FolateNCT03421483
Assessing Colonic Folate Absorption & Metabolism
A study testing Folic Acid supplementation and Adult Multivitamin in people with Folate, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Folate
- What is being tested?
- Folic Acid supplementation and Adult Multivitamin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- 17 Dec 2018to 15 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Factors Affecting Colonic Folate Absorption and Metabolism in Humans
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.
Read the detailed description
The vitamin folate is necessary for one-carbon metabolism in processes such as amino acid and nucleotide synthesis. As folate cannot be synthesized by mammals, it must be sourced from the diet and dietary supplements or generated by bacterial species present in the colon. There are a number of well-established adverse health outcomes associated with folate deficiency in humans, including congenital neural tube defects in newborns and colorectal cancer in adults. It has been proposed 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 from our team and others suggests that the colon may play a greater role in absorption of folate than previously understood. Specifically the amount of folate in the colon, much of it generated by the microbiome, can exceed dietary intakes of folate from natural sources. There are a number of gaps in knowledge regarding colonic folate absorption in humans. It is not known to what degree folate specific transporters such as proton coupled folate transporter (PCFT) and reduced folate carrier (RFC) are present in the colon of healthy humans. To date, the majority of studies conducted identifying the presence of RFC and PCFT in colonocytes have been performed using cell lines or tissue harvested from organ donors. To our knowledge, no study has investigated the mRNA and protein concentrations of both RFC and PCFT present in human colonic tissue retrieved as biopsies. It also remains to be determined if folate status influences RFC and PCFT expression at the level of the colon. Secondly, it remains unclear to what degree the two intestinal folate hydrolases, glutamate carboxypeptidase II (GCPII) and γ-glutamyl hydrolase (GGH) are present in colonic mucosa. To gain a more thorough understanding of the fundamental processes involved in folate absorption in the colon of humans, the following three objectives are proposed. The primary objective is to evaluate the impact of 0 and 400 µg supplemental folic acid on total folate concentrations within the colonic mucosa by measuring folate levels. The secondary objectives include evaluating the impact of 0 and 400 µg supplemental folic acid on the regulation of PCFT and RFC in the ileum and colon by assessing the expression of mRNA transcripts and proteins, and determining the degree to which GCPII and GGH are present in the lumen of the ileum and colon by quantifying enzyme activity and expression of mRNA transcripts and proteins. To accomplish this, a 16-week longitudinal open-labelled randomized clinical trial will be conducted. Recruitment and screening will require three separate steps comprised of an initial invitation to participate, followed by a telephone screening session to determine eligibility and finally a baseline in-person study visit prior to enrollment into the intervention phase of the study. Once enrolled, participants will be asked to follow a diet low in synthetic folic acid for the duration of the study. At enrollment, subjects will be randomized to receive a multivitamin supplement and either 0 or 400 µg folic acid. Follow-up study visits will take place at week 8 and week 16 where anthropometric measurements, blood and colonic tissue biopsies (Week 16 only) from the terminal ileum, cecum, ascending colon, and descending colon will be collected for analysis. 24-hour dietary recalls will be collected throughout the study to observe folate and caloric intake. Plasma, RBC folate levels, and colonic mucosa folate content will be determined via microbial assay. GCPII and GGH enzyme activity will be determined according to the Krumdieck and Baugh method with modification. PCFT and RFC expression will be determined via semi-quantitative real-time PCR and protein samples will be extracted in a Western Blot Analysis using RIPA lysis and extraction buffer. The proposed study will further our understanding of the fundamental processes of folate metabolism and absorption in the colon. Results from this study may help to establish the optimal intakes of dietary folate, meeting the requirements of humans, without the potential health risks related to over-exposure to folate.
- Conditions
- Folate
- Being tested
- Folic Acid supplementation, Adult Multivitamin
- Keywords
- Folate, Absorption, Metabolism, Colon, Receptor, Enzyme
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic Acid supplementationDietary supplement
Participants receive a 400 microgram Folic Acid supplement
Adult MultivitaminDietary supplement
Participants will receive an adult multivitamin supplement
| Study group | Role | What they receive |
|---|---|---|
| Folic Acid supplementation | Active comparator | Participants receive an adult multivitamin supplement along with a folic acid supplement Receives: Dietary Supplement: Folic Acid supplementation; Dietary Supplement: Adult Multivitamin |
| No supplementation | Placebo comparator | Participants only receive an adult multivitamin supplement Receives: Dietary Supplement: Adult Multivitamin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 months
Secondary outcomes (4)
PCFT
Evaluate the impact of 0 and 400 µg supplemental folic acid on the regulation of PCFT in the ileum and colon by assessing the expression of mRNA transcripts and proteins
Measured: 4 months
RFC
Evaluate the impact of 0 and 400 µg supplemental folic acid on the regulation of RFC in the ileum and colon by assessing the expression of mRNA transcripts and proteins
Measured: 4 months
GCPII
Determine the degree to which GCPII is present in the lumen of the ileum and colon by quantifying enzyme activity and expression of mRNA transcripts and proteins
Measured: 4 months
GGH
Determine the degree to which GGH is present in the lumen of the ileum and colon by quantifying enzyme activity and expression of mRNA transcripts and proteins
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start17 Dec 2018
- Primary completion15 Oct 2023 (estimated)
- Study completion15 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for FolateStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Natural Sciences and Engineering Research Council, Canada
- Responsible party
- Principal investigator, Deborah O'Connor, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03421483
- Sponsor's protocol ID
- 1000059584
- Status last verified
- Oct 2022
- First submitted
- 8 Jan 2018
- Last updated
- 26 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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/
PubMed 23193625Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011 Aug 1;437(3):357-72. doi: 10.1042/BJ20110326.
PubMed 21749321Mason 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.
PubMed 27890600De 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.
PubMed 17625125Lakoff 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.
PubMed 25332326Qiu 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.
PubMed 17129779Dudeja 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.
PubMed 9227476Kumar 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.
PubMed 9045638Paniz 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.
PubMed 28724658Chakraborty 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.
PubMed 26255550Farrell 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.
PubMed 38157986
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Factors Affecting Colonic Folate Absorption and Metabolism in Humans
- ClinicalTrials.gov ID
- NCT03421483
- Acronym / sponsor ID
- 1000059584
- Conditions
- Folate
- Keywords
- Folate, Absorption, Metabolism, Colon, Receptor, Enzyme
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Natural Sciences and Engineering Research Council, Canada
- Study start
- 17 Dec 2018 (actual)
- Primary completion
- 15 Oct 2023 (estimated)
- Study completion
- 15 Oct 2023 (estimated)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The vitamin folate is necessary for one-carbon metabolism in processes such as amino acid and nucleotide synthesis. As folate cannot be synthesized by mammals, it must be sourced from the diet and dietary supplements or generated by bacterial species present in the colon. There are a number of well-established adverse health outcomes associated with folate deficiency in humans, including congenital neural tube defects in newborns and colorectal cancer in adults. It has been proposed 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 from our team and others suggests that the colon may play a greater role in absorption of folate than previously understood. Specifically the amount of folate in the colon, much of it generated by the microbiome, can exceed dietary intakes of folate from natural sources. There are a number of gaps in knowledge regarding colonic folate absorption in humans. It is not known to what degree folate specific transporters such as proton coupled folate transporter (PCFT) and reduced folate carrier (RFC) are present in the colon of healthy humans. To date, the majority of studies conducted identifying the presence of RFC and PCFT in colonocytes have been performed using cell lines or tissue harvested from organ donors. To our knowledge, no study has investigated the mRNA and protein concentrations of both RFC and PCFT present in human colonic tissue retrieved as biopsies. It also remains to be determined if folate status influences RFC and PCFT expression at the level of the colon. Secondly, it remains unclear to what degree the two intestinal folate hydrolases, glutamate carboxypeptidase II (GCPII) and γ-glutamyl hydrolase (GGH) are present in colonic mucosa. To gain a more thorough understanding of the fundamental processes involved in folate absorption in the colon of humans, the following three objectives are proposed. The primary objective is to evaluate the impact of 0 and 400 µg supplemental folic acid on total folate concentrations within the colonic mucosa by measuring folate levels. The secondary objectives include evaluating the impact of 0 and 400 µg supplemental folic acid on the regulation of PCFT and RFC in the ileum and colon by assessing the expression of mRNA transcripts and proteins, and determining the degree to which GCPII and GGH are present in the lumen of the ileum and colon by quantifying enzyme activity and expression of mRNA transcripts and proteins. To accomplish this, a 16-week longitudinal open-labelled randomized clinical trial will be conducted. Recruitment and screening will require three separate steps comprised of an initial invitation to participate, followed by a telephone screening session to determine eligibility and finally a baseline in-person study visit prior to enrollment into the intervention phase of the study. Once enrolled, participants will be asked to follow a diet low in synthetic folic acid for the duration of the study. At enrollment, subjects will be randomized to receive a multivitamin supplement and either 0 or 400 µg folic acid. Follow-up study visits will take place at week 8 and week 16 where anthropometric measurements, blood and colonic tissue biopsies (Week 16 only) from the terminal ileum, cecum, ascending colon, and descending colon will be collected for analysis. 24-hour dietary recalls will be collected throughout the study to observe folate and caloric intake. Plasma, RBC folate levels, and colonic mucosa folate content will be determined via microbial assay. GCPII and GGH enzyme activity will be determined according to the Krumdieck and Baugh method with modification. PCFT and RFC expression will be determined via semi-quantitative real-time PCR and protein samples will be extracted in a Western Blot Analysis using RIPA lysis and extraction buffer. The proposed study will further our understanding of the fundamental processes of folate metabolism and absorption in the colon. Results from this study may help to establish the optimal intakes of dietary folate, meeting the requirements of humans, without the potential health risks related to over-exposure to folate.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Folic Acid supplementation | Active comparator | Dietary Supplement: Folic Acid supplementation, Dietary Supplement: Adult MultivitaminParticipants receive an adult multivitamin supplement along with a folic acid supplement |
| No supplementation | Placebo comparator | Dietary Supplement: Adult MultivitaminParticipants only receive an adult multivitamin supplement |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folic Acid supplementationParticipants receive a 400 microgram Folic Acid supplement | Dietary supplement | Folic Acid supplementation |
| Adult MultivitaminParticipants will receive an adult multivitamin supplement | Dietary supplement | Folic Acid supplementation, No supplementation |
Primary outcome
Colonic folate levels
Time frame: 4 months
Evaluate the impact of 0 and 400 µg supplemental folic acid on total folate concentrations within the colonic mucosa by measuring folate levels
4 secondary outcomes
PCFT
Time frame: 4 months
RFC
Time frame: 4 months
GCPII
Time frame: 4 months
GGH
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2022.
- Background: PubMed 23193625Institute 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/
- Background: PubMed 21749321Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011 Aug 1;437(3):357-72. doi: 10.1042/BJ20110326.
- Background: PubMed 27890600Mason 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.
- Background: PubMed 17625125De 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.
- Background: PubMed 25332326Lakoff 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.
- Background: PubMed 17129779Qiu 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.
- Background: PubMed 9227476Dudeja 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.
- Background: PubMed 9045638Kumar 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.
- Background: PubMed 28724658Paniz 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.
- Background: PubMed 26255550Chakraborty 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.
- Derived from this study: PubMed 38157986Farrell 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Folic Acid supplementation and Adult Multivitamin in people with Folate, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Colonic folate levels (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03421483, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2022; AzTrials last refreshed its copy on 3 Nov 2026.