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Losing Weight and Keeping It Off: New Guidelines and Strategies
Cynthia Knapp Dlugosz, BSPharm
Owner
Being in Balance Coaching
Ann Arbor, Michigan
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Development and Support
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This activity was developed by the American Pharmacists Association and supported by an independent educational grant from Janssen Scientific Affairs, LLC.
Accreditation Information
The American Pharmacists Association is accredited by theAccreditation Council for Pharmacy Education as a provider of continuing pharmacy education (CPE). This activity, Losing Weight and Keeping It Off: New Guidelines and Strategies, is approved for 1.5 hours of CPE credit (0.15 CEUs). The ACPE Universal Activity Number assigned by the accredited provider is: 0202‐0000‐13‐211‐L01‐P. To obtain CPE credit for this activity, participants will be required to actively participate in the entire webinar and complete an online assessment and evaluation located at www.pharmacist.com/education by September 23, 2013.
Initial Release Date: September 9, 2013Target Audience: PharmacistsACPE Activity Type: Knowledge‐basedLearning Level: 2Fee: There is no fee for this activity
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Disclosures Cynthia Knapp Dlugosz, BSPharm declares no conflicts of
interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria.
APhA’s editorial staff declares no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see the Education and Accreditation Information section at www.pharmacist.com/education.
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Learning Objectives
At the completion of this activity, participants will be able to: Summarize current clinical practice guidelines for the
identification and treatment of obesity Explain the concept of energy balance and identify
important gaps in the understanding of this concept Discuss noteworthy new information regarding optimal
lifestyle interventions for weight loss and maintenance Describe existing drug therapy options for chronic
weight management in terms of efficacy, adverse effects, monitoring, and other key characteristics
List emerging treatment options for weight loss and maintenance
Cynthia Knapp Dlugosz, BSPharm
Certified Integrative Health Coach
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THE PROBLEM AND THE GUIDELINES
“Current” Obesity Guidelines
1998
American Heart AssociationAmerican College of Cardiology
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Body Mass Index (BMI)
Weight (kg) Weight (lb)
Height (m2) Height (in2)OR 703
BMI Classification
Normal weight = 18.5–24.9
Overweight = 25.0–29.9
Obesity
Class I: 30.0–34.9
Class II: 35.0–39.9
Class III: ≥40.0 (extreme obesity)
http://www.nhlbi.nih.gov/health/health‐topics/topics/obe/diagnosis.html
Overweight ObeseHealthy
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Prevalence of Obesity
Prevalence of obesity began to increase after 1980
There was a dramatic increase in obesity in the United States from 1990 through 2010
http://www.cdc.gov/obesity/data/adult.html
Estimated Average Food Consumption
2,169
2,614
0
500
1,000
1,500
2,000
2,500
3,000
1970 2010
kcal/day
http://www.ers.usda.gov/data‐products/food‐availability‐%28per‐capita%29‐data‐system/summary‐findings.aspx#.UhFyqj9Cr3E
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[CDC Obesity Trends slides available at:http://www.cdc.gov/obesity/data/adult.html]
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Prevalence in Adults
More than two thirds of adults (≥20 years) are overweight or obese
Specifically:
69.2% of adults are overweight or obese
35.9% are obese
6.3% are extremely obese
By 2030:
42% will be obese
11% will be extremely obese
Flegal KM et al. JAMA. 2012;307(5):491–7.
Finkelstein EA et al. Am J Prev Med. 2012;42(6):563–70.
Prevalence in Children
31.8% of children and teens are overweight or obese
16.9% are obese
BMI ≥95th percentile on BMI‐for‐age growth charts
Ogden CL et al. JAMA. 2012;307(5):483‐90.
Current NHLBI Guidelines
Who should lose weight?
BMI ≥30
BMI 25–29.9 + ≥2 risk factors
High‐risk waist circumference + ≥2 risk factors
• Men >40 in
• Women >35 in
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Risk Factors
Cigarette smoking
Hypertension
LDL ≥160 mg/dL*
HDL <35 mg/dL
Impaired fasting glucose (FPG 100–125 mg/dL)
Family history of premature CHD
MI, sudden death in male relative ≤55 years or female relative ≤65 years
Age ≥45 years (men)
≥55 years (women)**
**Or postmenopausal*Or 130–159 mg/dL + ≥2 other risk factors
Initial Approach to Weight Loss
Target: reduce body weight by 10% from baseline over 6 months
Rate: 1–2 lb/wk
• 0.5–1 lb/wk may be more realistic at lower starting weights
Strategy: energy deficit of 500–1,000 kcal/day
• 300–500 kcal/day at lower starting weights
Components: dietary therapy, increased physical activity, behavior therapy
Guide to Selecting Treatment
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults
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Comorbidities
CHD
Dyslipidemia
Hypertension
Sleep apnea
Type 2 diabetes
USPSTF Recommendation Statement
BMI ≥30
Offer or refer patients to intensive, multicomponent behavioral interventions
Average expected weight loss 8.8–15.4 lb
September 2012
“…obesity [is] a disease requiring a range of medical interventions to advance obesity
treatment and prevention.”
AMA Policy, June 2013
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UNDERSTANDING ENERGY BALANCE
First Law of Thermodynamics
Body weight cannot change if, over a specified time, energy intake and
energy output are equal
Hill JO et al. Circulation. 2012;126:126–32.
OUTPUTPhysical Activity
Calories
INTAKECalories From
Food
ENERGY BALANCE
Components of Energy Intake
Macronutrient Energy (kcal/g)Carbohydrates(starches, sugar)
4
Protein 4
Fat 9
Alcohol 7
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Components of Energy Output
Resting metabolic rate
Amount of energy expended under restful conditions
Includes calories needed to support vital functions
Thermic effect of food Food digestion, absorption,
storage
Activity energy expenditure Exercise
Nonexercise activity thermogenesis (NEAT)
RMR = 60%–75%
AEE = 15%–35%
TEF = 8%–10%
Problem #1:
There’s a we still don’t know
How Does Energy Balance Occur?
How is energy balance regulated?
Over what time period?
OUTPUTPhysical Activity
Calories
INTAKECalories From
Food
ENERGY BALANCE
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How Many Calories Do We Need?
Activity Level
Age (yr) Sedentary Moderate Active
Women
19–30 2,000 2,000–2,200 2,400
31–50 1,800 2,000 2,200
51+ 1,600 1,800 2,000–2,200
Men
19–30 2,400 2,600–2,800 3,000
31–50 2,200 2,400–2,600 2,800–3,000
51+ 2,000 2,200–2,400 2,400–2,800
Dietary Guidelines for Americans, 2010
Target Calories for Weight Loss?
Weight (lb) Sedentary Light Activity
140 1,200 1,203
150 1,200 1,265
160 1,200 1,326
170 1,200 1,388
180 1,202 1,450
190 1,256 1,512
Moore TJ et al. The Dash Diet for Weight Loss. 2012.
Obesity: Food, Activity, or Both?
OUTPUTPhysical Activity
Calories
INTAKECalories From
Food
ENERGY BALANCE
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What Drives Weight Regain?
• Leptin suppresses appetite
• Weight loss = leptin
• PYY suppresses appetite, counters ghrelin
• Ghrelin stimulates appetite
• Weight loss = ghrelin
http://www.scripps.edu/zorrilla/research.html
More Unknowns
Is BMI the best indicator of obesity and health risk?
Can obesity become “irreversible”? Bumaschny VF et al. J Clin Invest. 2012;122(11):4203–12
Does genetic analysis have a role in weight management? Patients with FTO rs9939609 A allele are 70% more likely
to become obese
FTO regulates ghrelin• Karra E et al. J Clin Invest. 2013;123:3539–5
More Unknowns
How do “hedonic eating” and neural control of appetite figure in?
Can we become “addicted” to eating?
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Copyright © 2012 American Medical Association. All rights reserved.
Neural Correlates of Food Addiction
Arch Gen Psychiatry. 2011;68(8):808–16. Gearhardt AN et al.
Dorsolateral prefrontal cortex
Caudate
Lateral orbitofrontal cortex
Glycemic Index
Glycemic index is the degree to which a specific food raises blood glucose level
Glucose or white bread used as reference standard (GI = 100)
• GI >70 = high
• GI <45 = low
Highly processed carbohydrates (the “whites”) tend to have high GI
• White bread, pasta, rice, potatoes, sugar
High GI = Food Addiction?
plasma glucose
hunger
Selectively stimulate brain regions associated with reward, craving
Lennerz BS et al. Am J Clin Nutr. 2013 Jun 26. [Epub ahead of print]
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Problem #2:
We have no data, or existing data are misleading
Copyright © 2012 American Medical Association. All rights reserved.
The Energy Content of Restaurant Foods Without Stated Calorie Information
JAMA Intern Med. 2013;173(14):1292–9. Urban LE at al.
Mean (SD) Gross Energy of the Most Popular Meals in the Most Prevalent Independent Restaurant Categories
The red line represents one third of the mean daily energy requirement for the average adult (667 kcal).
Figure Legend:
Inaccurate Calorie Counts?
Stated Measured
250 kcal
252 kcal
315 kcal
306 kcal
Urban LE et al. J Am Diet Assoc. 2010;110:116–23.
Urban LE et al. JAMA. 2011;306(3):287–293.
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Problem #3:
We got the math wrong
The Gospel of Energy Balance
3,500 calories = 1 lb
Chronic energy imbalance of:
100 kcal/day = 10 lb/yr
500 kcal/day = 1 lb/wk
140
142
144
146
148
150
152
0 1 2 3 4 5 6
Weight (lb)
Week
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My Weight Loss Journey
Feb 2008
Feb 2009
Feb 2010
Changing Energy Needs
Increasing body weight
• RMR
• AEE
Decreasing body weight
• RMR
• AEE
Hall KD et al. Lancet. 2011;378:826–37.
The “3,500 calorie per pound” rule does not account for dynamic physiological adaptations that
occur with decreased body weight
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The New Math
10 kcal in energy intake = 1 lb in body weight
Permanent 10 kcal change
Eventual change of 1 lb when body weight reaches new steady state
1 year to achieve 50% of weight loss
3 years to achieve 95% of weight loss
Hall KD et al. Lancet. 2011;378:826–37.
So a 500‐calorie deficit could be expected to result in a 25‐lb weight loss in 1 year, not 25 weeks
Body Weight Simulator
http://bwsimulator.niddk.nih.gov/
THE ROLE OF DIET AND EXERCISE
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Diet vs Exercise
Dietary therapy (reduced‐calorie eating plan) is most important for weight loss
Physical activity is especially important for weight loss maintenance
Diet CompositionsFat Content Carb
Content Protein Content
Examples
High(55%–65%)
Low (<20%; <100 g/day)
High(25%–30%)
Dr. Atkins New Diet Revolution
The Carbohydrate Addict’s Diet
Moderate(25%–35%)
Moderate(35%–50%)
High(25%–30%)
The South Beach Diet
The Zone Diet
Moderate(20%–30%)
High(55%–60%)
Moderate(15%–20%)
USDA
DASH diet
Weight Watchers
Low/very low (<19%)
Very high (>65%)
Moderate(10%–20%)
Eat More, Weigh Less (Ornish)
Pritikin
Freedman MR et al. Obes Res. 2001;9(suppl 1):1S–40S.
The Bottom Line
Adherence is more important than macronutrient composition
Dansinger ML et al. JAMA. 2005;293 (1):43–53.
Gardner CD et al. JAMA. 2007;297(9):969–77.
Alhassan S et al. Int J Obes. 2008;32(6):985–91.
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Physical Activity Guidelines
For overall health
150 minutes moderate‐intensity aerobic activity each week
To meet weight control goals
≥300 moderate‐intensity aerobic activity each week
Physical Activity Tips
Walking or jogging burns ~100 calories/mile
Vigorous‐intensity activity is more time efficient for weight control
SAY IT AIN’T SO…If you ran a 26‐mile marathon, you would burn 2,600 calories—i.e., 900 calories below what’s needed to lose 1 lb of fat
THE ROLE OF PHARMACOTHERAPY
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Mechanisms of Action
Nutrient absorption
• Decrease appetite
• Increase satiety
Energy intake
Energy expenditure
What We Know
Medication alone without diet/lifestyle change is not effective
Achieve modest weight loss
4%–6% more than lifestyle changes
Weight regain occurs when drug therapy is discontinued
Approved for Long‐Term Use
Drug DosageMechanism of Action Adverse Effects
Orlistat(Xenical, alli)
120 mg tid Lipase inhibitor: decreased absorption of fat
Soft/liquid/oily stools, fecal urgency, flatulence, bloating, abdominal pain, dyspepsia
Sibutramine(Meridia)
10–15 mg qd
Appetite suppressant: combined norepinephrine and serotonin reuptake inhibitor
Modest increases in heart rate and blood pressure, nervousness, insomnia
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FDA Approval Criteria for Therapy
Efficacy benchmarks
Difference in mean weight loss ≥5% after 1 year
≥35% of subjects lose ≥5% of baseline body weight after 1 year
Secondary endpoints
Blood pressure and pulse
Lipoprotein lipids
Fasting glucose/insulin
A1C (type 2 diabetes)
Waist circumference
First New Agents Since 1999
Lorcaserin (Belviq) Selective serotonin 2C
receptor agonist 10 mg twice daily Appetite suppression,
satiety enhancement C‐IV Pregnancy category X
Phentermine/topiramate(Qsymia) Sympathomimetic +
antiepileptic agent Once daily in AM Fixed combinations/dose
titration Appetite suppression,
satiety enhancement C‐IV (phentermine) Contraindicated in
pregnancy (oral clefts) Limited distribution
through certified pharmacies
Discontinue if ≥5% weight loss not
achieved after 12 weeks
Discontinue if ≥5% weight loss not
achieved after 12 weeks
Lorcaserin Efficacy
• 3,182 patients
• Average weight loss ~13 lb at 1 yearBLOOM
• 4,008 patients; 79.8% female
• Average weight loss ~13 lb at 1 yearBLOSSOM
• 604 patients with type 2 diabetes
• Average weight loss ~11 lb at 1 year
• Improvements in A1C, fasting glucoseBLOOM‐DM
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Effects of the Study Drug on Body Weight, According to Study Group
47.5%
22.6%
−5.8 kg
Smith SR et al. N Engl J Med. 2010;363:245‐56.
Body Weight Change From Baseline to Week 52
Fidler MC et al. J Clin Endocrinol Metab. 2011;96:3067–77.
©2011 by Endocrine Society
47.2%
22.6%
−5.8%
Randomized Placebo‐Controlled Clinical Trial of Lorcaserin for Weight Loss in Type 2 Diabetes Mellitus: The BLOOM‐DM Study
37.5%
16.3%
−4.5%
O’Neil PM et al. Obesity. 2012; 20(7): 1426–36.
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Lorcaserin Adverse Effects
BLOOM, BLOSSOM
Headache
Dizziness
Fatigue
Nausea
Dry mouth
Constipation
BLOOM‐DM
Hypoglycemia
Headache
Back pain
Cough
Fatigue
Nasopharyngitis
Nausea
Lorcaserin Safety
Serotonin syndrome
Valvular heart disease
Cognitive impairment
Psychiatric disorders
Depression, suicidal ideation
Priapism
Phentermine/Topiramate Dosing
Initiate Qsymia3.75 mg/23 mg daily
for 14 days
Increase to recommended dose Qsymia 7.5 mg/46 mg
once daily
Evaluate weight loss after 12 weeks
If patient has not lost ≥3% of baseline body weight, discontinue drug or escalate dose
To escalate:
Increase to Qsymia11.25 mg/ 69 mg daily
for 14 days
Increase to Qsymia15 mg/92 mg once
daily
Evaluate weight loss 12 weeks after dose
escalation
If a patient has not lost ≥5% of baseline
body weight, discontinue drug
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Phentermine/Topiramate Dosing
Qsymia 3.75 mg/23 mg and Qsymia 11.25 mg/69 mg are for titration purposes only
Avoid dosing Qsymia in evening due to possibility of insomnia
To discontinue Qsymia:
Discontinue gradually to avoid precipitating a seizure
Take Qsymia 15 mg/92 mg every other day for at least 1 week before stopping treatment altogether
Phentermine/Topiramate Efficacy
• 2,487 patients (70% female)
• 2 or more comorbidities
• Average weight loss ~20 lb at 1 yearCONQUER
• 52‐week CONQUER extension study
• 676 patients continued
• Average weight loss ~22 lb at 2 yearSEQUEL
• 1,267 patients, BMI ≥35EQUIP
Effects of low‐dose, controlled‐release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo‐controlled, phase 3 trial
Gadde KM. Lancet. 2011; 377 (9774): 1341–52.
62%
70%
37%
48%
−9.8%
−7.8%
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Mean (95% CI) Percentage Weight Loss From Baseline to Week 108
Garvey WT et al. Am J Clin Nutr. 2011;95:297–308.
©2012 by American Society for Nutrition
−9.3%
−10.5%
Summary Results
At highest dose:
~75% achieved ≥5% weight loss
~50% achieved ≥10% weight loss
Mean weight loss ~22 lb
In EQUIP, significant improvements in:
Waist circumference
Blood pressure
Lipids
Fasting serum glucose
Phentermine/Topiramate Adverse Effects
Paresthesia
Dizziness
Dysgeusia
Insomnia
Constipation
Dry mouth
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Phentermine/Topiramate Safety
Contraindications
Pregnancy
Glaucoma
Hyperthyroidism
During or within 14 days of taking monoamine oxidase inhibitors
Phentermine/Topiramate Warnings
Negative pregnancy test before treatment, monthly thereafter
Monitor heart rate
Monitor for depression, suicidal thoughts
May cause mood, sleep disorders
May cause disturbances in attention, memory
On the Horizon
Bupropion + naltrexone (Contrave)
FDA did not approve in January 2011
Requested long‐term cardiovascular safety study
Light Study currently underway
Bupropion + zonisamide (Empatic)
Beginning phase 3 trials
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On the Horizon
Metformin?
Exenatide?
Liraglutide?
GLP‐1 receptor agonists?
Tesofensine?
Melanocortin‐4 receptor agonists?
NPY receptor ligands?
And so on…
Exercise in a Pill?
“…treatment of diet‐induced obese mice with a REV‐ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidemia and hyperglycemia.”
Solt LA et al. Nature. 2012;485(7396):62–8.Woldt E et al. Nat Med. 2013;19:1039–46.
What We Don’t Know
Do we need medications for weight maintenance rather than weight loss?
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MAINTAINING WEIGHT LOSS
Successful Weight Maintenance
Weight regain <6.6 lb in 2 years
Sustained reduction in waist circumference ≥1.6 in
National Weight Control Registry
Founded in 1993 Rena Wing, PhD (Brown University/University of Pittsburgh)
James Hill, PhD (University of Colorado)
Longitudinal, prospective study of >5,000 adults Lost ≥30 lb
Maintained weight loss for ≥1 yr
Registry members have lost an average of 66 lband kept it off for 5.5 yr Weight loss range 30–300 lb
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How Do They Keep Weight Off?
Successful weight loss maintainers continue to act like recently successful weight losers for many years after their weight loss
—Rena Wing and Suzanne Phelan
Am J Clin Nutr. 2005;82(suppl):222S–5S.
They Eat Less
• Women ~1,300 kcal/day
• Men ~1,700 kcal/day
• Butmay be underestimated by 20%–30%
Continue to consume a low‐calorie, low‐fat diet
They Exercise More
• Mean 2,621 ± 2,252 kcal/wk• 60–75 min moderate‐intensity activity per day
• 35–45 min vigorous activity per day
• But considerable variability• 25.3% report <1,000 kcal/wk
• 34.9% report >3,000 kcal/wk
Engage in high levels of
physical activity
Catenacci VA et al. Obesity. 2008;16:153–61.
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Other Strategies
78% eat breakfast every day
75% weigh themselves at least once a week
62% watch <10 hours of television per week
http://www.nwcr.ws/Research/default.htm
What We Don’t Know
Would an individual approach to macronutrient content facilitate long‐term weight maintenance?
Adaptive Thermogenesis Theory
Group
Total Energy Expenditure (kcal/day)
Difference From Predicted (kcal/day)
Weight stable 2,871 ± 251 11 ± 110
Recent weight loss 2,357 ± 149 −460 ± 56
Sustained weight loss 2,443 ± 203 −422 ± 104
Rosenbaum M et al. Am J Clin Nutr. 2008;88:906–12.
Biggest effect on activity energy expenditure
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Energy Expenditure After Weight Loss
Test Diets
Fat Content
Carb Content
Protein Content
REE (kcal/d)
TEE
(kcal/d)
Very low carb
60% 10% 30% 1,643 3,137
Low glycemic index
40% 40% 20% 1,614 2937
Low fat 20% 60% 20% 1,576 2,812
Ebbeling CB et al. JAMA. 2012;307(24):2627–34.
WHERE DOES ALL THIS LEAVE US?
My #1 recommendation…
Do you want to lose weight?
Do you want to weigh less?
OR
…is a question
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Losing weight and keeping it off require a renovation of your entire life for the remainder of your life
—Joel Hoffman, Executive ProducerThe Weight of the Nation (HBO documentary)
If you want to weigh less…
“Except for the fortunate few people who are not going to gain weight no matter what they do, you can’t live life today in our society and maintain
a normal weight.”
—James O. Hill, PhDUniversity of Colorado Center
for Human Nutrition
My Recommendations
Make sure you reallywant it
Start with the end in mind
Consider your habits to create a
calorie deficit
Know that you’re in it for the long
haul
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DASH Diet for Weight Loss
timeweightmoneystuff.com
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