Table 2

Improvement of metabolic health with tRES-HESP coformulation in the HATFF study

VariableStudy groupPlacebotRES-HESPΔ + tRES-HESP from: baseline [postsupplement]Significance P from: baseline [postsupplement]ANOVA/ Friedman
BaselinePostsupplementBaselinePostsupplement
Urinary pyrraline (nmol/mg creatinine)All12.1 (6.4–15.8)10.6 (7.8–15.0)8.8 (5.1–13.4)8.2 (5.1– 21.3)
PBMC Glo1 activity (mU/mg protein)All1,300 ± 1361,155 ± 1511,343 ± 1561,414 ± 150— [259 (22%)]— [<0.05]<0.02
Highly overweight1,346 ± 1541,156 ± 1851,345 ± 1891,463 ± 177— [307 (27%)]— [<0.05]<0.02
Obese1,451 ± 2421,085 ± 2531,140 ± 2461,413 ± 264— [328 (30%)]— [<0.05]
Plasma methylglyoxal (nmol/L)Highly overweight166 ± 28228 ± 30160 ± 29133 ± 18— [−84 (−37%)]— [<0.05]
Plasma d-lactate (μmol/L)All8.28 ± 0.818.56 ± 0.737.46 ± 0.778.31 ± 0.73
OGIS (mL ⋅ min−1 ⋅ m−2)Highly overweight513 ± 23541 ± 21506 ± 22548 ± 2342 (8%) [—]<0.02 [—]<0.05
Obese488 ± 32522 ± 32489 ± 29547 ± 3058 (12%) [—]<0.02 [—]
Fasting plasma insulin (pmol/L)All39.6 ± 6.338.2 ± 5.243.1 ± 6.936.0 ± 3.2
OGTT 90-min plasma insulin (pmol/L)Highly overweight291 (142–487)326 (223–422)303 (177–508)240 (110–452)
FPG (mmol/L)Highly overweight3.92 ± 0.123.80 ± 0.134.02 ± 0.153.82 ± 0.16−0.20 (−5%) [—]<0.04 [—]<0.01
Obese3.76 ± 0.113.80 ± 0.163.92 ± 0.163.58 ± 0.16−0.34 (−9%) [—]<0.02 [—]<0.05
AUCg (mmol/L ⋅ h)Highly overweight11.0 ± 0.710.5 ± 0.610.8 ± 0.79.9 ± 0.6−0.9 (−8%) [—]0.052 [—]<0.03
BMI (kg/m2)Obese34.2 ± 0.734.3 ± 0.634.0 ± 0.733.8 ± 0.6— [−0.5 (−1%)]— [<0.05]<0.02
Body weight (kg)Obese93.2 (84.0–109.4)93.6 (84.1–108.8)93.8 (83.7–106.6)93.3 (83.2 –107.7)— [−0.3 (−0.3%)]— [<0.05]
eGFR (mL/min)All99 ± 2101 ± 297 ± 2100 ± 23 (3%) [—]<0.03 [—]<0.02
Plasma urea (mmol/L)All4.60 ± 0.194.35 ± 0.184.67 ± 0.174.23 ± 0.15−0.44 (−9%) [—]<0.01 [—]<0.01
Plasma acetoacetate (μmol/L)All61 (42–135)74 (49–113)62 (48–127)77 (65–125)
Plasma β-hydroxybutyrate (μmol/L)All27 (16–47)24 (13–46)26(18–49)22 (11–46)
A1C (mmol/mol)All36.7 ± 0.836.5 ± 0.836.8 ± 0.836.5 ± 0.9
A1C (%)5.5 ± 0.15.5 ± 0.15.5 ± 0.15.5 ± 0.1
OGTT 2-h glucose (mmol/L)All4.28 ± 0.324.20 ± 0.264.40 ± 0.294.40 ± 0.26
HOMA-IR (mmol/L × mU/L)All0.75 (0.46–1.22)0.68 (0.42–1.25)0.85 (0.38–1.56)0.69 (0.49–1.34)
Systolic BP (mmHg)All131 ± 2132 ± 3131 ± 3133 ± 3
Diastolic BP (mmHg)All81.7 ± 1.982.9 ± 2.383.4 ± 2.183.3 ± 2.3
Total cholesterol (mmol/L)All5.48 ± 0.395.72 ± 0.285.35 ± 0.315.53 ± 0.28
LDL/VLDL cholesterol (mmol/L)All3.93 ± 0.264.16 ± 0.234.01 ± 0.234.06 ± 0.23
HDL cholesterol (mmol/L)All1.36 ± 0.101.39 ± 0.111.36 ± 0.101.37 ± 0.11
Triglycerides (mmol/L)All0.810 ± 0.1320.719 ± 0.1220.650 ± 0.1100.655 ± 0.092
Endothelin-1 (pg/mL)All1.66 ± 0.171.61 ± 0.141.66 ± 0.121.64 ± 0.15
CRP (μg/mL)All2.32 (0.99–5.46)2.37 (0.63–3.75)2.23 (0.82–3.97)1.74 (0.76–3.91)
sE-selectin (mg/mL)All39.0 ± 2.938.8 ± 3.239.2 ± 3.038.3 ± 3.0
sVCAM1 (ng/mL)All453 ± 16449 ± 13437 ± 12445 ± 14
Cystatin-c (ng/mL)All676 ± 28678 ± 29692 ± 32691 ± 31
Albumin-to-creatinine ratio (mg albumin/mmol creatinine)All0.257 (0.171–0.483)0.261 (0.147–0.790)0.231 (0.150–0.465)0.264 (0.159–0.581)
FMD (mm)All0.18 (0.07–0.49)0.26 (0.07–0.47)0.17 (0.10–0.35)0.12 (0.06–0.31)
GTND (mm)All0.41 (0.36–0.77)0.44 (0.28–0.76)0.45 (0.37– 0.75)0.38 (0.29– 0.53)
Plasma sICAM-1All257 ± 13284 ± 15280 ± 13276 ± 13<0.01
Plasma protein MG-H1 (mmol/mol Arg)All0.370 (0.348–0.447)0.380 (0.340–0.420)0.357 (0.330–0.408)0.381 (0.353–0.416)
Plasma protein dityrosine (μmol/mol Tyr)All28.6 ± 2.726.6 ± 2.629.6 ± 2.923.5 ± 1.7−6.1 (−21%) [—]<0.01 [—]<0.02
Total urinary MG-H1 free adduct (nmol/mg creatinine)All20.1 (16.3–30.6)22.7 (16.6–29.3)19.7 (12.5–30.4)19.8 (14.9–27.4)
Endogenous urinary MG-H1 free adduct (nmol/mg creatinine)All13.4 ± 2.113.5 ± 3.713.1 ± 2.811.3 ± 3.1−1.8 (−14%) [—]<0.01 (<0.01)<0.01
Urinary pentosidine free adduct (pmol/mg creatinine)All10.8 (6.8–20.2)12.7 (5.7–23.6)10.8 (7.4–21.8)7.4 (4.3–16.5)−3.4 (−32%) [—]<0.05 [—]
  • Data are mean ± SEM or median (lower–upper quartile) unless otherwise indicated. For obese, highly overweight/obese, and all study groups, n = 11, 20, and 29, respectively. Variables failing to achieve or approach significance are given in Supplementary Table 1. tRES-HESP treatment changes, Δ + tRES-HESP, are absolute (percentage) changes from baseline, and changes with respect to postsupplement placebo control are in square brackets. Related significance levels are also given where P < 0.05 and, in one case, borderline failure of significance, P = 0.052. There were not statistically significant differences induced by placebo. BP, blood pressure; eGFP, estimated glomerular filtration rate; sE-selectin, soluble E-selectin.