Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users
Low chronic vitamin B-6 status can occur in a subset of women who use oral contraceptives (OCs) with uncertain metabolic consequences. An insufficiency of cellular pyridoxal 5'-phosphate (PLP), which is the coenzyme form of vitamin B-6, may impair many metabolic processes including one-carbon a...
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| Veröffentlicht in: | The American journal of clinical nutrition 2015-09, Vol.102 (3), p.616-625 |
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| creator | Rios-Avila, Luisa Coats, Bonnie Ralat, Maria Chi, Yueh-Yun Midttun, Øivind Ueland, Per M Stacpoole, Peter W Gregory, 3rd, Jesse F |
| description | Low chronic vitamin B-6 status can occur in a subset of women who use oral contraceptives (OCs) with uncertain metabolic consequences. An insufficiency of cellular pyridoxal 5'-phosphate (PLP), which is the coenzyme form of vitamin B-6, may impair many metabolic processes including one-carbon and tryptophan metabolism.
We investigated the effects of vitamin B-6 supplementation on the in vivo kinetics of one-carbon metabolism and the concentration of one-carbon and tryptophan metabolites in vitamin B-6-deficient OC users.
A primed, constant infusion of [(13)C5]methionine, [3-(13)C]serine, and [(2)H3]leucine was performed on 10 OC users (20-40 y old; plasma PLP concentrations |
| doi_str_mv | 10.3945/ajcn.115.113159 |
| format | Article |
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We investigated the effects of vitamin B-6 supplementation on the in vivo kinetics of one-carbon metabolism and the concentration of one-carbon and tryptophan metabolites in vitamin B-6-deficient OC users.
A primed, constant infusion of [(13)C5]methionine, [3-(13)C]serine, and [(2)H3]leucine was performed on 10 OC users (20-40 y old; plasma PLP concentrations <30 nmol/L) before and after 28 d of supplementation with 10 mg pyridoxine hydrochloric acid/d. In vivo fluxes of total homocysteine remethylation, the remethylation of homocysteine from serine, and rates of homocysteine and cystathionine production were assessed. Targeted metabolite profiling was performed, and data were analyzed by using orthogonal partial least-squares-discriminant analysis and paired t tests adjusted for multiple testing.
Pyridoxine supplementation increased the mean ± SD plasma PLP concentration from 25.8 ± 3.6 to 143 ± 58 nmol/L (P < 0.001) and decreased the leucine concentration from 103 ± 17 to 90 ± 20 nmol/L (P = 0.007) and glycine concentration from 317 ± 63 to 267 ± 58 nmol/L (P = 0.03). Supplementation did not affect in vivo rates of homocysteine remethylation or the appearance of homocysteine and cystathionine. A multivariate analysis showed a clear overall effect on metabolite profiles resulting from supplementation. Leucine, glycine, choline, cysteine, glutathione, trimethylamine N-oxide, and the ratios glycine:serine, 3-hydroxykynurenine:kynurenine, 3-hydroxykynurenine:3-hydroxyanthranilic acid, and 3-hydroxykynurenine:anthranilic acid were significant discriminating variables.
Consistent with previous vitamin B-6-restriction studies, fluxes of one-carbon metabolic processes exhibited little or no change after supplementation in low-vitamin B-6 subjects. In contrast, changes in the metabolic profiles after supplementation indicated perturbations in metabolism, suggesting functional vitamin B-6 deficiency. This study was registered at clinicaltrials.gov as NCT01128244.</description><identifier>ISSN: 0002-9165</identifier><identifier>EISSN: 1938-3207</identifier><identifier>DOI: 10.3945/ajcn.115.113159</identifier><identifier>PMID: 26201817</identifier><language>eng</language><publisher>United States: American Society for Clinical Nutrition, Inc</publisher><subject>3-Hydroxyanthranilic Acid - metabolism ; Adult ; Biomarkers - blood ; Carbon - metabolism ; Contraceptives, Oral - administration & dosage ; Contraceptives, Oral - adverse effects ; Cystathionine - blood ; Dietary Supplements ; Female ; Glycine - blood ; Homocysteine - blood ; Humans ; Kinetics ; Kynurenine - analogs & derivatives ; Kynurenine - blood ; Leucine - blood ; Metabolism ; Metabolites ; Methionine - blood ; Methylamines - blood ; Multivariate Analysis ; Pyridoxal Phosphate - blood ; Pyridoxine - administration & dosage ; Pyridoxine - blood ; Serine - blood ; Tryptophan - blood ; Vitamin B 6 Deficiency - blood ; Vitamin B 6 Deficiency - etiology ; Vitamin deficiency ; Young Adult</subject><ispartof>The American journal of clinical nutrition, 2015-09, Vol.102 (3), p.616-625</ispartof><rights>2015 American Society for Nutrition.</rights><rights>Copyright American Society for Clinical Nutrition, Inc. Sep 1, 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-33328957e0ab484718bd067510bc9c652e591d6de77a7782a85f8dc64772b893</citedby><cites>FETCH-LOGICAL-c399t-33328957e0ab484718bd067510bc9c652e591d6de77a7782a85f8dc64772b893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26201817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rios-Avila, Luisa</creatorcontrib><creatorcontrib>Coats, Bonnie</creatorcontrib><creatorcontrib>Ralat, Maria</creatorcontrib><creatorcontrib>Chi, Yueh-Yun</creatorcontrib><creatorcontrib>Midttun, Øivind</creatorcontrib><creatorcontrib>Ueland, Per M</creatorcontrib><creatorcontrib>Stacpoole, Peter W</creatorcontrib><creatorcontrib>Gregory, 3rd, Jesse F</creatorcontrib><title>Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users</title><title>The American journal of clinical nutrition</title><addtitle>Am J Clin Nutr</addtitle><description>Low chronic vitamin B-6 status can occur in a subset of women who use oral contraceptives (OCs) with uncertain metabolic consequences. An insufficiency of cellular pyridoxal 5'-phosphate (PLP), which is the coenzyme form of vitamin B-6, may impair many metabolic processes including one-carbon and tryptophan metabolism.
We investigated the effects of vitamin B-6 supplementation on the in vivo kinetics of one-carbon metabolism and the concentration of one-carbon and tryptophan metabolites in vitamin B-6-deficient OC users.
A primed, constant infusion of [(13)C5]methionine, [3-(13)C]serine, and [(2)H3]leucine was performed on 10 OC users (20-40 y old; plasma PLP concentrations <30 nmol/L) before and after 28 d of supplementation with 10 mg pyridoxine hydrochloric acid/d. In vivo fluxes of total homocysteine remethylation, the remethylation of homocysteine from serine, and rates of homocysteine and cystathionine production were assessed. Targeted metabolite profiling was performed, and data were analyzed by using orthogonal partial least-squares-discriminant analysis and paired t tests adjusted for multiple testing.
Pyridoxine supplementation increased the mean ± SD plasma PLP concentration from 25.8 ± 3.6 to 143 ± 58 nmol/L (P < 0.001) and decreased the leucine concentration from 103 ± 17 to 90 ± 20 nmol/L (P = 0.007) and glycine concentration from 317 ± 63 to 267 ± 58 nmol/L (P = 0.03). Supplementation did not affect in vivo rates of homocysteine remethylation or the appearance of homocysteine and cystathionine. A multivariate analysis showed a clear overall effect on metabolite profiles resulting from supplementation. Leucine, glycine, choline, cysteine, glutathione, trimethylamine N-oxide, and the ratios glycine:serine, 3-hydroxykynurenine:kynurenine, 3-hydroxykynurenine:3-hydroxyanthranilic acid, and 3-hydroxykynurenine:anthranilic acid were significant discriminating variables.
Consistent with previous vitamin B-6-restriction studies, fluxes of one-carbon metabolic processes exhibited little or no change after supplementation in low-vitamin B-6 subjects. In contrast, changes in the metabolic profiles after supplementation indicated perturbations in metabolism, suggesting functional vitamin B-6 deficiency. This study was registered at clinicaltrials.gov as NCT01128244.</description><subject>3-Hydroxyanthranilic Acid - metabolism</subject><subject>Adult</subject><subject>Biomarkers - blood</subject><subject>Carbon - metabolism</subject><subject>Contraceptives, Oral - administration & dosage</subject><subject>Contraceptives, Oral - adverse effects</subject><subject>Cystathionine - blood</subject><subject>Dietary Supplements</subject><subject>Female</subject><subject>Glycine - blood</subject><subject>Homocysteine - blood</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Kynurenine - analogs & derivatives</subject><subject>Kynurenine - blood</subject><subject>Leucine - blood</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Methionine - blood</subject><subject>Methylamines - blood</subject><subject>Multivariate Analysis</subject><subject>Pyridoxal Phosphate - blood</subject><subject>Pyridoxine - administration & dosage</subject><subject>Pyridoxine - blood</subject><subject>Serine - blood</subject><subject>Tryptophan - blood</subject><subject>Vitamin B 6 Deficiency - blood</subject><subject>Vitamin B 6 Deficiency - etiology</subject><subject>Vitamin deficiency</subject><subject>Young Adult</subject><issn>0002-9165</issn><issn>1938-3207</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1P3DAQhq2qVVloz9wqS730EvBHHNvHFlGohNQeuEeOPVG9JHZqOyv2F_K3alhaJA6juTzvOyM9CJ1ScsZ1K87N1oYzSkUdToV-gzZUc9VwRuRbtCGEsEbTThyh45y3hFDWqu49OmIdI1RRuUEPv_bJu3jvA-C8LssEM4Riio8BuwgZh1iwmQok7APe-V3Ed5Ut3mYcRxwDNNakodIzFDPEyecZD2vBc3R-9LVgMaWmw2vcBIdL2i8lLr_NS7rUxNOhYua6vzVd40Nex9FbXx_DMZkJ2xhKMhaW4neA1wwpf0DvRjNl-Pi8T9Dt98vbi-vm5ufVj4uvN43lWpeGc86UFhKIGVrVSqoGRzopKBmstp1gIDR1nQMpjZSKGSVG5WzXSskGpfkJ-nKoXVL8s0Iu_eyzhWkyAeKaeyqVYLwVQlT08yt0G9cU6nOVooRUX7St1PmBsinmnGDsl-Rnk_Y9Jf2j4v5RcV8V9wfFNfHpuXcdZnD_-X9O-V9Yuaa8</recordid><startdate>201509</startdate><enddate>201509</enddate><creator>Rios-Avila, Luisa</creator><creator>Coats, Bonnie</creator><creator>Ralat, Maria</creator><creator>Chi, Yueh-Yun</creator><creator>Midttun, Øivind</creator><creator>Ueland, Per M</creator><creator>Stacpoole, Peter W</creator><creator>Gregory, 3rd, Jesse F</creator><general>American Society for Clinical Nutrition, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T7</scope><scope>7TS</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7U7</scope></search><sort><creationdate>201509</creationdate><title>Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users</title><author>Rios-Avila, Luisa ; Coats, Bonnie ; Ralat, Maria ; Chi, Yueh-Yun ; Midttun, Øivind ; Ueland, Per M ; Stacpoole, Peter W ; Gregory, 3rd, Jesse F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-33328957e0ab484718bd067510bc9c652e591d6de77a7782a85f8dc64772b893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>3-Hydroxyanthranilic Acid - metabolism</topic><topic>Adult</topic><topic>Biomarkers - blood</topic><topic>Carbon - metabolism</topic><topic>Contraceptives, Oral - administration & dosage</topic><topic>Contraceptives, Oral - adverse effects</topic><topic>Cystathionine - blood</topic><topic>Dietary Supplements</topic><topic>Female</topic><topic>Glycine - blood</topic><topic>Homocysteine - blood</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Kynurenine - analogs & derivatives</topic><topic>Kynurenine - blood</topic><topic>Leucine - blood</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Methionine - blood</topic><topic>Methylamines - blood</topic><topic>Multivariate Analysis</topic><topic>Pyridoxal Phosphate - blood</topic><topic>Pyridoxine - administration & dosage</topic><topic>Pyridoxine - blood</topic><topic>Serine - blood</topic><topic>Tryptophan - blood</topic><topic>Vitamin B 6 Deficiency - blood</topic><topic>Vitamin B 6 Deficiency - etiology</topic><topic>Vitamin deficiency</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rios-Avila, Luisa</creatorcontrib><creatorcontrib>Coats, Bonnie</creatorcontrib><creatorcontrib>Ralat, Maria</creatorcontrib><creatorcontrib>Chi, Yueh-Yun</creatorcontrib><creatorcontrib>Midttun, Øivind</creatorcontrib><creatorcontrib>Ueland, Per M</creatorcontrib><creatorcontrib>Stacpoole, Peter W</creatorcontrib><creatorcontrib>Gregory, 3rd, Jesse F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Toxicology Abstracts</collection><jtitle>The American journal of clinical nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rios-Avila, Luisa</au><au>Coats, Bonnie</au><au>Ralat, Maria</au><au>Chi, Yueh-Yun</au><au>Midttun, Øivind</au><au>Ueland, Per M</au><au>Stacpoole, Peter W</au><au>Gregory, 3rd, Jesse F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users</atitle><jtitle>The American journal of clinical nutrition</jtitle><addtitle>Am J Clin Nutr</addtitle><date>2015-09</date><risdate>2015</risdate><volume>102</volume><issue>3</issue><spage>616</spage><epage>625</epage><pages>616-625</pages><issn>0002-9165</issn><eissn>1938-3207</eissn><abstract>Low chronic vitamin B-6 status can occur in a subset of women who use oral contraceptives (OCs) with uncertain metabolic consequences. An insufficiency of cellular pyridoxal 5'-phosphate (PLP), which is the coenzyme form of vitamin B-6, may impair many metabolic processes including one-carbon and tryptophan metabolism.
We investigated the effects of vitamin B-6 supplementation on the in vivo kinetics of one-carbon metabolism and the concentration of one-carbon and tryptophan metabolites in vitamin B-6-deficient OC users.
A primed, constant infusion of [(13)C5]methionine, [3-(13)C]serine, and [(2)H3]leucine was performed on 10 OC users (20-40 y old; plasma PLP concentrations <30 nmol/L) before and after 28 d of supplementation with 10 mg pyridoxine hydrochloric acid/d. In vivo fluxes of total homocysteine remethylation, the remethylation of homocysteine from serine, and rates of homocysteine and cystathionine production were assessed. Targeted metabolite profiling was performed, and data were analyzed by using orthogonal partial least-squares-discriminant analysis and paired t tests adjusted for multiple testing.
Pyridoxine supplementation increased the mean ± SD plasma PLP concentration from 25.8 ± 3.6 to 143 ± 58 nmol/L (P < 0.001) and decreased the leucine concentration from 103 ± 17 to 90 ± 20 nmol/L (P = 0.007) and glycine concentration from 317 ± 63 to 267 ± 58 nmol/L (P = 0.03). Supplementation did not affect in vivo rates of homocysteine remethylation or the appearance of homocysteine and cystathionine. A multivariate analysis showed a clear overall effect on metabolite profiles resulting from supplementation. Leucine, glycine, choline, cysteine, glutathione, trimethylamine N-oxide, and the ratios glycine:serine, 3-hydroxykynurenine:kynurenine, 3-hydroxykynurenine:3-hydroxyanthranilic acid, and 3-hydroxykynurenine:anthranilic acid were significant discriminating variables.
Consistent with previous vitamin B-6-restriction studies, fluxes of one-carbon metabolic processes exhibited little or no change after supplementation in low-vitamin B-6 subjects. In contrast, changes in the metabolic profiles after supplementation indicated perturbations in metabolism, suggesting functional vitamin B-6 deficiency. This study was registered at clinicaltrials.gov as NCT01128244.</abstract><cop>United States</cop><pub>American Society for Clinical Nutrition, Inc</pub><pmid>26201817</pmid><doi>10.3945/ajcn.115.113159</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The American journal of clinical nutrition, 2015-09, Vol.102 (3), p.616-625 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 3-Hydroxyanthranilic Acid - metabolism Adult Biomarkers - blood Carbon - metabolism Contraceptives, Oral - administration & dosage Contraceptives, Oral - adverse effects Cystathionine - blood Dietary Supplements Female Glycine - blood Homocysteine - blood Humans Kinetics Kynurenine - analogs & derivatives Kynurenine - blood Leucine - blood Metabolism Metabolites Methionine - blood Methylamines - blood Multivariate Analysis Pyridoxal Phosphate - blood Pyridoxine - administration & dosage Pyridoxine - blood Serine - blood Tryptophan - blood Vitamin B 6 Deficiency - blood Vitamin B 6 Deficiency - etiology Vitamin deficiency Young Adult |
| title | Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users |
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