Chapter 4 80 Epidemiological and clinical studies Epidemiological studies have shown an inverse relationship between magnesium and the risk of developing hypertension 6–8. Such studies used dietary magnesium measured by questionnaires, circulating magnesium levels, or urinary magnesium excretion to assess the relationship between magnesium status and risk of hypertension. A recently published meta-analysis of prospective cohort studies (in total >180,000 participants of whom >20,000 developed hypertension) suggested an inverse relationship between dietary magnesium intake and risk of hypertension; a 100 mg/day increment in magnesium intake was associated with a 5% lower risk of hypertension 9. Besides demonstrating associations between low dietary magnesium, assessed as a single nutrient, and hypertension risk, effects of dietary patterns on BP have also been studied 10,11. For example, it has been shown that the Dietary Approaches to Stop Hypertension (DASH) diet, which can be characterized by high fruit, vegetable and lowfat dairy intake, can reduce BP 12. Moreover, it was demonstrated that a higher DASH score was associated with a higher urinary magnesium excretion, suggesting that this diet is rich in magnesium 13. Han and others also studied the relation between serum magnesium and hypertension and found that the association was borderline significant (relative risk = 0.91; 95% CI: 0.80, 1.02) 9.This could probably be explained by the fact that serum magnesium poorly represents magnesium status, because only 1% over the total body magnesium content is present in the circulation, whereas the 99% resides in the intracellular compartment. In addition, magnesium homeostasis is regulated via the balance between intestinal absorption and renal excretion. Thus, low circulating magnesium can be compensated by decreased urinary excretion or increased intestinal absorption. In line with these observations, we have studied the association between urinary magnesium excretion and risk of hypertension in a general population-based cohort 14. We found that each 1-unit increment in ln-transformed urinary magnesium excretion was significantly associated with a 21% lower risk of hypertension, independent of several risk factors, including body mass index, smoking status, parental history of hypertension and alcohol consumption. However, no association between plasma magnesium and risk of hypertension was found and, moreover, plasma magnesium was weakly correlated with urinary magnesium excretion, further supporting the assumption that circulating magnesium less reliably reflects dietary magnesium intake. The effect of magnesium supplementation on BP has been studied in clinical trials since publication of a landmark trial in 1983 15. In this trial, hypertensive patients receiving either magnesium
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