Short-Term Vitamin B-6 Restriction Does Not Affect Plasma Concentrations of Hydrogen Sulfide Biomarkers Lanthionine and Homolanthionine in Healthy Men and Women

Abstract

Background: Suboptimal vitamin B-6 status is associated with increased cardiovascular disease risk, although the mechanism is unknown. The synthesis of the vasodilator hydrogen sulfide occurs through side reactions of the transsulfuration enzymes cystathionine β-synthase and cystathionine γ-lyase, with pyridoxal 5'-phosphate as a coenzyme. Two proposed hydrogen sulfide biomarkers, lanthionine and homolanthionine, are produced concurrently.

Objective: To determine whether hydrogen sulfide production is reduced by vitamin B-6 deficiency, we examined the relations between plasma concentrations of lanthionine and homolanthionine, along with other components of the transsulfuration pathway (homocysteine, cystathionine, and Cys), in a secondary analysis of samples from 2 vitamin B-6 restriction studies in healthy men and women.

Methods: Metabolite concentrations were measured in plasma from 23 healthy adults (12 men and 11 women) before and after 28-d controlled dietary vitamin B-6 restriction (0.37 ± 0.04 mg/d). Vitamin B-6 restriction effects on lanthionine and homolanthionine concentrations were assessed. Associations between hydrogen sulfide biomarkers, transsulfuration metabolites, and functional indicators of vitamin B-6 deficiency were analyzed by linear regression.

Results: Preprandial plasma lanthionine and homolanthionine concentrations ranged from 89.0 to 372 nmol/L and 5.75 to 32.3 nmol/L, respectively, in healthy adults. Mean lanthionine and homolanthionine concentrations were not affected by vitamin B-6 restriction (P < 0.66), with marked heterogeneity of individual responses. After restriction, homolanthionine was positively associated with functional indicators of vitamin B-6 deficiency, which differed from hypothesized negative associations. Plasma lanthionine was positively correlated with the concentration of its precursor, Cys, before (R2 = 0.36; P = 0.002) and after (R2 = 0.37; P = 0.002) restriction. Likewise, homolanthionine concentration was positively correlated with its precursor homocysteine, but only in vitamin B-6 adequacy (R2 = 0.41; P < 0.001).

Conclusions: The resiliency of plasma lanthionine and homolanthionine concentrations after short-term vitamin B-6 restriction suggests a minimal effect of moderate vitamin B-6 deficiency on hydrogen sulfide production. Additional research is needed to better understand the metabolism and disposal of these biomarkers in humans. This study was registered at clinicaltrials.gov as NCT00877812.

Keywords: cystathionine β-synthase; cystathionine γ-lyase; homolanthionine; hydrogen sulfide; lanthionine; vitamin B-6.

Conflict of interest statement

Author disclosures: BN DeRatt, MA Ralat, and JF Gregory, no conflicts of interest.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

Human plasma concentrations of homolanthionine (A) and lanthionine (B) before and after 28-d dietary vitamin B-6 restriction. Dashed lines are female subjects and solid lines are male subjects; n = 23.

FIGURE 2

Relations between lanthionine and its precursor Cys (A and B) and between homolanthionine and its precursor homocysteine (C and D) in human plasma before and after 28-d dietary vitamin B-6 restriction; n = 23.

FIGURE 3

Relation between lanthionine and homolanthionine in human plasma before (A) and after (B) 28-d dietary vitamin B-6 restriction; n = 23.