In a small controlled study (n=28) an 8-week supervised combined aerobic-resistance program improved tremor subscore and 6-minute walk distance in people with PD while exploratory labs showed a decrease in vitamin D3 that remained significant after FDR correction.

Findings support short-term symptomatic benefit of structured exercise and suggest metabolic signals worth follow-up, but the study's small size, short duration and lack of mechanistic data limit its direct value for drug discovery or target identification.

Exercise is increasingly recognized as a key component of Parkinson's disease (PD) management, but data on short-term combined aerobic-resistance training (ART) on motor and metabolic parameters remain limited. In this controlled study, 28 patients with PD (median Hoehn & Yahr stage= 2, IQR 1.75-2.0) were allocated to an 8-week supervised ART group (n= 19) or a stretching-only control group (n = 9). Training consisted of two 45-minute sessions weekly. Primary outcomes were MDS-UPDRS-III, Sit-to-Stand Test (STS), and Six-Minute Walk Test (6MWT). Fasting laboratory parameters were exploratory given the small sample size and absence of an a priori power analysis. Between-group post-intervention differences were analyzed using ANCOVA (baseline as covariate); exploratory biochemical outcomes were controlled for multiple comparisons using Benjamini-Hochberg false discovery rate (FDR). ART improved the MDS-UPDRS-III tremor subscore (p = 0.004) and6MWT distance (p = 0.003), with no significant effects on other motor or functional outcomes. In exploratory laboratory analyses, unadjusted between-group differences were observed for HDL cholesterol (p =0.014), vitamin D3 (p = 0.003), TSH (p = 0.042), and homocysteine (p =0.019); after FDR correction, only vitamin D3 remained significant (qFDR= 0.039). Total cholesterol, LDL, and VLDL showed non-significant decreases. An eight-week ART program improved tremor and walking endurance inpatients with PD, while other motor outcomes remained unchanged. Exploratory changes in selected biochemical markers were detected (including a decrease in vitamin D3); their clinical relevance remains unclear and should be evaluated in larger, well-powered randomized studies.