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CompletedNCT02276014BETASNP2Updated Oct 6, 2015

Effect of SNPs in the BCMO1 Enzyme

An interventional study of Beta-carotene in Beta-carotene Bioavailability and Vitamin A Deficiency, sponsored by Newcastle-upon-Tyne Hospitals NHS Trust. Completed at 1 site in United Kingdom. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-10-06.

Sponsored by Newcastle-upon-Tyne Hospitals NHS Trust · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
85
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
Female
01

Study 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. 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.

02

Conditions studied

  • Beta-carotene Bioavailability
  • Vitamin A Deficiency

Keywords

  • Beta carotene
  • Retinol
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • Smoking.
  • Diabetes.
  • Gastrointestinal diseases.
  • Renal and hepatic diseases.
  • Hyperlipidaemia.
  • Preformed dietary retinol intake above 60% of reference nutrient intake (RNI) values.
  • 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.
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
85 participants (actual)

Study arms

  • Other
    Supplement A

    Beta-carotene 7mg formulation A

    Dietary Supplement: Beta-carotene

  • Other
    Supplement B

    Beta-carotene 7mg formulation B

    Dietary Supplement: Beta-carotene

  • Other
    Supplement C

    Beta-carotene 7mg formulation C

    Dietary Supplement: Beta-carotene

Interventions

  • Dietary supplementBeta-carotene
05

What researchers measure

Primary outcomes

  1. 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)

  2. 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)

06

Study locations

1 site
  • Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary
    Newcastle upon Tyne, Tyne & Wear NE1 4LP, United Kingdom
07

References and documents

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 24158962 ↗
  • Lietz 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 22113863 ↗
  • Grune 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 20980645 ↗
  • Leung 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 19103647 ↗
  • Furr 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 ↗
08

Registry details

Key details

Study ID
NCT02276014
Lead sponsor
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators
Newcastle University, DSM Nutritional Products, Inc.
Responsible party
Sponsor
First posted
Oct 27, 2014
Start date
Apr 2012
Primary completion
Sep 2014
Completion
Sep 2014
Last update
Oct 6, 2015

Study contacts

Georg Lietz, PhD
principal investigator · Newcastle University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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