Table 1.
(A) Study phases and timings, (B) characteristics of the study group and analysed subgroups modified from our earlier publication [
(B) 0-Control4-Day Health, HC-LCDGA vs. PlaceboStudy GroupWhole Group (N = 27)LC Subgroup (N = 17)HC Subgroup (N = 10)DGA Group (N = 17)Placebo Group (N = 10)Mean age (years)56 years
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Figure 1. End products of the HO-1 pathway in blood 12 h after the last DGA or placebo dose: (A) Mean (±SEM) blood bilirubin concentration, (B) Mean (±SEM) blood Fe concentration. Notes: (1) The Day21 DGA and Placebo averages are indexed to Day0 so that Day21 fully reflects the change from Day0. (2) * and ** indicate paired t-test, # indicates non-paired t-test between the%-changes from Day0 to Day21.
Figure 1. End products of the HO-1 pathway in blood 12 h after the last DGA or placebo dose: (A) Mean (±SEM) blood bilirubin concentration, (B) Mean (±SEM) blood Fe concentration. Notes: (1) The Day21 DGA and Placebo averages are indexed to Day0 so that Day21 fully reflects the change from Day0. (2) * and ** indicate paired t-test, # indicates non-paired t-test between the%-changes from Day0 to Day21.
Figure 2. Bilirubin associated Day21 anti-inflammatory, fat metabolic, and mRNA expression effects: (A) scatter diagram and R2 of the percent changes from Day0 to Day21 between GlycA and bilirubin, (B) scatter diagram and R2 of the percent changes from Day0 to Day21 between blood triglycerides and bilirubin, (C) scatter diagram and R2 of the percent changes from Day4 to Day21 between IL-6 and bilirubin, (D) mean (±SEM) blood IL-6 concentration, (E) mean (±SEM) mRNA expression of HIF-1α from collected WBCs. Notes: (1) In (D,E), the Day21 DGA and placebo averages are indexed to Day0 so that Day21 fully reflects the change from Day0. (2) * and ** indicate paired t-test, # indicates non-paired t-test between the %-changes from Day0 to Day21. In (A–C), the p-values are based on an F-test. (3) One Day21 observation was deducted from (B) as an outlier. Additionally, one Day0 IL-6 observation was excluded from (D) when comparing the changes from Day0 to Day21 in the placebo group against the DGA group.
Figure 2. Bilirubin associated Day21 anti-inflammatory, fat metabolic, and mRNA expression effects: (A) scatter diagram and R2 of the percent changes from Day0 to Day21 between GlycA and bilirubin, (B) scatter diagram and R2 of the percent changes from Day0 to Day21 between blood triglycerides and bilirubin, (C) scatter diagram and R2 of the percent changes from Day4 to Day21 between IL-6 and bilirubin, (D) mean (±SEM) blood IL-6 concentration, (E) mean (±SEM) mRNA expression of HIF-1α from collected WBCs. Notes: (1) In (D,E), the Day21 DGA and placebo averages are indexed to Day0 so that Day21 fully reflects the change from Day0. (2) * and ** indicate paired t-test, # indicates non-paired t-test between the %-changes from Day0 to Day21. In (A–C), the p-values are based on an F-test. (3) One Day21 observation was deducted from (B) as an outlier. Additionally, one Day0 IL-6 observation was excluded from (D) when comparing the changes from Day0 to Day21 in the placebo group against the DGA group.
Figure 3. HO-1 pathway end products excluding CO in blood 45 min after acute DGA dose: (A) 45 min average intraindividual percent change in bilirubin (±SEM), (B) similar 45 min change in Fe (±SEM), (C) scatter diagram between 45 min %-changes of bilirubin and Fe after acute DGA dose. Notes: ** indicate paired t-test, # indicates non-paired t-test between the %-changes in 45 min. In (C), the p-value is based on an F-test.
Figure 3. HO-1 pathway end products excluding CO in blood 45 min after acute DGA dose: (A) 45 min average intraindividual percent change in bilirubin (±SEM), (B) similar 45 min change in Fe (±SEM), (C) scatter diagram between 45 min %-changes of bilirubin and Fe after acute DGA dose. Notes: ** indicate paired t-test, # indicates non-paired t-test between the %-changes in 45 min. In (C), the p-value is based on an F-test.
Figure 4. 4-day DGA regimen activates hepatic bilirubin metabolism and Fe storage in the LC subgroup: (A) mean (±SEM) blood bilirubin in the HC and LC subgroups separately, (B) mean (±SEM) blood albumin in HC and LC subgroups separately, (C) cross correlation between intraindividual 4-day molar changes of albumin (vertical scale) and bilirubin (horizontal scale) in the LC subgroup. (D) mean (±SEM) blood ALP in the HC and LC subgroups separately, (E) mean (±SEM) blood Fe in the HC and LC subgroups separately, and (D) cross correlation between intra-individual four-day percent changes of Fe (vertical scale) and bilirubin (horizontal scale) in the whole group. Notes: * and ** indicate paired t-test from Day0 to Day4, # indicates non-paired t-test between the bilirubin concentration on Day4. In (C,F), the p-values are based on an F-test.
Figure 4. 4-day DGA regimen activates hepatic bilirubin metabolism and Fe storage in the LC subgroup: (A) mean (±SEM) blood bilirubin in the HC and LC subgroups separately, (B) mean (±SEM) blood albumin in HC and LC subgroups separately, (C) cross correlation between intraindividual 4-day molar changes of albumin (vertical scale) and bilirubin (horizontal scale) in the LC subgroup. (D) mean (±SEM) blood ALP in the HC and LC subgroups separately, (E) mean (±SEM) blood Fe in the HC and LC subgroups separately, and (D) cross correlation between intra-individual four-day percent changes of Fe (vertical scale) and bilirubin (horizontal scale) in the whole group. Notes: * and ** indicate paired t-test from Day0 to Day4, # indicates non-paired t-test between the bilirubin concentration on Day4. In (C,F), the p-values are based on an F-test.
Figure 5. 4-day DGA regimen activates the LC subgroup: (A) mean (±SEM) blood TGs in the HC and LC subgroups separately, (B,C) cross correlation between intra-individual four-day percent changes of TGs (vertical scale) and (B) blood bilirubin (horizontal scale) and (C) blood Fe (horizontal scale) in the whole group. (D) Mean (±SEM) blood GlycA in the HC and LC subgroups separately. (E,F) Cross correlation between intraindividual four-day percent changes of GlycA (vertical scale) and € blood bilirubin (horizontal scale) and (F) blood Fe (horizontal scale) in the whole group. Notes: * and ** indicate paired t-test from Day0 to Day4, # indicates non-paired t-test between the TGs and GlycA concentrations on Day0. In (B,C) and (E,F), the p-values are based on an F-test.
Figure 5. 4-day DGA regimen activates the LC subgroup: (A) mean (±SEM) blood TGs in the HC and LC subgroups separately, (B,C) cross correlation between intra-individual four-day percent changes of TGs (vertical scale) and (B) blood bilirubin (horizontal scale) and (C) blood Fe (horizontal scale) in the whole group. (D) Mean (±SEM) blood GlycA in the HC and LC subgroups separately. (E,F) Cross correlation between intraindividual four-day percent changes of GlycA (vertical scale) and € blood bilirubin (horizontal scale) and (F) blood Fe (horizontal scale) in the whole group. Notes: * and ** indicate paired t-test from Day0 to Day4, # indicates non-paired t-test between the TGs and GlycA concentrations on Day0. In (B,C) and (E,F), the p-values are based on an F-test.
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