The Relationship Between Vitamin B12 and Telomere Length: A Systematic Review
Vitamin B12 and Telomere Length
DOI:
https://doi.org/10.24925/turjaf.v11i12.2485-2492.6381Keywords:
Vitamin B12, telomere length, methylation, inflammation, mortalityAbstract
Telomeres are natural nucleoprotein structures that cover the ends of chromosomes. The phenomenon of telomere shortening, which plays a crucial role in maintaining the stability of the genome, occurs gradually over time when cells undergo division due to the end replication issue. Multiple studies have demonstrated a correlation between telomere shortening and a range of illnesses, including diabetes, dyslipidemia, cardiovascular disease, cancer, and mortality. Diet and lifestyle can affect telomere length. There exists a beneficial association between telomere length and the Mediterranean diet, particularly with regards to the consumption of dietary fiber derived from whole grains and vegetables. Micronutrients such as vitamins and trace elements also play a role in cell metabolism. Some micronutrients, such as vitamin D, folate, and vitamin B12, are associated with telomere biology and cellular aging. Vitamin B12 is essential for DNA synthesis and epigenetic methylation processes. The present systematic review examines the results from clinical trials conducted in humans evaluating the role of vitamin B12 on telomere length. Cellular senescence is a state characterized by inflammation, altered cellular metabolism, genomic instability, and telomere dysfunction, which can be induced by changes in methylation patterns and oxidative stress. Vitamin B12 maintains antioxidative defense. Through these pathways, sufficient amounts of vitamin B12 may potentially play a role in the restoration of DNA damage. Most of the evidence is based on very few randomized clinical trials. Therefore, more extensive prospective cohort studies and better-designed randomized clinical trials are required to validate the correlations outlined in this review.
References
An Y, Feng L, Zhang X, Wang Y, Wang Y, Tao L, Qin Z, Xiao R. 2019. Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1. Clinical Epigenetics, 11(1), 1-19. doi: 10.1186/s13148-019-0741-y
Ankar A, Kumar A. 2022. Vitamin B12 deficiency. [Updated 2022 Oct 22]. StatPearls Publishing. [Internet]. Treasur e Island (FL): StatPearls Publishing.
Boachie J, Adaikalakoteswari A, Samavat J, Saravanan P. 2020. Low vitamin B12 and lipid metabolism: evidence from pre-clinical and clinical studies. Nutrients, 12(7), 1925. doi: 10.3390/nu12071925
Boughanem H, Hernandez-Alonso P, Tinahones A, Babio N, Salas-Salvadó J, Tinahones F J, Macias-Gonzalez M. 2020. Association between serum vitamin B12 and global DNA methylation in colorectal cancer patients. Nutrients, 12(11), 3567. doi: 10.3390/nu12113567
Bull C F, O'Callaghan N J, Mayrhofer G, Fenech M F. 2009. Telomere length in lymphocytes of older South Australian men may be inversely associated with plasma homocysteine. Rejuvenation Research, 12(5), 341-349. doi: 10.1089/rej.2009.0868
Canudas S, Becerra-Tomás N, Hernández-Alonso P, Galié S, Leung C, Crous-Bou M, De Vivo I, Gao Y, Gu Y, Meinilä J. 2020. Mediterranean diet and telomere length: a systematic review and meta-analysis. Advances in Nutrition, 11(6), 1544-1554. doi: 10.1093/advances/nmaa079
Chen L, Tan K M L, Gong M, Chong M F, Tan K H, Chong Y S, Meaney M J, Gluckman P D, Eriksson J G, Karnani N. 2022. Variability in newborn telomere length is explained by inheritance and intrauterine environment. BMC Medicine, 20(1), 20. doi: 10.1186/s12916-021-02217-9
Chou Y F, Yu C C, Huang R F S. 2007. Changes in mitochondrial DNA deletion, content, and biogenesis in folate-deficient tissues of young rats depend on mitochondrial folate and oxidative DNA injuries. The Journal of Nutrition, 137(9), 2036-2042. doi: 10.1093/jn/137.9.2036
Dhillon V S, Zabaras D, Almond T, Cavuoto P, James-Martin G, Fenech M. 2017. Whey protein isolate improves vitamin B12 and folate status in elderly Australians with subclinical deficiency of vitamin B12. Molecular Nutrition and Food Research, 61(5). doi: 10.1002/mnfr.201600915
Di Micco R, Krizhanovsky V, Baker D. 2021. d’Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol, 22(2), 75-95. doi: 10.1038/s41580-020-00314-w
Fenech M. 2012. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 733(1-2), 21-33. doi: 10.1016/j.mrfmmm.2011.11.003
Froese D S, Fowler B, Baumgartner M R. 2019. Vitamin B12, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation. Journal of Inherited Metabolic Disease, 42(4), 673-685. doi: 10.1002/jimd.12009
Green R, Miller J W. 2022. Vitamin B12 deficiency. In Vitamins and Hormones, 119, 405–439. doi: 10.1016/bs.vh.2022.02.003
Güneşliol B E, Karaca E, Ağagündüz D, Acar Z A. 2023. Association of physical activity and nutrition with telomere length, a marker of cellular aging: a comprehensive review. Critical Reviews in Food Science and Nutrition, 63(5), 674-692. doi: 10.1080/10408398.2021.1952402
Herrmann W, Herrmann M. 2022. The controversial role of HCY and vitamin B deficiency in cardiovascular diseases. Nutrients, 14(7), 1412. doi: 10.3390/nu14071412
Jiang-Hua Q, De-Chuang J, Zhen-Duo L, Shu-de C, Zhenzhen L. 2014. Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B 6, and vitamin B 12 intakes. Tumor Biology, 35, 11895-11901. doi: 10.1007/s13277-014-2456-1
Langan R C, Goodbred A J. 2017. Vitamin B12 deficiency: recognition and management. American Family Physician, 96(6), 384-389.
Liu J J, Prescott J, Giovannucci E, Hankinson S E, Rosner B, De Vivo I. 2013. One-carbon metabolism factors and leukocyte telomere length. The American Journal of Clinical Nutrition, 97(4), 794-799. doi: 10.3945/ajcn.112.051557
Ma F, Lv , Du, Y, Chen H, Liu , Zhao, J, Gao Y, An P, Zhou X, Song A. 2019. Association of leukocyte telomere length with mild cognitive impairment and Alzheimer’s disease: role of folate and homocysteine. Dementia and Geriatric Cognitive Disorders, 48(1-2), 56-67. doi: 10.1159/000501958
Nettleton J A, Diez-Roux A, Jenny N S, Fitzpatrick A L, Jacobs Jr D R. 2008. Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA). The American Journal of Clinical Nutrition, 88(5), 1405-1412. doi: 10.3945/ajcn.2008.26429
Nomura S J, Robien K, Zota A R. 2017. Serum folate, vitamin B-12, vitamin A, γ-tocopherol, α-tocopherol, and carotenoids do not modify associations between cadmium exposure and leukocyte telomere length in the general US adult population. The Journal of Nutrition, 147(4), 538-548. doi: 10.3945/jn.116.243162
Owen M D, Baker B C, Scott E M, Forbes K. 2021. Interaction between metformin, folate and vitamin B12 and the potential impact on fetal growth and long-term metabolic health in diabetic pregnancies. International Journal of Molecular Sciences, 22(11), 5759. doi: 10.3390/ijms22115759
Paul L. 2011. Diet, nutrition and telomere length. The Journal of Nutritional Biochemistry, 22(10), 895-901. doi: 10.1016/j.jnutbio.2010.12.001
Praveen G, Shalini T, Sivaprasad M, Reddy G B. 2020. Relative telomere length and mitochondrial DNA copy number variation with age: association with plasma folate and vitamin B12. Mitochondrion, 51, 79-87. doi: 10.1016/j.mito.2020.01.007
Pusceddu I, Farrell C-J L, Di Pierro A M, Jani E, Herrmann W, Herrmann M. 2015. The role of telomeres and vitamin D in cellular aging and age-related diseases. Clinical Chemistry and Laboratory Medicine (CCLM), 53(11), 1661-1678. doi: 10.1515/cclm-2014-1184
Pusceddu I, Herrmann M, Kirsch S H, Werner C, Hübner U, Bodis M, Laufs U, Wagenpfeil S, Geisel J, Herrmann W. 2016. Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation. European Journal of Nutrition, 55, 1863-1873. doi: 10.1007/s00394-015-1003-1
Pusceddu I, Herrmann M, Kirsch S H, Scharnagl H, Werner C, Hübner U, Bodis M, Laufs U, Widmann T, Wagenpfeil S, Geisel J, Herrmann W. 2016. One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation. European Journal of Nutrition, 56(5), 1887–1898. doi: 10.1007/s00394-016-1231-z
Pusceddu I, Herrmann W, Kleber, M E, Scharnagl H, März W, Herrmann M. 2019. Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study. Aging, 11(17), 7083. doi: 10.18632/aging.102238
Raftopoulou C, Paltoglou G, Charmandari E. 2022. Association between Telomere Length and Pediatric Obesity: A Systematic Review. Nutrients, 14(6), 1244. doi: 10.3390/nu14061244
Rossiello F, Jurk D, Passos J F, d’Adda di Fagagna F. 2022. Telomere dysfunction in ageing and age-related diseases. Nature Cell Biology, 24(2), 135-147. doi: 10.1038/s41556-022-00842-x
Schellnegger M, Lin A C, Hammer N, Kamolz L-P. 2022. Physical activity on telomere length as a biomarker for aging: a systematic review. Sports Medicine-Open, 8(1), 111. doi: 10.1186/s40798-022-00503-1
Shay J W, Wright W E. 2019. Telomeres and telomerase: three decades of progress. Nature Reviews Genetics, 20(5), 299-309. doi: 10.1038/s41576-019-0099-1
Shin C, Baik I. 2016. Leukocyte telomere length is associated with serum vitamin B12 and homocysteine levels in older adults with the presence of systemic inflammation. Clinical Nutrition Research, 5(1), 7-14. doi: 10.7762/cnr.2016.5.1.7
Silverstein W K, Cheung M C, Lin Y. 2022. Vitamin B12 deficiency. Canadian Medical Association journal, 194(24), 843-843. doi: 10.1503/cmaj.220306
Taub M A, Conomos M P, Keener R, Iyer K R, Weinstock J S, Yanek L R, Lane J, Miller-Fleming T W, Brody J A, Raffield L M. 2022. Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genomics, 2(1), 100084. doi: 10.1016/j.xgen.2021.100084
Tchkonia T, Zhu Y, Van Deursen J, Campisi J, Kirkland J L. 2013. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. The Journal of Clinical Investigation, 123(3), 966-972. doi: 10.1172/JCI64098
Tucker L A. 2019. Serum and dietary folate and vitamin b 12 levels account for differences in cellular aging: evidence based on telomere findings in 5581 US adults. Oxidative Medicine and Cellular Longevity, 2019, 4358717. doi: 10.1155/2019/4358717
Ulak M, Kvestad I, Chandyo R K, Schwinger C, Basnet S, Shrestha M, Ranjitkar S, Nguyen L V, Corona-Pérez D, De Vivo I, Ueland P M, McCann A, Strand T A. 2023. The effect of vitamin b12 supplementation on leukocyte telomere length in mildly stunted nepalese children: a secondary outcome of a randomized controlled trial. The Journal of Nutrition, 3166(23), 72669-2. doi: 10.1016/j.tjnut.2023.10.015
Welendorf C, Nicoletti C F, de Souza Pinhel M A, Noronha N Y, de Paula B M F, Nonino C B. 2019. Obesity, weight loss, and influence on telomere length: New insights for personalized nutrition. Nutrition, 66, 115-121. doi: 10.1016/j.nut.2019.05.002
Wilson S L, Liu Y, Robinson W P. 2016. Placental telomere length decline with gestational age differs by sex and TERT, DNMT1, and DNMT3A DNA methylation. Placenta, 48, 26-33. doi: 10.1016/j.placenta.2016.10.001
Zarei M, Zarezadeh M, Hamedi Kalajahi F, Javanbakht M H. 2021. The relationship between vitamin D and telomere/telomerase: A comprehensive review. The Journal of Frailty & Aging, 10, 2-9. doi: 10.14283/jfa.2020.33
Zhang W, Peng S-F, Chen L, Chen H-M, Cheng X-E, Tang Y-H. 2022. Association between the Oxidative Balance Score and Telomere Length from the National Health and Nutrition Examination Survey 1999-2002. Oxidative Medicine and Cellular Longevity, 2022, 1345071. doi: 10.1155/2022/1345071
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