Vitamins

Diagnosis

Indications for Testing

• Vitamin B₁₂ – patients at risk
  • Malabsorption, use of H₂ receptor antagonists, proton-pump inhibitors, vegetarian diet
• Vitamin D – patients at risk
  • Poor nutritional intake, limited sun exposure, malabsorption, liver failure, or renal insufficiency
  • Aged adults and patients taking antiseizure medicine
• Other vitamins – symptoms consistent with deficiency and risk for deficiency

Laboratory Testing

• Order specific testing based on symptoms
• For B₁₂ deficiency – concurrent folate level testing recommended; refer to the following for more information
  • Anemia
  • Megaloblastic anemia
  • Alcohol abuse
• For vitamin D deficiency – order 25-hydroxy vitamin D by chemiluminescence, if available
  • 20-30 ng/mL – defined as insufficiency
  • <20 mg/ng/mL – defined as deficiency
  • Do not order 1,25-dihydroxy testing; fractionation testing for D₂ and D₃ not necessary for initial evaluation of vitamin D deficiency

Screening

Monitoring

Clinical Background

Vitamins are required in the diet because they are not adequately synthesized in the human body.

• Only small amounts are necessary to catalyze essential biochemical reactions
• Most deficiencies are rare in healthy persons in the U.S.
  • Exceptions for vitamins B₁₂ and D 
  • Exceptions in gastric bypass patients, celiac disease patients, alcoholics, and persons with inadequate nutrition (eg, the elderly) or malabsorptive defects
• Disease states generally result from poor diet
• Body stores vary by vitamin
  • Thiamine (B₁) and folate stores are small and rapidly depleted
  • Cobalamin (B₁₂) stores are large
• Vitamins play several roles in disease processes
  • Diseases can cause vitamin deficiency
  • Vitamin deficiency or excess can cause disease
  • High doses of certain vitamins can be used to manage some diseases
    • Niacin – hyperlipidemia
    • Vitamin D – osteoporosis
    • Pyridoxine – treatment of first trimester nausea
    • Folate – prevention of neural tube defect
• Water soluble vitamins

  Water Soluble Vitamins
  Vitamin	Disease States
  B1 (thiamine) Catalyzes reactions that produce energy Sources – legumes, nuts, whole grains Inhibitors – alcohol, coffee, loop diuretics, raw fish, shellfish, tea	Vitamin B1 deficiency Mainly found in alcoholics in U.S. Wet beriberi – high-output cardiac failure Dry beriberi – symmetrical peripheral neuropathy Wernicke encephalopathy – beriberi combined with alcoholism; horizontal nystagmus, ophthalmoplegia, cerebellar ataxia, mental impairment Wernicke-Korsakoff syndrome – coexistence of additional loss of memory and confabulatory psychosis Vitamin B1 toxicity – rare reports of anaphylaxis
  B2 (riboflavin) Catalyzes reactions that produce energy; coenzyme in the flavoproteins that participate in tissue oxidation and respiration processes Sources – broccoli, eggs, enriched breads, fish, lean meats, legumes, milk, other dairy products Inhibitors – sunlight rapidly degrades the vitamin in foodstuffs	Vitamin B2 deficiency Mucocutaneous lesions including magenta tongue, angular stomatosis, seborrhea, cheilosis Vitamin B2 toxicity None reported; gastrointestinal tract can only absorb limited quantities
  B3 (niacin) Catalyzes the metabolism of fatty acids, amino acids and carbohydrates Sources – beans, eggs, meat, milk Inhibitors – B2 or B6 deficiency reduces conversion of tryptophan to niacin; drugs that may interfere with metabolism include alcohol, amitriptyline, chlorpromazine, imipramine	Vitamin B3 deficiency Mainly found in alcoholics in U.S. Can occur in carcinoid and Hartnup diseases Pellagra – pigmented rash in sun-exposed areas (Casal necklace), bright red tongue, diarrhea, apathy As drug therapy, flushing and headache frequently accompany treatment doses Vitamin B3 toxicity Hepatotoxicity is most serious problem Glucose intolerance, macular edema, macular cysts
  B5 (pantothenic acid) Functions in the metabolism and biosynthesis of many compounds Sources – broccoli, egg yolk, liver, yeast Inhibitors – none	Vitamin B5 deficiency Deficiency has only been demonstrated experimentally; may have caused burning feet syndrome in prisoners Gastrointestinal disturbance, depression, paresthesias, ataxia, hypoglycemia Vitamin B5 toxicity – none reported
  B6 (pyridoxal 5’-phosphate) Coenzyme in transaminase reactions Sources – legumes, meats, nuts, wheat bran Inhibitors – drugs such as cycloserine, isoniazid,  L-dopa, penicillamine	Vitamin B6 deficiency Seborrhea, glossitis, seizures, neuropathy, depression, confusion, microcytic anemia Vitamin B6 toxicity – severe sensory neuropathy
  B7 (biotin) Coenzyme in transfer of carbonyl groups Sources – beans, egg yolks, liver, soy, yeast Inhibitors – egg whites	Biotin deficiency Only demonstrated in patients with short bowel syndrome receiving total parenteral nutrition Adults – mental status changes, anorexia, nausea, seborrheic rash Infants – hypotonia, lethargy, apathy, alopecia and rash on ears Biotin toxicity – None reported
  Folate (B9, folic acid, folacin) Coenzyme in metabolic reactions Sources – fortified breads, cereals and grain products, fruits, leafy vegetables, organ meats, yeast Inhibitors – anticonvulsants, chemotherapy agents, malabsorptive disorders (sprue), methotrexate	Folate deficiency Megaloblastic anemia – no neurologic symptoms Fetal open neural tube defects May be related to increased development of certain cancers Folate toxicity – none reported
  B12 (cobalamin) Cofactor for enzymatic reactions, metabolism of odd chain fatty acids, and methylation of homocysteine Sources – animal products, dairy products Inhibitors – achlorhydria, H2 receptor antagonists, overgrowth of intestinal organisms (eg, short bowel syndrome), proton-pump inhibitor drugs	Vitamin B12 deficiency Deficiency found in ~30% of people >60 years. Megaloblastic (macrocytic) anemia Neurologic manifestations – loss of vibratory and position sense, abnormal gait, dementia, depression, loss of bowel and bladder control Vitamin B12 toxicity – none reported
  C (ascorbic acid) Coenzyme in formation of collagen and synthetic reactions Free radical scavenger with antioxidant activity Sources – citrus fruits, green vegetables, potatoes, tomatoes Inhibitors – smoking, hemodialysis	Vitamin C deficiency Scurvy – bleeding into skin, inflamed and bleeding gums, bleeding into joints, impaired bone growth Vitamin C toxicity – elevated liver enzymes, abdominal pain, diarrhea

• Fat soluble vitamins

  Fat Soluble Vitamins
  Vitamin	Disease States
  A (retinol) Required for normal vision, growth and differentiation of epithelial tissue as well as bone growth, immunity, reproduction and embryonic development Sources – beef, egg yolk, fish, liver, vegetables Inhibitors – ethanol, mineral oil, neomycin, cholestyramine	Vitamin A deficiency Ophthalmic – xerophthalmia, Bitot spots, corneal ulcers Dermatologic – hyperkeratotic skin lesions Vitamin A toxicity Acute – increased intracranial pressure, vertigo, diplopia, seizures, headaches Chronic – cheilosis, glossitis, alopecia, bone pain, hyperlipidemia, liver fibrosis
  D (calcitriol) Hormone precursor Required for calcium absorption, bone metabolism, regulation of cell development and the immune system Sources – dairy, egg yolks, fish oils, fortified foods; also synthesized in response to ultraviolet radiation Inhibitors – barbiturates, isoniazid, phenobarbital, phenytoin, rifampin, sunblock	Vitamin D deficiency Children – rickets and rachitic rosaries (expansion of growth plate) Adults – 33% of older adults are deficient (estimated) Osteomalacia, osteoporosis; hypocalcemia and hypophosphatemia with impaired mineralization of bone matrix; associated with cardiovascular disease, cancer (colon, breast), autoimmune disease Vitamin D toxicity Rare; associated with ≥10,000 IU/day intake (not seen until 25(OH)D ≥150 ng/mL)
  E (tocopherol) Coenzyme in formation of collagen, synthetic reactions, antioxidant activity and free radical scavenger Sources – sunflower oil, safflower oil, wheat germ, soybean Inhibitors – none	Vitamin E deficiency Almost exclusively in severe and prolonged malabsorptive disorders Peripheral neuropathy – areflexia, ataxia, ophthalmoplegia, skeletal myopathy Vitamin E toxicity Reduced platelet aggregation, interference with warfarin treatment
  K (phylloquinone [K1], menaquinone [K2]) Essential for carboxylation of glutamic acid residues in proteins required for coagulation Sources – butter, coffee, egg yolk, green leafy vegetables, ground beef, milk, pears Inhibitors – broad spectrum antibiotics, warfarin	Vitamin K deficiency Hemorrhage of mucous membranes and gastrointestinal tract Vitamin K toxicity Infants – hemolytic anemia and hyperbilirubinemia

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Vitamin B1 (Thiamine), Plasma 0080389 Method: Quantitative High Performance Liquid Chromatography	Assess thiamine concentration in plasma to monitor vitamin B1 concentration in patients receiving supplementation
25-Hydroxyvitamin D2 and D3 by Tandem Mass Spectrometry, Serum 2002348 Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry	Assess vitamin D concentration ARUP is unable to provide reliable results for specimens from infants (less than one year of age), since highly specialized test methodology is required; ARUP will refer all infant specimens to a lab that is able to perform this methodology
Vitamin B12 0070150 Method: Quantitative Chemiluminescent Immunoassay	Assess vitamin B12 concentration
Folate, Serum 0070070 Method: Quantitative Chemiluminescent Immunoassay	Assess folate concentration in serum
Vitamin B12 with Reflex to Methylmalonic Acid, Serum (Vitamin B12 Deficiency) 0055662 Method: Quantitative Chemiluminescent Immunoassay/Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry	Assess vitamin B12 concentration Rule out pernicious anemia
Folate, RBC 0070385 Method: Quantitative Chemiluminescent Immunoassay	Preferred specimen for assessment of folate concentration
Vitamin D, 1, 25-Dihydroxy 0080385 Method: Quantitative Radioimmunoassay	Primarily indicated during patient evaluations for hypercalcemia and renal failure Should not be used to diagnose vitamin D deficiency; however, normal result does not rule out vitamin D deficiency Recommended test for diagnosing vitamin D deficiency is Vitamin D 25-hydroxy