reducing the amount that can be presented to the liver for 25-hydroxylation. As noted previously, vitamin D is absorbed with fat as part of chylomicrons and is taken up first by peripheral tissues that express lipoprotein lipase, especially adipose tissue and skeletal muscle. This pathway predicts that increased adiposity should lead to lower serum 25OHD levels and, conversely, that weight loss should reduce peripheral sequestration and enable higher 25OHD levels. Consistent with this, not only does increasing adiposity correlate with lower 25OHD levels, but also a few studies of modest weight loss have found the circulating 25OHD levels to increase despite no increased intake of vitamin D from diet or sunlight exposure (Riedt et al., 2005; Reinehr et al., 2007; Zittermann et al., 2009; Tzotzas et al., 2010). The measured increase in serum 25OHD levels in overweight and obese individuals was about 1.5 nmol/L for a 100 IU/day vitamin D intake over 12 months (Sneve et al., 2008; Zittermann et al., 2009). Others found that obese subjects show a lower rise in serum 25OHD levels in response to both oral vitamin D intake and UVB exposure (Wortsman et al., 2000) or in a retrospective analysis in response to 700 IU/day vitamin D₃ supplementation (Blum et al., 2008). It is interesting that in severely obese individuals after malabsorptive gastric bypass surgery, vitamin D supplementation resulted in a marked rise in serum 25OHD level of approximately 3 nmol/100 IU intake when the dose was 800 to 2,000 IU/day, but only a 1 nmol/L rise when intake was increased to 5,000 IU/day (Goldner et al., 2009).

African American ancestry Serum 25OHD levels are lower in African Americans compared with light-skinned population groups (Looker et al., 2008), yet the risk for fracture is lower for African Americans than for other ethnic groups (Aloia, 2008). It should be noted, however, that there is a wide range of variability among individuals of any race or ethnicity (Aloia, 2008). Serum 25OHD levels in African Americans and whites have been shown to be similarly responsive to vitamin D supplementation at 40°N latitude (equivalent to Philadelphia or Indianapolis), increasing by 1 to 2 nmol/L per 100 IU/day at a dose of 3,440 IU/day (Aloia et al., 2008), although at doses below 2,000 IU/day, serum 25OHD levels do not increase above 50 nmol/L in African American girls (Talwar et al., 2007). The significance of maintaining a higher serum 25OHD level in African Americans is not understood at this time because of a lack of evidence on extra-skeletal effects of vitamin D.

Size and frequency of dose Dosing of vitamin D daily, weekly, or monthly has been tested, and there are reports of annual dosing as well. The results of a study by Chel et al. (2008) suggested that daily (600 IU/day) and weekly doses of vitamin D will increase serum 25OHD levels more than monthly doses, but Ish-Shalom et al. (2008) using a dose of 1,500 IU/day