Assessing Colonic Folate Absorption & Metabolism

NCT03421483 | Unknown

• 1 other identifier: 1000059584
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Folate, a B-vitamin, is necessary in metabolic processes such as amino acid and nucleotide synthesis. Since folate cannot be synthesized by mammals, it must be consumed as foods and dietary supplements or generated by bacteria present in the colon. There are many known adverse health outcomes associated with folate deficiency in humans such as neural tube defects in newborns and colorectal cancer in adults. It has also been proposed that supra-physiological folate status can also be detrimental since it can lead to changes in immune function and the masking of vitamin B12 deficiency. It is generally believed that dietary sources of folate are primarily absorbed in the small intestine, however recent evidence suggests the colon may play a more significant role in the absorption of folate than previously understood. The aim of this study is to assess how folic acid supplementation influences colonic folate absorption and metabolism in humans. This will be accomplished by assessing the expression of two major folate transporters responsible for folate absorption in the colon. Participants will be randomized to receive multivitamins with either 0 or 400 µg folic acid during a 16-week randomized clinical trial in which blood and colonic tissue biopsies will be collected and analyzed. The total folate concentrations and expression of folate transporters in colonocytes will be measured to confirm levels and evaluate the impact of supplemental folic acid. The expression of two folate hydrolases responsible for converting naturally occurring folate to its bioavailable form will also be evaluated. This work will lead to a deeper understanding of colonic folate absorption and metabolism, resulting in more appropriate dietary and supplemental folate recommendations.

Conditions

Folate

Keywords

Folate; Absorption; Metabolism; Colon; Receptor; Enzyme

Outcome Measures

Primary Outcomes (1)

• Colonic folate levels

  Evaluate the impact of 0 and 400 µg supplemental folic acid on total folate concentrations within the colonic mucosa by measuring folate levels

  4 months

Secondary Outcomes (4)

• PCFT

  4 months

• RFC

  4 months

• GCPII

  4 months

• GGH

  4 months

Study Arms (2)

Folic Acid supplementation

ACTIVE COMPARATOR

Participants receive an adult multivitamin supplement along with a folic acid supplement

Dietary Supplement: Folic Acid supplementation; Dietary Supplement: Adult Multivitamin

No supplementation

PLACEBO COMPARATOR

Participants only receive an adult multivitamin supplement

Dietary Supplement: Adult Multivitamin

Interventions

Folic Acid supplementation DIETARY_SUPPLEMENT

Participants receive a 400 microgram Folic Acid supplement

Folic Acid supplementation

Adult Multivitamin DIETARY_SUPPLEMENT

Participants will receive an adult multivitamin supplement

Folic Acid supplementation; No supplementation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males \>18 years old and \<75 years old;
• Females who are pre-menopausal that have had a hysterectomy or tubal ligation, post-menopausal (at least 1 year) and \<75 years old;
• Describe themselves as generally healthy.
• Recommended to have a colonoscopy examination by their Doctor

You may not qualify if:

• They have a history of gastrointestinal disease (such as Crohn's disease, ulcerative colitis, celiac disease) and/ or gastrointestinal cancers;
• They have had a previous colon resection;
• They are regularly using medications that may affect gastrointestinal pH or folate metabolism (e.g. proton pump inhibitors, phenytoin, phenobarbital, primidone, or have used oral antibiotics within the last 2 weeks);
• On a regular basis they consume \>2 alcoholic drinks/day for women or \>3/day for men;
• They are currently smokers;
• They are folic acid supplement users or have used folic acid supplements or multivitamins containing folic acid in the last 4 months;
• They have a bleeding disorder (such as hemophilia)
• They are unlikely able to discontinue anti-coagulant therapy prior to colonoscopy

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Natural Sciences and Engineering Research Council, Canada: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (11)

• Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. Available from http://www.ncbi.nlm.nih.gov/books/NBK114310/

  PMID: 23193625 BACKGROUND

• Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011 Aug 1;437(3):357-72. doi: 10.1042/BJ20110326.

  PMID: 21749321 BACKGROUND

• Mason JB, Tang SY. Folate status and colorectal cancer risk: A 2016 update. Mol Aspects Med. 2017 Feb;53:73-79. doi: 10.1016/j.mam.2016.11.010. Epub 2016 Nov 24.

  PMID: 27890600 BACKGROUND

• De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, Evans JA, Van den Hof MC, Zimmer P, Crowley M, Fernandez B, Lee NS, Niyonsenga T. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med. 2007 Jul 12;357(2):135-42. doi: 10.1056/NEJMoa067103.

  PMID: 17625125 BACKGROUND

• Lakoff A, Fazili Z, Aufreiter S, Pfeiffer CM, Connolly B, Gregory JF 3rd, Pencharz PB, O'Connor DL. Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate. Am J Clin Nutr. 2014 Nov;100(5):1278-86. doi: 10.3945/ajcn.114.091785. Epub 2014 Sep 3.

  PMID: 25332326 BACKGROUND

• Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. 2006 Dec 1;127(5):917-28. doi: 10.1016/j.cell.2006.09.041.

  PMID: 17129779 BACKGROUND

• Dudeja PK, Torania SA, Said HM. Evidence for the existence of a carrier-mediated folate uptake mechanism in human colonic luminal membranes. Am J Physiol. 1997 Jun;272(6 Pt 1):G1408-15. doi: 10.1152/ajpgi.1997.272.6.G1408.

  PMID: 9227476 BACKGROUND

• Kumar CK, Moyer MP, Dudeja PK, Said HM. A protein-tyrosine kinase-regulated, pH-dependent, carrier-mediated uptake system for folate in human normal colonic epithelial cell line NCM460. J Biol Chem. 1997 Mar 7;272(10):6226-31. doi: 10.1074/jbc.272.10.6226.

  PMID: 9045638 BACKGROUND

• Paniz C, Bertinato JF, Lucena MR, De Carli E, Amorim PMDS, Gomes GW, Palchetti CZ, Figueiredo MS, Pfeiffer CM, Fazili Z, Green R, Guerra-Shinohara EM. A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults. J Nutr. 2017 Sep;147(9):1677-1685. doi: 10.3945/jn.117.247445. Epub 2017 Jul 19.

  PMID: 28724658 BACKGROUND

• Chakraborty H, Nyarko KA, Goco N, Moore J, Moretti-Ferreira D, Murray JC, Wehby GL. Folic Acid Fortification and Women's Folate Levels in Selected Communities in Brazil - A First Look. Int J Vitam Nutr Res. 2014;84(5-6):286-94. doi: 10.1024/0300-9831/a000215.

  PMID: 26255550 BACKGROUND

• Farrell CC, Khanna S, Hoque MT, Plaga A, Basset N, Syed I, Biouss G, Aufreiter S, Marcon N, Bendayan R, Kim YI, O'Connor DL. Low-dose daily folic acid (400 mug) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial. Am J Clin Nutr. 2024 Mar;119(3):809-820. doi: 10.1016/j.ajcnut.2023.12.018. Epub 2023 Dec 28.

  PMID: 38157986 DERIVED

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Scientist

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: February 5, 2018
• Study Start: December 17, 2018
• Primary Completion: October 15, 2023
• Study Completion: October 15, 2023
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)