Elevated plasma 4-pyridoxic acid in renal insufficiency

Stephen P. Coburn, Robert D. Reynolds, J. Dennis Mahuren, Wayne E. Schaltenbrand, Yao Wang, Karen L. Ericson, Michael P. Whyte, Yvonne M. Zubovic, Paula J. Ziegler, David L. Costill, William J. Fink, David R. Pearson, Thomas A. Pauly, K. George Thampy, Jacobo Wortsman

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: Renal insufficiency is associated with altered vitamin B-6 metabolism. We have observed high concentrations of 4-pyridoxic acid, the major catabolite of vitamin B-6 metabolism, in plasma during renal insufficiency. Objective: The objective was to evaluate the renal handling of 4-pyridoxic acid and the effects of renal dysfunction on vitamin B-6 metabolism. Design: We measured the renal clearance of 4-pyridoxic acid and creatinine in 17 nonpregnant, 17 pregnant, and 16 lactating women. We then examined the influence of vitamin B-6 or alkaline phosphatase activity on the ratio of 4-pyridoxic acid to pyridoxal (PA:PL) in plasma in 10 men receiving a low (0.4 mg pyridoxine·HCl/d) or high (200 mg pyridoxine·HCl/d) vitamin B-6 intake for 6 wk, in 10 healthy subjects during a 21-d fast, in 1235 plasma samples from 799 people screened for hypophosphatasia, and in 67 subjects with a range of serum creatinine concentrations. Results: Renal clearance of 4-pyridoxic acid was 232 ± 94 mL/min in nonpregnant women, 337 ± 140 mL/min in pregnant women, and 215 ± 103 mL/min in lactating healthy women. These values were approximately twice the creatinine clearance, indicating that 4-pyridoxic acid is at least partially eliminated by tubular secretion. Elevated plasma creatinine concentrations were associated with marked elevations in 4-pyridoxic acid and PA:PL. PA:PL was not affected by wide variations in vitamin B-6 intake or by the wide range of pyridoxal-P concentrations encountered while screening for hypophosphatasia. Conclusions: Plasma 4-pyridoxic acid concentrations are markedly elevated in renal insufficiency. Plasma PA:PL can distinguish between increases in 4-pyridoxic acid concentrations due to increased dietary intake and those due to renal insufficiency.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Issue number1
StatePublished - Jan 5 2002
Externally publishedYes


  • 4-Pyridoxic acid
  • Lactation
  • Pregnancy
  • Pyridoxal
  • Pyridoxal-P
  • Renal function
  • Vitamin B-6
  • Women

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