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Vitamin Deficiency
Michelle E. Szczepanik, MD
Christopher D. Meyering, DO
image BASICS
DESCRIPTION
  • Vitamins are essential micronutrients required for normal metabolism, growth, and development.
  • Deficiencies are less common in the Western world but certain populations are at increased risk.
  • Regulations mandating vitamin supplementation in food products, adequate food supply, and availability of vitamin supplements all make vitamin deficiencies in the Western world lower.
  • Toxicity is rare in water-soluble vitamins; however, is possible with fat-soluble vitamins (A, D, E, K).
EPIDEMIOLOGY
Incidence
  • Predominant age
    • Geriatric population, pregnant women, exclusively breastfed infants, and individuals with certain chronic disease states
  • Individuals from Africa and Southeast Asia are at increased risk.
  • True incidence is unknown as most vitamin deficiencies are asymptomatic.
Prevalence
  • Varies by age groups, comorbid conditions, geography, and setting (i.e., urban, rural)
  • The prevalence of vitamin B12 deficiency is around 6% in those <60 years of age but increases to around 20% after the age of 60 (1).
  • Vitamin D deficiency has become increasingly recognized and its prevalence is increased in individuals with darker skin pigmentation, obesity, low dietary intake of vitamin D, or low sunlight exposure.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Deficiencies usually related to disease can develop under healthy conditions and generally occur due to 1 of 5 mechanisms:
    • Reduced intake
    • Diminished absorption
    • Increased use
    • Increased demand
    • Increased excretion
  • Chronic disease states: HIV, malabsorption (such as celiac sprue and short bowel syndrome), chronic liver and kidney disease, alcoholism, malignancies, pernicious anemia, and rare inborn errors of metabolism
  • Bariatric surgeries: gastric bypass, gastrectomy, small or large bowel resection
  • Predisposition related to certain drugs: prednisone, phenytoin, isoniazid, protease inhibitors, methotrexate, phenobarbital, alcohol, nitrous oxide, H2 receptor antagonists, metformin, colchicine, cholestyramine, 5-fluorouracil, 6-mercaptopurine, azathioprine, chloramphenicol, proton pump inhibitors, chronically used antibiotics, penicillamine, and hydralazine
  • Malnutrition, imbalanced nutrition, obesity, fad diets, extreme vegetarianism, total parenteral nutrition, bulimia/anorexia, and other eating disorders
  • Dialysis
  • Parasitic infestation
Genetics
  • Cystic fibrosis
  • Hartnup disease
  • Rare genetic predisposition
    • Autoimmune disease (e.g., pernicious anemia)
    • Congenital enzyme deficiencies (e.g., biotinidase or holocarboxylase synthetase deficiency)
    • Transcobalamin II deficiency
    • Ataxia and vitamin E deficiency (AVED)
  • A-&bgr;-lipoproteinemia
RISK FACTORS
Poverty, malnutrition, chronic disease states, advanced age, dietary restrictions, bariatric surgery, and exclusively breastfed infants
GENERAL PREVENTION
  • Ingesting large and varied amounts of vitamins increases risk of toxicity and drug-drug interactions.
  • Antioxidant supplement use has not been shown to impact cancer incidence and, in some studies, has increased risk of death (2).
  • Avoidance of restrictive diets decreases the likelihood of vitamin deficiency.
  • In particular age groups or with certain risk factors, vitamin supplementation may be recommended.
  • U.S. Preventive Services Task Force (USPSTF) recommends vitamin D supplementation in communitydwelling adults aged 65 years or older who are at increased risk for falls (3)[B].
  • USPSTF recommends against low-dose supplementation with vitamin D (<400 IU) and calcium (<1,000 mg) to reduce fracture risk in noninstitutionalized populations and concluded that data on the effects of higher doses were insufficient (3).
  • USPSTF recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg of folic acid (4)[A].
  • USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer (2).
  • The American Academy of Pediatrics recommends that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth (5).
COMMONLY ASSOCIATED CONDITIONS
Anemia, neuropathies, dermatitis, visual disturbances
image DIAGNOSIS
PHYSICAL EXAM
  • Neurologic exam: gait, memory/cognitive impairment, reflexes, sensory or motor impairment, peripheral neuropathy (1,6)
  • Oropharyngeal exam to look for glossitis, bleeding gums, hyperemic pharynx, stomatitis, cheilitis (1)
  • Skin exam to look for maculosquamous dermatitis, photosensitive pigmented dermatitis, ecchymosis and/or petechiae (6)
  • Visual assessment
DIFFERENTIAL DIAGNOSIS
Many conditions may mimic signs and symptoms of vitamin deficiencies.
  • Diabetes mellitus (DM), thyroid disorders, hyperparathyroidism, heart failure, Alzheimer disease, multiple sclerosis, substance abuse, toxic ingestions, and hematologic disorders/malignancies
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • No routine screening indicated.
  • Test if symptomatic or history indicates at high risk. If clinical characteristics are present, consider the following:
    • 25-OH vitamin D (5)
    • Prothrombin time (PT)/partial thromboplastin time (PTT)
    • Vitamin B12 and folate levels (1)
    • Serum homocysteine and methylmalonic acid levels if high suspicion of vitamin B12 deficiency with normal serum B12 level (6)
    • Retinol serum level, retinol binding protein
  • Ancillary tests include the following:
    • BUN, calcium, phosphorus, magnesium
    • Albumin, liver function tests
    • CBC
    • Parathyroid hormone
  • Bone densitometry indicated in the following (11)[A]:
    • Women 65 years of age or older without previous known fractures or risk factors
    • Women <65 years old whose 10-year fracture risk is equal to that of a 65-year-old white woman without additional risk factors.
    • According to the United States fracture risk assessment tool (FRAX), the 10-year fracture risk for a 65-year-old white woman without risk factors is 9.3%.
  • Give bariatric surgery patients additional consideration as they are at risk for deficiencies. Laparoscopic gastric banding is less frequently associated with vitamin deficiencies (10).
  • Cyanocobalamin, thiamine, vitamin A
  • Disease states from vitamin deficiency
    • Vitamin A (retinol): night blindness, complete blindness, xerophthalmia
    • Vitamin B1 (thiamine)
      • Wernicke encephalopathy: acute syndrome with memory disturbance, truncal ataxia, nystagmus, ophthalmoplegia
      • Korsakoff syndrome: anterograde and retrograde amnesia, confabulation
      • Dry beriberi: symmetric motor and sensory peripheral neuropathy, paresthesias, loss of reflexes
      • Wet beriberi: neuropathy with cardiovascular symptoms of peripheral vasodilation, highoutput failure, dyspnea, and tachycardia
      • P.1125

      • Infantile beriberi: loud piercing cry, cyanosis, tachycardia, cardiomegaly, dyspnea, vomiting, seizures
    • Vitamin B2 (riboflavin): glossitis, stomatitis, cheilitis, hyperemia of the pharyngeal mucosal membranes, normocytic-normochromic anemia
    • Vitamin B3 (niacin): pellagra: photosensitive pigmented dermatitis, dementia, and diarrhea
    • Vitamin B5 (pantothenic acid): paresthesias and dysthesias, anemia
    • Vitamin B6 (pyridoxine): dermatitis, cheilosis, atrophic glossitis, stomatitis, neuropathy
    • Vitamin B9 (folate): megaloblastic anemia, rarely manifest neurologic symptoms
    • Vitamin B12 (cobalamin): pernicious anemia, shuffling broad-based gait, atrophic glossitis, loss of vibration and position sense, cognitive impairment
    • Vitamin C (ascorbic acid): scurvy: ecchymoses, bleeding gums, petechiae, hyperkeratosis, arthralgias, impaired wound healing
    • Vitamin D (calciferol): rickets, osteomalacia
    • Vitamin E: neuromuscular disorders and hemolysis
    • Vitamin K: easy bruising, mucosal bleeding, melena, hematuria
    • Biotin: changes in mental status, dysesthesias, nausea, maculosquamous dermatitis of the extremities
image TREATMENT
MEDICATION
  • Ask patients about any herbal or dietary supplements and encourage them to bring in vitamin and supplement bottles for review.
  • Assess for potential adverse drug effects/reactions. Patients with alcohol dependence should receive thiamine, folic acid, and MVI.
  • Treat patients with suspected thiamine deficiency with 100 mg thiamine prior to IV fluids containing glucose to prevent precipitation of Korsakoff psychosis (10).
  • If there is concomitant B12 and folate deficiency, then start B12 first to avoid precipitating subacute combined degeneration of the spinal cord (1).
  • Consider obtaining prealbumin/albumin levels and a dietary consult for malnourished patients.
  • Bariatric surgery patients will need lifelong vitamin supplementation; there are no consensus practice guidelines for supplement dosing regimens (12)
Geriatric Considerations
  • Vitamin B12 deficiency exists in around 20% of the general population ≥60 years of age. Treat symptomatic or severe deficiency with an intramuscular (IM) injection of cyanocobalamin 1,000 &mgr;g/day 3 times a week for 2 weeks. If there are neurologic symptoms then give the same dose of cyanocobalamin every other day for 3 weeks or until symptoms have resolved. To prevent recurrence or treat mild deficiency, use a regimen of oral B12 1,000 &mgr;g/day or an IM injection of B12 1,000 &mgr;g every month (6). Low-dose oral therapy with 50 to 150 &mgr;g/day may be considered for mild cases (1). High-dose (1,000 to 2,000 &mgr;g/day) oral treatment is as effective as monthly IM injections, but use caution in patients with malabsorption or compliance issues (1,6)[C].
  • >40% of elderly in United States are vitamin D deficient. Deficiency is defined as a serum 25-OH vitamin D level of <20 ng/mL. Treatment of vitamin D deficiency is 50,000 IU of oral ergocalciferol weekly for 8 weeks (3,10,13)[B].
Pediatric Considerations
  • Vitamin K deficiency bleeding (9)
    • Neonates may exhibit signs of vitamin K deficiency because they require 1 week of life to establish intestinal flora which manufactures vitamin K.
    • Condition peaks 2 to 10 days after birth: bleeding from the umbilical stump and/or circumcision site, generalized bruising, and GI hemorrhage
    • Infrequent in developed countries due to routine injection of newborns with vitamin K (1 mg)
  • Vitamin D deficiency: Vitamin D supplementation (400 IU/day) is recommended in all exclusively breastfed infants starting in the first few days of life (5)[A].
  • All nonbreastfed infants and older children drinking <1,000 mL/day of vitamin D-fortified formula or milk should receive a vitamin D of 400 IU/day (5).
  • Adolescents may receive a vitamin D supplement of 400 IU/day (5).
  • Morbidly obese and minority children are at increased risk for vitamin D deficiency (14).
  • In children age >6 months in developing countries, vitamin A supplementation has been shown to decrease mortality (7)[B].
  • Vitamin deficiency associated with developmental delay.
Pregnancy Considerations
All pregnant women and women of childbearing age considering pregnancy are strongly encouraged to take a multivitamin containing at least 0.4 mg folic acid daily to prevent neural tube defects (4)[A].
image ONGOING CARE
DIET
Vitamins are best utilized by the body from food intake. Supplements should be used where it is not feasible to ingest the recommended amount of a particular vitamin.
PATIENT EDUCATION
  • In healthy adults, multivitamins have no value in a patient with an adequate diet and may increase risk of some cancers.
  • Drug-drug interactions may occur between vitamins and some medications. Patients should report all supplements along with medications to their health care provider.
  • Risk of vitamin toxicity occurs most commonly with the fat-soluble vitamins (A, D, E, K).
PROGNOSIS
Most vitamin deficiencies are fully reversible if treated without undue delay.
REFERENCES
1. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226.
2. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: recommendation statement. Am Fam Physician. 2015;91(1):52D-52F.
3. LeBlanc ES, Zakher B, Daeges M, et al. Screening for vitamin D deficiency: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;162(2):109-122.
4. Wolff T, Witkop CT, Miller T, et al. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;150(9):632-639.
5. Wagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding, et al. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142-1152.
6. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160.
7. World Health Organization. Guideline: Vitamin A Supplementation in Infants and Children 6-59 Months of Age. Geneva, Switzerland: World Health Organization; 2011.
8. Lauer B, Spector N. Vitamins. Pediatr Rev. 2012; 33(8):339-351.
9. Schulte R, Jordan LC, Morad A, et al. Rise in late onset vitamin K deficiency bleeding in young infants because of omission or refusal of prophylaxis at birth. Pediatr Neurol. 2014;50(6):564-568.
10. Tack J, Deloose E. Complications of bariatric surgery: dumping syndrome, reflux and vitamin deficiencies. Best Pract Res Clin Gastroenterol. 2014;28(4):741-749.
11. U.S. Preventive Services Task Force. Screening for osteoporosis: recommendation statement. Am Fam Physician. 2011;83(10):1197-1200.
12. Pournaras DJ, le Roux CW. After bariatric surgery, what vitamins should be measured and what supplements should be given? Clin Endocrinol. 2009;71(3):322-325.
13. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.
14. Turer CB, Lin H, Flores G. Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics. 2013;131(1):e152-e161.
Codes
&NA;
ICD10
  • E56.9 Vitamin deficiency, unspecified
  • E56.0 Deficiency of vitamin E
  • E55.9 Vitamin D deficiency, unspecified
Clinical Pearls
&NA;
  • Obtain a thorough dietary history.
  • Specifically ask patients about supplement use.
  • Vitamin D supplementation is recommended in community-dwelling adults aged 65 years or older who are at increased risk for falls (3). All women planning or capable of pregnancy should take a daily supplement containing 0.4 to 0.8 mg of folic acid (4). All infants and children, including adolescents, should have a minimum daily intake of 400 IU of vitamin D beginning soon after birth (5).