Effect of SNPs in the BCMO1 Enzyme (BETASNP2)

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. 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.

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.

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