High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort
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Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length.
We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study (n = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay.
There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp (P < 0.01). There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper four quintiles of plasma folate (P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort (P = 0.015).
High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.
KeywordsTelomere length Folate Multivitamins Folic acid fortification
Support from United States Department of Agriculture Cooperative Agreement 51520-008-04S, National Heart Lung and Blood Institute, Framingham Heart Study (NHLBI/NIH Contract #N01-HC-25195) and Boston University School of Medicine. Any opinions, findings, conclusion or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the United States Department of Agriculture.
Conflict of interest
The authors declare that they have no conflict of interest.
- 12.Woods DD (1964) The function of folic acid in cellular metabolism. Proc R Soc Med 57:388–390Google Scholar
- 13.James SJ, Yin L, Swendseid ME (1989) DNA strand break accumulation, thymidylate synthesis and NAD levels in lymphocytes from methyl donor-deficient rats. J Nutr 119:661–664Google Scholar
- 15.Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, Olivieri O, Jacques PF, Rosenberg IH, Corrocher R, Selhub J (2002) A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci USA 99:5606–5611CrossRefGoogle Scholar
- 21.Horne DW, Patterson D (1988) Lactobacillus casei microbiological assay of folic acid derivatives in 96-well microtiter plates. Clin Chem 34:2357–2359Google Scholar
- 22.Choumenkovitch SF, Selhub J, Wilson PW, Rader JI, Rosenberg IH, Jacques PF (2002) Folic acid intake from fortification in United States exceeds predictions. J Nutr 132:2792–2798Google Scholar
- 23.Husdan H, Rapoport A (1968) Estimation of creatinine by the Jaffe reaction. A comparison of three methods. Clin Chem 14:222–238Google Scholar
- 27.Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, Beveridge AJ, Rafelt S, Moore J, Nelson C, Soranzo N, Zhai G, Valdes AM, Blackburn H, Leach IM, de Boer RA, Kimura M, Aviv A, Consortium WTCC, Goodall AH, Ouwehand W, van Veldhuisen DJ, van Gilst WH, Navis G, Burton PR, Tobin MD, Hall AS, Thompson JR, Spector T, Samani NJ (2010) Common variants near TERC are associated with mean telomere length. Nat Genet 42:197–199Google Scholar
- 32.Wang H, Odegaard A, Thyagarajan B, Hayes J, Cruz KS, Derosiers MF, Tyas SL, Gross MD (2012) Blood folate is associated with asymptomatic or partially symptomatic Alzheimer’s disease in the Nun study. J Alzheimer dis 28:637–645Google Scholar
- 37.Ericson U, Borgquist S, Ivarsson MIL, Sonestedt E, Gullberg B, Carlson J, Olsson H, Jirstram K, Wirfolt E (2010) Plasma folate concentrations are positively associated with risk of estrogen receptor β negative breast cancer in a Swedish nested case control study. J Nutr 140:1661–1668CrossRefGoogle Scholar
- 38.Inoue-Choi M, Greenlee H, Oppeneer SJ, Robien K (2014) The association between postdiagnosis dietary supplement use and total mortality differs by diet quality among older female cancer survivors. Cancer Epidemiol Biomarkers Prev. doi: 10.1158/1055-9965.EPI-13-1303
- 43.Wills L, Clutterbuck PW, Evans BD (1937) A new factor in the production and cure of macrocytic anaemias and its relation to other haemopoietic principles curative in pernicious anaemia. Biochem J 31:2136–2147Google Scholar
- 51.Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, Selhub J, McTiernan A, Yasui Y, Oral E, Potter JD, Ulrich CM (2006) Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 136:189–194Google Scholar