Context: Vitamin D deficiency, common in South Asians, is a risk factor for metabolic syndrome, type 2 diabetes and ischemic heart disease. Vitamin D receptor [VDR] activation depends on activated vitamin D (1,25(OH)₂D) concentration, reflecting opposing actions of 25-OHD-1- hydroxylase (1-(OH)ase) for formation and 25(OH)D-24-hydroxylase [24(OH)ase] for catabolism. We previously reported circulating 1,25(OH)₂D contributed to determination of VDR-protein levels and VDR genotype was a determinant of both VDR mRNA and VDR-protein in South Asians.

Objective: We hypothesized that chewing betel-nut, an addictive habit common throughout South Asian communities, contributes to hypovitaminosis-D by modulating either enzyme regulating circulating 1,25(OH)₂D concentration.

Design: Peripheral blood mononuclear cell [PBMC] 1-(OH)ase & 24(OH)ase mRNA concentrations were measured and examined in relation to cross-sectional data on the vitamin-D axis, diet, smoking, betel-usage, including PBMC VDR-RNA and VDR-protein content in a pilot study of 33 healthy British Bangladeshis.

Results: PBMC 24(OH)ase mRNA correlated positively and serum 1,25(OH)₂D negatively with betel-quids/day {r = +0.49, P = 0.006 and r = -0.486, P = 0.006 respectively}. Independent determinants for 24(OH)ase included betel-quids/day [P < 0.0001] and serum 25-OHD [P = 0.024]. Independent determinants for serum 1,25(OH)₂D were gender, smoking and betel-quids/day. PBMC 1-(OH)ase mRNA correlated inversely with VDR mRNA [r= -0.44; P = 0.013]; its independent determinants being 1-(OH)ase mRNA, serum 1,25(OH)₂D, 25-OHD and VDR TaqI and Bsm1 polymorphisms (P = 0.005-0.0001)].

Conclusions. Betel chewing is a more powerful independent determinant of increased 24(OH)ase expression and of decreased serum calcitriol than serum 25-OHD, supporting the hypothesis that this habit could aggravate the effects of vitamin-D deficiency.