## 3 Results and Discussion
### Grade of recommendation GPP, (88%) Consensus
#### Grade of recommendation GPP, (90%) Consensus. _Comment--HMB and essential amino acids:_  
Supplements rich in leucine, essential amino acids, HMB, and creatine need further study in critically ill patients. Supplementation with HMB seems to provide the strongest evidence in this respect, with an improvement in nitrogen balance in patients with high catabolism. Administration of essential amino acids has been shown to improve body composition and nutritional status in other pathologies associated with increased muscle catabolism [119]. Studies conducted in patients with moderate/severe COPD [120] have shown that supplementation with a high proportion of leucine-enriched essential amino acids is associated with increased protein anabolism [32]. Increased physical capacity, fat-free mass, muscle strength, SaO\({}_{2}\), serum albumin, and quality of life scales, as well as a decrease in cognitive impairment progression, have also been observed in patients with severe COPD who do not meet the criteria for participation in pulmonary rehabilitation programs [121]. _Comment--Omega-3, Vit D and leucine:_  
There are numerous published interventions with a very heterogeneous methodology, including supplements enriched in carbohydrates and fatty acids, essential amino acids, whey protein rich in BCAAs, creatine, and polyunsaturated fatty acids (PUFAs) (natural ligands of peroxisome proliferatorator-activated receptors). Initial studies with fat-enriched supplements do not appear to show a significant benefit; however, more recent studies using carbohydrate and PUFA-enriched formulations appear to show improved physical training in selected patients [15]. In a study of 86 patients with moderate inspiratory limitation, low lung diffusion capacity, adequate protein intake, and decreased levels of vitamin D and DHA, the administration of a supplement enriched in omega-3, vitamin D, and leucine for 4 months in association with physical exercise (in both groups) showed statistically significant differences in the increase in muscle mass, levels of Vit D, EPA, and DHA, and the number of steps achieved [111]. \begin{table}
\begin{tabular}{l c} \hline \hline \multicolumn{2}{c}{**Grade of Recommendation**} \\ \hline Monitor levels of ions, especially magnesium, & *** \\ calcium, phosphorus & \\ \hline Vit D if deficient (\textless{}20 ng/mL) & ** \\ \hline HMB and essential amino acids & * \\ \hline Omega-3, Vit D and leucine & N \\ \hline Antioxidant vitamins A, C and E, and selenium & N \\ \hline \hline \multicolumn{2}{l}{**Recommend; ** Suggest; * Advise; N: Not positioning.} \\ \end{tabular}
\end{table} 
Table 8: Grade of recommendation according to GARIN’s position on supplementation with micronutrients and trace elements. Some studies also show a reduction in exacerbations after vitamin D supplementation in patients with previous deficiency [58; 99]. Vitamin D supplementation is, therefore, recommended in patients with deficiency (<20 ng/mL), with a clear benefit in the prevention of falls, especially in association with calcium. A dose of 800 IU with 1 g of calcium is recommended. Supplementation with higher doses requires further study [122; 15; 123]. The addition of leucine and carbohydrates to protein supplements, either alone or in combination, has not been shown to increase protein anabolism compared with high-protein supplementation alone [94; 116]. _Comment--Antioxidant vitamins:_  
Several studies show antioxidant vitamin deficiency rates of up to 81% [58; 99; 124]. The use of magnesium and vitamin C-enriched whey formulations [67] has shown a decrease in inflammatory markers as well as an increase in fat-free mass, grip strength, and quality of life tests in patients with moderate/severe COPD. In different systematic reviews, vitamin C supplementation has not demonstrated relevant clinical benefits in patients with pulmonary pathology [99]. However, more recent publications show contradictory results.