Alternate day fastingFor weight loss and heart disease risk reduction

Krista Varady, Ph.D.Associate Professor of NutritionUniversity of Illinois, Chicago

65% of Americans are overweight or obese

Obesity greatly increases the risk of coronary heart disease (CHD)

Losing weight helps to lower the risk of CHD

Most commonly used weight loss intervention: Calorie restriction (CR)

What is Calorie restriction (CR)?

Reducing energy intake

by 15-40% of daily needs

What is Calorie restriction (CR)?

Calorie restriction is effective for weight loss

Chaston TB & Dixon JB, Int J Obesity. 2008.

Chaston TB & Dixon JB, Int J Obesity. 2008.

Weight loss 10-15% in 3 months

Calorie restriction is effective for weight loss

Problem with calorie restriction:Dietary adherence begins to decline after 8

weeks

How can we increase adherence to calorie

restriction to ensure consistent weight loss?

Perhaps by only requiring calorie restriction

every other day?

Day of ad libitum feeding Day of 75% restriction

Feed day Fast dayDay of ad libitum feeding Day of 75% restriction

Alternate day fasting (ADF)

In this way, the person always gets to look forward

to the day of eating anything they want

Fast day Feed day

How did the idea of ADF come about?

Fasting in the absence

of weight loss

How did the idea of ADF come about?

Fasting in the absence

of weight loss

Effect on cell proliferation rates

of various tissues (Cancer risk)

How did the idea of ADF come about?

But the mice always lost weight!

Would we see the same weight loss in humans with ADF?

?

STUDY 1 – Pilot study

Study objectives

• Is ADF an effective strategy for weight loss?

• What is the effect of this diet on CHD risk parameters?

• What dietary adaptations occur in individuals

undergoing ADF?

Figure 1.1 Study design: Pilot study

Week 1-2 Week 3-6 Week 7-10

Body weightBody compositionBlood draw

Body weightBody compositionBlood draw

Body weightBody compositionBlood draw

Body weightBody composition

Blood draw

Table 1.1 Nutrient composition of the fast day meals provided

Varady KA et al, AJCN. 2009.

Meals were prepared for individual subjects

in a metabolic kitchen

Table 1.2 Subject characteristics at baseline who completed the study

Varady KA et al, AJCN. 2009.

Figure 1.2 Body weight changes

Varady KA et al, AJCN. 2009.

-5.6 kg

Table 1.3 Body composition changes

Bhutani et al, Obesity. 2010.

All values reported as mean SEM.

* Significantly different from baseline (week 3), P < 0.05 (One-factor ANOVA with Bonferroni analysis)

Is ADF effective for weight loss?

Bhutani et al, Obesity. 2010.

All values reported as mean SEM.

* Significantly different from baseline (week 3), P < 0.05 (One-factor ANOVA with Bonferroni analysis)

Table 1.3 Body composition changes

Bhutani et al, Obesity. 2010.

All values reported as mean SEM.

* Significantly different from baseline (week 3), P < 0.05 (One-factor ANOVA with Bonferroni analysis)

Table 1.3 Body composition changes

Is ADF cardio-protective?

What is the effect of ADF on CHD risk

parameters?

Is ADF cardio-protective?Figure 1.3 LDL cholesterol concentrations

Week 7 Week 10

Feed day Fast day Feed day Fast day

Bhutani et al, Obesity. 2010.

Figure 1.4 HDL cholesterol concentrations

Bhutani et al, Obesity. 2010.

Week 7 Week 10

Feed day Fast day Feed day Fast day

Bhutani et al, Obesity. 2010.

Figure 1.5 Triglyceride concentrations

Week 7 Week 10

Feed day Fast day Feed day Fast day

Figure 1.6 Systolic blood pressure changes

Varady KA et al, AJCN. 2009.

-6 mmHg

Figure 1.7 Heart rate changes

Varady KA et al, AJCN. 2009.

- 4 beats/min

• Dietary adherence?

• Amount of food consumed on feed

day?

• Overall energy restriction?

What dietary adaptations occur

in individuals undergoing ADF?

Adherence to fast day diet assessed using an “Extra food log”

What dietary adaptations occur with ADF?

Figure 1.8 Adherence to fast day diet

Varady KA et al, AJCN. 2009.

Figure 1.9 Hyperphagic response on feed day to lack of food on fast day

Klempel MC et al, Nutr J. 2010.

Feed day intake: 110% of needs

Figure 1.10 Percent energy restriction at each week of the trial

Klempel MC et al, Nutr J. 2010.

37% restriction

How are hunger and satiety affected?

Hunger was measured by a validated visual analog scale (VAS)

Figure 1.11 Hunger during each week of the trial

Klempel MC et al, Nutr J. 2010.

Figure 1.12 Satiety during each week of the trial

Klempel MC et al, Nutr J. 2010.

Is ADF potentially effective for weight loss?

YES

All previous studies of ADF

used a low-fat background

diet (25% fat)

All previous studies of ADF

used a low-fat background

diet (25% fat)

But most Americans

consume a diet high in fat

(35-45% fat)

All previous studies of ADF

used a low-fat background

diet (25% fat)

But most Americans

consume a diet high in fat

(35-45% fat)

Is ADF still effective with a high-fat background diet?

STUDY 2 – High fat/low fat study

Study objectives

• Do similar changes in weight occur on an ADF high-fat

diet?

• What is the effect of an ADF high-fat diet on CHD risk?

Figure 2.1 Study design: High fat study

ADF-LF group

ADF-HF group

Table 2.1 Nutrient composition of the feed and fast day meals provided

Klempel MC et al, 2012. Metabolism.

Table 2.2 Subject characteristics at baseline

Klempel MC et al, 2012. Metabolism.

Figure 2.2 Body weight changes

-5.3 kg LF

-6.5 kg HF

Klempel MC et al, 2012. Metabolism.

Figure 2.3 Body composition changes

Klempel MC et al, 2012. Metabolism.

Figure 2.4 Waist circumference changes

-10.1 cm LF

-10.0 cm HF

Klempel MC et al, 2012. Metabolism.

Figure 2.5 Plasma lipid changes

Klempel MC et al, 2012. Metabolism.

Are the beneficial effects of ADF

still observed with a high fat background diet?

YES

STUDY 3 – Exercise study

Study objectives

• Is it possible to exercise on the fast day?

• What are the effects this combination therapy on body

weight?

• What are the effects on CHD risk?

Figure 3.1 Study design: ADF plus exercise

Table 3.1 Subject characteristics at baseline

Combination

ADF Exercise Control

n 18 25 24 16

Age (y) 45 5 42 2 42 2 49 2

Body weight (kg)

91 6 94 3 93 2 93 5

BMI (kg/m2) 35 1 35 1 35 1 35 1

Waist circum (cm)

92 1 100 2 98 2 99 3

Total-C (mg/dl) 190 10 171 8 181 6 185 7

LDL-C (mg/dl) 125 9 113 8 113 5 119 6

HDL-C (mg/dl) 50 3 49 2 51 2 52 3

TG (mg/dl) 77 7 81 7 74 6 97 13No significant differences between groups (One-way ANOVA)

Figure 3.2 Percent exercise sessions scheduled by subjects on feed/fast day

Bhutani S et al, 2013. Int J Sports Nutr.

Figure 3.3 Percent cheating on the fast day in relation to timing of the exercise session

Bhutani S et al, 2013. Int J Sports Nutr.

Figure 3.4 Changes in body weight and body composition after 12 weeks

Means with different letters significantly different (P < 0.05; One-way ANOVA).

Bhutani S et al, 2013. Obesity.

Table 3.2 Change in plasma lipids and LDL particle size after 12 weeks

Combination

ADF Exercise Control

Total-C (% change) -2 5 7 4 0 3 1 4

LDL-C (% change) -12 5 -1 6 0 5 3 5

HDL-C (% change) 18 9 a 0 4 b 2 3 b 8 5 b

TG (% change) 13 11 6 6 7 6 5 7

LDL size (Å) 4 1 a 5 1 a 1 1 b 0 1 b

Large LDL (% change)

7 5 15 3 1 5 1 4

Small LDL (% change)

-7 2 a -12 3 a -1 4 b 1 3 bMeans with different letters significantly different for each parameter (P < 0.05; One-way ANOVA).

Bhutani S et al, 2013. Obesity.

Table 3.2 Change in plasma lipids and LDL particle size after 12 weeks

Combination

ADF Exercise Control

Total-C (% change) -2 5 7 4 0 3 1 4

LDL-C (% change) -12 5 -1 6 0 5 3 5

HDL-C (% change) 18 9 a 0 4 b 2 3 b 8 5 b

TG (% change) 13 11 6 6 7 6 5 7

LDL size (Å) 4 1 a 5 1 a 1 1 b 0 1 b

Large LDL (% change)

7 5 15 3 1 5 1 4

Small LDL (% change)

-7 2 a -12 3 a -1 4 b 1 3 bMeans with different letters significantly different for each parameter (P < 0.05; One-way ANOVA).

Bhutani S et al, 2013. Obesity.

Weight loss

• ADF produces a 3-7 kg weight loss after 8-12 weeks• ADF-HF diets are just as effective as ADF-LF diets for

weight loss• Adding endurance exercise may enhance weight loss

Body composition

• Fat mass decreased, with potential retention of lean mass

• Waist circumference decreases by 4-10 cm

Summary of findings

Coronary heart disease risk

• LDL cholesterol reduced by 0-25%

• Triglycerides lowered by 0-30%

• Systolic blood pressure also decreased

• ADF-HF is just as effective as ADF-LF for CHD risk

reduction

• Adding endurance exercise may increase HDL

cholesterol levels

Summary of findings

Dietary adaptations

• Approximately 110% of energy needs consumed on the

feed day to compensate for the lack of food on the fast

day

• 80-90% of subjects can adhere to ADF short-term

• Hunger decreases after 2 weeks of diet

Summary of findings

Goal is to examine whether ADF is effective for weight maintenance,

and to compare ADF to daily calorie restriction

Hypothesized findings (from grant application)

Year-long ADF study currently underway…

All of these findings are summarized in the book:

US version

UK version

Many thanks to my students… Faculty

• Surabhi Bhutani (PhD Student) Dr. Shane Phillips

• Monica Klempel (PhD Student) Dr. Daniel Corcos

• John Trepanowski (PhD Student) Dr. Carol Braunschweig

• Cynthia Kroeger (PhD Student) Dr. Eric Ravussin

• Kristin Hoddy (PhD Student) Dr. Sally Freels

• Adrienne Barnosky (Postdoc) Dr. Marian Fitzgibbon

Funding

• NIH National Heart Lung and Blood Institute R01HL106228-01• American Heart Association 09SDG2170077 and

12PRE8350000 • International Life Sciences Institute • UIC Chancellor’s Discovery Fund (Co-PI Shane Phillips)

Acknowledgements