Effects of magnesium citrate, magnesium oxide and magnesium sulfate on arterial stiffness 137 6 Strengths and limitations We performed a relatively large multiple-arm, randomized, double-blind, placebocontrolled trial, allowing comparison of different magnesium formulations. Previous trials mainly administered only a single magnesium formulation,while the varying formulations between studies introduces significant heterogeneity 23. Furthermore, the compliance to the treatment groups was excellent as both showed by increased 24 h urinary magnesium excretion as well as the low rate of returned capsules. Another strength is that we measured c-fPWV, currently the gold standard for the quantification of arterial stiffness 32. Finally, our data showed that dietary intake according to food diaries did not change during the study. This strongly suggests that our findings were not influenced by changes in eating habits, since the participants maintained their usual diet. Some limitations need to be addressed. First, the current study was not sufficiently powered to perform subgroup analyses, since the subgroup analyses were not included in our main analyses, on which the sample size calculation was based. Therefore, these analyses are exploratory and hypothesis-generating and must be confirmed by further RCTs. Second, we did not measure 24-h ambulatory blood pressure, which is generally a more accurate method to measure the blood pressure. Instead,we measured office blood pressure four times according to a strict protocol 33. Furthermore, it is well known that magnesium is the second most abundant intracellular cation. However, we did not study intracellular magnesium concentrations. It would therefore have been very interesting if we would have measured the intracellular concentration of magnesium. Unfortunately, this was not included in the study protocol and we did not collect samples to allow for measurement of the intracellular magnesium concentration. It would be interesting if future studies could include such measurements. Another limitation is that we did not record the direct carotid-femoral distance, as recommended by European Network for Non-Invasive Investigation of Large Arteries 22, but rather the distance suprasternal notch and the umbilicus as required for calculation of c-fPWV by the SphygmoCor software that we used. It should, however, be noted that a strong correlation of 0.97 between c-fPWV calculated based on 80% of the direct carotid-femoral distance and c-fPWV calculated based on the distance suprasternal notch and the umbilicus has been reported 34. Finally, the clinical measurements in the current study were performed by three investigators, of which one investigator performed the vast majority of the measurements and the other two were appointed as co-operators. Although all the co-operators were well trained by the main operator for several weeks, it may have
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