Calories, Carbs, or Quality? What Matters Most for Body Weight - PowerPoint PPT Presentation

Calories, Carbs, or Quality? What Matters Most for Body Weight Kevin D. Hall, Ph.D. National Institute of Diabetes & Digestive & Kidney Diseases National Institutes of Health October 17, 2019

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Erroneous Weight Loss Projections 3500 kcal per lb rule 3 3

Calories In & Out are NOT Independent Calories Out Calories In 4 4

Feedback Regulation of Body Weight Calories Out Calories In Leptin, etc. 5 5

Mathematical Modeling of Metabolism      ∆  P PI ˆ = + χ D D       dG   P P ρ = − + + − − CI DNL GNG GNG G P 3 CarbOx P PI ( )   d   ×     CI G G   G Keys b C P F dt ˆ = init DNL = D D   ( ) d G G + G G K d G dF 2   ( ) ρ = + ε − − − ε −   init DNL init 3 M FI M DNL KU 1 KTG FatOx 3 F [ ] ˆ F FFA TG d excr k = + dt   D D L L   F F diet PA F   dP Keys ρ = − − PI GNG ProtOx P P ( ) ( ) dt  + − × − +  S K 1 A B exp k CI CI B dL L   L L L L b L τ = − diet L { } = + + + FFM BM ECF ECP LCM ( ) L diet dt S S + − L K MAX 0, F F 1 L L Keys = + + + + + + BM ECF ECP ICW P G ICS ˆ       ρ δ + υ = + + + + + + + + BM ECF ECP ICW P (1 h ) G (1 h ) ICS M M = + ρ = ψ − GNG FI C G D G L 1 P G       F ρ F C PA δ + υ M M       dECF 1 ( ) ( ) ( ) F TG TG init init = ∆ − ξ − − ξ − + ∆ Na ECF ECF 1 CI CI ECF [ ] diet Na init CI b dt Na         ∆ ∆ P CI PI ( ) ˆ = − Γ + Γ + χ     GNG GNG     ∆ d ECF   ( ) P P C P P CI PI τ = ξ − − ∆   BW BW ECF         Keys b b BW BW init dt    ˆ      D D PI G = + + TEE TEF PAE RMR = ρ − − KTG D  A  F F  exp k exp k      ( ) ( ) ˆ   K F K P G = + γ + γ − − ∆ + − − + γ + PI G RMR E M FFM M G 1 h ECF ECF F  K D D            c B B FFM B g init F K F F b init ( ) ρ <   + − ε + − ε + + − ε 0, if KTG KTG (1 ) DNL (1 )( GNG GNG ) 1 KTG K thresh d g F P K   ( ) = ρ ρ − KU KU KTG KTG   dP dF dG excr K max K thresh , else + η + η + ε + η + η + η + η + η N ( ) D D D   ( ) − KTG KTG N excr P P P P F F F G G G dt dt dt   max thresh { } ( ) ( ) ( ) ˆ   + + ∆ + λ ∆ − < EI EI T , if EI EI w ( D D ) w MAX 0, 1 S CI CI G G G dT   τ =  1 b b G G G C C b min = f  ( ) T λ ∆ − C dt EI EI T , else   Z   2 b ( ) ˆ w D D dM F F F = ∑ = f γ ˆ γ i F Z FFM i dFFM  = + − + × i CarbOx GNG GNG G P 3 f TEE { } ( ) ( ) ( ) ( ) ( ) ˆ f p C + + − δ + υ δ + υ ( ) w MAX 0, 1 P D D S exp k γ = γ  + − σ  ˆ 1 1 T   P sig P P A A b b  = FFM FFM = + × f FatOx KetOx f TEE P F Z ( ) = δ + σ + υ PAE 1 T BW BW  = × ProtOx f TEE dP P 6 τ sig = ∆ − S PI PI P = α + α + α TEF FI PI CI PI P b sig F P C dt  

Mathematical Modeling of Metabolism Baseline Demographics & Anthropometrics Body Weight Physical Activity Mathematical Model of Human Metabolism Body Fat Food Intake KD Hall et al. The Lancet 378:826-37 (2011) 7 7

Corrected Weight Loss Projections Dynamic Model 3500 kcal per lb rule KD Hall et al. The Lancet 378:826-37 (2011) 8 8

Feedback Control of Appetite? Calories Out Calories In Leptin, etc. 9 9

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Math Models to Calculate Calorie Intake? Baseline Demographics & Anthropometrics Calorie Expenditure Mathematical Model Calorie Intake Body Weight of Human Metabolism Body Fat A. Sangvhi et al. Am J Clin Nutr. 102:353-358 (2015) 11 11 11

Validation: Caloric Restriction for 2 Years 74 DLW+DXA 72 measurements Body Weight (kg) N=140 70 68 66 64 62 0 13 26 39 52 65 78 91 104 Time (weeks) Mean ± 95% CI A. Sangvhi et al. Am J Clin Nutr. 102:353-358 (2015) 12

Mean CALERIE 2 Energy Intake Changes 0-26 weeks 26-52 weeks 52-78 weeks 78-104 weeks 0 Energy Intake Change (kcal/d) -100 -200 N=115 N=117 -300 N=125 -400 DLW/DXA Model vs DLW/DXA -500 within 40 kcal/d Model N=135 -600 Mean ± 95% CI A. Sangvhi et al. Am J Clin Nutr. 102:353-358 (2015) 13 13 13

How to Increase Calorie Expenditure? ?? Calories Out Calories In Leptin, etc. 14 14

How to Increase Calorie Expenditure? ?? Calories Out Calories In ~90 g/d glucose Leptin, etc. 15 15

Weight Changes during SGLT2 Inhibition 0 Δ Body Weight (kg) -1 N=153 adults with Obesity & Type 2 diabetes treated with canagliflozin -2 -3 -4 -5 0 6 12 18 24 30 36 42 48 54 Time (weeks) D. Polidori, A. Sanghvi, R. Seeley, K.D. Hall. Obesity, 24:2289 (2016) 16 16

Intake Changes during SGLT2 Inhibition 500 Δ Energy Intake (kcal/d) 400 300 200 ~95 kcal/d 100 per kg BW loss 0 -100 0 6 12 18 24 30 36 42 48 54 Time (weeks) D. Polidori, A. Sanghvi, R. Seeley, K.D. Hall. Obesity, 24:2289 (2016) 17 17

Feedback Regulation of Body Weight ~95 kcal/d ~25 kcal/d per kg per kg Calories Out Calories In Leptin, etc. D. Polidori, A. Sanghvi, R. Seeley, K.D. Hall. Obesity, 24:2289 (2016) 18 18

Lifestyle Induced Weight & Fat Loss Body Fat Body Weight Mean ± 95% CI J Guo et al. Am J Clin Nutr 107:558–65 (2018). 19 19 19

Corresponding Energy Balance Dynamics Expenditure Exponential decay of diet adherence? Intake Mean ± 95% CI J Guo et al. Am J Clin Nutr 107:558–65 (2018). 20 20 20

Interpreting Lifestyle Weight Loss Appetite increases ~95 kcal/d per kg weight lost Perceived Effort Intake Mean ± 95% CI J Guo et al. Am J Clin Nutr 107:558–65 (2018). 21 21

Large & Persistent Perceived Effort Perceived Effort Intake Mean ± 95% CI J Guo et al. Am J Clin Nutr 107:558–65 (2018). 22 22

The Promise of Low Carb Diets 23

Carbohydrate-Insulin Model of Obesity “the metabolic effects of carbohydrate [to increase insulin] cause the adipocyte to take in, store, and trap too many calories. Subsequently, energy expenditure declines and hunger increases” DS Ludwig & MI Friedman JAMA 311:2167-68 (2014) .

Fat Loss Requires Carbohydrate Reduction? “Any diet that succeeds does so because the dieter restricts fattening carbohydrates…Those who lose fat on a diet do so because of what they are not eating – the fattening carbohydrates” Gary Taubes, W hy we get fat and what to do about it (2011). 25

Isocaloric 30% Calorie Restricted Diets Mean ± 95% CI KD Hall et al. Cell Metabolism 22:427-436 (2015) . 26

Only RC Diet Decreased Insulin Secretion 20 N=19 men & women with obesity 24 hr C-peptide (% change) 10 0 RC -10 RF NS -20 Mean ± 95% CI * p<0.01 -30 vs baseline * -40 p = 0.001 KD Hall et al. Cell Metabolism 22:427-436 (2015) . 27

Only RC Diet Increased Fat Oxidation Burning N=19 men & women with obesity Carbs ** ** ** Burning Fat Mean ± 95% CI ** p<0.001 KD Hall et al. Cell Metabolism 22:427-436 (2015) . 28

More Cumulative Body Fat Loss with RF ** N=19 men & women with obesity 0 Cumulative Fat Change (g) ** -100 ** -200 RC data -300 RC model -400 RF data -500 RF model -600 0 1 2 3 4 5 6 Mean ± 95% CI Time (days) ** p<0.001 KD Hall et al. Cell Metabolism 22:427-436 (2015) . 29

Only RC Decreases Energy Expenditure Sleep 24 hour 40 20 Δ Energy Expenditure 0 -20 NS (kcal/d) RC data -40 -60 RF data -80 NS Mean ± SE * p<0.005 -100 vs baseline * -120 * -140 Mean ± SE p = 0.0024 p = 0.099 KD Hall et al. Cell Metabolism 22:427-436 (2015) . 30

The Low Carb Community Responds Recently, a study in Cell Metabolism by Kevin Hall from the National Institutes of Health attracted a lot of buzz in the news and online…[but] there were some real problems with the study • The low-carb diet wasn’t low at all , actually, with 29 percent of calories coming from carbs, including refined carbs. A true low-carb diet would have less than 10 percent of calories from carbs. • It was a very short-duration study (only six days) conducted on only nineteen people who were contained in a metabolic ward where all the food was provided…It showed what happened in a vacuum but not in real life. Mark Hyman, MD Eat Fat, Get Thin (2016)

Hypothetical Extended Duration Study 0.95 24hr Respiratory Qotient 0.9 RC data 0.85 RC model RF data 0.8 RF model Fat Adaptation? 0.75 -3 -2 -1 0 1 2 3 4 5 6 Time (days) 32