Contents - IARC

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