Mg loading and exercise on COPD Amaral AF et al. The overall set of results indicates that the improvement in exercise performance that is associated with the Mg treatment does not appear to be secondary to changes in the heart function. An additional potential contributing mechanism to the present findings is that the Mg treatment led to a higher efficacy of the exercise mechanism itself. The acute loading of Mg may have influenced the muscle contraction or the peripheral energy production process in this setting. Animal studies have shown that Mg administration leads to increases in the glucose available to tissues, decreases in lactate release and increases in pyruvate production (36-39). In addition, Mg oral supplementation in athletes has been shown to increase glucose blood levels during exercise via ACTH and cortisol discharge (39). Most importantly, because Mg is a cofactor that binds to ATP molecules, increases in intracellular Mg may also improve ATP production and glucose utilization (40). It has also been suggested that Mg supplementation may enhance the endothelial function by increasing the local NO availability, decreasing platelet aggregation, and reducing oxidative stress (41,42). Although the VO2 and VCO2 of the overall group of patients did not differ between treatments, the RER showed a small but significant increase after the Mg infusion (0.06; p = 0.023). This finding could be better explained by a change in the metabolic profile, with an Mg-induced rise in glucose utilization, as previously suggested. The present study has several limitations, including the small number of patients enrolled, the lack of a standard inquiry for dietary Mg ingestion, the lack of an adequate measurement of exercise dynamic hyperinflation, and the need for biochemical determinations during exercise. Dynamic inspiratory capacity evaluations and biochemical measurements, such as blood lactate and glucose levels, would permit less speculative explanations for the observed improvements in exercise performance. As Mg has sub- stantial metabolic actions, it would be more informative if the present study had also measured intracellular Mg concentrations. In addition, technical problems did not permit the determination of the aerobic threshold in eight COPD patients, which precluded an adequate analysis of the data related to this parameter in the group. The effects of Mg on peak exercise, although statistically significant, were small, with a mean load addition of 8 w. The clinical meaning of this finding is presently unknown, but it appears that it should be of little relevance. Additionally, this level of improvement was obtained with mean Mg plasma levels of approximately 3 mEq/L, which are substantially higher than in the typical physiological range (1.5–2.5 MEq/L). On the other hand, intracellular Mg levels may be more important than plasma measurements. Certainly, definitive answers to the questions generated by this paper will only be possible after clinical trials involving the oral supplementation of Mg in COPD patients for longer periods. The acute IV loading of 2 g of Mg was associated with a reduction in static hyperinflation and increases in the load reached with incremental maximal exercise tests. Post-hoc analyses indicated that the positive exercise response was due to improvements in respiratory mechanics. The present results suggest that higher circulating levels of Mg may be beneficial for COPD patients. These findings also indicate the need for further studies investigating the effects of 620 CLINICS 2012;67(6):615-621 chronic dietary supplementation with Mg on the pulmonary function parameters and exercise tolerance of stable COPD patients. AUTHOR CONTRIBUTIONS Amaral AF and Cresceˆncio JC conceived the study and were responsible for the data collection and tabulating. Gallo Jr L and Vianna EO conceived the study and were responsible for the manuscript writing. Vannucchi H conceived the study and was responsible for the biochemical measurements. Martinez JA conceived the study and was responsible for the statistical analysis and manuscript writing. REFERENCES 1. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewestam A. Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta. 2000;294(1-2):1-26. 2. Finstad EW, Newhouse IJ, Lukaski HC, Mcaulifffe JE,Stewart CR. The effects of magnesium supplementation on exercise performance. Med Sci Sports Exerc. 2001;33(3):493-8. 3. Newhouse IJ, Finstad EW. The effects of magnesium supplementation on exercise performance. Clin J Sport Med. 2000;10:195-200. 4. Lukaski HC, Nielsen FH. 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