Chapter 6 134 Discussion The primary aim of this study was to assess the effects of a relatively high dose of magnesium supplementation on c-fPWV and blood pressure. A total daily dose of 450 mg/d was based on previous RCTs that suggested a greater blood pressure-lowering effect with a higher total daily dose of magnesium 13,14. Furthermore, no prior study previously compared the efficacy of different magnesium formulations to pinpoint whether vascular effects may be driven by magnesium or the accompanying anion. Therefore, the main novel aspects of this trial are the higher magnesium dose and the head-to-head comparison among various types of magnesium supplements. In contrast with our hypothesis, magnesium citrate supplementation of 450 mg/d for 24-wks did neither change arterial stiffness nor blood pressure. Furthermore, compared with magnesium citrate treatment, magnesium oxide and magnesium sulfate did not significantly change c-fPWV. In a secondary analysis,magnesium sulfate supplementation did significantly improve c-fPWV at 24-wks in a subgroup with higher arterial stiffness at baseline. Effects of magnesium citrate and oxide supplementation on c-fPWV at 24-wks were in a similar direction, although not significantly different from placebo in these instances. Although these subgroup analyses should be interpreted with caution as it was not pre-specified in the study protocol, this result suggests that oral magnesium supplementation is indeed effective to improve arterial stiffness in individuals with prevalent increased arterial stiffness. The current trial was mainly designed to confirm the previously observed effect of magnesium citrate supplementation on arterial stiffness, now with a slightly higher dose. In this previous study, we found a significant effect on c-fPWV by 1.0 m/s after 24 weeks 10. Interestingly, the effect size that we observed in individuals with prevalent increased arterial stiffness in the current study is similar to what we previously found. To our knowledge, this is the first study that performed a head-to-head comparison between various magnesium formulations in terms of effects on arterial stiffness and blood pressure. Previous studies that addressed the effects of oral magnesium supplementation on vascular function markers deliberately chose a magnesium formulation based on their proposed bioavailability, whereas evidence regarding the bioavailability of magnesium formulations is still scarce. A higher bioavailability may yield greater effects, as more magnesium is absorbed and enters the circulation. Organic formulations, such as magnesium citrate or magnesium gluconate, are generally preferred over inorganic formulations, such as magnesium oxide and magnesium sulfate 16,24. However, a recent meta-analysis showed that the inorganic formulations
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