Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females
Abstract
:1. Introduction
2. Results
2.1. Suppression of Ketosis Increases BMI and Fat Mass
2.2. Adherence
2.3. Suppression of Ketosis Is Associated with Increases in Insulin, IGF-1, Glucose and T3
2.4. Oral Glucose Tolerance Tests
2.4.1. Between Phases (P1 vs. P2 vs. P3) OGTT Glucose Response
2.4.2. Within-Phase Glucose Response during a 5 h OGTT
2.4.3. Following Plateau, Blood Glucose Concentration Increased during Ketosis Suppression
2.4.4. Between Phases (P1 vs. P2 vs. P3) OGTT Insulin Response
2.4.5. Within-Phase Insulin Response during a 5 h OGTT
2.4.6. Between Phases (P1 vs. P2 vs. P3) OGTT BHB Response
2.4.7. Within-Phase BHB Response during a 5 h OGTT
2.5. Suppression of Ketosis Is Associated with Increases in Inflammatory Liver Markers
2.6. Ketosis Maintains Lower Levels of EGF, VEGF and MCP-1
3. Discussion
3.1. Macroscopic Changes/Anthropometrics
3.2. Insulin, IGF-1, and Glucose
3.3. Thyroid—Free T3
3.4. OGTT
3.5. Liver Markers
3.5.1. GGT
3.5.2. PAI-1
3.6. Cytokines
3.6.1. VEGF and EGF
3.6.2. MCP-1
4. Strengths and Limitations
5. Translational Importance
6. Materials and Methods
6.1. Ethical Approval
6.2. Participants
6.3. Study Design
6.4. Anthropometric Measurements
6.5. Metabolic Measurements
6.6. Blood Collection
6.7. Blood Profiling Analysis
6.8. Oral Glucose Tolerance Test
6.9. Statistical Analysis
6.10. Sample Size Calculation
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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P1 | P2 | P3 | ANOVA p Value | P1 vs. P2 | P2 vs. P3 | P1 vs. P3 | |
---|---|---|---|---|---|---|---|
Age (years) | 32.30 (±8.97) | ||||||
Height (cm) | 160.95 (±7.28) | ||||||
Weight (kg) | 52.99 (±4.24) | 55.65 (±4.10) | 53.93 (±4.04) | <0.0001 | 0.0002 | <0.0001 | 0.7888 |
BMI | 20.52 (±1.39) | 21.54 (±1.30) | 20.82 (±1.46) | <0.0001 | <0.0001 | 0.0025 | 0.0197 |
Waist/Hip | 0.75 (±0.03) | 0.77 (±0.03) | 0.74 (±0.03) | <0.0001 | 0.0015 | <0.0001 | 0.5361 |
Waist/Height | 0.43 (±0.03) | 0.45 (±0.03) | 0.43 (±0.03) | <0.0001 | 0.0009 | <0.0001 | >0.9999 |
Fat mass (kg) | 14.21 (±2.55) | 15.88 (±2.23) | 14.78 (±2.20) | <0.0001 | 0.0008 | 0.0057 | 0.1016 |
TBW (L) | 28.15 (±2.87) | 29.15 (±2.96) | 28.42 (±3.15) | 0.0005 | 0.0016 | 0.0262 | 0.3473 |
RQ | 0.66 (±0.05) | 0.72 (±0.06) | 0.65 (±0.06) | 0.0096 | 0.0427 | 0.0005 | 0.8606 |
Systole (mmHg) | 103.25 (±6.24) | 103.70 (±10.17) | 100.00 (±9.54) | 0.1455 | 0.9753 | 0.1746 | 0.2274 |
Diastole (mmHg) | 70.75 (±4.91) | 69.45 (±7.14) | 68.15 (±7.36) | 0.3227 | 0.8044 | 0.7147 | 0.1715 |
Mean Capillary BHB Concentration (mmol/L) | |||||
---|---|---|---|---|---|
Participant | No of Tests Taken | % of Tests Fulfilled Out of 252 | P1 | P2 | P3 |
1011 | 251 | 99.6 | 2.7 | 0.1 | 2.3 |
1021 | 252 | 100 | 2.8 | 0.1 | 2.2 |
1031 | 252 | 100 | 2.6 | 0.1 | 1.8 |
1041 | 252 | 100 | 1.5 | 0.2 | 1.6 |
1051 | 251 | 99.6 | 1.7 | 0 | 1.6 |
1061 | 245 | 97.22 | 0.7 | 0.1 | 0.8 |
1071 | 248 | 98.41 | 1.7 | 0.2 | 2.4 |
1081 | 250 | 99.21 | 2 | 0.1 | 1.2 |
1091 | 251 | 99.6 | 1.8 | 0.1 | 2.5 |
1101 | 252 | 100 | 1.5 | 0.1 | 2.4 |
Mean | 250.4 | 99.37 | 1.9 | 0.1 | 1.9 |
±SD | 2.15 | 0.85 | 0.7 | 0.1 | 0.6 |
Capillary BHB (mmol/L) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
≥ 0.5 | > 0.3 | ≤ 0.3 | < 0.1 | |||||||||
Participant | P1 | P2 | P3 | P1 | P2 | P3 | P1 | P2 | P3 | P1 | P2 | P3 |
1011 | 100.00 | 2.38 | 95.18 | 100.00 | 4.76 | 98.80 | 0.00 | 95.24 | 1.20 | 0.00 | 28.57 | 0.00 |
1021 | 100.00 | 2.38 | 88.10 | 100.00 | 2.38 | 94.05 | 0.00 | 97.62 | 5.95 | 0.00 | 60.71 | 0.00 |
1031 | 100.00 | 2.38 | 92.86 | 100.00 | 2.38 | 95.24 | 0.00 | 97.62 | 4.76 | 0.00 | 59.52 | 0.00 |
1041 | 98.81 | 0.00 | 100.00 | 100.00 | 8.33 | 100.00 | 0.00 | 91.67 | 0.00 | 0.00 | 13.10 | 0.00 |
1051 | 100.00 | 0.00 | 97.62 | 100.00 | 1.19 | 98.81 | 0.00 | 98.81 | 0.00 | 0.00 | 94.05 | 0.00 |
1061 | 94.05 | 0.00 | 82.93 | 97.62 | 0.00 | 90.24 | 2.38 | 100.00 | 9.76 | 0.00 | 37.97 | 0.00 |
1071 | 96.30 | 4.82 | 97.62 | 97.53 | 4.82 | 97.62 | 2.47 | 95.18 | 2.38 | 0.00 | 1.20 | 0.00 |
1081 | 96.39 | 0.00 | 90.48 | 98.80 | 1.20 | 95.24 | 1.20 | 98.80 | 4.76 | 0.00 | 33.73 | 0.00 |
1091 | 98.81 | 0.00 | 98.80 | 100.00 | 1.19 | 100.00 | 0.00 | 98.81 | 0.00 | 0.00 | 21.43 | 0.00 |
1101 | 96.43 | 0.00 | 98.81 | 100.00 | 0.00 | 100.00 | 0.00 | 100.00 | 0.00 | 0.00 | 54.76 | 0.00 |
P1 | P2 | P3 | ANOVA p Value | P1 vs. P2 | P2 vs. P3 | P1 vs. P3 | |
---|---|---|---|---|---|---|---|
Insulin (pmol/L) | 33.60 (± 8.63) | 59.80 (± 14.69) | 31.60 (± 9.38) | <0.0001 | 0.0002 | <0.0001 | 0.5361 |
IGF-1 (µg/L) | 149.30 (± 32.96) | 273.40 (± 85.66) | 136.90 (± 39.60) | 0.0015 | 0.0045 | 0.0055 | 0.4124 |
Glucose (mmol/L) | 4.36 (± 0.53) | 5.12 (± 0.59) | 4.41 (± 0.30) | 0.0015 | 0.0088 | 0.0177 | 0.9469 |
BHB (mmol/L) | 2.43 (± 1.28) | 0.18 (± 0.13) | 2.31 (± 0.71) | 0.0001 | 0.0012 | <0.0001 | 0.9854 |
IGFBP-3 (mg/mL) | 3.69 (± 0.56) | 4.41 (± 1.27) | 3.67 (± 0.70) | 0.2357 | 0.3621 | 0.4272 | 0.9361 |
IGF-1/IGFBP-3† | 0.14 (± 0.03) | 0.25 (± 0.08) | 0.15 (± 0.04) | 0.0584 | 0.0870 | 0.1554 | 0.9049 |
TSH (mU/L) | 1.40 (± 0.74) | 1.56 (± 0.75) | 1.25 (± 0.81) | 0.3065 | 0.2334 | 0.4498 | 0.7742 |
Free T3 (pmol/L) | 3.81 (± 0.28) | 5.51 (± 0.72) | 4.05 (± 0.54) | <0.0001 | <0.0001 | 0.0015 | 0.3040 |
Reverse T3 (nmol/L) | 0.29 (± 0.09) | 0.26 (± 0.10) | 0.25 (± 0.09) | 0.6039 | 0.7030 | 0.9674 | 0.6323 |
T4 (pmol/L) | 13.51 (± 1.61) | 13.24 (± 1.49) | 12.65 (± 0.66) | 0.2125 | 0.8795 | 0.3059 | 0.2099 |
P1 | P2 | P3 | ANOVA p Value | P1 vs. P2 | P2 vs. P3 | P1 vs. P3 | |
---|---|---|---|---|---|---|---|
Triglycerides (mg/dL) | 66.80 (± 28.00) | 66.10 (± 21.09) | 79.30 (± 45.88) | 0.5018 | 0.9972 | 0.6629 | 0.6270 |
Total cholesterol (mg/dL) | 231.50 (± 62.42) | 188.50 (± 30.28) | 210.20 (± 43.44) | 0.0335 | 0.0802 | 0.2132 | 0.1061 |
HDL cholesterol (mg/dL) | 70.10 (± 10.37) | 72.70 (± 13.59) | 69.80 (± 11.84) | 0.6231 | 0.7460 | 0.6762 | 0.9943 |
LDL cholesterol (mg/dL) † | 4.46 (± 2.03) | 3.13 (± 0.91) | 3.96 (± 1.34) | 0.0888 | 0.1798 | 0.3280 | 0.1498 |
Triglycerides/HDL (mmol/L) | 1.01 (± 0.55) | 0.95(± 0.38) | 1.25 (± 0.90) | 0.3804 | 0.9478 | 0.5358 | 0.5515 |
CRP (Ultra-Sensitive) (mg/L) § | 1.00 (± 1.19) | 1.16 (± 1.56) | 1.35 (± 2.23) | 0.7103 | 0.9938 | 0.7477 | 0.7728 |
Gamma-GT (U/L) | 9.60 (± 3.13) | 12.40 (± 2.55) | 9.70 (± 2.50) | 0.0029 | 0.0087 | 0.0286 | 0.9885 |
Cortisol (µg/dL) | 12.62 (± 5.27) | 11.27 (± 5.85) | 13.19 (± 5.22) | 0.3574 | 0.6886 | 0.4087 | 0.8258 |
PAI-1 (ng/mL) | 13.34 (± 6.85) | 16.69 (± 6.26) | 17.05 (± 5.58) | 0.0431 | 0.0428 | 0.9483 | 0.1373 |
P1 | P2 | P3 | ANOVA p Value | P1 vs. P2 | P2 vs. P3 | P1 vs. P3 | |
---|---|---|---|---|---|---|---|
EGF (pg/mL) | 33.02 (± 30.96) | 50.13 (± 38.19) | 37.82 (± 26.81) | 0.0139 | 0.0450 | 0.3473 | 0.0478 |
VEGF (pg/mL) | 93.93 (± 54.30) | 147.33 (± 100.03) | 134.80 (± 98.79) | 0.0147 | 0.0314 | 0.2102 | 0.0801 |
Interferon-γ (pg/mL) | 1.14 (± 2.64) | 0.72 (± 1.05) | 0.57 (± 0.90) | 0.3755 | 0.7019 | 0.2452 | 0.6019 |
(MCP-1) (pg/mL) | 103.98 (± 39.30) | 192.53 (± 84.73) | 128.52 (± 51.80) | 0.0026 | 0.0137 | 0.0175 | 0.2622 |
TNF-α (pg/mL) | 2.23 (± 1.75) | 2.66 (± 1.26) | 2.09 (± 0.97) | 0.1387 | 0.3887 | 0.0785 | 0.8430 |
IL-1a (pg/mL) | 0.30 (± 0.40) | 0.26 (± 0.25) | 0.26 (± 0.25) | 0.3230 | 0.6266 | 0.5406 | 0.5104 |
IL-1b (pg/mL) | 2.23 (± 3.42) | 1.85 (± 2.02) | 1.71 (± 2.04) | 0.3090 | 0.7045 | 0.0381 | 0.4989 |
IL-2 (pg/mL) | 1.92 (± 1.48) | 1.71 (± 1.16) | 1.94 (± 1.37) | 0.2932 | 0.4409 | 0.7569 | 0.3809 |
IL-4 (pg/mL) | 2.14 (± 0.80) | 2.06 (± 0.99) | 2.25 (± 1.17) | 0.4635 | 0.5358 | 0.5138 | 0.9090 |
IL-6 (pg/mL) | 0.95 (± 0.80) | 1.22 (± 1.11) | 0.84 (± 0.56) | 0.5034 | 0.9238 | 0.5677 | 0.5771 |
IL-8 (pg/mL) | 8.91 (± 9.56) | 8.60 (± 5.93) | 8.08 (± 6.30) | 0.6738 | 0.9966 | 0.5725 | 0.8009 |
IL-10 (pg/mL) | 0.61 (± 0.37) | 0.68 (± 0.46) | 0.53 (± 0.25) | 0.4323 | 0.9084 | 0.4420 | 0.5573 |
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Cooper, I.D.; Kyriakidou, Y.; Edwards, K.; Petagine, L.; Seyfried, T.N.; Duraj, T.; Soto-Mota, A.; Scarborough, A.; Jacome, S.L.; Brookler, K.; et al. Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females. Int. J. Mol. Sci. 2023, 24, 15621. https://doi.org/10.3390/ijms242115621
Cooper ID, Kyriakidou Y, Edwards K, Petagine L, Seyfried TN, Duraj T, Soto-Mota A, Scarborough A, Jacome SL, Brookler K, et al. Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females. International Journal of Molecular Sciences. 2023; 24(21):15621. https://doi.org/10.3390/ijms242115621
Chicago/Turabian StyleCooper, Isabella D., Yvoni Kyriakidou, Kurtis Edwards, Lucy Petagine, Thomas N. Seyfried, Tomas Duraj, Adrian Soto-Mota, Andrew Scarborough, Sandra L. Jacome, Kenneth Brookler, and et al. 2023. "Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females" International Journal of Molecular Sciences 24, no. 21: 15621. https://doi.org/10.3390/ijms242115621