Figure 4. Treatment effects on urinary nocturnal melatonin, serum vitamin D3 and serum C-reactive protein (CRP) level in placebo and MSDK groups. (A) Nocturnal hourly melatonin secretion in the urine was measured at month 12 (n=10 per group), by collecting all urine samples between 10pm and 6am and measuring using urinary melatonin-sulfate ELISA kit. Each point in the scatter plots represents an individual’s urine melatonin-sulfate level, in placebo (open circle, red) or MSDK (closed circle, blue). *p ≤ 0.05 versus placebo at month 12; Unpaired one-tailed t-test with Welch’s correction. Serum levels of (B) Vitamin D3 and (C) CRP were measured at months 0, 6 and 12, using specific ELISA kits. Each point in the scatter plots represents the concentration for a single subject at a specific time point, in the placebo (open circle, red) or MSDK (closed circle, blue). *p ≤ 0.05 versus placebo at similar time point; Longitudinal analysis for repeated measures using generalized linear mixed model (GLMM) approach, considering groups and times as fixed effects and subjects nested within the groups as random.