The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Dietary Protocol
2.2.1. Inpatient Meals
2.2.2. Study Beverages and Outpatient Meals
2.3. Hepatic Lipid Imaging
Hepatic Lipid Content Quantification
2.4. Insulin Sensitivity
2.5. Twenty-Four Hour Serial Blood Collection
2.6. Statistical Analyses
3. Results
3.1. Hepatic Lipid Content (MRI-PDFF)
3.2. Insulin Sensitivity
3.3. Post-Meal Lactate, Glucose and Insulin Concentrations
3.4. Mediation Analysis
3.4.1. Hepatic Lipid Content
3.4.2. Indices of Insulin Sensitivity
4. Discussion
Study Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | Aspartame | 10% HFCS | 17.5% HFCS | 25% HFCS |
---|---|---|---|---|
Age (years) | 25.4 ± 6.2 1 | 27.7 ± 6.0 | 24.1 ± 5.0 | 26.8 ± 6.6 |
Sex (M/F) | 11/12 | 9/9 | 7/9 | 15/13 |
Weight (kg) | 71.8 ± 10.6 | 70.9 ± 10.3 | 69.9 ± 14.3 | 72.9 ± 14.5 |
BMI (kg/m2) | 24.8 ± 3.3 | 24.9 ± 3.8 | 24.2 ± 3.3 | 24.9 ± 4.0 |
Waist circumference (cm) | 75.2 ± 6.4 | 76.2 ± 9.3 | 73.3 ± 7.7 | 77.0 ± 10.1 |
Body fat (%) | 27.1 ± 9.8 | 26.8 ± 9.8 | 25.9 ± 9.9 | 26.0 ± 9.7 |
Energy requirement (kcal/d) | 2354 ± 322 | 2323 ± 247 | 2326 ± 375 | 2390 ± 350 |
Systolic blood pressure (mmHg) | 112.4 ± 11.5 | 114.9 ± 9.8 | 114.9 ± 8.4 | 117.1 ± 10.0 |
Diastolic blood pressure (mmHg) | 69.2 ± 8.6 | 72.8 ± 8.2 | 71.3 ± 4.7 | 72.7 ± 7.2 |
FST triglyceride (mmol/L) | 1.1 ± 0.6 | 1.4 ± 0.8 | 1.2 ± 0.6 | 1.2 ± 0.6 |
FST total cholesterol (mmol/L) | 3.9 ± 0.7 | 4.2 ± 0.7 | 4.3 ± 0.9 | 4.1 ± 0.9 |
FST HDL-cholesterol (mmol/L) | 1.02 ± 0.19 | 1.14 ± 0.29 | 1.20 ± 0.24 | 1.18 ± 0.35 |
FST glucose (mmol/L) | 5.02 ± 0.37 | 4.96 ± 0.31 | 4.98 ± 0.34 | 5.03 ± 0.35 |
FST insulin (pmol/L) | 88.2 ± 37.5 | 83.3 ± 23.6 | 79.2 ± 20.8 | 90.3 ± 37.5 |
MSRF | 1.2 ± 1.0 | 0.9 ± 0.8 | 0.7 ± 1.0 | 1.1 ± 1.0 |
FST AST (U/L) | 23.1 ± 8.4 | 25.3 ± 8.5 | 22.1 ± 5.2 | 22.1 ± 5.6 |
FST ALT (U/L) | 23.4 ± 20.1 | 22.2 ± 5.9 | 20.6 ± 8.1 | 21.5 ± 8.9 |
Outcome | Aspartame (n = 23) | 10% HFCS (n = 18) | 17.5% HFCS (n = 16) | 25% HFCS (n = 28) | Effect of | p-Value |
---|---|---|---|---|---|---|
Hepatic Lipid Content (MRI-PDFF, %) | Dose 2 | 0.016 | ||||
Baseline | 1.6 ± 0.8 1 | 1.2 ± 0.2 | 1.4 ± 0.3 | 2.3 ± 0.8 | Sex 3 | 0.13 |
Intervention | 1.4 ± 0.7 | 1.3 ± 0.2 | 1.6 ± 0.3 | 2.8 ± 0.9 | MSRF 4 | 0.033 |
Predicted M ISI (arbitrary units) | Dose | 0.0072 | ||||
Baseline | 1.52 ± 0.06 | 1.54 ± 0.06 | 1.60 ± 0.06 | 1.52 ± 0.05 | Sex | 0.44 |
Intervention | 1.55 ± 0.05 | 1.54 ± 0.05 | 1.56 ± 0.06 | 1.45 ± 0.07 | MSRF | 0.33 |
Matsuda ISI (arbitrary units) | Dose | 0.0087 | ||||
Baseline | 3.6 ± 0.3 | 3.7 ± 0.2 | 3.5 ± 0.2 | 3.3 ± 0.2 | Sex | 0.67 |
Intervention | 3.9 ± 0.3 | 3.5 ± 0.3 | 3.2 ± 0.3 | 3.0 ± 0.3 | MSRF | 0.59 |
OGTT Glucose AUC (mmol/L × 3 h) | Dose | 0.0004 | ||||
Baseline | 20.9 ± 0.7 | 19.2 ± 0.8 | 19.1 ± 1.0 | 21.1 ± 0.7 | Sex | 0.75 |
Intervention | 19.9 ± 0.7 | 19.7 ± 0.9 | 20.3 ± 1.2 | 22.5 ± 0.9 | MSRF | 0.99 |
OGTT Insulin AUC (pmol/L × 3 h) | Dose | 0.0004 | ||||
Baseline | 1392 ± 184 | 1033 ± 65 | 1292 ± 162 | 1335 ± 106 | Sex | 0.89 |
Intervention | 1229 ± 151 | 1188 ± 97 | 1376 ± 165 | 1625 ± 154 | MSRF | 0.31 |
HOMA-IR (arbitrary units) | Dose | 0.11 | ||||
Baseline | 3.0 ± 0.2 | 3.0 ± 0.3 | 2.5 ± 0.2 | 3.0 ± 0.2 | Sex | 0.97 |
Intervention | 2.9 ± 0.2 | 2.9 ± 0.3 | 2.8 ± 0.2 | 3.3 ± 0.3 | MSRF | 0.0087 |
Lactate AMP (mmol/L) | Dose | <0.0001 | ||||
Baseline | 0.68 ± 0.06 | 0.62 ± 0.06 | 0.69 ± 0.06 | 0.73 ± 0.06 | Sex | 0.66 |
Intervention | 0.73 ± 0.04 | 1.01 ± 0.07 | 1.50 ± 0.11 | 1.60 ± 0.09 | MSRF | 0.61 |
Glucose AMP (mmol/L) | Dose | <0.0001 | ||||
Baseline | 1.77 ± 0.19 | 1.88 ± 0.18 | 1.90 ± 0.22 | 2.04 ± 0.18 | Sex | 0.17 |
Intervention | 1.87 ± 0.19 | 2.30 ± 0.16 | 2.63 ± 0.18 | 2.96 ± 0.21 | MSRF | 0.69 |
Insulin AMP (pmol/L) | Dose | 0.095 | ||||
Baseline | 544.5. ± 84.0 | 424.3 ± 46.5 | 525.0 ± 62.5 | 506.9 ± 45.1 | Sex | 0.80 |
Intervention | 567.4 ± 75.7 | 450.7 ± 35.4 | 588.9 ± 54.2 | 595.9 ± 48.6 | MSRF | 0.19 |
Body Weight (kg) | Dose | 0.017 | ||||
Baseline | 71.8 ± 2.2 | 70.9 ± 2.4 | 69.9 ± 3.6 | 72.9 ± 2.7 | Sex | 0.079 |
Intervention | 71.7 ± 2.2 | 70.9 ± 2.4 | 70.2 ± 3.7 | 73.7 ± 2.8 | MSRF | 0.15 |
HFCS Dose | Hepatic Lipid Content | Predicted M ISI | Matsuda ISI | Glucose OGTT AUC | Insulin OGTT AUC | Uric Acid 24 h AUC | Post-Meal Lactate AMP | Post-Meal Glucose AMP | apoCIII PP | TG 24 h AUC | TG PP | Body Weight | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HFCS dose | R | 1.000 | 0.256 | −0.285 | −0.238 | 0.372 | 0.371 | 0.608 | 0.632 | 0.406 | 0.385 | 0.319 | 0.521 | 0.303 |
p-value | 0.034 | 0.018 | 0.049 | 0.002 | 0.002 | <0.0001 | <0.0001 | 0.001 | 0.001 | 0.008 | <0.0001 | 0.011 | ||
Hepatic Lipid Content | R | 0.256 | 1.000 | −0.236 | −0.232 | 0.148 | 0.263 | 0.308 | 0.119 | 0.276 | 0.547 | 0.440 | 0.337 | 0.290 |
p-value | 0.034 | 0.051 | 0.056 | 0.226 | 0.029 | 0.010 | 0.330 | 0.022 | <0.0001 | 0.000 | 0.005 | 0.016 | ||
Predicted M ISI | R | −0.285 | −0.236 | 1.000 | 0.672 | −0.638 | −0.582 | −0.191 | −0.192 | −0.057 | −0.382 | −0.192 | −0.215 | −0.152 |
p-value | 0.018 | 0.051 | <0.0001 | <0.0001 | <0.0001 | 0.115 | 0.114 | 0.643 | 0.001 | 0.115 | 0.076 | 0.213 | ||
Matsuda ISI | R | −0.238 | −0.232 | 0.672 | 1.000 | −0.502 | −0.690 | −0.096 | −0.293 | −0.123 | −0.233 | −0.016 | −0.127 | 0.163 |
p-value | 0.049 | 0.056 | <0.0001 | <0.0001 | <0.0001 | 0.435 | 0.015 | 0.314 | 0.054 | 0.898 | 0.299 | 0.182 | ||
Glucose OGTT AUC | R | 0.372 | 0.148 | −0.638 | −0.502 | 1.000 | 0.597 | 0.193 | 0.295 | 0.249 | 0.163 | 0.126 | 0.168 | −0.013 |
p-value | 0.002 | 0.226 | <0.0001 | <0.0001 | <0.0001 | 0.113 | 0.014 | 0.039 | 0.181 | 0.302 | 0.168 | 0.916 | ||
Insulin OGTT AUC | R | 0.371 | 0.263 | −0.582 | −0.690 | 0.597 | 1.000 | 0.157 | 0.305 | 0.161 | 0.181 | 0.055 | 0.196 | −0.055 |
p-value | 0.002 | 0.029 | <0.0001 | <0.0001 | <0.0001 | 0.199 | 0.011 | 0.187 | 0.136 | 0.652 | 0.107 | 0.656 | ||
Uric acid 24 h AUC | R | 0.608 | 0.308 | −0.191 | −0.096 | 0.193 | 0.157 | 1.000 | 0.304 | 0.314 | 0.296 | 0.166 | 0.259 | 0.347 |
p-value | <0.0001 | 0.010 | 0.115 | 0.435 | 0.113 | 0.199 | 0.011 | 0.009 | 0.014 | 0.172 | 0.032 | 0.003 | ||
Post-meal Lactate AMP | R | 0.632 | 0.119 | −0.192 | −0.293 | 0.295 | 0.305 | 0.304 | 1.000 | 0.464 | 0.230 | 0.124 | 0.266 | 0.020 |
p-value | <0.0001 | 0.330 | 0.114 | 0.015 | 0.014 | 0.011 | 0.011 | <0.0001 | 0.058 | 0.311 | 0.027 | 0.868 | ||
Post-meal Glucose AMP | R | 0.406 | 0.276 | −0.057 | −0.123 | 0.249 | 0.161 | 0.314 | 0.464 | 1.000 | 0.191 | 0.261 | 0.301 | 0.059 |
p-value | 0.001 | 0.022 | 0.643 | 0.314 | 0.039 | 0.187 | 0.009 | <0.0001 | 0.116 | 0.030 | 0.012 | 0.628 | ||
apoCIII PP | R | 0.385 | 0.547 | −0.382 | −0.233 | 0.163 | 0.181 | 0.296 | 0.230 | 0.191 | 1.000 | 0.723 | 0.640 | 0.252 |
p-value | 0.001 | <0.0001 | 0.001 | 0.054 | 0.181 | 0.136 | 0.014 | 0.058 | 0.116 | <0.0001 | <0.0001 | 0.037 | ||
TG 24 h AUC | R | 0.319 | 0.440 | −0.192 | −0.016 | 0.126 | 0.055 | 0.166 | 0.124 | 0.261 | 0.723 | 1.000 | 0.772 | 0.285 |
p-value | 0.008 | 0.000 | 0.115 | 0.898 | 0.302 | 0.652 | 0.172 | 0.311 | 0.030 | <0.0001 | <0.0001 | 0.018 | ||
TG PP | R | 0.521 | 0.337 | −0.215 | −0.127 | 0.168 | 0.196 | 0.259 | 0.266 | 0.301 | 0.640 | 0.772 | 1.000 | 0.184 |
p-value | <0.0001 | 0.005 | 0.076 | 0.299 | 0.168 | 0.107 | 0.032 | 0.027 | 0.012 | <0.0001 | <0.0001 | 0.130 | ||
Body weight | R | 0.303 | 0.290 | −0.152 | 0.163 | −0.013 | −0.055 | 0.347 | 0.020 | 0.059 | 0.252 | 0.285 | 0.184 | 1.000 |
p-value | 0.011 | 0.016 | 0.213 | 0.182 | 0.916 | 0.656 | 0.003 | 0.868 | 0.628 | 0.037 | 0.018 | 0.130 |
Outcome (Absolute Change) | R for Effect of HFCS Dose w/o Mediator | Mediator (Absolute Change) | R for Effect of HFCS Dose w/Mediator | Attenuation (%) |
---|---|---|---|---|
OGTT Insulin | 0.371 | Hepatic Lipid Content | 0.314 | 15 |
Hepatic Lipid Content | 0.256 | OGTT Insulin | 0.166 | 35 |
Postprandial apoCIII | 0.385 | Hepatic Lipid Content | 0.25 | 35 |
Hepatic Lipid Content | 0.259 | Postprandial apoCIII | 0.048 | 81 |
Uric acid 24h AUC | 0.608 | Hepatic Lipid Content | 0.536 | 12 |
Hepatic Lipid Content | 0.256 | Uric acid 24h AUC | 0.084 | 67 |
Post-meal glucose AMP | 0.406 | Hepatic Lipid Content | 0.338 | 17 |
Hepatic Lipid Content | 0.256 | Post-meal glucose AMP | 0.153 | 40 |
Body weight | 0.303 | Hepatic Lipid Content | 0.23 | 24 |
Hepatic Lipid Content | 0.256 | Body weight | 0.171 | 33 |
Predicted M ISI | −0.285 | Postprandial apoCIII | −0.149 | 48 |
Postprandial apoCIII | 0.385 | Predicted M ISI | 0.284 | 26 |
Matsuda | −0.238 | Post-meal lactate AMP | −0.068 | 71 |
Post-meal lactate AMP | 0.632 | Matsuda | 0.576 | 9 |
OGTT Insulin | 0.371 | Post-meal lactate AMP | 0.23 | 38 |
Post-meal lactate AMP | 0.632 | OGTT Insulin | 0.56 | 12 |
OGTT Glucose | 0.372 | Post-meal lactate AMP | 0.238 | 36 |
Post-meal lactate AMP | 0.632 | OGTT Insulin | 0.556 | 11 |
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Sigala, D.M.; Hieronimus, B.; Medici, V.; Lee, V.; Nunez, M.V.; Bremer, A.A.; Cox, C.L.; Price, C.A.; Benyam, Y.; Abdelhafez, Y.; et al. The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults. Nutrients 2022, 14, 1648. https://doi.org/10.3390/nu14081648
Sigala DM, Hieronimus B, Medici V, Lee V, Nunez MV, Bremer AA, Cox CL, Price CA, Benyam Y, Abdelhafez Y, et al. The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults. Nutrients. 2022; 14(8):1648. https://doi.org/10.3390/nu14081648
Chicago/Turabian StyleSigala, Desiree M., Bettina Hieronimus, Valentina Medici, Vivien Lee, Marinelle V. Nunez, Andrew A. Bremer, Chad L. Cox, Candice A. Price, Yanet Benyam, Yasser Abdelhafez, and et al. 2022. "The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults" Nutrients 14, no. 8: 1648. https://doi.org/10.3390/nu14081648