br Table Di erence in Blood
Table 3 Diﬀerence in Blood Levels and Diet Intake of Magnesium, Calcium, and the Ca/Mg ratio with Level of % genetic African ancestry in self-reported Black Men.
% genetic African ancestry
p-value: Kruskal-Wallis test for diﬀerences in median values across % genetic African ancestry categories.
were also not linked with prostate cancer, although a higher Ca/Mg ratio as estimated by food frequency questionnaire was significantly associated with lower prostate cancer risk among black, but not white, men.
Dietary sources provide most needed magnesium, with high levels found in spinach, whole grains, beans, dairy foods, nuts, certain fish, and possibly water if there is a high mineral content. Recent data from National Health and Nutrition Examination Survey report that most U.S. adults are magnesium deficient, with 79% of U.S. adults reporting magnesium intake below the U.S. Recommended Daily Allowance . Hypomagnesemia may be asymptomatic, but magnesium deficiency is linked severe morbidity associated with an inflammatory response or metabolic dysregulation, including insulin resistance [28,29], fasting Tirapazamine levels , Type 2 diabetes , cardiovascular disease [32,33], colorectal cancer [34–36] and colorectal adenomas [35,37]. Magnesium is also inversely linked with blood C-reactive protein (CRP) levels [38–40], while induced magnesium deficiency in rodents leads to increased plasma IL6 levels  and increased markers of oxidative stress [19,41]. Human intervention studies that administered magne-sium supplements or magnesium replacement led to lower fasting glucose levels , increased high-density lipoprotein (HDL) , and improved insulin sensitivity [28,43–45]. Evidence that magnesium supplementation alters pro-inflammatory markers has been suggested in a limited number of small studies, but eﬀects are less clear and re-quires further investigation [44,46].
Analysis of the Atherosclerosis Risk in Communities (ARIC) study found black vs. white men had significantly lower dietary magnesium intake (143 vs. 159 mg/1000 Kcal, p < 0.001, respectively) and serum magnesium levels (1.92 vs. 2.02 ng/ml, p < 0.001, respectively) [9,10]. Indeed, many of the conditions linked with magnesium defi-ciency also appear to be diseases in which blacks experience greater risk or a poorer prognosis [47–51]. We previously reported that black men had significantly lower blood magnesium levels compared to white men in a study of men who were seeking a diagnostic prostate biopsy (2.03 vs. 2.16 ng/ml, p < 0.01, n = 51 vs. 441, respectively) . The pre-sent report confirms this prior observation. We cannot say with cer-tainty why black men had lower blood magnesium levels. There was an absence of any trend between blood magnesium levels and % genetic African ancestry, however genetic variation between race groups not encompassed by the % genetic African ancestry marker panel could certainly play a role. Dietary magnesium intake was also significantly lower among black men, suggesting dietary diﬀerences between race groups may be involved. However, the correlation between diet and blood magnesium levels was weak. The observed race diﬀerences in blood magnesium were small and may thus be a consequence of dif-ferences in the intake of specific food items not analyzed here, perhaps combined with genetic diﬀerences or diﬀerences in exposure to other environmental sources of magnesium.
Calcium has long held an interest in cancer, as calcium plays es-sential messenger roles regulating cell cycle proliferation and apoptosis
Associations between blood Mg, Ca, Ca/Mg Levels and prostate cancer, by race and PC grade.
*OR is eﬀect prostate cancer association for diﬀerence between 25th and 75th percentile of magnesium (Mg), calcium (Ca), or Ca/Mg ratio within controls for each race group. Analyses are run separately within each race group and adjusted for age, BMI, and study center. # Analysis of Ca/Mg that controls for Mg and Ca levels as well as age, BMI, and study center.
a P-int – p-interaction between Mg, Ca, or Ca/Mg with race group on prostate cancer risk in full dataset.
Associations between diet Magnesium, Calcium, and Ca/Mg ratio Levels and prostate cancer, by race and prostate cancer grade.
N (case/ctl) blacks
N (case/ctl) whites
*OR is eﬀect prostate cancer association for diﬀerence between 25th and 75th percentile of magnesium (Mg), calcium (Ca), or Ca/Mg within controls for each race group. Analyses are run separately within each race group and adjusted for age, BMI, study center, and total energy intake. ** P-int – p-interaction between Mg, Ca, or Ca/Mg with race group on prostate cancer risk in full dataset.
. However, the literature is inconsistent, with dietary calcium as-sociated with increased risk of aggressive prostate cancer  but also with increased risk of non-aggressive prostate cancer risk  or a reduced prostate cancer risk [14,15]. There is perhaps some greater consistency in reported foods rich in calcium such as dairy or milk in-take [52–54]. Fewer studies have considered the opposing interaction between calcium and magnesium. Calcium and magnesium compete for intestinal absorption, transport, and renal reabsorption [16–18]. In vitro and in vivo, magnesium administration inhibits calcium activity while magnesium deficiency increases calcium retention and activity [19–21]. Increasing the ratio of calcium-to-magnesium (Ca/Mg) in the medium of cultured DU145 prostate cells increased proliferation, con-sistent with a biological interaction between calcium and magnesium . Results of the current study are in contrast to our prior study, in that blood calcium levels or the blood Ca/Mg ratio in the current study were not significantly associated with prostate cancer in black or white men. A recent case-only analysis reported that black men diagnosed with aggressive prostate cancer had a higher dietary Ca/Mg ratio compared to black men diagnosed with less aggressive prostate cancer . However, we found dietary Ca/Mg ratio was significantly pro-tective for high-grade prostate cancer within black men. Reasons for this inconsistency with a prior study may involve the use biopsy ne-gative controls compared to controls with non-aggressive prostate cancer, and further investigation is needed to understand the mechan-isms underlying this eﬀect.