Vitamin B6, Plasma

CPT: 84207
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Synonyms

  • B6
  • B6, Vitamin
  • PLP
  • Pyridoxal-5-Phosphate
  • Pyridoxine

Expected Turnaround Time

4 - 6 days


Related Information


Related Documents


Specimen Requirements


Specimen

Plasma (EDTA), protected from light


Volume

0.5 mL


Minimum Volume

0.25 mL (Note: This volume does not allow for repeat testing.)


Container

Lavender-top (EDTA) tube; amber plastic transport tube with amber-top. (If amber tubes are unavailable, cover standard transport tube completely, top and bottom, with aluminum foil. Identify specimen with patient's name directly on the container and on the outside of the aluminum foil. Secure with tape.) For amber plastic transport tube and amber-top, order LabCorp item No. 23594.


Collection

Collect blood by venipuncture into a lavender-top tube containing EDTA and mixed immediately by gentle inversion at least six times to ensure adequate mixing. The plasma must be separated and protected from light in an amber transport tube with amber stopper. Specimens should be stored refrigerated or frozen immediately and maintained at temperature during shipping and at the testing facility. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.


Storage Instructions

Refrigerate or freeze and protect from light.


Stability Requirements

Temperature

Period

Room temperature

3 days

Refrigerated

15 days

Frozen

15 days

Freeze/thaw cycles

Stable x6


Causes for Rejection

Anticoagulants other than EDTA; specimen not protected from light


Test Details


Use

Detect vitamin B6 deficiency


Limitations

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

Liquid chromatography-tandem mass spectrometry (LC/MS-MS)


Reference Interval

Age/Gender

Vitamin B6 (µg/L)

All

3.4 – 65.2

Deficiency:

< 3.4

Marginal:

3.4 – 5.1

Adequate:

> 5.1

Upper limit of reference interval established by Labcorp internal study.

PLP concentrations of more than 5.1 µg/L have been traditional indicators of adequate vitamin B6 status in adults.3 However, the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) used a plasma PLP level of 3.4 µg/L as the major indicator of adequacy to calculate the Recommended Dietary Allowances (RDAs) for adults.1,3


Additional Information

Vitamin B6 occurs as an alcohol (pyridoxine), an aldehyde (pyridoxal), and an amine (pyridoxamine). These forms are phosphorylated in the 5'-position to produce the physiologically active coenzymes that are critical to their biological function. Eukaryotes cannot synthesize vitamin B6 molecules from smaller compounds and as a result require dietary B6 for the synthesis of 5'-phosphate vitamins. Pyridoxal 5'Phosphate (PLP), the most clinically significant coenzyme form of vitamin B6, is the form most commonly measured in plasma.1-3

PLP serves as a coenzyme for more than 100 enzymes that catalyze key steps in the metabolism of amino acids, neurotransmitters, nucleic acids, heme, and lipids.1,4,5 Vitamin B6 is a critical cofactor for enzymes involved in energy homeostasis through glycogen degradation and gluconeogenesis.5 Inverse associations have been shown between plasma PLP and chronic or acute disease, including rheumatoid arthritis, cardiovascular disease, deep vein thrombosis, and cancer.4-16 A number of epidemiologic studies have shown reduced concentrations of circulating PLP in association the acute phase marker C-reaction protein13-17 and with inflammatory markers.18-19 Diminished vitamin B6 levels are frequently observed without any indication of a lower dietary intake or excessive catabolism of the vitamin, or congenital defects in its metabolism.4 Research is ongoing to determine if these lower vitamin B6 levels are caused by the mobilization of this coenzyme to the site of inflammation for use by the PLP-dependent enzymes4 or due increased catabolism of vitamin B6 during inflammation.5

PLP serves as a coenzyme for δ-aminolevulinate synthase, which catalyzes the first step in heme biosynthesis.1,5 B6 deficiency can produce a hypochromic form of anemia characterized by the presence of ring sideroblasts (iron positive granules deposited about the nucleus of red cell precursors). Occasionally the anemia may have megaloblastic characteristics. Inherited abnormalities of apoenzymes that bind with pyridoxal phosphate are responsible for newborn conditions characterized by mental retardation, skeletal deformities, thrombotic conditions, osteoporosis, and visual defects. Some inherited abnormalities of vitamin B6 metabolism and transport are associated with aminoacidurias including homocystinuria, hypermethioninemia, cystathioninuria.21 A number of studies have demonstration an inverse association between plasma PLP levels and the risk of developing colorectal cancer.20 A recent meta- analysis indicated that the risk of developing this type of cancer decreased by 49% for every 100-pmol/mL increase in blood PLP level.20

Vitamin B6 deficiency can occur in individuals with a variety of genetic conditions including antiquitin deficiency,21 pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency22 and hyperprolinemia type II (pyrroline-5- carboxylate dehydrogenase deficiency.23 Vitamin B6 levels can be decreased in malabsorption conditions including inflammatory disease of the small bowel and as a consequence of jejunoileal bypass.4,5 Several drugs, including oral contraceptive agents, levodopa, isoniazid, cycloserine, and pyrazinoic acid may cause B6 depletion.1 B6 levels may be decreased with pregnancy, lactation and alcoholism.1 Infants can develop deficiency when fed formula rendered B6 depleted by excessive heating.

Markedly elevated plasma PLP levels are observed in cases of hypophosphatasia (HPP), an inborn error of metabolism caused by a loss-of-function mutation(s) within the gene for the cell surface enzyme, tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP).24-28 This disorder is characterized by low serum alkaline phosphatase activity and increased plasma levels of TNSALP substrates including inorganic pyrophosphate, phosphatidylethanolamine and PLP. Clinical features can include childhood rickets, adult osteomalacia and dental abnormalities. These symptoms are thought to occur as a result of the accumulation of inorganic pyrophosphate which inhibits hydroxyapatite crystal formation and growth, leading to defective skeletal and dental mineralization. PLP, carried in the plasma on albumin, must be de-phosphorylated by TNSALP for pyridoxal to cross cell membranes. Once inside the cell, the pyridoxal is regenerated as PLP to allow it to function as a coenzyme. The diminished TNSALP of individuals with HPP leads to an accumulation of the PLP substrate in plasma. HPP patients do not typically experience B6 related symptoms. However, the extent of PLP elevation has been related to the disease severity.28


Footnotes

1. Food and Nutrition Board, Institute of Medicine. Vitamin B6. In: Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998: 150-195.23193625
2. Lamers Y. Indicators and methods for folate, vitamin B-12, and vitamin B-6 status assessment in humans. Curr Opin Clin Nutr Metab Care. 2011 Sep;14(5):445-454.21832901
3. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5'-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008 May;87(5):1446-1454.18469270
4. Paul L, Ueland PM, Selhub J. Mechanistic perspective on the relationship between pyridoxal 5'-phosphate and inflammation. Nutr Rev. 2013 Apr;71(4):239-244.23550784
5. Ulvik A, Midttun O, Pedersen ER, Eussen SJ, Nygård O, Ueland PM. Evidence for increased catabolism of vitamin B-6 during systemic inflammation. Am J Clin Nutr. 2014 Jul;100(1):250-255.24808485
6. Roubenoff R, Roubenoff RA, Selhub J, et al. Abnormal vitamin B6 status in rheumatoid cachexia. Association with spontaneous tumor necrosis factor alpha production and markers of inflammation. Arthritis Rheum. 1995 Jan; 38(1):105-109.7818558
7. Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest J Jr. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. Am J Cardiol. 1995 Jun 1;75(16):1107-1111.7762494
8. Saibeni S, Cattaneo M, Vecchi M, et al. Low vitamin B6 plasma levels, a risk factor for thrombosis in inflammatory bowel disease; role of inflammation and correlation with acute phase reactants low vitamin B6 levels and IBD. Am J Gastroenterol. 2003 Jan; 98(1):112-117.12526945
9. Cattaneo M, Lombardi R, Lecchi A, Bucciarelli P, Mannucci PM. Low plasma levels of vitamin B6 are independently associated with a heightened risk of deep-vein thrombosis. Circulation. 2001 Nov 13;104(20):2442-2446.11705822
10. Le Marchand L, White KK, Nomura AM, et al. Plasma levels of B vitamins and colorectal cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2195-2201.19661077
11. Wei EK, Giovannucci E, Selhub J, Fuchs CS, Hankinson SE, Ma J. Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. J Natl Cancer Inst. 2005 May 4;97(9):684-692.15870439
12. Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998 Feb 4;279(5):359-364.9459468
13. Shen J, Lai CQ, Mattei J, Ordovas JM, Tucker KL. Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. Am J Clin Nutr. 2010 Feb; 91(2):337-342.19955400
14. Chiang EP, Bagley PJ, Selhub J, Nadeau M, Roubenoff R. Abnormal vitamin B(6) status is associated with severity of symptoms in patients with rheumatoid arthritis. Am J Med. 2003 Mar;114(4):283-287.12681455
15. Chiang EP, Smith DE, Selhub J, Dallal G, Wang YC, Roubenoff R. Inflammation causes tissue-specific depletion of vitamin B6. Arthritis Res Ther. 2005;7(6):R1254-1262.16277678
16. Friso S, Jacques PF, Wilson PW, Rosenberg IH, Selhub J. Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation. 2001 Jun 12;103(23):2788-2791.11401933
17. Ulvik A, Midttun O, Pedersen ER, Nygård O, Ueland PM. Association of plasma B-6 vitamers with systemic markers of inflammation before and after pyridoxine treatment in patients with stable angina pectoris. Am J Clin Nutr. 2012 May;95(5):1072-1078.22492365
18. Sakakeeny L, Roubenoff R, Obin M, et al. Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of US adults. J Nutr. 2012 Jul;142(7):1280-1285.22623384
19. Folsom AR, Desvarieux M, Nieto JF, Boland LL, Ballantyne CM, Chambless LE. B vitamin status and inflammatory markers. Atherosclerosis. 2003 Jul;169(1):169-174.12860264
20. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA. 2010 Mar 17;303(11):1077-1083.20233826
21. Mills PB, Struys E, Jakobs C, et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med. 2006 Mar;12(3):307-309.16491085
22. Mills PB, Surtees RA, Champion MP, et al. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)line 5#-phosphate oxidase. Hum Mol Genet. 2005 Apr 15;14(8):1077-1086.15772097
23. Walker V, Mills GA, Peters SA, Merton WL. Fits, pyridoxine, and hyperprolinaemia type II. Arch Dis Child. 2000 Mar;82(3):236-237.10685929
24. Mornet E. Hypophosphatasia. Orphanet J Rare Dis. 2007 Oct 4;2:40.17916236
25. Whyte MP, Mahuren JD, Vrabel LA, Coburn SP. Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. J Clin Invest. 1985 Aug;76(2):752-756.4031070
26. Iqbal SJ, Brain A, Reynolds TM, Penny M, Holland S. Relationship between serum alkaline phosphatase and and pyridoxal-5'-phosphate levels in hypophosphatasia. Clin Sci (Lond). 1998 Feb;94(2):203-206.9536930
27. Berkseth KE, Tebben PJ, Drake MT, Hefferan TE, Jewison DE, Wermers RA. Clinical spectrum of hypophosphatasia diagnosed in adults. Bone. 2013 May;54(1):21-27.23352924
28. Khandwala HM, Mumm S, Whyte MP. Low serum alkaline phosphatase activity and pathologic fracture; case report and brief review of hypophosphatasia diagnosed in adulthood. Endocr Pract. 2006 Nov-Dec;12(6):676-681.17229666

References

Cabo R, Kozik K, Milanowski M, Hernes S, et al. A simple high-performance liquid chromatography (HPLC) method for the measurement of pyridoxal-5-phosphate and 4-pyridoxic acid in human plasma. Clin Chim Acta. 2014 Jun 10; 433:150-156.24657184
U.S. Centers for Disease Control and Prevention. Second national report on biochemical indicators of diet and nutrition in the U.S. population 2012. Atlanta (GA): National Center for Environmental Health; April 2012. Available from: http://www.cdc.gov/nutritionreport.

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
004655 Vitamin B6, Plasma 95266-3 004656 Vitamin B6 ug/L 30552-4

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