Am J Clin Nutr

BackgroundFolate intakes that do not meet or greatly exceed requirements may be associated with negative health outcomes. A better understanding of contributors that influence the input side will help establish dietary guidance that ensures health benefits without associated risks. Colonic microbiota produce large quantities of folate, and [13C5]5-formyltetrahydrofolate infused during colonoscopy is absorbed. However, it is unclear if significant quantities of folate are absorbed in an intact microbiome.ObjectiveWe determined whether and how much of a physiologic dose of [13C5]5-formyltetrahydrofolate delivered in a pH-sensitive enteric caplet to an intact colonic microbiome is absorbed.DesignHealthy adults ingested a specially designed pH-sensitive acrylic copolymer\u2013coated barium sulfate caplet that contained 855 nmol (400 \u3bcg) [13C5]5-formyltetrahydrofolate. After a washout period 654 wk, subjects received an intravenous injection of the same compound (214 nmol). Serially collected blood samples before and after each test dose were analyzed by using a microbiological assay and liquid chromatography\u2013tandem mass spectrometry.ResultsCaplet disintegration in the colon was observed by fluoroscopic imaging for 6 subjects with a mean (\ub1SD) complete disintegration time of 284 \ub1 155 min. The mean (\ub1SEM) rate of appearance of [13C5]5-methyltetrahydrofolate in plasma was 0.33 \ub1 0.09 (caplet) and 5.8 \ub1 1.2 (intravenous) nmol/h. Likely because of the significant time in the colon, the mean apparent absorption across the colon was 46%.ConclusionsFolate is absorbed across the colon in humans with an undisturbed microbiome. This finding and previous observations of the size of the colonic depot of folate and its potential for manipulation by diet (eg, dietary fiber, oligosaccharides, and probiotics) suggest that an individual\u2019s dietary folate requirement may differ depending on the consumption of dietary constituents that affect the size and composition of their gastrointestinal microbiota. In addition, a systematic investigation of the role of colonic folate on gastrointestinal development and the prevention of colorectal cancer is warranted. This trial was registered at clinicaltrials.gov as NCT00941174.CC999999/Intramural CDC HHSUnited States/R01 DK072398/DK/NIDDK NIH HHSUnited States