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
  • 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
  • For vitamin D deficiency – order 25-hydroxy vitamin D by chemiluminescence, if available
    • 20-30 ng/mL – defined as insufficiency
    • <20 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

  • Consider vitamin D deficiency screening for patients at risk
    • Use 25-hydroxy vitamin D test for 
      • Institutionalized refugees
      • Celiac disease
      • Patients with osteoporosis
      • Patients from areas with high vitamin D deficiency
      • Older adults due to known risks of deficiency

Monitoring

  • Vitamin D
    • Monitor therapy response with 25-hydroxy vitamin D
    • Patients who do not appear to be responding to therapy – vitamin D2 or D3 testing may be helpful

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.
  • 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
  • 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 toxicitynone 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
Test Name and Number Recommended Use Limitations Follow Up
Vitamin B1 (Thiamine), Whole Blood 0080388
Method: Quantitative High Performance Liquid Chromatography

Preferred specimen for thiamine assessment in patients with suspected deficiency

   
Vitamin B2 (Riboflavin) 0081123
Method: Quantitative High Performance Liquid Chromatography

Assess riboflavin concentration in serum or plasma

   
Niacin (Vitamin B30092168
Method: Quantitative High Performance Liquid Chromatography

Assess niacin concentration in plasma

   
Vitamin B5 (Pantothenic Acid), Serum 2006982
Method: Quantitative Cell Based Assay

Assess pantothenic acid concentration

   
Vitamin B6 (Pyridoxal 5-Phosphate) 0080111
Method: Quantitative High Performance Liquid Chromatography

Assess concentration in plasma

Specimen collected following an 8-hour or overnight fast accurately indicates vitamin B6 nutritional status; non-fasting specimen concentration reflects recent vitamin intake

   
Vitamin B7 (Biotin)  2003184
Method: Bioassay

Assess biotin concentration

   
Vitamin B12 and Folate 0070160
Method: Quantitative Chemiluminescent Immunoassay

Assess vitamin B12  and folate concentration

   
Vitamin C (Ascorbic Acid), Plasma 0080380
Method: Quantitative High Performance Liquid Chromatography

Assess vitamin C concentration

   
Vitamin A (Retinol), Serum or Plasma 0080525
Method: Quantitative High Performance Liquid Chromatography

Assess vitamin A concentration

Includes measurement of retinol and retinyl palmitate concentration

This assay does not measure other vitamin A metabolites such as retinaldehyde or retinoic acid

 
Vitamin D, 25-Hydroxy 0080379
Method: Quantitative Chemiluminescent Immunoassay

Preferred screening test for vitamin D deficiency

Preferred test to monitor response to supplementation

   
Vitamin E, Serum or Plasma 0080521
Method: Quantitative High Performance Liquid Chromatography

Assess vitamin E concentration

Includes measurement of alpha tocopherol and gamma tocopherol concentrations

   
Vitamin K1, Serum 0099225
Method: Quantitative High Performance Liquid Chromatography

Assess vitamin K1 concentration

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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

Alternative screening test for vitamin D deficiency

Alternative test for monitoring response in individuals who are not responding to supplementation

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 Status) 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

Preferred test for individuals with hypercalcemia or renal failure in addition to Vitamin D, 25-Hydroxy testing

Normal result does not rule deficiency