Supplementary materials

Transcription

1 Supplementary materials Table S Adverse events identified by participants diary logs and blood hematologic and biochemical tests (n=2) group (n=) Placebo group (n=) P value for chi-squared test Asthma () ().32 Vulval tumor () ().32 Diarrhea () ().32 Gastroenteritis () ().32 Fever () ().32 Influenza 3 (3) 5 (5).47 Headache () ().32 Toothache () (). Fatigue 2 (2) 4 (4).4 Foot pain 5 (5) 2 (2).25 Knee pain 2 (2) ().6 Dry eye () ().32 Gum swelling () 2 (2).6 Cough () ().32 Anorexia () ().32 Scapular pain () 2 (2).56 Wrist pain () ().32 Low back pain 4 (4) ().7 Cold 25 (25) 23 (23).74 Platelet elevation () ().32 Asthenopia () ().32 Allergy to pollen 5 (5) 6 (6).4 Pharyngitis 3 (3) 2 (2).65 Cold sores () ().32 Bronchitis () ().32 Dizziness () 2 (2).6 Flank muscle pain () ().32 Inflammatory pseudotumor () ().32 Allergy rhinitis () 6 (6).3 Notes: Data are shown as n (%).

2 Table S2 Deviation identified during the study period by fasting blood test Reference ranges Deviation group Placebo group P value for (n=396)* (n=399)* chi-squared test White blood cells (/ L) (3.8) (2.8).4 2 (.5) 2 (.5).99 Red blood cells ( 4 / L) : (.8) 2 (3.).2 : (.5) 2 (.5).99 Hemoglobin (g/dl) : (.) ().44 : (2.) (2.5).65 Hematocrit (%) : (.8) 8 (2.).8 : (.8) (.3).3 Platelets ( 4 / L) (3.5) 8 (2.).48 3 (.8) (.3).3 AST (U/L) 4 2 (.5) 4 (.).42 4 (.) ().44 ALT (U/L) (.8) 5 (.3).48 () 5 (.3).25 LDH (U/L) (.8) 3 (.8).99 (.3) (.3). T-Bil (mg/dl).2.2 (2.5) 2 (5.3).46 () () - ALP (U/L) 325 (.3) (.3). () () - -GTP (U/L) : 8 : <3 4 (.) 9 (2.3).7 Total protein (g/dl) (.5) ().6 8 (2.) 3 (.8).3 Albumin (g/dl) (.3) ().32 3 (.8) (.3).3 Blood urea nitrogen (mg/dl) (4.3) 6 (.5).9 9 (2.3) 8 (4.5).8 Creatinine (mg/dl) : (3.) 2 (3.).99 : (.5) (.3).6 Uric acid (mg/dl) : (7.) 26 (6.5).76 : (.5) 4 (.).42 Sodium (meq/l) () () - () 2 (.5).6 Chloride (meq/l) (2.) 9 (2.3).82 (.3) ().32 Potassium (meq/l) (.3) 3 (.8).32 () () - Calcium (mg/dl) () 6 (.5).4 () () - Magnesium (mg/dl) (.8) (.3).3 3 (.8) 2 (.5).65 Serum iron ( g/dl) : 5 2 : (.5) 22 (5.5).2 3 (3.3) 4 (3.5).86 Notes: Data are shown as n (%). The sum of the total number of samples at week 4, week 8, week 2, and week 6. Abbreviations: AST, aspartate amino transferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; T-Bil, total-bilirubin; ALP, Alkaline phosphatase; -GTP, -Glutamyltranspeptidase. 2

3 Table S3 Changes in hematologic or hematological parameters Reference ranges Sex Group Screening Week 4 Week 8 Week 2 Week 6 (n=2) (n=99) (n=99) (n=98) (n=99) White blood cells (/ L) (598) 646 (94) 654 (75) 5978 (34) # 6389 (569) Placebo 642 (62) 63 (573) 6257 (58) 64 (44) # 674 (547) Red blood cells ( 4 / L) 54 (35) 56 (34) 5 (36) 492 (35) # 5 (4) : Placebo 54 (37) 52 (36) # 52 (37) # 497 (36) # 52 (35) : (3) 464 (26) 469 (29) 457 (3) 462 (28) Placebo 457 (3) 462 (3) 464 (27) # 449 (29) # 454 (28) Hemoglobin (g/dl) 5.5 (.9) 5.5 (.9) 5.7 (.8) 5. (.8) # 5.4 (.) : Placebo 5.6 (.9) 5.7 (.8) 5.8 (.8) 5.2 (.8) # 5.4 (.9) # : (.2) 3.4 (.3) 3.6 (.2) 3.2 (.) 3.3 (.) Placebo 3.5 (.) 3.5 (.) 3.6 (.) 3. (.) # 3.3 (.) # Hematocrit (%) 47.9 (2.4) 47.5 (2.6) 47.6 (2.6) 46.3 (2.4) 47.2 (2.6) # : Placebo 48. (2.6) 48. (2.3) 48. (2.) 47. (2.5) # 47.4 (2.4) : (3.) 42. (3.4) 42.3 (3.) 4.8 (2.8) 42. (2.6) Placebo 42.5 (2.6) 42.5 (3.) 42.5 (2.8) 4.5 (2.9) # 42. (3.) Platelet count ( 4 / L) (6.7) 3. (7.) 29.8 (6.9) 29.2 (6.5) # 29.5 (6.5) # Placebo 29.2 (6.6) 28.9 (6.) 29.5 (6.2) 28.3 (5.9) # 29.2 (6.) Notes: Data are shown as mean (standard deviation). # Significant difference from the screening value used by paired t tests (P<.5). There were no significant differences in any parameters between the two groups at any time points. 3

4 Table S4 Changes in blood biochemical parameters Reference ranges Sex Group Screening Week 4 Week 8 Week 2 Week 6 (n=2) (n=99) (n=99) (n=98) (n=99) AST (U/L) 4 22 (7) 2 (6) # 2 (6) 9 (5) # 2 (6) # Placebo 2 (7) 2 (5) 2 (7) 9 (5) # 9 (7) # ALT (U/L) (6) 22 (3) # 22 (2) # 2 () # 22 (3) # Placebo 23 (4) 2 (2) # 22 (4) 2 (2) # 2 (5) # LDH (U/L) (24) 79 (24) 8 (23) 68 (24) # 74 (24) # Placebo 79 (25) 79 (23) 78 (26) 72 (26) # 7 (26) # T-Bil (mg/dl) (.3).8 (.3).8 (.3).8 (.3).8 (.3) Placebo.8 (.3).8 (.3).8 (.3) #.8 (.3) #.8 (.3) # ALP (U/L) (48) 28 (5) 26 (47) # 95 (46) # 23 (49) # Placebo 2 (53) 22 (6) 2 (57) 92 (55) # 94 (55) # -GTP (U/L) 32 (6) 29 (3) 29 (2) 26 () # 29 (3) # : <8 Placebo 33 (5) 33 (5) 33 (6) 3 (5) # 32 (7) : <3 23 (2) 2 () 2 () 2 () # 2 (9) # Placebo 24 (3) 22 (3) 22 (2) 2 () # 2 () # Total protein (g/dl) (.4) 7.4 (.4) 7.5 (.4) 7.2 (.3) # 7.4 (.4) # Placebo 7.4 (.3) 7.4 (.3) 7.4 (.4) 7.2 (.3) # 7.3 (.3) # Albumin (g/dl) (.3) 4.5 (.3) 4.5 (.3) 4.4 (.3) # 4.5 (.3) # Placebo 4.5 (.3) 4.5 (.3) 4.5 (.3) 4.4 (.3) # 4.4 (.3) # Urea nitrogen (mg/dl) (3.) 2.8 (3.6) 2.7 (3.6) 2.8 (4.) 2.7 (3.6) Placebo 2.8 (3.5) 2. (3.2) # 2.7 (3.6) 2.4 (3.2) 2.9 (3.6) Creatinine (mg/dl).82 (.9).85 (.).85 (.9) #, *.87 (.) #.86 (.9) # :.6.4 Placebo.86 (.2).9 (.2) #.89 (.3) #.9 (.2) #.89 (.2) # : (.8).63 (.9).62 (.9).64 (.9).64 (.8) # Placebo.6 (.9).62 (.2).62 (.).64 (.9) #.63 (.9) # Uric acid (mg/dl) 6.4 (.) 6.5 (.2) 6.4 (.) 6.5 (.2) 6.6 (.2) : Placebo 6.3 (.2) 6.2 (.) 6.3 (.2) 6.2 (.2) 6.4 (.2) : (.) 4.8 (.2) 4.9 (.2) 4.7 (.) 4.9 (.2) Placebo 5. (.9) 4.9 (.) 4.9 (.9) 4.9 (.9) 4.9 (.) Sodium (meq/l) (2) 4 (2) 42 (2) # 4 (2) 4 (2) Placebo 4 (2) 4 (2) 42 (2) 4 (2) 4 (2) Chloride (meq/l) (2) 4 (2) 4 (2) 5 (2) # 5 (2) Placebo 4 (2) 4 (2) 4 (2) 5 (2) # 5 (2) # Potassium (meq/l) (.3) 4.4 (.2) # 4.4 (.3) # 4.3 (.3) 4.3 (.3) Placebo 4.3 (.3) 4.3 (.3) # 4.3 (.3) # 4.3 (.3) 4.3 (.3) Calcium (mg/dl) (.3) 9.6 (.3) 9.6 (.3) 9.5 (.3) # 9.5 (.3) Placebo 9.7 (.3) 9.6 (.4) 9.7 (.4) 9.6 (.3) # 9.6 (.3) # 4

5 Magnesium (mg/dl) Serum iron ( g/dl) : 5 2 : 4 8 Notes: Data are shown as mean (standard deviation). # Significant difference from the screening value used by paired t tests (P<.5). * Significant difference between the two groups used by unpaired t tests (P<.5). 2.2 (.) 2.2 (.) 2.2 (.) 2. (.) # 2. (.) # Placebo 2.2 (.2) 2.2 (.) 2.2 (.) 2. (.) # 2. (.) # 4 (39) 9 (37) 7 (33) 8 (33) 7 (4) Placebo 2 (42) 7 (38) 2 (44) 5 (39) 24 (43) 3 (54) 86 (47) # 9 (35) # 99 (45) 92 (45) Placebo 9 (38) (53) 98 (46) 95 (5) 92 (42) Abbreviations: AST, aspartate amino transferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; T-Bil, total-bilirubin; ALP, Alkaline phosphatase; -GTP, -Glutamyltranspeptidase; 5

6 Table S5 Changes in quantitative urinalysis parameters Reference ranges Group Screening Week 4 Week 8 Week 2 Week 6 (n=2) (n=99) (n=99) (n=98) (n=99) ph (.5) 6.2 (.6) 6.2 (.6) 6.3 (.6) 6.4 (.6) Placebo 6.2 (.6) 6.3 (.7) 6.2 (.6) 6.3 (.6) 6.3 (.6) Specific gravity (.8).2 (.7).9 (.7).9 (.8).9 (.7) Placebo.2 (.8).9 (.8).9 (.7).7 (.8) #.9 (.8) Notes: Data are shown as mean (standard deviation). # Significant difference from the screening value used by paired t tests (P<.5). There were no significant differences in either parameter between the two groups used by unpaired t tests (P<.5). 6

7 Table S6 Changes in qualitative urinalysis parameters Reference ranges Group Screening Week 4 Week 8 Week 2 Week 6 (n=2) (n=99) (n=99) (n=98) (n=99) * Urine protein (-) ( ) # Placebo Urine glucose (-) ( ) Placebo + Urobilinogen ( ) Placebo Bilirubin (-) Placebo Ketone body (-) Placebo # Occult blood (-) Placebo

8 Notes: Values indicate the number of participants. The symbols indicate the degree of each item: -, negative;, false-positive; +, positive (mild); 2+, positive (moderate); 3+, positive (serious). # Significant difference from the screening value used by Wilcoxon signed-rank tests (P<.5). * Significant difference between the two groups used by Mann-Whitney U test (P<.5)