**4. Results**

The dynamics of the MIP groups and drop-outs are presented in detail in Figure 1. From the 50 (100%) participants initially selected, only 35 participants (70%) completed the intervention. This is an expected experimental loss, as reported by several previous studies [55]. None of the dropouts left the intervention due to injuries or adverse responses. Reported deaths were due to acute events triggered by chronic clinical conditions. Table 3 shows the characterization of participants by MIP groups at the baseline, including nutritional, cognitive, frailty, anthropometric, and body composition status. No statistically significant differences in all the variables appeared, expect for time in residential care and nutritional status assessed by MNA (*p* < 0.05). However, all the groups were within the well-nourished category.



Notes: BMI: Body mass index; MNA: Mini nutritional assessment; M ± SD: Mean (standard and deviation); pts: Points; Kg/m2: Kilograms; cm: Centimeters; One-way ANOVA was used to compare groups, except for the Comorbidity index (Fisher Exact Test). BCAA Branched Chain Amino Acids.

#### *4.1. Biochemical Analysis*

Table 4 shows the results for IL-10, TNF-α and TNF-α/IL-10 ratio, MPO, albumin, 5TSS-Test, as well as Fried (score) and MMSE. Concerning the IL-10 levels, a classical antiinflammatory cytokine, not only no effects of time (*p* = 0.690) or time vs. experimental groups were found (CG, BCAAs, ME, and ME + BCAAs), F(degrees of freedom-df:9, 51) = 1.567, *p* = 150), but also Bonferroni post-hoc comparisons did not result in significant variations between time vs. groups (*p* > 0.05). Regarding the TNF-α levels, although we did not observe any interference of time on these pro-inflammatory cytokine levels (*p* > 0.05, Table 4, repeated ANOVA analyses revealed significant interactions between time vs. groups: F(df: 6.758, 47.303) = 2.524, *p* = 0.029. In addition, Bonferroni post-hoc comparisons showed not only higher TNF-α values in the ME + BCAAs group between T2 and T3 (*p* = 0.01), but also a significant decrease of TNF-α was observed between T3 and T4 within the same experimental group (ME + BCAAs, *p* < 0.01). The TNF-α values were unchanged in all other experimental groups. Regarding the TNF-α/IL-10 ratios, no significant variations were observed over time (*p* = 0.703) or within the interactions (time vs. group, *p* = 0.638).

Concerning MPO activity, Table 4 shows that this biomarker was not influenced by time (T1, T2, T3, and T4), except for a slight tendency regarding interactions (time vs. group): F(df: 9, 48) = 2.010, *p* = 0.059. Particularly, the Bonferroni post-hoc comparisons showed that the BCAAs group presented higher MPO activity after re-supplementation (T4) than the values found in the T2 time-point (after the first 16 weeks of the supplementation period, *p* = 0.026). No significant alterations in the MPO activity were observed in other comparisons between groups.

In terms of serum albumin (Table 4), a statistically significant difference in the effect of time was found (F(df: 1949; 46,784) = 3.841, *p* = 0.02), but no other (time vs. group) significant difference was detected between the albumin levels (*p* = 0.219). The pairwise comparison using Bonferroni post-hoc showed a decrease of albumin levels in the BCAAs group in the T3 time-point (after the washout period, *p* = 0.04) as compared to the values found in T1, whereas no other significant variations were observed in the other groups (*p* > 0.05).

#### *4.2. Five-Times-Sit-to-Stand-Test (5TSS test)*

Table 4 shows no effect of time (*p* = 0.841) or interactions (time vs. group, *p* = 0.846) on the time elapsed to perform the 5TSS test. However, post-hoc adjustments showed that the ME + BCAAs and BCAAs groups presented a significant reduction of the time elapsed to perform this test at time-points T2, T3, and T4 (*p* = 0.009, *p* = 0.014, and *p* = 0.024, respectively).


**Table 4.** Statistical analysis comparison of four time-points moments of multifactorial intervention for biochemical, cognitive profile, physical frailty index, and functional fitness test.

Notes: M ± SD: Mean (standard and deviation); ME: Multicomponent exercise; BCAA: Branched-chain amino acids; IL: Interleukin; TNF-α: Tumor Necrosis Factor-alpha; MPO: Myeloperoxidase; MMSE: Mini Mental State Exam; 5TSS test: Five-Times-Sit-to-Stand-Test; T1 to T2 (elastic-band exercise, 16 weeks, 8 weeks), T2 to T3 (wash-out), T3 to T4 (multicomponent exercise, 16 weeks). \* time versus group interactions. Statistically significant differences are denoted in bold.

#### *4.3. Cognitive Assessment*

The results obtained in the cognitive profile (Table 4), show that, at baseline (T1), 65.7% of the participants (*n* = 23) scored below the 24-point threshold in the MMSE test, indicating that a significant fraction of participants was within the mild/moderate cognitive impairment classification. In addition, at the same time-point (T1), significant differences were found for the cognitive score between the ME + BCAAs group and the other groups (*p* < 0.05). An effect of time (F(df: 3, 93) = 4.262, *p* = 0.007), but not interaction (time vs. group, *p* = 0.296), was observed for the MMSE results. The cognitive MMSE scores increased in the control group between T1 and T2 but decreased subsequently in T3 and T4 (*p* = 0.008). No significant alterations were observed in the other groups. At baseline, 45.7% of the participants were classified as frail and 54.3% as pre-frail.
