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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
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