Chapter 6 136 not statistically significant. On the other hand, in participants with dyslipidemia, c-fPWV was significantly increased after a 24-wk treatment with magnesium citrate supplements. The subgroup analyses also showed that oral magnesium supplementation was more effective in participants with increased arterial stiffness at baseline. Notably, the effect size in this group was comparable with the effect size that we found in our previous study. The interaction by age might be partly explained by the fact that ageing induces functional and structural changes in large elastic arteries, suggesting that the subgroup of older participants had prevalent increased arterial stiffness as well. Thus, our subgroup analyses might indicate that future trials should investigate effects of magnesium supplementation in study populations with more severe arterial stiffness, such as chronic kidney disease patients 27. GI adverse events induced by magnesium supplements are frequently reported. Particularly, osmotic diarrhea is often a result of high dosages of magnesium from dietary supplements. Therefore, the European Food Safety Authority has set the upper level for magnesium supplements to 350 mg/d 28. Magnesium oxide is often used for the treatment of constipation, due to its laxative properties. Magnesium sulfate, on the other hand, is often intravenously administered for treating and prevention of eclamptic seizures 29. As a consequence, trials using oral magnesium sulfate are scarce. To the best of our knowledge, this is the first study that assessed somatic and GI symptom severity of various magnesium formulations. Both scores were derived from the PHQ-15. In general, GI complaints are frequently reported by RCTs that administered magnesium supplements 30,31, however, these adverse events are often derived from patients diaries or non-validated questionnaires, without a formal quantification. In the current study, administering 450 mg/d of magnesium citrate yielded slightly more GI complaints at 12-wk compared with a placebo. However, this effect was not observed at the end of the trial. Furthermore, participants in the magnesium oxide group reported significantly less somatic and GI complaints at 12-wk and 24-wk compared with participants in the magnesium citrate group. Our findings may indicate that magnesium oxide supplements are better tolerated than magnesium citrate supplements, and are likely better tolerated than magnesium sulfate supplements. This is further substantiated by the fact that none of the participants from the magnesium oxide group discontinued the study treatment due to GI complaints, whereas 2 (4.3%) participants from the magnesium citrate group and 2 (4.3%) participants from the magnesium sulfate group reported GI complaints as the main reason for discontinuation.
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