The vegetarian lifestyle and DNA methylation
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Jürgen Geisel
Abstract
Vegetarians have a lower intake of vitamin B12 than omnivores do. Vitamin B12 deficiency (holotranscobalamin II <35pmol/L or methylmalonic acid >271nmol/L) was found in 58% of 71 vegetarians studied. Higher homocysteine levels (>12μmol/L) found in 45% indicate disturbed remethylation of homocysteine to methionine. The methylation of DNA is strongly linked to homocysteine metabolism. Since DNA methylation is an important epigenetic factor in the regulation of gene expression, alteration of the methylation pattern has been associated with aging, cancer, atherosclerosis and other diseases. Three observations indicate that DNA methylation could be diminished by a vegetarian lifestyle. The vegetarian diet has a low content of methionine, remethylation of homocysteine is reduced by vitamin B12 deficiency and elevated homocysteine levels can induce the generation of S-adenosylhomocysteine (SAH), a potent inhibitor of methyltransferases. In our study we observed a significant correlation between SAH and whole-genome methylation (r=−0.36, p<0.01). This observation underlines the role of SAH as a potent inhibitor of methyltransferases. The methylation status was not correlated with homocysteine or S-adenosylemethionine (SAM). These results indicate that the degree of methylation does not depend on the supply of methyl groups and that the reverse generation of SAH has no influence. In addition to whole-genome methylation, the specific promoter methylation of the p66Shc gene was studied. However, the latter did not correlate with SAH, SAM or homocysteine. Obviously, the promoter methylation of the p66Shc gene is controlled in a specific way, without following the general regulating influence of SAH. In conclusion, an inhibitory effect of SAH on whole-genome methylation was found, but from our data no interaction between vegetarian lifestyle and DNA methylation could be determined.
References
1. Schneede J, Dagnelie PC, van Staveren WA, Vollset SE, Refsum H, Ueland PM. Methylmalonic acid and homocysteine in plasmas as indicators of functional cobalamin deficiency in infants on macrobiotic diets. Pediatr Res 1994; 36:194–201.10.1203/00006450-199408000-00010Search in Google Scholar
2. Herrmann W, Schorr H, Purschwitz K, Rassoul F, Richter V. Total homocysteine, vitamin B(12), and total antioxidant status in vegetarians. Clin Chem 2001; 47:1094–101.10.1093/clinchem/47.6.1094Search in Google Scholar
3. Rasmussen SA, Fernhoff PM, Scanlon KS. Vitamin B12 deficiency in children and adolescents. J Pediatr 2001; 138:10–7.10.1067/mpd.2001.112160Search in Google Scholar
4. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr 2003; 78:131–6.10.1093/ajcn/78.1.131Search in Google Scholar
5. Bissoli L, Di F, V, Ballarin A, Mandragona R, Trespidi R, Brocco G, et al. Effect of vegetarian diet on homocysteine levels. Ann Nutr Metab 2002; 46:73–9.10.1159/000057644Search in Google Scholar
6. Poirier LA. The effect of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction. J Nutr 2002; 132:2336S–9S.10.1093/jn/132.8.2336SSearch in Google Scholar
7. Hoffmann DR, Marion DW, Cornatzer WE, Duerre JA. S-Adenosylmethionine and adenosylhomocysteine metabolism in isolated rat liver. Effects of L-methionine, L-homocysteine, and adenosine. J Biol Chem 1980; 255:10822–7.10.1016/S0021-9258(19)70381-0Search in Google Scholar
8. Hoffmann DR, Cornatzer WE, Duerre JA. Relationship between tissue levels of S-adenosylmethionine, S-adenosylhomocysteine, and transmethylation reactions. Can J Biochem 1979; 57:56–65.10.1139/o79-007Search in Google Scholar
9. Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000; 275:29318–23.10.1074/jbc.M002725200Search in Google Scholar
10. Bird A. The essentials of DNA methylation. Cell 1992; 70:5–8.10.1016/0092-8674(92)90526-ISearch in Google Scholar
11. Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 1982; 10:2709–21.10.1093/nar/10.8.2709Search in Google Scholar
12. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001; 293:1068–70.10.1126/science.1063852Search in Google Scholar
13. Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG, Bagley PJ, et al. 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 2002; 99:5606–11.10.1073/pnas.062066299Search in Google Scholar
14. Ingrosso D, Cimmino A, Perna AF, Masella L, De Santo NG, De Bonis ML, et al. Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 2003; 361:1693–9.10.1016/S0140-6736(03)13372-7Search in Google Scholar
15. Castro R, Rivera I, Struys EA, Jansen EE, Ravasco P, Camilo ME, et al. Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem 2003; 49:1292–6.10.1373/49.8.1292Search in Google Scholar
16. Narayanan S, McConnell J, Little J, Sharp L, Piyathilake CJ, Powers H, et al. Associations between two common variants C677T and A1298C in methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability in human lymphocytes in vivo. Cancer Epidemiol Biomarkers Prev 2004; 13:1436–43.10.1158/1055-9965.1436.13.9Search in Google Scholar
17. Bonsch D, Lenz B, Reulbach U, Kornhuber J, Bleich S. Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm 2004; 111:1611–6.10.1007/s00702-004-0232-xSearch in Google Scholar
18. Florl AR, Steinhoff C, Müller M, Seifert HH, Hader C, Engers RA, et al. Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation. Br J Cancer 2004; 91:985–94.10.1038/sj.bjc.6602030Search in Google Scholar
19. Purdom S, Chen QM. p66(Shc): at the crossroad of oxidative stress and the genetics of aging. Trends Mol Med 2003; 9:206–10.10.1016/S1471-4914(03)00048-0Search in Google Scholar
20. Napoli C, Martin-Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, et al. Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA 2003; 100:2112–6.10.1073/pnas.0336359100Search in Google Scholar PubMed PubMed Central
21. Ventura A, Luzi L, Pacini S, Baldari CT, Pelicci PG. The p66Shc longevity gene is silenced through epigenetic modifications of an alternative promoter. J Biol Chem 2002; 277:22370–6.10.1074/jbc.M200280200Search in Google Scholar PubMed
22. Loehrer FM, Angst CP, Brunner FP, Haefeli WE, Fowler B. Evidence for disturbed S-adenosylmethionine:S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions? Nephrol Dial Transplant 1998; 13:656–61.10.1093/ndt/13.3.656Search in Google Scholar PubMed
23. Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, Issa JP. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 2004; 32:e38.10.1093/nar/gnh032Search in Google Scholar PubMed PubMed Central
24. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10:111–3.10.1038/ng0595-111Search in Google Scholar PubMed
25. Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr 1994; 59:1213S–22S.10.1093/ajcn/59.5.1213SSearch in Google Scholar PubMed
26. Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S. S-Adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005; 28:195–204.10.1016/j.mcn.2004.09.007Search in Google Scholar PubMed
27. Detich N, Hamm S, Just G, Knox JD, Szyf M. The methyl donor S-adenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of S-adenosylmethionine. J Biol Chem 2003; 278:20812–20.10.1074/jbc.M211813200Search in Google Scholar PubMed
28. Pagnin E, Fadini G, de Toni R, Tiengo A, Calo L, Avogaro A. Diabetes induces p66shc gene expression in human peripheral blood mononuclear cells: relation to oxidative stress. J Clin Endocrinol Metab 2005; 90:1130–6.10.1210/jc.2004-1283Search in Google Scholar PubMed
29. Mann NJ, Sinclair AJ, Dudman NP, Guo XW, Elsworth GR, Wilson AK, et al. The effect of diet on plasma homocysteine concentrations in healthy male subjects. Eur J Clin Nutr 1999; 53:895–9.10.1038/sj.ejcn.1600874Search in Google Scholar PubMed
30. Newberne PM. Lipotropic factors and oncogenesis. Adv Exp Med Biol 1986; 206:223–51.10.1007/978-1-4613-1835-4_18Search in Google Scholar PubMed
©2005 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
Articles in the same Issue
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
