Dietary triggers of nonalcoholic. fat, carbohydrate or excess energy: a crossover trial.

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1 Dietary triggers of nonalcoholic fatty liver disease fat, carbohydrate or excess energy: a crossover trial. Kiri Sharp, Michael Schultz, Kirsten Coppell. Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin.

2 Outline Background Aims Methods Results Conclusions

3 Non-alcoholic fatty liver disease (NAFLD) Definition fat stored in the liver (>5% of volume). Spectrum of disorders. Management no pharmacological treatment; lifestyle change to reduce weight, treat associated conditions e.g. diabetes

4 Prevalence - Obesity

5 Prevalence - NAFLD

6 Dietary triggers?

7 Aim To compare the effect of high fat and high carbohydrate hypercaloric diets with high fat and high carbohydrate isocaloric diets on liver fat as measured by H-MRS in healthy normal weight women. Hypercaloric diet (3-5% weight gain, +500cal / day) Isocaloric diet (weight maintaining) High carbohydrate High fat High carbohydrate High fat 55-60% Refined carbohydrates 35-40% Saturated fats 55-60% Refined carbohydrates 35-40% Saturated fats

8 Methods Study Design Cross-over trial Eligibility Inclusion: Pre-menopausal women aged years old Body mass index (BMI) kg/m 2 Alcohol intake 2 standard drinks per day or 14 per week Comfortable with a small temporary weight gain (2-3kg) Comfortable with enclosed spaces (H-MRS scan) Healthy liver (no pre-existing liver conditions or liver abnormality on liver ultrasound) NOT: prediabetes, diabetes, pregnant, lactating, medications drugs or food allergies affecting the liver

9 Pre-experiment Pre-study screening (questionnaire + ultrasound) Pre-study assessment and measures Baseline 3-day Weighed Food Record (3d-WFR) 2 week Standard diet 3d-WFR midway Randomisation to dietary intervention

10 Dietary intervention Randomisation to: Hypercaloric OR isocaloric diet High carbohydrate diet 4 weeks High fat diet Washout Standard diet 8 weeks Washout Standard diet High fat diet 4 weeks High carbohydrate diet Follow up to return to baseline weight

11 Measures Duration What Measures Experimental diet 1 Washout Standard diet Experimental diet 2 4 weeks 8 weeks 4 weeks Pre & post diet: Clinical measures MRS scan Bloods Faecal sample During diet: 3d-WFR x1 Pre & post diet: Clinical measures MRS scan Bloods Faecal sample During diet: 3d-WFR x2 Weekly: Appointment Measures Food diary During diet: 3d-WFR x2 Weekly: Appointment Measures Food diary

12 Baseline characteristics Median Range Age (years) Weight (kg) BMI (kg/m²) Liver fat* (%) ALT (IU/L) GGT (IU/L) * As measured by H-MRS

13 Pre-study habitual diets Protein (%TE) Fat (%TE) Saturated fat (%TE) Carbohydrate (%TE) Fibre (g/day) AMDR < >25 Range % meeting AMDR

14 Energy content (kj) Dietary changes Participant Hypercaloric Baseline Std HHC Washout HHF Diet period Protein Fat Carbohydrate Alcohol

15 Energy content (kj) Results - Diet Participant Isocaloric Baseline Std IHC Washout IHF Diet period Protein Fat Carbohydrate Alcohol

16 Body weight changes Hypercaloric Diet Isocaloric Diet Median % change IQR P value High CHO High Fat High CHO High Fat Median % change IQR P value

17 ALT Hypercaloric Diet Isocaloric Diet Median change (%) IQR P value 0.04 High CHO High Fat High CHO High Fat Median change (%) IQR P value

18 ALT Energy (kj)

19 ALT - Hypercaloric diet

20 ALT - Isocaloric diet

21 GGT Hypercaloric Isocaloric Median % change IQR P value 0.43 High CHO High Fat High CHO High Fat Median % change IQR P value

22 AST Hypercaloric Isocaloric Median % change IQR P value High CHO High Fat High CHO High Fat Median % change IQR P value

23 Liver fat spectroscopy

24 Liver fat spectroscopy Hypercaloric Isocaloric Median % change IQR P value 0.07 High CHO High Fat High CHO High Fat Median % change IQR P value

25 Spectroscopy Energy (kj)

26 Spectroscopy Hypercaloric diet

27 Spectroscopy Isocaloric diet

28 Strengths / Limitations Strengths Crossover design Liver fat content measures Homogenous study population Good retention Dietary manipulation Limitations Variable dietary intake Weight fluctuation Relatively small sample size

29 Conclusions Excess energy contributing to bodyweight gain appears to increase liver enzymes and liver fat content The macronutrient source of excess energy appears to be less important than the effect of energy Changing the composition of the diet in an isocaloric context appears to have little effect on the liver

30 Acknowledgements Study participants Biostatistics - Andrew Gray Pacific Radiology Philippa Nelson Southern Community Labs Roger Barton Department of Medicine Funders Department of Medicine PhD scholarship

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