Metabolomic analysis of serum alpha-tocopherol among men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
Background/Objectives The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolit...
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| Published in | European journal of clinical nutrition Vol. 76; no. 9; pp. 1254 - 1265 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.09.2022
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0954-3007 1476-5640 1476-5640 |
| DOI | 10.1038/s41430-022-01112-7 |
Cover
| Abstract | Background/Objectives
The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.
Subjects/Methods
Metabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC–MS/GC–MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.
Results
A total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected
p
value (
p
< 2.79 × 10
−5
). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](
β
= 0.149;
p
= 8.65 × 10
−146
) and sphingomyelin (D18:2/18:1) (
β
= 0.035;
p
= 1.36 × 10
−30
). For amino acids, the strongest signals were aminoadipic acid (
β
= 0.021;
p
= 5.01 × 10
−13
) and
l
-leucine (
β
= 0.007;
p
= 1.05 × 10
−12
).
Conclusions
The large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer. |
|---|---|
| AbstractList | Background/ObjectivesThe role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.Subjects/MethodsMetabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC–MS/GC–MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.ResultsA total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10−5). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10−146) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10−30). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10−13) and l-leucine (β = 0.007; p = 1.05 × 10−12).ConclusionsThe large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer. The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.BACKGROUND/OBJECTIVESThe role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.Metabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC-MS/GC-MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.SUBJECTS/METHODSMetabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC-MS/GC-MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.A total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10-5). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10-146) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10-30). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10-13) and l-leucine (β = 0.007; p = 1.05 × 10-12).RESULTSA total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10-5). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10-146) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10-30). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10-13) and l-leucine (β = 0.007; p = 1.05 × 10-12).The large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer.CONCLUSIONSThe large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer. Background/Objectives The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state. Subjects/Methods Metabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC–MS/GC–MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors. Results A total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value ( p < 2.79 × 10 −5 ). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2]( β = 0.149; p = 8.65 × 10 −146 ) and sphingomyelin (D18:2/18:1) ( β = 0.035; p = 1.36 × 10 −30 ). For amino acids, the strongest signals were aminoadipic acid ( β = 0.021; p = 5.01 × 10 −13 ) and l -leucine ( β = 0.007; p = 1.05 × 10 −12 ). Conclusions The large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer. The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state. Metabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC-MS/GC-MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors. A total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10 ). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10 ) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10 ). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10 ) and l-leucine (β = 0.007; p = 1.05 × 10 ). The large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer. |
| Author | Albanes, Demetrius Huang, Jiaqi Lawrence, Wayne R. Sampson, Joshua N. Weinstein, Stephanie J. Lim, Jung-Eun |
| AuthorAffiliation | 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 2 National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China |
| AuthorAffiliation_xml | – name: 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA – name: 2 National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China |
| Author_xml | – sequence: 1 givenname: Wayne R. orcidid: 0000-0002-2992-5897 surname: Lawrence fullname: Lawrence, Wayne R. email: wayne.lawrence@nih.gov organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health – sequence: 2 givenname: Jung-Eun surname: Lim fullname: Lim, Jung-Eun organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health – sequence: 3 givenname: Jiaqi surname: Huang fullname: Huang, Jiaqi organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University – sequence: 4 givenname: Joshua N. surname: Sampson fullname: Sampson, Joshua N. organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health – sequence: 5 givenname: Stephanie J. orcidid: 0000-0002-3834-1535 surname: Weinstein fullname: Weinstein, Stephanie J. organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health – sequence: 6 givenname: Demetrius orcidid: 0000-0001-8330-4293 surname: Albanes fullname: Albanes, Demetrius email: daa@nih.gov organization: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35322169$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1017_S0954422423000112 crossref_primary_10_1007_s41999_023_00814_w crossref_primary_10_3389_fimmu_2024_1343301 crossref_primary_10_1038_s42003_023_04520_y crossref_primary_10_3389_fcvm_2024_1371805 |
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| ContentType | Journal Article |
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The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is... The role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the... Background/ObjectivesThe role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is... |
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| SubjectTerms | 692/308/174 692/53 alpha-Tocopherol Amino Acids beta Carotene Cancer Cardiovascular diseases Carotene Clinical Nutrition Disease prevention Epidemiology Etiology Fatty acids Glycerol Health risks High-performance liquid chromatography Humans Internal Medicine Isoleucine Leucine Lipid metabolism Lipids Liquid chromatography Male Medicine Medicine & Public Health Metabolic Diseases Metabolites Metabolomics Neoplasms - prevention & control Public Health Sphingomyelin Supplements Tocopherol Valine Vitamin E β-Carotene |
| Title | Metabolomic analysis of serum alpha-tocopherol among men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study |
| URI | https://link.springer.com/article/10.1038/s41430-022-01112-7 https://www.ncbi.nlm.nih.gov/pubmed/35322169 https://www.proquest.com/docview/2708890727 https://www.proquest.com/docview/2642885834 https://pubmed.ncbi.nlm.nih.gov/PMC9444878 |
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