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The relative dynamics of major one\u2010carbon metabolism branches can be assessed by relating the functional B\u2010vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs. We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre) and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B\u2010vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk. Furthermore, the relative contribution of potential confounders to the variance of the ratio\u2010based B\u2010vitamin markers was calculated by linear regression in a nested case\u2013control study of 613 CRC cases and 1,190 matched controls. Total B\u2010vitamin status was represented by a summary score comprising <jats:italic>Z<\/jats:italic>\u2010standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5\u2032\u2010phosphate and riboflavin. Associations with CRC risk were estimated using conditional logistic regression. We found that the ratio\u2010based B\u2010vitamin markers all outperformed tHcy as markers of total B\u2010vitamin status, in both CRC cases and controls. In addition, associations with CRC risk were similar for the ratio\u2010based B\u2010vitamin markers and total B\u2010vitamin status (approximately 25% lower risk for high <jats:italic>vs<\/jats:italic>. low B\u2010vitamin status). In conclusion, ratio\u2010based B\u2010vitamin markers were good predictors of total B\u2010vitamin status and displayed similar associations as total B\u2010vitamin status with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice.<\/jats:p>","DOI":"10.1002\/ijc.31606","type":"journal-article","created":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T12:06:43Z","timestamp":1526990803000},"page":"947-956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["One\u2010carbon metabolite ratios as functional B\u2010vitamin markers and in relation to colorectal cancer risk"],"prefix":"10.1002","volume":"144","author":[{"given":"Bj\u00f6rn","family":"Gylling","sequence":"first","affiliation":[{"name":"Department of Medical Biosciences, Pathology, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Myte","sequence":"additional","affiliation":[{"name":"Department of Radiation Sciences, Oncology, Ume\u00e5 University, Ume\u00e5, 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