Vitamins

Indications for Testing

Vitamin B₁₂ – at-risk populations
- Malabsorption, use of H₂ receptor antagonists, proton-pump inhibitors, vegetarian diet, aged adults
Vitamin D – at-risk populations
- Poor nutritional intake, limited sun exposure, malabsorption, liver failure, or renal insufficiency
- Aged adults
- Certain medications (eg, antiseizure and AIDS medications, glucocorticoids)
Vitamin K – patient with elevated INR and unresponsive to vitamin K supplementation (Choosing Wisely: 15 Things Physicians and Patients Should Question, 2016; American Society of Clinical Pathology)
Other vitamins – symptoms consistent with deficiency PLUS risk factor for deficiency

Laboratory Testing

Order specific testing based on symptoms and risk assessment
For B₁₂ deficiency – consider concurrent testing for folate level; refer to the following for more information
For vitamin D deficiency
- Testing not recommended while patient is ill – levels decrease with inflammation and acute illness but not true deficiency
- Order test for 25-hydroxy vitamin D by chemiluminescence if available
  - 25-hydroxy vitamin D is the major and most stable circulating form of vitamin D
- Recommended values – no consensus on optimal concentrations (Institute of Medicine, 2011)
  - 20-30 ng/mL – defined as insufficiency
  - <20 ng/mL – defined as deficiency
- Do not order 1,25-dihydroxy test unless patient has hypercalcemia or decreased renal function (ASCP's Pathology-Related Choosing Wisely Recommendations, 2015 [Endocrine Society and American Association of Clinical Endocrinologists])
- Fractionation testing for D₂ and D₃ not necessary for initial evaluation of vitamin D deficiency
  - Method used should ideally measure D₂ and D₃ metabolites equally

Universal screening
- Insufficient evidence to assess harms or benefits of universal screening for vitamin D deficiency (USPSTF, 2015)
- Do not perform as population-based screening (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015)
- Other societies recommend against universal screening
  - ACOG (2011)
  - Endocrine Society (2011)
  - American Academy of Pediatrics (2014)
  - American Geriatrics Society (2014)
At risk population screening
- Consider vitamin D deficiency screening for patients at risk
  - Institutionalized refugees
  - Celiac disease
  - Patients with osteoporosis
  - Patients from areas with high vitamin D deficiency
  - Older adults (age is a risk factor)

Vitamin D
- Monitor therapy response – check 25-hydroxy vitamin D 10-12 weeks after initiating therapy
- Patients who do not appear to be responding to therapy – vitamin D₂ or D₃ testing may be helpful

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 – vitamins B₁₂ and D
- Exceptions – 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 (eg, elderly, alcoholism)
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
- Therapeutic doses of certain vitamins can be used to manage some diseases
  - Niacin – hyperlipidemia
  - Vitamin D – osteoporosis
  - Pyridoxine – treatment for nausea during first trimester of pregnancy
  - Folate – prevention of neural tube defect

Water-soluble vitamins

Water-Soluble Vitamins
Vitamin	Deficiency	Toxicity
B₁ (thiamine) Catalyzes reactions that produce energy Sources – legumes, nuts, whole grains Inhibitors – alcohol, coffee, loop diuretics, raw fish, shellfish, tea	At risk population Alcoholism, malabsorption Clinical presentation 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	Rare reports of anaphylaxis Gastrointestinal tract can absorb only limited quantities
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 vitamin B₂ in foodstuffs	At risk population Alcoholism, malabsorption Clinical presentation Mucocutaneous lesions including magenta tongue, angular stomatosis, seborrhea, cheilosis	None reported; gastrointestinal tract can absorb only 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	At risk population Alcoholism, malabsorption, carcinoid, and Hartnup diseases Clinical presentation Pellagra – pigmented rash in sun-exposed areas (Casal necklace), bright-red tongue, diarrhea, apathy	Hepatotoxicity, 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	At risk population Deficiency has been only demonstrated experimentally	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	At risk population Rare Alcoholism, malabsorption Clinical presentation Seborrhea, glossitis, seizures, neuropathy, depression, confusion, microcytic anemia	Severe sensory neuropathy
B₇ (biotin) Coenzyme in transfer of carbonyl groups Sources – beans, egg yolks, liver, soy, yeast Inhibitors – egg whites	At risk population Rare Malabsorption Clinical presentation Adults – mental status changes, anorexia, nausea, seborrheic rash Infants – hypotonia, lethargy, apathy, alopecia and rash on ears	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	At risk population Alcoholism, certain drugs, malnutrition Clinical presentation Megaloblastic anemia without neurologic symptoms; glossitis, diarrhea, depression Maternal deficiency leads to fetal open neural tube defects	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	At risk population Malnutrition, alcoholism, vegan diet, autoimmune gastritis, older age Clinical presentation Megaloblastic (macrocytic) anemia Neurologic manifestations – loss of vibratory and position sense, abnormal gait, dementia, depression, loss of bowel and bladder control	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	At risk population Malnutrition Clinical presentation Scurvy – bleeding into skin, inflamed and bleeding gums, bleeding into joints, impaired bone grow	Elevated liver enzymes, abdominal pain, diarrhea

Water-Soluble Vitamins

Vitamin

Deficiency

Toxicity

B₁ (thiamine)

Catalyzes reactions that produce energy

Sources – legumes, nuts, whole grains

Inhibitors – alcohol, coffee, loop diuretics, raw fish, shellfish, tea

At risk population

Alcoholism, malabsorption

Clinical presentation

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

Rare reports of anaphylaxis

Gastrointestinal tract can absorb only limited quantities

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 vitamin B₂ in foodstuffs

At risk population

Alcoholism, malabsorption

Clinical presentation

Mucocutaneous lesions including magenta tongue, angular stomatosis, seborrhea, cheilosis

None reported; gastrointestinal tract can absorb only 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

At risk population

Alcoholism, malabsorption, carcinoid, and Hartnup diseases

Clinical presentation

Pellagra – pigmented rash in sun-exposed areas (Casal necklace), bright-red tongue, diarrhea, apathy

Hepatotoxicity, 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

At risk population

Deficiency has been only demonstrated experimentally

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

At risk population

Rare
Alcoholism, malabsorption

Clinical presentation

Seborrhea, glossitis, seizures, neuropathy, depression, confusion, microcytic anemia

Severe sensory neuropathy

B₇ (biotin)

Coenzyme in transfer of carbonyl groups

Sources – beans, egg yolks, liver, soy, yeast

Inhibitors – egg whites

At risk population

Rare
Malabsorption

Clinical presentation

Adults – mental status changes, anorexia, nausea, seborrheic rash
Infants – hypotonia, lethargy, apathy, alopecia and rash on ears

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

At risk population

Alcoholism, certain drugs, malnutrition

Clinical presentation

Megaloblastic anemia without neurologic symptoms; glossitis, diarrhea, depression
Maternal deficiency leads to fetal open neural tube defects

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

At risk population

Malnutrition, alcoholism, vegan diet, autoimmune gastritis, older age

Clinical presentation

Megaloblastic (macrocytic) anemia
Neurologic manifestations – loss of vibratory and position sense, abnormal gait, dementia, depression, loss of bowel and bladder control

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

At risk population

Malnutrition

Clinical presentation

Scurvy – bleeding into skin, inflamed and bleeding gums, bleeding into joints, impaired bone grow

Elevated liver enzymes, abdominal pain, diarrhea

Fat-soluble vitamins

Fat-Soluble Vitamins
Vitamin	Deficiency	Toxicity
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	At risk population Cirrhosis, malabsorption Clinical presentation Ophthalmic – xerophthalmia, Bitot spots, corneal ulcers Dermatologic – hyperkeratotic skin lesions	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 the body in response to ultraviolet radiation Inhibitors – barbiturates, isoniazid, phenobarbital, phenytoin, rifampin, sunblock	At risk population Malabsorption, elderly Clinical presentation Children – rickets and rachitic rosaries (expansion of growth plate) Adults – osteomalacia, osteoporosis, hypocalcemia, and hypophosphatemia with impaired mineralization of bone matrix	Rare; associated with ≥10,000 IU/day intake (not seen until 25(OH)D ≥150 ng/mL) Symptoms of hypercalcemia – tetany, weakness, anorexia, nausea
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	At risk population Malnutrition, severe and prolonged malabsorptive disorders Clinical presentation Peripheral neuropathy – areflexia, ataxia, ophthalmoplegia, skeletal myopathy Mild hemolytic anemia	Reduced platelet aggregation, interference with warfarin treatment Muscle weakness, fatigue, nausea
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	At risk population Malabsorption, malnutrition, breastfed infants Clinical presentation Hemorrhage of mucous membranes and gastrointestinal tract	None reported with phylloquinone orally Menaquinone may cause toxicity but would require very large doses

Fat-Soluble Vitamins

Vitamin

Deficiency

Toxicity

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

At risk population

Cirrhosis, malabsorption

Clinical presentation

Ophthalmic – xerophthalmia, Bitot spots, corneal ulcers
Dermatologic – hyperkeratotic skin lesions

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 the body in response to ultraviolet radiation

Inhibitors – barbiturates, isoniazid, phenobarbital, phenytoin, rifampin, sunblock

At risk population

Malabsorption, elderly

Clinical presentation

Children – rickets and rachitic rosaries (expansion of growth plate)
Adults – osteomalacia, osteoporosis, hypocalcemia, and hypophosphatemia with impaired mineralization of bone matrix

Rare; associated with ≥10,000 IU/day intake (not seen until 25(OH)D ≥150 ng/mL)

Symptoms of hypercalcemia – tetany, weakness, anorexia, nausea

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

At risk population

Malnutrition, severe and prolonged malabsorptive disorders

Clinical presentation

Peripheral neuropathy – areflexia, ataxia, ophthalmoplegia, skeletal myopathy
Mild hemolytic anemia

Reduced platelet aggregation, interference with warfarin treatment

Muscle weakness, fatigue, nausea

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

At risk population

Malabsorption, malnutrition, breastfed infants

Clinical presentation

Hemorrhage of mucous membranes and gastrointestinal tract

None reported with phylloquinone orally

Menaquinone may cause toxicity but would require very large doses

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.

Vitamin B1 (Thiamine), Whole Blood 0080388
Method: Quantitative High Performance Liquid Chromatography

Recommended Use

Use for nutritional assessment of vitamin B₁ (thiamine)

Preferred specimen for thiamine assessment in patients with suspected deficiency

Do not use to monitor thiamine supplementation

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

Recommended Use

Use for nutritional assessment of vitaminB₂

Assess riboflavin concentration in serum or plasma

Niacin (Vitamin B3) 0092168
Method: Quantitative High Performance Liquid Chromatography

Recommended Use

Assess niacin concentration in plasma

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

Recommended Use

Assess pantothenic acid concentration in serum

Vitamin B[6] (Pyridoxal 5-Phosphate) 0080111
Method: Quantitative High Performance Liquid Chromatography

Recommended Use

Use for nutritional assessment of vitamin B₆ in serum or 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 B[7] (Biotin) 2003184
Method: Bioassay

Recommended Use

Assess biotin concentration in serum

This test is NOT indicated for diagnosing patients with biotinidase deficiency or as a follow up of an abnormal newborn screen for biotinidase deficiency

Use in combination with other tests to confirm or monitor patients with biotinidase deficiency

Vitamin B12 and Folate 0070160
Method: Quantitative Chemiluminescent Immunoassay

Recommended Use

Aid in detection of vitamin B₁₂ and folate deficiency in individuals with macrocytic or unexplained anemia, or unexplained neurologic disease

Vitamin B12 with Reflex to Methylmalonic Acid, Serum (Vitamin B12 Status) 0055662
Method: Quantitative Chemiluminescent Immunoassay/Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Preferred reflex test for evaluating vitamin B₁₂ deficiency in individuals with macrocytic or unexplained anemia, or unexplained neurologic disease

Reflex pattern – if Vitamin B₁₂ is less than 300 pg/mL, then methylmalonic acid, serum (Vitamin B₁₂Status) will be added

Folate, RBC 0070385
Method: Quantitative Chemiluminescent Immunoassay

Recommended Use

Preferred specimen for assessment of folate concentration in whole blood

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

Recommended Use

Use for nutritional assessment of vitamin C in plasma

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

Recommended Use

Use for nutritional assessment of vitamin A in serum or plasma

Includes measurement of retinol and retinyl palmitate concentration

Limitations

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

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

Recommended Use

Preferred test to diagnose vitamin D insufficiency and monitor response to therapy

Testing is recommended only for patients at risk for vitamin D insufficiency

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

Recommended Use

Use for nutritional assessment of vitamin E in plasma

Includes measurement of alpha tocopherol and gamma tocopherol concentrations

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

Recommended Use

Use for nutritional assessment of vitamin K₁ in serum

Guidelines

Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011; 94(1): 348S-358S. PubMed

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jun 2017]

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad H, Weaver CM, Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7): 1911-30. PubMed

Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011 :PubMed

LeFevre ML, U.S. Preventive Services Task Force. Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015; 162(2): 133-40. PubMed

Yetley EA, Coates PM, Johnson CL. Overview of a roundtable on NHANES monitoring of biomarkers of folate and vitamin B-12 status: measurement procedure issues. Am J Clin Nutr. 2011; 94(1): 297S-302S. PubMed

Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin R, Durazo-Arvizu RA, Eckfeldt JH, Green R, Gregory JF, Hoofnagle AN, Jacobsen DW, Jacques PF, Lacher DA, Molloy AM, Massaro J, Mills JL, Nexo E, Rader JI, Selhub J, Sempos C, Shane B, Stabler S, Stover P, Tamura T, Tedstone A, Thorpe SJ, Coates PM, Johnson CL, Picciano MF. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr. 2011; 94(1): 313S-321S. PubMed

Yetley EA, Pfeiffer CM, Phinney KW, Fazili Z, Lacher DA, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin R, Durazo-Arvizu RA, Eckfeldt JH, Green R, Gregory JF, Hoofnagle AN, Jacobsen DW, Jacques PF, Molloy AM, Massaro J, Mills JL, Nexo E, Rader JI, Selhub J, Sempos C, Shane B, Stabler S, Stover P, Tamura T, Tedstone A, Thorpe SJ, Coates PM, Johnson CL, Picciano MF. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr. 2011; 94(1): 303S-312S. PubMed

General References

Chawla J, Kvarnberg D. Hydrosoluble vitamins. Handb Clin Neurol. 2014; 120: 891-914. PubMed

Davies DJ, Baxter JM, Baxter JN. Nutritional deficiencies after bariatric surgery. Obes Surg. 2007; 17(9): 1150-8. PubMed

Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014; 349: g5226. PubMed

LeBlanc ES, Zakher B, Daeges M, Pappas M, Chou R. Screening for vitamin D deficiency: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015; 162(2): 109-22. PubMed

Marian M, Sacks G. Micronutrients and older adults Nutr Clin Pract. 2009; 24(2): 179-95. PubMed

Merrigan SD, Owen WE, Straseski JA. Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay. Clin Lab. 2015; 61(3-4): 283-8. PubMed

Mooney S, Leuendorf J, Hendrickson C, Hellmann H. Vitamin B6: a long known compound of surprising complexity. Molecules. 2009; 14(1): 329-51. PubMed

Oberley MJ, Yang DT. Laboratory testing for cobalamin deficiency in megaloblastic anemia. Am J Hematol. 2013; 88(6): 522-6. PubMed

Orr K, Hume AL. An evidence-based update on vitamins. Med Health R I. 2010; 93(4): 122-4. PubMed

Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011; 364(3): 248-54. PubMed

Taylor CL, Thomas PR, Aloia JF, Millard PS, Rosen CJ. Questions About Vitamin D for Primary Care Practice: Input From an NIH Conference. Am J Med. 2015; 128(11): 1167-70. PubMed

Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011; 86(1): 50-60. PubMed

Wyness SP, Straseski JA. Performance characteristics of six automated 25-hydroxyvitamin D assays: Mind your 3s and 2s Clin Biochem. 2015; 48(16-17): 1089-96. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Barker T, Henriksen VT, Martins TB, Hill HR, Kjeldsberg CR, Schneider ED, Dixon BM, Weaver LK. Higher serum 25-hydroxyvitamin D concentrations associate with a faster recovery of skeletal muscle strength after muscular injury. Nutrients. 2013; 5(4): 1253-75. PubMed

Barker T, Leonard SW, Trawick RH, Martins TB, Kjeldsberg CR, Hill HR, Traber MG. Modulation of inflammation by vitamin E and C supplementation prior to anterior cruciate ligament surgery. Free Radic Biol Med. 2009; 46(5): 599-606. PubMed

Barker T, Martins TB, Hill HR, Kjeldsberg CR, Dixon BM, Schneider ED, Henriksen VT, Weaver LK. Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults. Eur J Appl Physiol. 2013; 113(6): 1523-34. PubMed

Barker T, Martins TB, Hill HR, Kjeldsberg CR, Dixon BM, Schneider ED, Henriksen VT, Weaver LK. Vitamin D sufficiency associates with an increase in anti-inflammatory cytokines after intense exercise in humans. Cytokine. 2014; 65(2): 134-7. PubMed

Barker T, Martins TB, Hill HR, Kjeldsberg CR, Henriksen VT, Dixon BM, Schneider ED, Dern A, Weaver LK. Different doses of supplemental vitamin D maintain interleukin-5 without altering skeletal muscle strength: a randomized, double-blind, placebo-controlled study in vitamin D sufficient adults. Nutr Metab (Lond). 2012; 9(1): 16. PubMed

Barker T, Martins TB, Kjeldsberg CR, Trawick RH, Hill HR. Circulating interferon-γ correlates with 1,25(OH)D and the 1,25(OH)D-to-25(OH)D ratio. Cytokine. 2012; 60(1): 23-6. PubMed

Clark ZD, Frank EL. Development and implementation of an HPLC-ECD method for analysis of vitamin C in plasma using single column and automatic alternating dual column regeneration. Practical Laboratory Medicine. [Accessed: APR 2017]

Coelho D, Kim JC, Miousse IR, Fung S, Moulin Md, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nürnberg P, Thiele H, Robenek H, Höhne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge EA, Majewski J, Rosenblatt DS, Fowler B, Rutsch F, Baumgartner MR. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet. 2012; 44(10): 1152-5. PubMed

Genzen JR, Gosselin JT, Wilson TC, Racila E, Krasowski MD. Analysis of vitamin D status at two academic medical centers and a national reference laboratory: result patterns vary by age, gender, season, and patient location. BMC Endocr Disord. 2013; 13: 52. PubMed

Illson ML, Dempsey-Nunez L, Kent J, Huang Q, Brebner A, Raff ML, Watkins D, Gilfix BM, Wittwer CT, Rosenblatt DS. High resolution melting analysis of the MMAB gene in cblB patients and in those with undiagnosed methylmalonic aciduria. Mol Genet Metab. 2013; 110(1-2): 86-9. PubMed

Johnson-Davis KL, Moore SJ, Owen WE, Cutler JM, Frank EL. A rapid HPLC method used to establish pediatric reference intervals for vitamins A and E. Clin Chim Acta. 2009; 405(1-2): 35-8. PubMed

Jovanovich A, Chonchol M, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G, Kendrick J, HOST Investigators. Racial differences in markers of mineral metabolism in advanced chronic kidney disease. Clin J Am Soc Nephrol. 2012; 7(4): 640-7. PubMed

Kushnir MM, Nelson GJ, Frank EL, Rockwood AL. High-Throughput Analysis of Methylmalonic Acid in Serum, Plasma, and Urine by LC-MS/MS. Method for Analyzing Isomers Without Chromatographic Separation. Methods Mol Biol. 2016; 1378: 159-73. PubMed

Kushnir MM, Shushan B, Roberts WL, Pasquali M. Serum acylcarnitines and vitamin B12 deficiency. Clin Chem. 2002; 48(7): 1126-8. PubMed

Laha TJ, Strathmann FG, Wang Z, de Boer IH, Thummel KE, Hoofnagle AN. Characterizing antibody cross-reactivity for immunoaffinity purification of analytes prior to multiplexed liquid chromatography-tandem mass spectrometry. Clin Chem. 2012; 58(12): 1711-6. PubMed

Lu J, Frank EL. Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem. 2008; 54(5): 901-6. PubMed

Strathmann FG, Sadilkova K, Laha TJ, LeSourd SE, Bornhorst JA, Hoofnagle AN, Jack R. 3-epi-25 hydroxyvitamin D concentrations are not correlated with age in a cohort of infants and adults. Clin Chim Acta. 2012; 413(1-2): 203-6. PubMed