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Vitamin D and Cancer<br />
al.,2006; Arunabh et al.,2003; Wortsman et al.,2000; Yanoff et al.,2006; van Dam et al.,2007; Liel et<br />
al.,1988; Compston et al.,1981; Hey et al.,1982; Buffington et al.,1993; Parikh et al.,2004; Florez et<br />
al.,2007; Hypponen and Power,2006, 2007). This negative association is independent from other<br />
factors such as age, sex and race (Parikh et al.,2004), and also from the seasons. Nonetheless, the<br />
greatest difference between lean, overweight and obese subjects in serum 25-hydroxyvitamin D<br />
levels was observed for peak levels reached during the summer and the autumn (Bolland et al.,2007).<br />
At the end of winter, differences were less pronounced.<br />
The negative association between 25-hydroxyvitamin D and overweight and obesity is less<br />
pronounced with body mass index (BMI = (weight in kg)/(height in cm) 2 ), than with the percentage<br />
body mass constituted in fat tissues. Wortsman et al.,2000 observed an increase in serum 25hydroxyvitamin<br />
D levels in obese and non-obese subjects after exposure to UVB irradiation. The<br />
increase was less in obese subjects and the content of 7-dehydrocholesterol in the skin wasn’t<br />
different between the obese and non-obese subjects. Obese people can have the same skin capacity<br />
to produce vitamin D, but the release of metabolites into the circulation is altered, possibly because of<br />
sequestration in the subcutaneous fat (Wortsman et al.,2000).<br />
Arunabh et al.,2003 found in young healthy women a progressive decrease of serum 25hydroxyvitamin<br />
D concentration with increasing percentage body fat content measured by dual<br />
energy x-ray absorptiometry. The inverse relation between serum 25-hydroxyvitamin D level and BMI<br />
was less pronounced. The same findings were done in 453 Dutch women aged 65 years old and over<br />
after adjustment for age, smoking and season (Snijder et al.,2005; van Dam et al.,2007) (Figure 7.2),<br />
as well as in 121 Spanish women of mean age 45 (Vilarrasa et al.,2007). So, using BMI as a proxy for<br />
body fat underestimates the inverse association between body fat composition and circulating vitamin<br />
D metabolites and the percentage of the body constituted of fat tissues.<br />
The prevalence of low levels of serum 25-hydroxyvitamin D in obese individuals has been<br />
attributed different reasons. A decreased exposure to sunlight because of limited mobility has been<br />
postulated, but also a negative feedback from elevated circulating 1α,25-dihydroxyvitamin D and PTH<br />
levels on the hepatic synthesis of 25-hydroxyvitamin D and excessive storage of vitamin D<br />
metabolites in the adipose tissue (Liel et al.,1988; Compston et al.,1981; Worstman et al.,2000;<br />
Mawer et al.,1972; Bell et al.,1985). Recent studies have found high serum PTH levels to be<br />
associated with obesity, regardless of age, sex and race (Kamycheva et al.,2004; Parikh et al.,2004;<br />
Yanoff et al.,2006), especially with total amount of fat tissues (Snijder et al.,2005). This secondary<br />
hyperparathyroidism ceases after a return to normal weight.<br />
7.3.4 Smoking<br />
Smoking has been associated with changes in vitamin D metabolism and smokers have been<br />
shown to have lower vitamin D status in most (Brot et al.,1999; Hermann et al.,2000; Supervia et<br />
al.,2006) but not all (Kimlin et al.,2007) studies. It remains to be determined if and why smoking may<br />
affect vitamin D status and whether smoking cessation leads to a normalisation of circulating vitamin D<br />
levels. It has been speculated that such changes may relate to increased activity of some liver<br />
enzymes induced by smoking (Kimlin et al.,2007), but they could also be due to decreased sun<br />
exposure, reduced dermal production, increased vitamin D catabolism or other dietary and lifestyle<br />
differences between smokers and non-smokers. Serum PTH levels are also lower in smokers than in<br />
non–smokers (Jorde et al.,2005), the 1α,25-dihydroxyvitamin D-PTH axis seems blunted and<br />
intestinal calcium absorption is impaired (Need et al.,2002). Lower vitamin D status and impaired<br />
intestinal calcium absorption would explain the higher prevalence of osteoporosis among smokers<br />
(Brot et al.,1999).<br />
7.3.5 Physical activity<br />
Physical activity is associated with increased vitamin D status (Scragg et al., 1995; Looker,<br />
2007). The mechanism by which physical activity increases serum 25-hydroxyvitamin D levels<br />
remains speculative. Physical activity could also just be a surrogate measure for sun exposure,<br />
healthier lifestyle, a diet richer in vitamin D and calcium, less overweight, and so on.<br />
7.3.6 Skin pigmentation and ethnicity<br />
37