β-Carotene, the most abundant provitamin A carotenoid in the diet, is converted to retinal by β-carotene 15,15'-monoxygenase (BCMO1). However, β-carotene absorption and conversion into retinal is extremely variable among individuals, with proportions of low responders to dietary β-carotene as high as 45%. Recently, 2 common nonsynonymous single nucleotide polymorphisms (SNPs) within the BCMO1 coding region (R267S; rs12934922 and A379V; rs7501331) revealed reduced catalytic activity, confirming that genetic variations contribute to the low responder phenotype. Because 4 SNPs 5' upstream from the BCMO1 gene were recently shown to affect circulating carotenoid concentrations, the current study aimed to investigate the effects of these SNPs on β-carotene conversion efficiency. Three of the 4 polymorphisms (rs6420424, rs11645428, and rs6564851) reduced the catalytic activity of BCMO1 in female volunteers by 59, 51, and 48%, respectively. The TG-rich lipoprotein fraction retinyl palmitate:β-carotene ratio was negatively correlated with the G allele of rs11645428 (r = -0.44; P = 0.018), whereas it was positively correlated with the G allele of rs6420424 (r = 0.53; P = 0.004) and the T allele of rs6564851 (r = 0.41; P = 0.028). Furthermore, large inter-ethnic variations in frequency of affected alleles were detected, with frequencies varying from 43 to 84% (rs6420424), 52 to 100% (rs11645428), and 19 to 67% (rs6564851). In summary, a range of SNPs can influence the effectiveness of using plant-based provitamin A carotenoids to increase vitamin A status in at-risk population groups and this effect may vary depending on ethnic origin.

In humans, varying amounts of absorbed β-carotene are oxidatively cleaved by the enzyme β,β-carotene 15,15'-monooxygenase 1 (BCMO1) into two molecules of all-trans-retinal. The other carotenoid cleavage enzyme β,β-carotene 9',10'-dioxygenase (BCDO2) cleaves β-carotene at the 9',10' double bond forming β-apo-10'-carotenal and β-ionone. Although the contribution of BCDO2 to vitamin A formation has long been debated, BCMO1 is currently considered the key enzyme for retinoid metabolism. Furthermore, BCMO1 has limited enzyme activity towards carotenoids other than provitamin A carotenoids, whereas BCDO2 exhibits a broader specificity. Both enzymes are located at different sites within the cell, with BCMO1 being a cytosolic protein and BCDO2 being located in the mitochondria. Expression of BCMO1 in tissues other than the intestine has recently revealed its function for tissue-specific retinoid metabolism with importance in embryogenesis and lipid metabolism. On the other hand, biological activity of BCDO2 metabolites has been shown to be important in protecting against carotenoid-induced mitochondrial dysfunction. Single-nucleotide polymorphisms (SNPs) such as R267S and A379V in BCMO1 can partly explain inter-individual variations observed in carotenoid metabolism. Advancing knowledge about the physiological role of these two enzymes will contribute to understanding the importance of carotenoids in health and disease.

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Havforskningsinstituttets institusjonelle arkiv Brage IMR - Institutional repository of the Institute of Marine Research b r a g e i m rDette er forfatters siste versjon av den fagfellevurderte artikkelen, vanligvis omtalt som postprint. I Brage IMR er denne artikkelen ikke publisert med forlagets layout fordi forlaget ikke tillater dette. Du finner lenke til forlagets versjon i Brage-posten. Det anbefales at referanser til artikkelen hentes fra forlagets side. Ved lenking til artikkelen skal det lenkes til post i Brage IMR, ikke direkte til pdf-fil.This is the author's last version of the article after peer review and is not the publisher's version, usually referred to as postprint. You will find a link to the publisher's version in Brage IMR. It is recommended that you obtain the references from the publisher's site.Linking to the article should be to the Brage-record, not lear vacuoles and goblet cell hypertrophy and hyperplasia (4 -8) . 39Furthermore, substituting vegetable oils (VO) for fish oil (FO) 40 ingredients naturally decreases the high n-3:n-6 PUFA ratio of 41 a carnivorous fish's evolutionary consistent diet (9) . Alteration 42 of the dietary n-3:n-6 PUFA ratio can subsequently affect 43 the production of potent bioactive lipidic mediators of inflam-44 mation, termed as 'eicosanoids', which are synthesised from 45 C20 PUFA in cellular membranes (10) . 46In opposition to mammals, EPA (20 : 5n-3) predominates . Abbreviations: AA, arachidonic acid; ANF, anti-nutritional factor; COX-2, cyclo-oxygenase-2; cPLA 2 , cytosolic phospholipase A 2 ; DGLA, dihomo-g-linolenic acid; FM, fishmeal; FMFO, control diet of 100 % FM and 100 % fish oil; FO, fish oil; PLA 2 , phospholipase A 2 ; PP, plant protein; Tris, 2-amino-2-hydroxymethylpropane-1,3-diol; VO, vegetable oil; 40PP70VO, 40 % PP and 70 % VO replacement in diet; 80PP35VO, 80 % PP and 35 % VO replacement in diet; 80PP70VO, 80 % PP and 70 % VO replacement in diet.

Background: Retinol isotope dilution (RID) is used to determine vitamin A total body stores (TBS) after an oral dose of a vitamin A stable isotope. The generally accepted prediction equation proposed by Olson’s group in 1989 (Furr et al. Am J Clin Nutr 1989;49:713–6) includes factors related to dose absorption and retention, isotope equilibration in plasma compared with stores, catabolism during the mixing period, and the optimal time for measuring plasma isotope enrichment.Objectives: The objectives were 1) to develop a modified RID equation and identify an earlier sampling time for predicting TBS and 2) to improve prediction in individuals as well as groups.Methods: To develop a modified RID equation, we used results of model-based compartmental analysis [the Simulation, Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org)] of plasma [13C10]retinol kinetic data from 32 previously studied, healthy young adults of European ancestry who had moderate vitamin A intakes and who ingested 2.95 μmol [13C10]retinyl acetate.Results: We examined the time dependence of factors in the prediction equation related to absorption/retention (Fa) and isotope equilibration (S) and determined that 4 or 5 d postdosing was the optimal sampling time. TBS calculated by the equation TBS = Fa x S x (1/SAp), where SAp is plasma retinol specific activity (fraction of dose/μmol), were highly correlated with model-predicted TBS (r = 0.95 and 0.96 for 4 and 5 d, respectively; P < 0.001); predictions for individuals were also highly correlated (Rs = 0.94 and 0.94; P < 0.001).Conclusion: The equation TBS ≈ 0.5 × (1/SAp) accurately predicted vitamin A TBS in this group of 32 healthy young adults and its individual members with the use of data from 1 blood sample taken 4 d after isotope administration.