TABLE 3.
Intervention effects on blood-based biomarkers, HR-QoL, liver fat, and liver function parameters1
| Baseline | Week 12 | ||||
|---|---|---|---|---|---|
| Mean ± SD (95% CI) | Mean ± SD (95% CI) | Loge relative change2 | P value3 overall | ||
| Blood-based biomarkers | |||||
| LDL cholesterol, mg/dL | ICR | 124.5 ± 22.4 (119.0, 130.0) | 115.3 ± 28.3 (108.4, 122.2) | −7.5 ± 2.6 | 0.74 |
| CCR | 122.5 ± 31.5 (114.9, 130.0) | 116.1 ± 26.3 (109.5, 122.7) | −7.9 ± 2.1 | ||
| Control | 130.4 ± 27.3 (124.0, 136.8) | 119.8 ± 23.9 (114.1, 125.5) | −8.7 ± 2.4 | ||
| HDL cholesterol, mg/dL | ICR | 54.1 ± 14.4 (50.7, 57.6) | 49.6 ± 13.8 (46.2, 53.0) | −8.7 ± 2.5 | 0.39 |
| CCR | 56.2 ± 16.3 (52.3, 60.1) | 50.4 ± 14.7 (46.7, 54.1) | −12.3 ± 1.8 | ||
| Control | 51.8 ± 11.8 (49.1, 54.5) | 47.2 ± 10.5 (44.7, 49.7) | −9.2 ± 1.9 | ||
| Cholesterol, mg/dL | ICR | 205.0 ± 30.8 (197.6, 212.4) | 185.1 ± 36.8 (176.1, 194.1) | −10.9 ± 2.3 | 1.00 |
| CCR | 202.9 ± 39.3 (193.5, 212.4) | 186.6 ± 31.8 (178.6, 194.6) | −10.6 ± 1.4 | ||
| Control | 211.8 ± 36.1 (203.4, 220.2) | 191.1 ± 31.3 (183.7, 198.5) | −9.7 ± 1.7 | ||
| Triglycerides, mg/dL | ICR | 130.0 ± 83.8 (110.0, 150.1) | 100.6 ± 47.5 (89.0, 112.3) | −20.7 ± 6.0 | 0.68 |
| CCR | 121.2 ± 66.3 (105.3, 137.1) | 100.8 ± 48.4 (88.7, 112.9) | −19.2 ± 3.4 | ||
| Control | 145.0 ± 85.5 (125.1, 164.8) | 120.5 ± 59.2 (106.5, 134.5) | −13.2 ± 4.9 | ||
| Insulin, mU/L | ICR | 11.6 ± 5.4 (10.3, 12.9) | 10.8 ± 5.6 (9.4, 12.2) | −6.3 ± 6.6 | 0.19 |
| CCR | 12.6 ± 6.9 (11.0, 14.3) | 9.7 ± 5.1 (8.4, 11.0) | −19.3 ± 5.2 | ||
| Control | 12.7 ± 7.3 (11.0, 14.4) | 11.7 ± 7.3 (10.0, 13.5) | −9.1 ± 5.7 | ||
| HOMA-IR | ICR | 2.7 ± 1.3 (2.4, 3.0) | 2.4 ± 1.3 (2.1, 2.7) | −9.0 ± 7.2 | 0.11 |
| CCR | 3.0 ± 1.7 (2.5, 3.4) | 2.1 ± 1.2 (1.8, 2.4) | −27.1 ± 5.9 | ||
| Control | 3.0 ± 1.8 (2.6, 3.4) | 2.6 ± 1.8 (2.2, 3.1) | −14.3 ± 6.3 | ||
| IGF-1, ng/mL | ICR | 108.9 ± 31.3 (101.3, 116.6) | 120.1 ± 38.4 (110.7, 129.5) | 11.7 ± 4.7 | 0.50 |
| CCR | 115.1 ± 36.6 (105.9, 124.9) | 115.4 ± 37.6 (105.9, 124.9) | 3.4 ± 5.5 | ||
| Control | 121.4 ± 32.1 (114.0, 128.9) | 125.9 ± 44.9 (115.3, 136.6) | 2.5 ± 4.2 | ||
| Glucose, mg/dL | ICR | 92.7 ± 7.5 (90.9, 94.5) | 89.9 ± 7.2 (88.1, 91.6) | −2.9 ± 1.2 | 0.04 |
| CCR | 93.9 ± 7.5 (92.1, 95.7) | 87.2 ± 7.8 (85.2, 89.2) | −7.6 ± 1.2 | ICR vs. CCR P = 0.01 CCR vs. Control P = 0.16 ICR vs. Control P = 0.24 | |
| Control | 93.5 ± 7.4 (91.8, 95.3) | 89.0 ± 9.5 (86.8, 91.3) | −5.2 ± 1.4 | ||
| Adiponectin, ng/mL | ICR | 18.3 ± 12.5 (15.3, 21.3) | 17.5 ± 11.0 (14.8, 20.2) | −5.2 ± 3.9 | 0.94 |
| CCR | 17.1 ± 10.3 (14.6, 19.6) | 16.2 ± 9.3 (13.9, 18.5) | −7.5 ± 3.6 | ||
| Control | 16.6 ± 10.2 (14.2, 19.0) | 15.5 ± 9.8 (13.2, 17.9) | −7.9 ± 4.1 | ||
| Leptin, ng/mL | ICR | 25.2 ± 24.0 (19.4, 31.0) | 16.8 ± 16.2 (12.8, 20.7) | −47.9 ± 9.2 | 0.78 |
| CCR | 23.3 ± 19.8 (18.6, 28.1) | 15.9 ± 16.9 (11.6, 20.2) | −48.4 ± 6.5 | ||
| Control | 25.9 ± 25.0 (20.1, 31.7) | 18.9 ± 22.0 (13.7, 24.1) | −44.3 ± 8.2 | ||
| Resistin, ng/mL | ICR | 5.7 ± 2.5 (5.1, 6.3) | 6.5 ± 2.7 (5.9, 7.2) | 14.4 ± 5.3 | 0.55 |
| CCR | 5.8 ± 2.3 (5.3, 6.4) | 6.7 ± 2.4 (6.1, 7.3) | 16.7 ± 4.5 | ||
| Control | 5.6 ± 2.4 (5.0, 6.2) | 6.9 ± 2.8 (6.2, 7.6) | 20.8 ± 4.3 | ||
| CRP, ng/pL | ICR | 4.2 ± 4.0 (3.2, 5.2) | 4.2 ± 5.0 (3.0, 5.4) | −17.0 ± 8.5 | 0.45 |
| CCR | 4.1 ± 3.8 (3.2, 5.0) | 3.2 ± 3.2 (2.4, 4.0) | −24.5 ± 10.8 | ||
| Control | 5.4 ± 7.9 (3.6, 7.2) | 4.0 ± 4.2 (3.0, 5.0) | −25.1 ± 13.3 | ||
| IL-6, ng/µL | ICR | 1.3 ± 1.0 (1.1, 1.5) | 1.4 ± 1.1 (1.1, 1.7) | 5.6 ± 8.7 | 0.10 |
| CCR | 1.5 ± 1.4 (1.2, 1.8) | 1.7 ± 1.7 (1.3, 2.1) | 12.1 ± 7.7 | ||
| Control | 1.9 ± 3.0 (1.2, 2.6) | 1.6 ± 1.8 (1.2, 2.0) | −8.0 ± 8.1 | ||
| IL-8, ng/µL | ICR | 11.3 ± 5.1 (10.1, 12.6) | 10.6 ± 5.0 (9.3, 11.8) | −8.8 ± 3.9 | 0.51 |
| CCR | 9.8 ± 4.3 (8.8, 10.9) | 10.4 ± 4.5 (9.2, 11.5) | −0.3 ± 3.9 | ||
| Control | 12.2 ± 19.4 (7.7, 16.7) | 12.4 ± 13.6 (9.2, 15.6) | 6.6 ± 5.5 | ||
| IFN-γ, ng/µL | ICR | 13.1 ± 10.0 (10.7, 15.4) | 23.4 ± 77.4 (4.5, 42.4) | 4.8 ± 12.3 | 0.90 |
| CCR | 16.3 ± 14.4 (12.8, 19.7) | 21.1 ± 38.5 (11.5, 30.8) | 1.1 ± 10.0 | ||
| Control | 17.7 ± 23.8 (12.2, 23.2) | 24.9 ± 53.8 (12.2, 37.7) | 1.5 ± 12.7 | ||
| TNF-α, ng/µL | ICR | 4.6 ± 2.7 (3.9, 5.2) | 4.4 ± 2.7 (3.8, 5.1) | −0.5 ± 2.7 | 0.72 |
| CCR | 4.7 ± 2.8 (4.0, 5.3) | 4.3 ± 2.7 (3.6, 5.0) | −2.5 ± 2.3 | ||
| Control | 4.2 ± 2.6 (3.6, 4.8) | 4.4 ± 2.6 (3.8, 5.0) | 1.5 ± 2.7 | ||
| BDNF, ng/mL | ICR | 2.1 ± 0.6 (1.9, 2.2) | 1.9 ± 0.5 (1.8, 2.0) | −10.2 ± 2.1 | 0.22 |
| CCR | 2.2 ± 0.8 (2.1, 2.4) | 2.1 ± 0.4 (2.0, 2.2) | −6.7 ± 3.2 | ||
| Control | 2.1 ± 0.6 (1.9, 2.2) | 2.0 ± 0.6 (1.8, 2.1) | −4.5 ± 2.6 | ||
| SHBG, nM | ICR | 36.4 ± 24.3 (30.5, 42.3) | 42.0 ± 27.1 (35.4, 48.6) | 15.0 ± 5.1 | 0.68 |
| CCR | 40.7 ± 38.0 (31.5, 49.9) | 44.4 ± 28.3 (37.0, 51.7) | 11.9 ± 6.2 | ||
| Control | 35.2 ± 18.6 (30.8, 39.6) | 39.2 ± 25.1 (33.3, 45.2) | 6.8 ± 6.1 | ||
| Women only (n = 75) | |||||
| Estrone, pg/mL | |||||
| Premenopausal | ICR | 42.6 ± 12.1 (34.5, 50.7) | 38.3 ± 16.6 (27.2, 49.4) | −21.8 ± 16.2 | 0.72 |
| CCR | 39.4 ± 22.3 (26.5, 52.4) | 44.7 ± 33.5 (22.2, 67.1) | 10.1 ± 27.6 | ||
| Control | 56.0 ± 37.0 (36.8, 75.2) | 51.2 ± 32.6 (33.4, 69.0) | −8.2 ± 16.3 | ||
| Postmenopausal | ICR | 33.5 ± 13.7 (27.5, 39.5) | 39.2 ± 18.1 (31.3, 47.1) | 11.7 ± 8.2 | 0.82 |
| CCR | 34.0 ± 17.2 (25.9, 42.1) | 36.5 ± 18.6 (27.6, 45.3) | 9.1 ± 5.6 | ||
| Control | 30.1 ± 12.0 (24.7, 35.6) | 33.4 ± 16.3 (25.4, 41.5) | 13.2 ± 15.7 | ||
| Testosterone, ng/mL | ICR | 0.5 ± 0.2 (0.4, 0.6) | 0.5 ± 0.2 (0.4, 0.6) | 0.7 ± 9.1 | 0.50 |
| CCR | 0.5 ± 0.4 (0.4, 0.6) | 0.4 ± 0.2 (0.3, 0.5) | 1.8 ± 27.0 | ||
| Control | 0.6 ± 0.2 (0.5, 0.6) | 0.5 ± 0.2 (0.4, 0.6) | −12.7 ± 6.4 | ||
| Men only (n = 75) | |||||
| Estrone, pg/mL | ICR | 39.6 ± 13.1 (35.0, 44.2) | 36.9 ± 11.2 (32.8, 41.0) | −10.3 ± 5.4 | 0.93 |
| CCR | 39.0 ± 14.5 (34.0, 43.9) | 35.6 ± 12.3 (31.2, 40.0) | −10.7 ± 5.2 | ||
| Control | 35.7 ± 11.9 (31.7, 39.8) | 31.4 ± 9.1 (28.3, 34.5) | −11.6 ± 4.5 | ||
| Testosterone, ng/mL | ICR | 4.3 ± 1.8 (3.7, 5.0) | 4.1 ± 1.7 (3.5, 4.7) | −4.4 ± 9.5 | 0.37 |
| CCR | 3.6 ± 1.4 (3.1, 4.1) | 4.2 ± 2.5 (3.3, 5.1) | 4.9 ± 11.0 | ||
| Control | 3.7 ± 2.0 (3.0, 4.4) | 3.6 ± 1.7 (3.0, 4.2) | −5.2 ± 12.6 | ||
| HR-QoL | |||||
| PCS | ICR | 53.6 ± 6.8 (51.9, 55.4) | 53.3 ± 8.1 (51.3, 55.4) | −2.2 ± 3.1 | 0.37 |
| CCR | 52.7 ± 7.0 (51.0, 54.5) | 54.4 ± 6.1 (52.8, 55.9) | 3.6 ± 1.6 | ||
| Control | 51.2 ± 8.1 (49.2, 53.2) | 51.9 ± 7.5 (50.1, 53.7) | 1.6 ± 2.7 | ||
| MCS | ICR | 49.7 ± 11.2 (46.8, 52.6) | 51.7 ± 11.4 (48.8, 54.6) | 3.8 ± 5.1 | 0.82 |
| CCR | 49.3 ± 9.5 (46.9, 51.6) | 50.8 ± 11.3 (47.9, 53.7) | 0.9 ± 3.7 | ||
| Control | 50.3 ± 9.3 (48.0, 52.5) | 53.1 ± 7.0 (51.4, 54.8) | 6.3 ± 2.6 | ||
| Liver fat and function parameters | |||||
| Liver fat, % | ICR | 7.7 ± 4.6 (6.5, 8.8) | 5.2 ± 3.4 (4.3, 6.0) | −37.0 ± 8.6 | 0.11 |
| CCR | 8.4 ± 8.0 (6.4, 10.3) | 6.1 ± 5.6 (4.7, 7.5) | −34.6 ± 5.1 | ||
| Control | 7.1 ± 4.7 (5.9, 8.2) | 5.7 ± 4.4 (4.6, 6.8) | −24.8 ± 6.2 | ||
| GGT, U/L | ICR | 27.0 ± 14.4 (23.5, 30.4) | 19.4 ± 11.1 (16.6, 22.1) | −34.6 ± 5.5 | 0.20 |
| CCR | 25.6 ± 14.4 (22.1, 29.0) | 20.9 ± 10.5 (19.9, 26.4) | −21.9 ± 4.3 | ||
| Control | 28.9 ± 18.1 (24.6, 33.0) | 23.8 ± 15.5 (20.1, 27.5) | −21.4 ± 3.3 | ||
| AST, U/L | ICR | 23.4 ± 5.2 (22.2, 24.7) | 19.6 ± 4.7 (18.5, 20.7) | −16.9 ± 3.0 | 0.15 |
| CCR | 23.3 ± 6.0 (21.9, 24.7) | 21.5 ± 5.0 (20.2, 22.8) | −8.5 ± 3.6 | ||
| Control | 22.7 ± 4.9 (21.5, 23.8) | 21.0 ± 4.6 (19.9, 22.0) | −8.4 ± 3.3 | ||
| ALT, U/L | ICR | 27.4 ± 10.4 (24.9, 29.9) | 20.8 ± 11.1 (18.1, 23.5) | −30.4 ± 4.2 | 0.08 |
| CCR | 26.6 ± 12.3 (23.7, 29.6) | 23.9 ± 10.8 (21.6, 26.9) | −9.8 ± 5.6 | ||
| Control | 26.5 ± 10.9 (24.0, 29.1) | 22.1 ± 8.1 (20.2, 24.1) | −17.0 ± 3.3 | ||
1Data were included from 150 participants; statistical analyses were performed with the use of an intention-to-treat approach. ALT, alanine transaminase; AST, aspartame transaminase; BDNF, brain-derived neurotropic factor; CCR, continuous calorie restriction; CRP, C-reactive protein; GGT, gamma-glutamyl transpeptidase; HR-QoL, health-related quality of life; ICR, intermittent calorie restriction; IFN-γ, interferon gamma; IGF-1, insulin-like growth factor 1; MCS, mental component summary score; PCS, physical component summary score; SHBG, sex hormone-binding globulin.
2Means ± SEMs of individual loge relative changes between baseline and postintervention; calculated as ln(value week 12/value baseline) x 100.
3 P values for time-by-treatment interactions across all 3 study groups (overall) were calculated with linear mixed models adjusted for age and sex. No adjustment was made for multiple comparisons. If the “P value overall” was significant (P < 0.05), P values for time-by-treatment interactions (also from linear mixed models adjusted for age and sex) of post hoc 2-group comparisons, i.e., ICR compared with CCR, ICR compared with Control, and CCR compared with Control, are shown.