Effect of SNPs in the BCMO1 Enzyme

Vitamin A Deficiency Clinical Trial

— BETASNP2  

Official title:

Effect of SNPs in the Beta-carotene 15, 15'-Monooxygenase (BCMO1) Enzyme on Retinol Formation and Beta-carotene Plasma Responses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02276014
• Other study ID #: 2011-01-18-BETASNP2
• Secondary ID: REC 11/NE/0211
• Status: Completed
• Phase: N/A
• First received: October 21, 2014
• Last updated: October 5, 2015
• Start date: April 2012
• Est. completion date: September 2014

Study information

• Verified date: October 2015
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Beta-carotene Bioavailability
• Night Blindness
• Vitamin A Deficiency

Intervention

Dietary Supplement:
• Beta-carotene

Locations

Country	Name	City	State
United Kingdom	Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary	Newcastle upon Tyne	Tyne & Wear

Sponsors (3)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust	DSM Nutritional Products, Inc., Newcastle University

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

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. Review. — View Citation

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. — View Citation

Leung WC, Hessel S, Méplan 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. — View Citation

Lietz G, Oxley A, Leung W, Hesketh J. Single nucleotide polymorphisms upstream from the ß-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. — View Citation

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 ß-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration versus time curve (AUC) of beta-carotene		Pharmacokinetic measures (0,1,4,36,46,57,60 days post-dose)	No
Primary	Area under the plasma concentration versus time curve (AUC) of [13C]retinol		Pharmacokinetic measures (0,1,2,3,4,8,10,22,36,46,57,58,59,60,64,66,78,92,113 days post-dose)	No