The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults
| العنوان: | The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults |
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| المؤلفون: | Joshua W. Miller, Daniela Hampel, Sergey N. Fedosov, Ralph Green, Setareh Shahab-Ferdows, Dmitry Grapov, Oliver Fiehn, Lindsay H. Allen, Danielle J Harvey, Alex Brito, John W. Newman, Theresa L. Pedersen, Ricardo Uauy, Johannes F. Fahrmann |
| المصدر: | The Journal of nutrition, vol 147, iss 10 Brito, A, Grapov, D, Fahrmann, J, Harvey, D, Green, R, Miller, J, Fedosov, S, Shahab-Ferdows, S, Hampel, D, Pedersen, T, Fiehn, O, Newman, J, Uauy, R & Allen, L 2017, ' The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults ', Journal of Nutrition, vol. 147, no. 10, pp. 1839–1849 . https://doi.org/10.3945/jn.117.248278 |
| بيانات النشر: | eScholarship, University of California, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Vitamin, Male, medicine.medical_specialty, Aging, Homocysteine, Population, Clinical Trials and Supportive Activities, Methylmalonic acid, Medicine (miscellaneous), 03 medical and health sciences, chemistry.chemical_compound, Metabolomics, Food Sciences, Animal Production, acylcarnitines, Clinical Research, Internal medicine, medicine, Metabolome, Humans, Genomics, Proteomics, and Metabolomics, Vitamin B12, Peripheral Nerves, nerve function, education, Aged, vitamin B-12, Nutrition, education.field_of_study, 030109 nutrition & dietetics, Methionine, Nutrition and Dietetics, Nutrition & Dietetics, Neurosciences, Evaluation of treatments and therapeutic interventions, Vitamin B 12 Deficiency, metabolomics, Mitochondria, omics, Vitamin B 12, Endocrinology, chemistry, 6.1 Pharmaceuticals, Female, plasmalogens |
| الوصف: | Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized. Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion. Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography–tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated. Results: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001), and reduced tHcy and serum MMA (P < 0.001). Metabolomic changes from before to after treatment included increases (P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism—that is, methionine and cysteine—were reduced (P < 0.001). Direct significant correlations (P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function. Multiple connections were identified with primary metabolites (e.g., an inverse relation between vitamin B-12 markers and tryptophan, tyrosine, and pyruvic, succinic, and citric acids, and a direct correlation between the nerve score and arginine). Conclusions: The human serum metabolome in vitamin B-12 deficiency and the changes that occur after supplementation are characterized. Metabolomics revealed connections between vitamin B-12 status and serum metabolic markers of mitochondrial function, myelin integrity, oxidative stress, and peripheral nerve function, including some previously implicated in Alzheimer and Parkinson diseases. This trial was registered at www.controlled-trials.com as ISRCTN02694183. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33226dccf0d7a17dacdeb83869b1e24e https://escholarship.org/uc/item/9mg5g69b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....33226dccf0d7a17dacdeb83869b1e24e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |