*3.1. Participant Characteristics*

Participants were recruited from June 2020 to December 2021. Thirty-nine participants randomized to the placebo (*n* = 13), CIT (*n* = 13), and CIT+GSH (*n* = 13) completed the study (Figure 1). Compliance to the supplements were 94.9 ± 1.3%, 95.7 ± 1.1%, and 95.5 ± 1.2% for placebo, CIT, and CIT+GSH groups, respectively. No adverse effects of the supplementations were reported by participants during the study.

Participant characteristics at baseline did not differ among the groups, except for FBG (Table 1). FBG was higher in CIT+GSH compared to the placebo but not to CIT (*p* = 0.29).



Values are the mean ± SD or number (*n*) of participants. Abbreviations: BMI, body mass index; WC, waist circumference; FBG, fasting blood glucose; CIT, citrulline; GSH, glutathione; ARB, angiotensin receptor blocker; ACE, angiotensin converting enzyme; † vs. placebo.

### *3.2. Flow-Mediated Dilation and Arterial Stiffness*

Baseline FMD and PWV segments did not differ among the groups. There was a timeby-group interaction for FMD. CIT+GSH increased the FMD by 2.9% (*p* = 0.045) compared with placebo, but not with CIT (*p* = 0.18) (Figure 2). A low effect size was seen between CIT and placebo (*d* = 0.32) and, although insignificant (*p* = 0.10), there was a moderate effect size between CIT+GSH and CIT (*d* = 0.67). To compliment the significant increase in FMD, there was a high effect size between CIT+GSH and placebo (*d* = 0.91, *p* = 0.03). The change in FMD from 0–4 weeks was correlated with the baseline FMD (Figure 3). The Pearson correlation coefficient for placebo, CIT, and CIT+GSH were −0.26 (*p* = 0.39), 0.16 (*p* = 0.60), and −0.68 (*p =* 0.01), respectively. There were no significant time-by-group interactions for cfPWV, crPWV, cdPWV, or faPWV. However, CIT+GSH supplementation decreased crPWV (arm PWV) by 0.66 ± 0.93 m/s (*p* = 0.05, Table 2).

**Figure 2.** Changes (Δ) in brachial artery flow-mediated dilation (ΔFMD%) from 0 to 4 weeks. Abbreviations: CIT, citrulline; CIT+GSH, CIT+glutathione. \* *p* < 0.05 vs. placebo.

**Figure 3.** Relationship between changes (Δ) in the brachial artery flow-mediated dilation (ΔFMD%) from 0 to 4 weeks and baseline (0 week) FMD%. Abbreviations: CIT, citrulline; CIT+GSH, CIT+glutathione.


**Table 2.** Brachial artery endothelial function and arterial stiffness.

Values are the mean ± SD. Abbreviations: cfPWV, carotid-femoral PWV; crPWV, carotid-radial PWV; cdPWV, carotid-distal PWV; CIT, citrulline; CIT+GSH, CIT+glutathione; faPWV, femoral-ankle PWV. *p*-values are the time-by-group interaction from two-way repeated measures ANOVA. \* *p* < 0.05 vs. before; ‡ *p* < 0.05 vs. placebo.
