Table 5.
NMR-measured small molecule metabolite levels at baseline, and changes from baseline at 12, and 24 months a.
| Ad libitum group (n = 75) | Calorie restriction group (n = 143) | Between-group p-value b | |
|---|---|---|---|
| Total BCAAs (µM) | |||
| Baseline | 310.1 (7.3) | 313.2 (4.6) | 0.42 |
| Change at month 12 | 3.47 (4.83) | −13.85 (3.67)*** | 0.003 |
| Change at month 24 | 9.55 (4.86) | −9.20 (3.79)* | 0.002 |
| Valine (µM) | |||
| Baseline | 182.5 (3.8) | 184.0 (2.6) | 0.80 |
| Change at month 12 | −0.45 (2.47) | −8.44 (1.88)*** | 0.008 |
| Change at month 24 | 3.52 (2.50) | −6.99 (1.94)*** | 0.0006 |
| Leucine (µM) | |||
| Baseline | 92.3 (3.1) | 92.5 (1.7) | 0.67 |
| Change at month 12 | 3.45 (2.31) | −3.42 (1.75) | 0.014 |
| Change at month 24 | 4.04 (2.44) | −2.55 (1.88) | 0.027 |
| Isoleucine (µM) | |||
| Baseline | 36.0 (1.5) | 36.7 (0.9) | 0.38 |
| Change at month 12 | 0.75 (1.20) | −0.78 (0.90) | 0.59 |
| Change at month 24 | 1.73 (1.11) | 0.78 (0.85) | 0.96 |
| Alanine (µM) | |||
| Baseline | 274.7 (8.9) | 275.2 (6.7) | 0.92 |
| Change at month 12 | −0.32 (7.65) | −31.48 (5.76)*** | 0.0008 |
| Change at month 24 | −0.58 (8.18) | −23.52 (6.32)*** | 0.023 |
| Fasting Glucose (mg/dL) | |||
| Baseline | 90.4(0.9) | 90.5 (0.7) | 0.92 |
| Change at month 12 | −0.64 (0.61) | −2.52 (0.46)*** | 0.011 |
| Change at month 24 | −0.44 (0.68) | −1.81 (0.53)** | 0.10 |
| Citrate (µM) | |||
| Baseline | 91.9 (2.3) | 93.1 (2.0) | 0.96 |
| Change at month 12 | −6.07 (2.13)** | −2.26 (1.60) | 0.27 |
| Change at month 24 | −2.73 (2.44) | −1.28 (1.87) | 1.0 |
| Total ketone bodies (µM) | |||
| Baseline | 196.9 (10.9) | 218.8 (11.5) | 0.87 |
| Change at month 12 | 9.04 (19.05) | 47.57 (14.09)** | 0.10 |
| Change at month 24 | −4.62 (16.71) | 34.47 (12.77)* | 0.055 |
| β-hydroxybutyrate (µM) | |||
| Baseline | 117.0 (7.1) | 128.3 (7.6) | 0.91 |
| Change at month 12 | −0.76 (11.70) | 23.23 (8.66)* | 0.09 |
| Change at month 24 | −7.90 (10.27) | 17.95 (7.86)* | 0.039 |
| Acetoacetate (µM) | |||
| Baseline | 52.2 (3.5) | 56.5 (2.8) | 0.40 |
| Change at month 12 | 10.20 (5.88) | 20.18 (4.37)*** | 0.33 |
| Change at month 24 | 6.51 (5.06) | 17.37 (3.89)*** | 0.16 |
| Acetone (µM) | |||
| Baseline | 27.7 (2.1) | 34.0 (2.6) | 0.44 |
| Change at month 12 | −2.77 (3.07) | 4.86 (2.27) | 0.043 |
| Change at month 24 | −5.39 (2.24)* | −0.33 (1.72) | 0.06 |
Abbreviations: BCAA, branched chain amino acids.
a
Baseline values are the observed mean (SE); change scores are the least-squares adjusted means (SE) from the ITT repeated measures analysis.
b
Between-group p-value tests for a significant between-group difference in the change score at the time point. All comparisons are controlled for baseline values. All p-values reflect Bonferroni corrections, truncated at 1.0, as appropriate (see text).
*, **, and *** indicated within group differences at the P < 0.05, 0.01, and 0.001 values, respectively. Between group significant findings p < 0.0017 are bolded and italicized for emphasis.