Breast cancer [36]. The high cost of treating patients with these diseases is an escalating public health problem, possibly exacerbated as the prevalence of the circulating alpha-Amanitin web levels of 25(OH)D below 75 nmol/L (as a risk factor) continues to increase. 3. Factors Affecting Circulating 25(OH)D Concentration in Response to Vitamin D Supplementation There are many factors which can influence the way individuals respond to, and metabolize supplemental vitamin D. From the available evidence, we categorized factors into two groups; (1) factors associated with the individual characteristics and biological parameters; and (2) factors associated with environment and treatment strategy. All factors within each category will be discussed in more detail in the following sections. 3.1. Biological and Demographic Characteristics Determinants Several biological and demographic factors, including baseline 25(OH)D, age, BMI or body fat percentage, ethnicity and calcium intake, have been well examined in relation to the response to vitamin D supplementation (Table 1). However, other variables, such as genetics, oestrogen use, dietary fat AZD0156 manufacturer content and composition and some diseases and medications have been investigated to a lesser extent. In this section the evidence for these potential determinants will be examined. 3.1.1. Basal 25(OH)D Concentration Baseline 25(OH)D concentration has been consistently shown to make a significant contribution to variance in 25(OH)D response to vitamin D supplementation (Table 1) [10,14,15,37?0]. Because hepatic hydroxylation of vitamin D may be a saturable process [40], response to vitamin D supplementation could well be affected by baseline 25(OH)D concentrations. Baseline 25(OH)D concentration explained 20.2 of the variation in 25(OH)D response to vitamin D supplementation in a cohort of Middle Eastern women (n = 62) [15]. In response to supplementation with daily 4000 IU vitamin D for 14 days, Trang et al. (1998) showed that change in 25(OH)D concentration had a significant inverse correlation with baseline 25(OH)D concentrations [44]. The largest increase was seen in subjects in the first tertile (10?4 nmol/L), followed by those in the second tertile (35?9 nmol/L) and then those in the third tertile (50?6 nmol/L); +30.6 ?16.2, +25.5 ?11.7 and +13.3 ?3.9 nmol/L, respectively (p = 0.02). Bacon et al. (2009) demonstrated that deficient subjects (<50 nmol/L) receiving a loading dose of 500,000 IU had larger incremental change in their 25(OH)D concentrations at one month than non-deficient subjects (50 nmol/L), 71.0 [95 CI, 58.0?4.0] vs. 50.0 [95 CI, 38.0?3.0] nmol/L (p = 0.03), respectively [43]. Similarly, Canto-Costa et al. (2006) found that while the mean increase was 25.4 nmol/L in subjects with 25(OH)D concentrations <50 nmol/L, it was 13.0 nmol/L in those with 25(OH)D concentrations >50 nmol/L (p < 0.05). The participants were housebound elderly men and women (n = 42) and received weekly 7000 IU vitamin D3 supplements for 12 weeks [37].Nutrients 2015, 7 Table 1. Demographic and biological factors predicting circulating 25(OH)D response to vitamin D supplementation.Relationship with Population CharacteristicsAloia et al. (2008) [10]Healthy men and women (n = 138)Randomised double blind placebo control trial/6 months//Dosing at baseline started with daily 2000 IU D3 and daily 4000 IU D3 for those with >50 and 50 nmol/L, respectively. Then, the intake was modified. Randomised double blind trial/8 months/Single dose of 5.Breast cancer [36]. The high cost of treating patients with these diseases is an escalating public health problem, possibly exacerbated as the prevalence of the circulating levels of 25(OH)D below 75 nmol/L (as a risk factor) continues to increase. 3. Factors Affecting Circulating 25(OH)D Concentration in Response to Vitamin D Supplementation There are many factors which can influence the way individuals respond to, and metabolize supplemental vitamin D. From the available evidence, we categorized factors into two groups; (1) factors associated with the individual characteristics and biological parameters; and (2) factors associated with environment and treatment strategy. All factors within each category will be discussed in more detail in the following sections. 3.1. Biological and Demographic Characteristics Determinants Several biological and demographic factors, including baseline 25(OH)D, age, BMI or body fat percentage, ethnicity and calcium intake, have been well examined in relation to the response to vitamin D supplementation (Table 1). However, other variables, such as genetics, oestrogen use, dietary fat content and composition and some diseases and medications have been investigated to a lesser extent. In this section the evidence for these potential determinants will be examined. 3.1.1. Basal 25(OH)D Concentration Baseline 25(OH)D concentration has been consistently shown to make a significant contribution to variance in 25(OH)D response to vitamin D supplementation (Table 1) [10,14,15,37?0]. Because hepatic hydroxylation of vitamin D may be a saturable process [40], response to vitamin D supplementation could well be affected by baseline 25(OH)D concentrations. Baseline 25(OH)D concentration explained 20.2 of the variation in 25(OH)D response to vitamin D supplementation in a cohort of Middle Eastern women (n = 62) [15]. In response to supplementation with daily 4000 IU vitamin D for 14 days, Trang et al. (1998) showed that change in 25(OH)D concentration had a significant inverse correlation with baseline 25(OH)D concentrations [44]. The largest increase was seen in subjects in the first tertile (10?4 nmol/L), followed by those in the second tertile (35?9 nmol/L) and then those in the third tertile (50?6 nmol/L); +30.6 ?16.2, +25.5 ?11.7 and +13.3 ?3.9 nmol/L, respectively (p = 0.02). Bacon et al. (2009) demonstrated that deficient subjects (<50 nmol/L) receiving a loading dose of 500,000 IU had larger incremental change in their 25(OH)D concentrations at one month than non-deficient subjects (50 nmol/L), 71.0 [95 CI, 58.0?4.0] vs. 50.0 [95 CI, 38.0?3.0] nmol/L (p = 0.03), respectively [43]. Similarly, Canto-Costa et al. (2006) found that while the mean increase was 25.4 nmol/L in subjects with 25(OH)D concentrations <50 nmol/L, it was 13.0 nmol/L in those with 25(OH)D concentrations >50 nmol/L (p < 0.05). The participants were housebound elderly men and women (n = 42) and received weekly 7000 IU vitamin D3 supplements for 12 weeks [37].Nutrients 2015, 7 Table 1. Demographic and biological factors predicting circulating 25(OH)D response to vitamin D supplementation.Relationship with Population CharacteristicsAloia et al. (2008) [10]Healthy men and women (n = 138)Randomised double blind placebo control trial/6 months//Dosing at baseline started with daily 2000 IU D3 and daily 4000 IU D3 for those with >50 and 50 nmol/L, respectively. Then, the intake was modified. Randomised double blind trial/8 months/Single dose of 5.
