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serum 25OHD levels at or above 100 nmol/L compared with those with levels between 50 to 75 nmol. Further, the association was strongest for whites, participants in northern latitudes (> 35°N), and participants whose blood was collected in summer months. Thus, a pooled analysis of large cohort studies suggests an association for increased risk of pancreatic cancer with serum 25OHD levels greater than 100 nmol/L that is not consistently seen in analyses of individual large cohorts.

Prostate cancer Regarding prostate cancer, Tuohimaa et al. (2004) found a higher risk of prostate cancer for those with serum 25OHD levels above 80 nmol/L. The subjects were 67 men, mostly from Norway. Although another study from Finland (Tuohimaa et al., 2004) also found an association between serum 25OHD levels and prostate cancer at levels above 80 nmol/L, a study conducted by Faupel-Badger et al. (2007) also in Finland did not find a relationship.

Cardiovascular Risk

Although Linden (1974) observed that myocardial infarct patients in Norway were more likely than matched controls to have consumed vitamin D in excess (greater than 1,200 IU/day), two later studies (Schmidt-Gayk et al., 1977; Vik et al., 1979) failed to confirm these results. Melamed et al. (2008) examined data from 3,439 persons in the NHANES 2001 to 2004 surveys to determine the relationship between serum 25OHD level and peripheral arterial disease (defined as an ankle-brachial index < 0.9). The researchers noted that there was a lower risk of CVD mortality in men and women at levels of 75 to 122 nmol/L, but a higher risk of CVD mortality in women at levels above 125 nmol/L. Recently, Ginde et al. (2009), in a prospective cohort analysis of NHANES III data (1988 to 1994) on serum 25OHD levels in adults ages 65 years and older (n = 3,408) over a median 7.3-year follow-up, examined CVD mortality. Analysis of fully adjusted data indicated an inverse relationship between CVD mortality and baseline serum 25OHD level of 50.0 to 74.9 nmol/L. Risk began to increase at approximately 75 nmol/L and then it declined after 100 nmol/L.

Analyses from the Framingham Offspring Study (Wang et al., 2008), which followed 1,739 participants (mean age 59 years) with an average follow-up at 5.4 years, found a significant relationship between low serum 25OHD levels and incident cardiovascular risk. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event; vitamin D deficiency as defined in the study (serum 25OHD level < 37.5 nmol/L) was associated with increased risk for cardiovascular events. However, a closer look at the individuals with the highest serum 25OHD levels suggests that there was no additional reduction in risk with 25OHD levels above 75 nmol/L and even that the dose–response relationship may be U-shaped or

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