Beta-carotene BioavailabilityBETASNP2NCT02276014
Effect of SNPs in the BCMO1 Enzyme
A study testing Beta-carotene in people with Beta-carotene Bioavailability and Vitamin A Deficiency, run by Newcastle-upon-Tyne Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
Summary: Chronic intake of foods low in vitamin A (retinol) and provitamin A forming an unbalanced diet with little variety is common in young individuals in the United Kingdom (UK) population and can lead to subclinical micronutrient deficiency. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Beta-carotene Bioavailability, Vitamin A Deficiency
- What is being tested?
- Beta-carotene
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2012to Sep 2014
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy individual.
- Female.
- Between 18 and 45 years of age.
- Caucasian.
- BMI between 18 and 30 kg/m2.
- Subject willing and able to give written informed consent.
Who cannot join
- Smoking.
- Diabetes.
- Gastrointestinal diseases.
- Renal and hepatic diseases.
- Hyperlipidaemia.
- Preformed dietary retinol intake above 60% of reference nutrient intake (RNI) values.
Show all 14Show fewer
- Recreational drug use.
- Multi-vitamin consumption.
- Pregnancy.
- Menopause.
- Allergy or sensitivity to study products or ingredients.
- Blood donation 3 months prior to screening.
- Participation in other clinical study 4 weeks prior to study start.
- Suspected inability or unwillingness to comply with study procedures.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary
Newcastle upon Tyne, Tyne & Wear, NE1 4LP
About this study
Official title: Effect of SNPs in the Beta-carotene 15, 15'-Monooxygenase (BCMO1) Enzyme on Retinol Formation and Beta-carotene Plasma Responses
Summary:
Chronic intake of foods low in vitamin A (retinol) and provitamin A forming an unbalanced diet with little variety is common in young individuals in the United Kingdom (UK) population and can lead to subclinical micronutrient deficiency. Provitamin A sources such as β-carotene are cleaved centrally by the β-carotene 15,15'-monooxygenase (BCMO1) into retinal, the precursor of retinol. However, the amount of β-carotene and retinol produced after ingestion of β-carotene is highly variable between healthy individuals, with approximately 40% of the subjects being classified as low responders. Several stable isotope studies have shown a large disparity between the most efficient converters and the most inefficient converters of β-carotene with variations of up to 8-fold. It is possible that differences in β-carotene response may be due to single nucleotide polymorphisms (SNPs) in genes involved in aspects of β-carotene conversion. Previous work has shown that carriers of both, the 379V and 267S+379V BCMO1 variant alleles had a reduced ability to convert β-carotene. More importantly, 44% of the western population have the 379V haplotype. A high percentage of the Western population may therefore not be able to achieve adequate vitamin A intake if dietary β-carotene is a major source of their vitamin A intake. This is of particular relevance to vegetarians, to young individuals aged 19-24 years who have lower intakes of preformed retinol than any other age group, and to pregnant women. The aim of this study is to establish whether the maximum recommended dose for β-carotene of 7mg/day by the British Expert Committee on Vitamins and Minerals (EVM) can overcome the SNP effect in the BCMO1 enzyme.
Read more
Hypothesis:
The investigators hypothesize that the current maximum recommended intake of 7 mg of β-carotene per day cannot overcome the low convertor phenotype in BCMO1 to fulfill vitamin A requirements in these people.
- Being tested
- Beta-carotene
- Keywords
- Beta carotene, Retinol
- Medical subject headings
- Vitamin A Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beta-caroteneDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Supplement A | Other | Beta-carotene 7mg formulation A Receives: Dietary Supplement: Beta-carotene |
| Supplement B | Other | Beta-carotene 7mg formulation B Receives: Dietary Supplement: Beta-carotene |
| Supplement C | Other | Beta-carotene 7mg formulation C Receives: Dietary Supplement: Beta-carotene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration versus time curve (AUC) of beta-carotene
Measured: Pharmacokinetic measures (0,1,4,36,46,57,60 days post-dose)
Area under the plasma concentration versus time curve (AUC) of [13C]retinol
Measured: Pharmacokinetic measures (0,1,2,3,4,8,10,22,36,46,57,58,59,60,64,66,78,92,113 days post-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2014 (estimated)
- Study startApr 2012
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Beta-carotene BioavailabilityStudies of the same condition, open and under way.
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle University, dsm-firmenich Switzerland AG
- Responsible party
- Sponsor
- Investigators
- Georg Lietz, PhD, Principal investigator, Newcastle University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276014
- Sponsor's protocol ID
- 2011-01-18-BETASNP2
- Other IDs
- REC 11/NE/0211
- Acronym
- BETASNP2
- Status last verified
- Oct 2015
- First submitted
- 21 Oct 2014
- Last updated
- 6 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Oxley A, Berry P, Taylor GA, Cowell J, Hall MJ, Hesketh J, Lietz G, Boddy AV. An LC/MS/MS method for stable isotope dilution studies of beta-carotene bioavailability, bioconversion, and vitamin A status in humans. J Lipid Res. 2014 Feb;55(2):319-28. doi: 10.1194/jlr.D040204. Epub 2013 Oct 24.
PubMed 24158962Lietz G, Oxley A, Leung W, Hesketh J. Single nucleotide polymorphisms upstream from the beta-carotene 15,15'-monoxygenase gene influence provitamin A conversion efficiency in female volunteers. J Nutr. 2012 Jan;142(1):161S-5S. doi: 10.3945/jn.111.140756. Epub 2011 Nov 23.
PubMed 22113863Grune T, Lietz G, Palou A, Ross AC, Stahl W, Tang G, Thurnham D, Yin SA, Biesalski HK. Beta-carotene is an important vitamin A source for humans. J Nutr. 2010 Dec;140(12):2268S-2285S. doi: 10.3945/jn.109.119024. Epub 2010 Oct 27.
PubMed 20980645Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. 2009 Apr;23(4):1041-53. doi: 10.1096/fj.08-121962. Epub 2008 Dec 22.
PubMed 19103647Furr HC, Green MH, Haskell M, Mokhtar N, Nestel P, Newton S, Ribaya-Mercado JD, Tang G, Tanumihardjo S, Wasantwisut E. Stable isotope dilution techniques for assessing vitamin A status and bioefficacy of provitamin A carotenoids in humans. Public Health Nutr. 2005 Sep;8(6):596-607. doi: 10.1079/phn2004715.
PubMed 16236189
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of SNPs in the Beta-carotene 15, 15'-Monooxygenase (BCMO1) Enzyme on Retinol Formation and Beta-carotene Plasma Responses
- ClinicalTrials.gov ID
- NCT02276014
- Acronym / sponsor ID
- BETASNP2 / 2011-01-18-BETASNP2
- Keywords
- Beta carotene, Retinol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- Newcastle University, dsm-firmenich Switzerland AG
- Study start
- Apr 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 27 Oct 2014 (estimated)
- 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.
Summary:
Chronic intake of foods low in vitamin A (retinol) and provitamin A forming an unbalanced diet with little variety is common in young individuals in the United Kingdom (UK) population and can lead to subclinical micronutrient deficiency. Provitamin A sources such as β-carotene are cleaved centrally by the β-carotene 15,15'-monooxygenase (BCMO1) into retinal, the precursor of retinol. However, the amount of β-carotene and retinol produced after ingestion of β-carotene is highly variable between healthy individuals, with approximately 40% of the subjects being classified as low responders. Several stable isotope studies have shown a large disparity between the most efficient converters and the most inefficient converters of β-carotene with variations of up to 8-fold. It is possible that differences in β-carotene response may be due to single nucleotide polymorphisms (SNPs) in genes involved in aspects of β-carotene conversion. Previous work has shown that carriers of both, the 379V and 267S+379V BCMO1 variant alleles had a reduced ability to convert β-carotene. More importantly, 44% of the western population have the 379V haplotype. A high percentage of the Western population may therefore not be able to achieve adequate vitamin A intake if dietary β-carotene is a major source of their vitamin A intake. This is of particular relevance to vegetarians, to young individuals aged 19-24 years who have lower intakes of preformed retinol than any other age group, and to pregnant women. The aim of this study is to establish whether the maximum recommended dose for β-carotene of 7mg/day by the British Expert Committee on Vitamins and Minerals (EVM) can overcome the SNP effect in the BCMO1 enzyme.
Hypothesis:
The investigators hypothesize that the current maximum recommended intake of 7 mg of β-carotene per day cannot overcome the low convertor phenotype in BCMO1 to fulfill vitamin A requirements in these people.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Supplement A | Other | Dietary Supplement: Beta-caroteneBeta-carotene 7mg formulation A |
| Supplement B | Other | Dietary Supplement: Beta-caroteneBeta-carotene 7mg formulation B |
| Supplement C | Other | Dietary Supplement: Beta-caroteneBeta-carotene 7mg formulation C |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy individual.
- Female.
- Between 18 and 45 years of age.
- Caucasian.
- BMI between 18 and 30 kg/m2.
Key exclusion criteria (14 listed)
- Smoking.
- Diabetes.
- Gastrointestinal diseases.
- Renal and hepatic diseases.
- Hyperlipidaemia.
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 |
|---|---|---|
| Beta-carotene | Dietary supplement | Supplement A, Supplement B, Supplement C |
Primary outcome
Area under the plasma concentration versus time curve (AUC) of beta-carotene
Time frame: Pharmacokinetic measures (0,1,4,36,46,57,60 days post-dose)
Area under the plasma concentration versus time curve (AUC) of [13C]retinol
Time frame: Pharmacokinetic measures (0,1,2,3,4,8,10,22,36,46,57,58,59,60,64,66,78,92,113 days post-dose)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2015.
- Background: PubMed 24158962Oxley A, Berry P, Taylor GA, Cowell J, Hall MJ, Hesketh J, Lietz G, Boddy AV. An LC/MS/MS method for stable isotope dilution studies of beta-carotene bioavailability, bioconversion, and vitamin A status in humans. J Lipid Res. 2014 Feb;55(2):319-28. doi: 10.1194/jlr.D040204. Epub 2013 Oct 24.
- Background: PubMed 22113863Lietz G, Oxley A, Leung W, Hesketh J. Single nucleotide polymorphisms upstream from the beta-carotene 15,15'-monoxygenase gene influence provitamin A conversion efficiency in female volunteers. J Nutr. 2012 Jan;142(1):161S-5S. doi: 10.3945/jn.111.140756. Epub 2011 Nov 23.
- Background: PubMed 20980645Grune T, Lietz G, Palou A, Ross AC, Stahl W, Tang G, Thurnham D, Yin SA, Biesalski HK. Beta-carotene is an important vitamin A source for humans. J Nutr. 2010 Dec;140(12):2268S-2285S. doi: 10.3945/jn.109.119024. Epub 2010 Oct 27.
- Background: PubMed 19103647Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. 2009 Apr;23(4):1041-53. doi: 10.1096/fj.08-121962. Epub 2008 Dec 22.
- Background: PubMed 16236189Furr HC, Green MH, Haskell M, Mokhtar N, Nestel P, Newton S, Ribaya-Mercado JD, Tang G, Tanumihardjo S, Wasantwisut E. Stable isotope dilution techniques for assessing vitamin A status and bioefficacy of provitamin A carotenoids in humans. Public Health Nutr. 2005 Sep;8(6):596-607. doi: 10.1079/phn2004715.
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.
Georg Lietz, PhD principal investigator
Newcastle University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Beta-carotene in people with Beta-carotene Bioavailability and Vitamin A Deficiency, run by Newcastle-upon-Tyne Hospitals NHS Trust at 1 site in United Kingdom.
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 6 inclusion and 14 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: finished, as of the sponsor's last update on 6 Oct 2015. 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 United Kingdom. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area under the plasma concentration versus time curve (AUC) of beta-carotene (time frame: Pharmacokinetic measures (0,1,4,36,46,57,60 days post-dose)). The study lists 2 primary outcomes in all. 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 NCT02276014, which also lists 5 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 6 Oct 2015; AzTrials last refreshed its copy on 1 Nov 2026.