Magnesium and blood pressure: A physiology-based approach 79 4 Introduction Hypertension is a global public health problem, being responsible for 12.8% of all deaths worldwide 1. Hypertension is a major risk factor for stroke, myocardial infarction, peripheral artery disease and other chronic diseases such as chronic kidney disease (CKD). Conversely, hypertension is present in more than 80% of CKD patients and it contributes to the progression of CKD towards ESRD 2. Risk factors for hypertension include, but are not limited to, age, race, family history, obesity, physical inactivity, and tobacco use. Furthermore, high sodium and calcium intake, as well as low potassium and magnesium intake, has been linked with hypertension 3. Magnesium is the second most abundant intracellular cation in the human body and acts as a cofactor for more than 300 enzymes. During the last century, dietary magnesium intake in the US population has declined from ~500 mg/d to ~175-225 mg/d.4 This alarming trend runs in parallel with the massive increase in prevalence of diabetes and hypertension, fueling the concept that there may be a relationship between magnesium deficiency and these cardiovascular risk factors. This has been further substantiated by the fact that magnesium plays an important role in many physiological processes in the body, such as insulin metabolism. Indeed, not surprisingly, magnesium deficiency has been linked with several cardiovascular risk factors, including diabetes and hypertension, and chronic diseases such as cardiovascular disease and CKD 5. Recently, several meta-analyses have summarized prospective cohort studies and randomized controlled trials, demonstrating an inverse relationship between magnesium intake and hypertension risk as well as a BP-lowering effect of magnesium supplementation. Yet, data addressing the underlying mechanisms remain scarce. The aim of this review is to summarize available data on the potential mechanisms linkingmagnesiumwith BP,using a physiology-based approach.We structure our analysis according to components of BP physiology, including cardiac output determined by the stroke volume and heart rate, and the total peripheral resistance, which depends on vascular structure and function. Using this approach, we aim to provide a mechanistic basis providing further support to the existing studies (which will be addressed briefly) positioning magnesium supplementation as a promising (adjunct) approach for the treatment of hypertension.
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