> Table of Contents > Vitamin Deficiency
Vitamin Deficiency
Michelle E. Szczepanik, MD
Christopher D. Meyering, DO
image BASICS
  • 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).
  • 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.
  • 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.
  • 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
  • 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
Poverty, malnutrition, chronic disease states, advanced age, dietary restrictions, bariatric surgery, and exclusively breastfed infants
  • 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).
Anemia, neuropathies, dermatitis, visual disturbances
  • 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
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
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
  • 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].
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.
  • 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).
Most vitamin deficiencies are fully reversible if treated without undue delay.
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.
  • E56.9 Vitamin deficiency, unspecified
  • E56.0 Deficiency of vitamin E
  • E55.9 Vitamin D deficiency, unspecified
Clinical Pearls
  • 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).