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Christopher Gardner, PhD Rehnborg Farquhar Professor of Medicine

Stanford Prevention Research Center Stanford University

Changing my Weight Destiny: Can I Choose a Diet

that Better Matches my Biology?

Outline Ø  Background and Context Ø  DietFits: Design & Methods

Ø  Preliminary Results

Ø  Preliminary Conclusions

Ø Future Directions

Ø Take Home Points

Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults

The Evidence Report. National Institutes of Health. Obesity Research 1998;6(Suppl)2:51S-209S.

≥55% energy from carbohydrate

≤30% energy from fat

and approximately 15% energy from protein

Carb Fat Protein >55%

<30%

~15%

All of the following are associated with weight loss AHA-style Step 1 Higher protein Higher protein Zone-type Lacto–ovo–vegetarian–style Low calorie Low carbohydrate Low fat Low fat vegan-style Lower fat, high-dairy Low–glycemic–load Macronutrient targeted diets Mediterranean style Moderate protein

With prescribed energy restriction, or Without formal prescribed energy restriction, but with a realized energy deficit.

…if reduction in dietary energy intake is achieved:

Acceptable macronutrient distribution ranges (AMDR)

Percentages of daily calories from carbohydrate, fat and protein sufficient to provide adequate total energy intake and nutrients while reducing the risk of chronic disease.

45-65% Carbohydrate

20-35% Fat

10-35% Protein

Carbs 45 60 45 55 65

Fats 35 20 25 30 25

Protein 20 20 30 15 10

Let’s call it Std American Diet (SAD) Low Fat / High Carb High Protein Food Pyramid / My Plate Hi Carb / Low Fat / Low Pro

Possible Combinations

Acceptable macronutrient distribution ranges (AMDR)

Carbs ~15 ~40 ~30 40

~75

Fats ~50 ~40 ~40 30

~10

Protein ~35 ~20 ~30 30

~15

Let’s call it Atkins Diet Mediterranean Diet Paleo Diet Zone Diet Ornish Very Low Fat Diet

= Outside AMDR

Outside the range of AMDR

Possible Combinations

-9 -8 -7 -6 -5 -4 -3 -2 -1 0

Base- line

8 weeks

6 months 1 year

Atkins

Zone Ornish

Percent weight change across time, by group

LEARN Weight change as % of baseline

Gardner, JAMA 2007;297:969-77

12-month net weight change (kg): Individual results

-30 -25 -20 -15 -10 -5 0 5 10 15 20

-30 -25 -20 -15 -10 -5 0 5 10 15 20

-30 -25 -20 -15 -10 -5 0 5 10 15 20

-30 -25 -20 -15 -10 -5 0 5 10 15 20

Gardner, JAMA 2007;297:969-77

12-month net weight change (kg): Individual results

-30 -25 -20 -15 -10 -5 0 5 10 15 20

-30 -25 -20 -15 -10 -5 0 5 10 15 20

-30 -25 -20 -15 -10 -5 0 5 10 15 20

-30 -25 -20 -15 -10 -5 0 5 10 15 20

Gardner, JAMA 2007;297:969-77

~65 lb RANGE of weight change

WITHIN each diet group.

From losing 45-55 lbs to gaining 10-15 lbs

Dansinger et al., Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk Reduction: A Randomized Trial. JAMA, 2005; 293:43-53

Outline Ø  Background and Context

Ø  DIETFITS: Design & Methods

Ø  Preliminary Results

Ø  Preliminary Conclusions

Ø Future Directions

Ø Take Home Points

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Do Genotype Patterns Predict Weight Loss Success for Low Carb vs. Low Fat Diets?

R01 DK091831 (2013-17), Nutrition Science Initiative (NuSI)

Christopher Gardner, PhD Professor of Medicine, Nutrition Scientist

DIETFITS Study

Diet Intervention Examining The Factors Interacting with Treatment Success

Healthy Low-Fat vs. Healthy Low-Carb

Reframe the Question What is the “best diet”?

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

What is the “best diet”?

Which diet is best

for whom?

Reframe the Question

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Main Hypothesis

12-month weight loss success WITHIN diet groups for both a Healthy Low-Fat & Healthy Low-Carb diet,

will differ by Genotype and Insulin Resistance

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Do Genotype Patterns Predict Weight Loss Success for Low Carb vs. Low Fat Diets? NIH, Nutrition Science Initiative, and donors

n=609 BMI 28-40 kg/m2

non-diabetic generally healthy adults 18-50 yrs (57% women)

Low Carbohydrate (n=305) .

Low Fat (n=304) Months 0 12 3 6

INTERVENTION: 22 group classes, 15-22 participants/group

XXXXXXXX X X X X X X X X X X X X X X

WEIGHT (1° outcome) X X X XBlood (DNA, lipids, glucose, insulin, OGTT, cytokines) X X X X

X X X XDiet Assessment (NDS-R)

Psychosocial (Questionnaires) X X X XDEXA, REE (Metabolic cart) X X X

Healthy Low-Fat vs. Healthy Low-Carb

Outline Ø  Background and Context

Ø  DIETFITS: Design & Methods

Ø  Preliminary Results Ø  Preliminary Conclusions

Ø Future Directions

Ø Take Home Points

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Macronutrient Distribution K

cals

0

500

1,000

1,500

2,000

2,500

Protein

Fat

Carb

22%

53%

24%

Low Fat

26%

23%

49%

Low Carb

21%

51%

26%

Low Fat

24%

27%

47%

Low Carb

21%

48%

29%

Low Fat

23%

30%

45%

Low Carb

Baseline 3-months 6-months 12-months

18%

45%

35%

Low Fat

45%

36%

Low Carb

17%

36%

45%

-35 -30 -25 -20 -15 -10

-5 0 5

10 15

-35 -30 -25 -20 -15 -10

-5 0 5

10 15

WeightC

hange(kg)

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

0

0RangeofWeightLossinBOTHgroups

Fromlosing~30kg(65lbs)togaining~10kg(~20lbs)

~40kg(85lb)rangeofresponsetothesamedietaryinstrucJon!!!

12-monthWeightChange(kg)(Eachbarrepresentsoneindividual)

-35 -30 -25 -20 -15 -10

-5 0 5

10 15

-35 -30 -25 -20 -15 -10

-5 0 5

10 15

WeightC

hange(kg)

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

12-monthWeightChange(kg)(Eachbarrepresentsoneindividual)0

0

>6,500 lbs lost

0

-10

-20

-30

10

kg

Low-Fat Low-Carb

Lowest Tertile

Middle Tertile

Highest Tertile

Lowest Tertile

Middle Tertile

Highest Tertile

Most Middle

Least Least

Most

Hypothesized DIET X INSULIN Difference:

Middle

Mean ± sem

0

-10

-20

-30

10

kg

Hypothesized DIET X GENOTYPE Difference:

Low-Fat Low-Carb

Matched

More

Mis- Matched

Less

Matched

More

Mis- Matched

Less

Low-Fat Genotype

Low-Carb Genotype

Mean ± sem

Low-Fat Genotype

Low-Carb Genotype

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Other Health Factors Healthy Low-Fat

Lower LDL-C Healthy Low-Carb Lower Triglycerides

Higher HDL-C

Similar Improvement (both diets) Glucose Insulin

Metabolic Syndrome Body Composition

Resting Energy Expenditure DIETFITS

Hlthy Low-Fat vs Hlthy Low-Carb

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

-70-60-50-40-30-20-100102030

ChangeinLeanandFatMass(lbs)at12Months

ChangeinTotalLean(lbs)-12M ChangeinTotalFat(lbs)-12M

HealthyLow-Fat HealthyLow-Carb

Poun

ds

Outline Ø  Background and Context

Ø  DIETFITS: Design & Methods

Ø  Preliminary Results

Ø  Preliminary Conclusions

Ø Future Directions

Ø Take Home Points DIETFITS

Hlthy Low-Fat vs Hlthy Low-Carb

Genome 3-SNP Multilocus Genotype

Pattern Not Helpful

Possibly an

alternate Genetic Risk

Score??

Metabolism

INS-30 - Not Helpful

Possibly an alternate parameter related to glucose-insulin dynamics?

Microbiome

Outline Ø  Background and Context

Ø  Design & Methods

Ø  Preliminary Results

Ø  Preliminary Conclusions

Ø  Future Directions

Ø  Take Home Points

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Healthy Low-Fat vs. Healthy Low-Carb

QUALITY ??

“...the study helped me change my

relationshipwith food.”

Quote from a highly successful participant

All of the following are associated with weight loss AHA-style Step 1 Higher protein Higher protein Zone-type Lacto–ovo–vegetarian–style Low calorie Low carbohydrate Low fat Low fat vegan-style Lower fat, high-dairy Low–glycemic–load Macronutrient targeted diets Mediterranean style Moderate protein

With prescribed energy restriction, or Without formal prescribed energy restriction, but with a realized energy deficit.

…if reduction in dietary energy intake is achieved:

Some participants possibly should have been screened for, and helped

with, emotional & psychological challenges

Emily Amundson Masters Student

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Genetic Risk Score

UK Biobank Axiom® Array

Liana Del Gobbo PhD

John Trepanowski

Glucose & Insulin Dynamics

Healthy Low-Fat vs. Healthy Low-Carb

Michelle Hauser

Jennifer Hartle

Sarah Farzinkhou

Lucia Aronica

Epigenetics

Microbiome

Erica&JusJnSonnenburg

PhDJulieParsonnet

MD

ErinAveryMS

LisaOffringaPhD

Cohort2–723samplesCohort3–538samples

Outline Ø  Background and Context

Ø  Design & Methods

Ø  Preliminary Results

Ø  Preliminary Conclusions

Ø  Future Directions

Ø  Take Home Points DIETFITS

Hlthy Low-Fat vs Hlthy Low-Carb

Diets

Veggies

Added Sugars

White Wheat Flour

Veggies

Added Sugars

White Wheat Flour

Improved relationship with food(i.e., don’t eat in car, cook more, eat meals with family)

Address emotional and psychological

issues related to food

Achieve calorie restriction without prescribing it (satiety)

Take Home Points

Abby King, PhD John Ioannidis, MD, DSc Manisha Desai, PhD

Erica & Justin Sonnenburg, PhD’s

Julie Parsonnet, MD Tracey McLaughlin MD, MPH Robert Haile

DrPH Megan Hitchins

PhD

Holden Maecker PhD Mark Davis

MD, PhD Kari Nadeau MD, PhD

Tim Assimes MD, PhD Josh Knowles

MD, PhD Erik Ingelsson MD, PhD

Valerie Alaimo

Josephine Hau

Sue Kirkpatrick

Sarah Farzinkhou

Dalia Perelman Jae Berman

Mollie Shimer Diane Demis

Lisa Offringa Katherine Dotter Jennifer Hartle Erin Avery

Alana Koehler Jennifer Robinson

Mandy Murphy

Sarah Mummah

Michelle Hauser

Antonella Dewell

Rise Cherin

Joe Rigdon

Emily Amundson

Thank you - Stay Tuned

DIETFITS Hlthy Low-Fat vs Hlthy Low-Carb

Questions ??