Article Figures & Data
Figures
- Figure 1.
Mean plasma concentrations of resveratrol (A), resveratrol-4′-O-glucuronide (B), resveratrol-3-O-glucuronide (C), and resveratrol-3-O-sulfate (D) versus time in healthy volunteers after the last of between 21 and 28 daily doses of resveratrol at either 0.5 g (black, closed circles), 1 g (green, open circles), 2.5 g (blue, squares), or 5 g (red, triangles). Values are the mean ± SD of 10 volunteers per dose level. The range of coefficients of variation (as % of the mean) for the individual data points is shown in parentheses.
- Figure 2.
Relationship between dose of resveratrol and maximal plasma concentration (Cmax; A) or area under the plasma concentration versus time curve (AUClast; B) for resveratrol (black, rhombi), resveratrol-4′-O-glucuronide (red, squares), resveratrol-3-O-glucuronide (green, triangles), and resveratrol-3-O-sulfate (blue, crosses) in healthy volunteers, after a dose of resveratrol at either 0.5, 1, 2.5, or 5 g ingested between days 21 and 28 of daily dosing. Values are the mean of 10 volunteers for each dose level. The range of coefficients of variation (as % of the mean) for individual data points is shown in parentheses.
- Figure 3.
Circulating levels of IGF-I (A) and IGFBP-3 (B) in individual healthy volunteers before and after consumption of resveratrol at 0.5, 1.0, 2.5, or 5.0 g daily for 28 d. Results of the statistical analysis by paired t test, i.e., mean differences between preintervention and postintervention levels (preintervention minus postintervention values in ng/mL), 95% confidence intervals (in parentheses) and P values, are shown for each group of 10 individuals below the graphs. Negative values signify an increase rather than a decrease in levels. Blood samples were taken just prior to the first dose of resveratrol and on day 29.
- Figure 4.
Maximal plasma concentrations (Cmax) of resveratrol (A), resveratrol-4′-O-glucuronide (B), resveratrol-3-O-glucuronide (C), and resveratrol-3-O-sulfate (D) in healthy volunteers who received either a single dose (open columns) or between 21 and 28 daily doses (closed columns) of resveratrol at either 0.5, 1, 2.5, or 5 g. Single dose results have been published previously (9). Values are the mean ± SD of 10 volunteers at each dose level (*, P < 0.05; **, P = 0.01; ***, P = 0.001; and ****, P < 0.0005).
Tables
- Table 1.
Number of healthy volunteers who experienced adverse events deemed intervention-related after daily ingestion of resveratrol for 29 d
Symptom No. of volunteers Dose (g) 0.5 1.0 2.5 5.0 Increased blood bilirubin Total 1 1 Conjugated 2 Unconjugated 2 Skin discoloration 1 Cystitis 1 Abdominal pain 4 3 Acne 1 Cramp 1 Diarrhea 2 (1*) 7 (2*, 1**) Discomfort on passing feces 1 Fatigue 1 Flatulence 1 2 Nausea 2 3 Pruritis 1 Chest pain 1 Dizziness 1 Dry mouth 1 Red/itchy eyes 1 Urine color change 1 NOTE: Overall number of volunteers per dose was 10 to 12.
Severity grading (NCI CTCAE v.4.0): no asterisk = 1; * = 2; ** = 3.
- Table 2.
Pharmacokinetic parameters of resveratrol and its three major metabolites in the plasma of healthy volunteers who received daily oral resveratrol for between 21 and 28 d (n = 10 per dose level)
Parameter Cmax (ng/mL)*,† Cav (ng/mL)*,† Tmax (h)‡ T1/2 (h)† AUClast (ng × h/mL)† Resveratrol, dose (g) 0.5 43.8 (89.4) [0.19] 9.93 (69.7) [0.04] 1.00 (0.25–5.0) 4.77 (62.1) 175 (83.7) 1.0 141 (68.9) [0.62] 22.8 (68.4) [0.10] 1.00 (0.25–1.82) 9.70 (37.5) 503 (79.3) 2.5 331 (59.2) [1.45] 48.1 (46.5) [0.21] 1.00 (0.23–4.97) 9.17 (42.0) 1,250 (40.0) 5.0 967 (53.5) [4.24] 126 (55.8) [0.55] 1.08 (0.5–1.5) 7.85 (25.1) 4,097 (107) Resveratrol-4′-O-glucuronide, dose (g) 0.5 186 (56.7) [0.82] 50.2 (51.1) [0.22] 1.27 (1.0–5.0) 3.78 (42.2) 1,331 (56.4) 1.0 710 (57.9) [3.12] 178 (64.8) [0.78] 1.50 (0.83–5.0) 5.77 (44.6) 3,774 (53.2) 2.5 1,137 (88.0) [4.99] 323 (66.9) [1.42] 1.50 (0.25–5.0) 8.14 (38.6) 7,245 (54.4) 5.0 2,323 (45.5) [10.2] 667 (61.3) [2.93] 1.50 (1.0–5.0) 7.55 (21.2) 19,984 (59.0) Resveratrol-3-O-glucuronide, dose (g) 0.5 184 (86.3) [0.81] 37.7 (56.2) [0.17] 1.27 (1.0–5.0) 4.98 (41.6) 875 (51.4) 1.0 588 (48.4) [2.45] 94.4 (28.9) [0.42] 1.50 (0.83–5.0) 5.50 (24.5) 2,087 (37.7) 2.5 1,546 (107) [6.78] 204 (64.0) [0.89] 1.42 (1.0–1.5) 6.43 (40.8) 5,300 (47.1) 5.0 3,886 (48.6) [17.1] 649 (34.8) [2.85] 1.50 (0.5–1.6) 5.19 (52.7) 22,084 (93.9) Resveratrol-3-O-sulfate, dose (g) 0.5 563 (35.1) [2.47] 118 (26.9) [0.52] 1.04 (1.0–5.0) 3.09 (15.3) 3,558 (51.6) 1.0 1,694 (35.2) [7.43] 377 (48.7) [1.65] 1.50 (0.83–5.0) 7.37 (51.4) 9,464 (42.3) 2.5 2,292 (50.7) [10.1] 604 (43.8) [2.65] 1.33 (1.0–1.5) 6.84 (40.6) 15,638 (39.0) 5.0 4,172 (40.3) [18.3] 1,384 (42.3) [6.07] 1.25 (0.25–5.0) 7.98 (29.6) 38,900 (49.5) Abbreviations: Cmax, maximal plasma concentration; Cav, average plasma concentration; Tmax, time of maximal plasma concentration (Cmax); T1/2, apparent first-order elimination half-life; AUClast, area under the plasma concentration versus time curve from time 0 to the last sampling blood draw collected.
- Table 3.
Apparent total body clearance and volume of distribution for resveratrol in healthy volunteers who received daily oral resveratrol for between 21 and 28 d (n = 10 per dose level)
Dose (g) Apparent total body clearance (L/h) Apparent volume of distribution (L) 0.5 2,771 (58.9)* 16,071 (56.5) 1.0 2,366 (63.9) 42,673 (86.1) 2.5 2,219 (42.5) 32,322 (44.5) 5.0 2,548 (100) 38,023 (133) ↵*Mean values with CV% in brackets.
Volume 70, Issue 22
