5%-16%.2,3,15,16 Assessing for elevated HC • Tapeworm
and MMA levels along with serum cobalamin, the preva-
lence increased to 21% in the same population.6 Congenital Intrinsic Factor or
Increased age is the primary risk factor for the devel- Transcobalamin II Deficiency
opment of cobalamin deficiency, primarily because of the Nutritional Deficiency
higher risk of malabsorption and malnutrition.3 • Vegan diet
Interestingly, the Framingham Offspring Study found little • Vegetarian diet in pregnancy
differences between age groups (26-49, 50-64, and 65-83)
and low levels of cobalamain.17 Other demographic factors Human Immunodeficiency Virus
such as sex, race, and ethnicity are not seen as significant in Hereditary Factors
predicting cobalamin deficiency.3,6 Pernicious anemia has
Drugs
been noted to be more widespread in people of Celtic,
• Biguanides (metformin)
Scandinavian, and African origins.11,13,18 Although cobal-
• Colchicine
amin deficiency is common in the elderly, the megaloblas-
• Neomycin
tic anemia related to it is uncommon.
• Nitrous oxide
• Proton pump inhibitors (omeparzole)
EVALUATION
aSignifies
Manifestations the most common etiology.
Cobalamin deficiency may take 3-4 years to develop
because of the small daily requirement (1 mcg) needed
and the large body stores (1000 mcg) of cobalamin found rhea, glossitis, and cheilosis. Fifty percent of patients
in the liver and throughout the body. The patient usually present with Hunter’s glossitis, in which the lingual
presents with subtle manifestations of moderate to severe papillae atrophy, leaving the tongue smooth and shiny.19
anemia, but as a result of the slow onset of cobalamin, The tongue may be painful, beefy red, or have red
patients are often severely anemic at the time of presenta- patches on the dorsum edges. These symptoms may lead
tion.9 Frequently, health care is sought for symptoms of to unwanted weight loss. Constipation or having several
cardiac, renal, genitourinary, gastrointestinal, infectious, semisolid bowel movements daily may be reported. On
mental, or neurological disorders.13 General manifesta- rare occasions patients may present with abdominal
tions of anemia such as fatigue, pallor, dizziness, dyspnea, rigidity and severe abdominal pain, which suggests
and muscle weakness may be seen. Patients with more spinal cord pathology.13
severe anemia may present with tachycardia, heart mur- Most patients with cobalamin deficiency exhibit
murs, and chest pain. Patients with pre-existing heart dis- some degree of neurologic symptoms, including sym-
ease are at risk for developing congestive heart failure metric paresthesias of the legs and arms, progressive
and coronary insufficiency. weakness, and eventually spastic ataxia with a loss of
Gastrointestinal intestinal symptoms seen in cobal- vibratory and position sense. Other neurologic symp-
amin anemia include anorexia, nausea, vomiting diar- toms are weakness, clumsiness, and an unsteady gait,
Diagnostics Differential
In addition to a thorough history and physical examina- The differential is lengthy and includes neurologic, gas-
tion, an analysis of laboratory findings is indicated to trointestinal, hepatic, and thyroid diagnoses, as well as
diagnose deficiency. A peripheral smear to evaluate red other possible anemias. Box 2 outlines other possibilities
cell indices will show a macrocytic anemia, with an that should be considered with patients presenting with
increased mean cell volume and mean cell hemoglobin. manifestations of megaloblastic anemia.
Other findings are hypersegmented neutrophils, large
platelets, and anisopoikilocytosis (erythrocytes of varying PUTTING IT ALL TOGETHER
sizes and abnormal shapes). Mild leukopenia, thrombocy- It has been suggested that all patients over 65 who are
topenia, or pancytopenia may be present.19,20 malnourished, present with cognitive impairment,
Other lab findings center on measurement of serum myelopathy, neuropathy, or reside in institutions should
cobalamin, RBC (or serum) folate concentrations; be screened for cobalamin (B12) deficiency.4,16,22,23 Both
metabolites, MMA, and HC levels; and intrinsic factor folate and cobalamin levels should be evaluated since
antibodies. Adding serum MMA and HC levels, which cobalamin and folate deficiencies often coexist.21 If both
are more sensitive and more reliable than the vitamin are within normal range, additional testing is not
levels, aids the provider in an accurate diagnosis of cobal- required. If the folate or cobalamin are less than the nor-
amin deficiency. Serum concentrations of HC and MMA mal range, providers should then check the MMA and
550 The Journal for Nurse Practitioners - JNP Volume 8, Issue 7, July/August 2012
total HC levels, both of which are sensitive indicators of
vitamin B12 deficiency.18 If both metabolites are normal, Box 2. Differentials
again, both deficiencies are ruled out. If both metabolites Alzheimer’s
are increased, cobalamin deficiency is confirmed (Table Achlorhydra
1).22 However, folate deficiency cannot be ruled out, and Alcoholic hepatitis
a serum folate level or RBC folate would be in order. If Aplastic anemia, toxic or idiopathic
methyimalonic acid is normal and the HC level is Bone marrow failure
increased, folate deficiency is likely. To aid in determining Celiac sprue
cause of cobalamin deficiency, intrinsic factor should be Cirrhosis
completed to diagnose pernicious anemia. Folate deficiency
Hemolytic anemia
MANAGEMENT Thyroid disorders
Prevention Immune thrombocytopenic purpura
Given the potential for serious neurological and hemato- Inflammatory bowel disease
logical side effects, the primary provider needs to be vig- Iron deficiency anemia
ilant and have a high degree of suspicion in certain Macrocytosis
populations at risk for cobalamin deficiency. This group Malabsorption disorders
includes all older adults over 50 who are not consuming Medications
fortified foods or supplements and patients with malab- Megaloblastic anemia
sorption disorders (eg, atrophic gastritis, chronic alco- Myelodysplastic syndrome
holism, gastric surgery, pancreatic insufficiency, or Multiple myeloma
chronic inflammatory disease of the ileum).1,19,23 All Neoplasm (gastric and colorectal)
patients who present with cognitive impairment should Neutropenia
be investigated for B12 deficiency.4,16,23,24 Other groups Pancreatic insufficiency
who should be screened include patients presenting with Psychiatric disorders: schizophrenia, dementia,
unexplained neurologic or hematologic signs or symp- senility, alzheimer’s
toms and pure vegans or strict vegetarians.3,21 Sprue, tropical
Thalassemia
Treatment Zollinger-Ellison syndrome
After establishing that the patient does indeed have a
cobalamin deficiency, treatment should be initiated imme-
diately. Determining the cause of the deficiency is still needed.3,5,21 Lower doses, such as 100 mcg, have been
somewhat controversial, and many clinicians treat patients recommended as an alternative to the 1000 mcg.1
if a diagnosis of low cobalamin is established.1 Adequate However, use of lower dose formulas may result in a
replacement of cobalamin is the goal of therapy. B12 is slower response, which may be critical when neurologic
available for parenteral use as cyanocobalamin or hydroxo- disease is present.17
cobalamin—the latter is thought to be retained better in Alternative treatment includes oral therapy after ini-
the body and therefore is more available to cells. A num- tial parenteral loading doses by ingestion of 1000-2000
ber of drug regimens have been suggested; the standard mcg every day. Because of the variable absorption of oral
protocol is to initially restore body stores by giving large B12, large daily doses are needed.2,3,6 Oral B12 replace-
daily doses of cobalamin administered parenterally, either ment for compliant patients has been shown to be safe,
intramuscular or deep subcutaneous. effective, and well tolerated. Serial cobalamin measure-
Cobalamin therapy is initiated by administering either ments at periodic intervals are suggested to ensure ade-
of the cobalamin formulas at 1000 mcg intramuscularly quate cobalamin levels have been obtained. New
(IM) every day for 1 or 2 weeks, followed by 1000 mcg therapies of cobalamin treatment include sublingual and
IM every week for 4-6 weeks. Afterward, a maintenance nasal spray or gel. These formulas are expensive and have
dose of 1000 mcg IM every month for life will be not been extensively studied.21
552 The Journal for Nurse Practitioners - JNP Volume 8, Issue 7, July/August 2012
21. Schrier SL. Diagnosis and treatment of vitamin B12 and folic acid.
lifespan. However, if not treated early, neurological com- http://www.uptodate.com/contents/diagnosis-and-treatment-of-vitamin-b12-
plications can become permanent. With the advent of the and-folic-acid-deficiency?source⫽search_result&selectedTitle⫽1%7E145.
Updated February 2, 2010. Accessed February 17, 2011.
Boomers turning 60 at a rate of 7-10,000/day,26 NPs 22. Aaron S, Kumar S, Vijayan J, et al. Clinical and laboratory features and
response to treatment in patients presenting with vitamin B12 deficiency-
have an extraordinary opportunity to use their assessment related neurological syndromes. Neurology India. 2005;53(1):55-58.
and detective skills in screening and uncovering a myriad 23. Eastley R, Wilcock GK, Bucks BS. Vitamin B12 deficiency in dementia and
cognitive impairment: the effects of treatment on neuropsychological
of disorders, including megaloblastic anemia.24 As pri- function. Int J Geriatr Psychiatry. 2000;15:226-233.
24. Knopman DS, DeKosky ST, Cmmings JL, et al. Practice parameter: diagnosis
mary providers NPs should have a high degree of suspi- of dementia (an evidence-based review). Report of the Quality Standards
cion for at-risk populations. Additionally, NPs should be Subcommittee of the American Academy of Neurology. Neurology.
2001;56(9):1143-1153.
aware that patients with certain medications, alcoholism, 25. Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin,
vitamin B6, folate, vitamin B12, pantothenic acid, biotin and choline.
vegan practices, and malabsoprtion/malnutrition syn- Washington, DC: National Academy Press; 2000.
26. US Securities and Exchange Commission. Oldest baby boomers turn 65.
dromes are at risk for cobalamin deficiency and should http://www.sec.gov/spotlight/seniors/oldestboomers2007.htm. Updated
be screened routinely. September 10, 2007. Accessed June 15, 2011.
References
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