Protein Appetiteand Leveraging

Richard D. Mattes, MPH, PhD, RDPurdue University

West Lafayette, IN, USAMay 5-6, 2015

Laboratory for Sensory and Ingestive Studies

Is a Calorie a Calorie?

Average bond energies, kcal/moleC-H 98O-H 110C-C 80C-O 78H-H 103C-N 65O=O 116 (2 x 58)C=O 187* (2 x 93.5)C=C 145 (2 x 72.5)

(* as found in CO2)

Dietary Approaches to Optimize Health

Dietary level

• Nutrients/food constituents

• Foods

• Diets

Examples

• Protein, Fiber, Calcium, Capsaicin

• Fruits, Vegetables, w\Whole Grains

• Glycemic Index, Vegan, Energy Density

Common assumption: A Calorie A Calorie

Protein Appetite

SpecificNon-Specific

Protein Appetite

SpecificNon-Specific

Deutsch et al., Physiol & Behav 1989;46:619-624

DiBattista D. Physiol & Behav 1991; 49: 263-269.

Rats and Mice

12 day restriction period

Protein-restricted – 1 hour access/24hr

Carbohydrate-restricted – 1 hour access/24hr

Jen et al., Physiol & Behav 1985;34:655-659

Ad Lib intake + Infusion CHO - 28-77%en FAT - 16-65%en PRO - 7-36%en

Mellinkoff et al., J Appl Physiol 1956;8:535-538

Vazquez et al., Physiol & Behav1982;28:513-519. Soup +

MSGSoup + Casein

Hydrolysate

113 infants with marasmus87 healthy control infants

60 second feeding trials

Murphy & Withee J Gerontol 1987;42:73-77

N = 20 18-26y/oN = 20 65-83y/o

Griffioen-Roose et al., AJCN 2012;95:32-38

37 lean adultsIso-energetic diets - 14 d 0.5g protein/kg BW/d – 2.5d 2.0g protein/kg BW/d – 2.5d

13% increase on low protein (p<0.001)

NS

Coelho et al., Appetite 2006;47: 352-360.

89 female undergraduates

• Protein restricted - 3d• Limit animal protein

• Carbohydrate restricted - 3d• Limit high CHO foods

• Control

0

20

40

60

80

100

0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00

Carbs

Carbs

0

20

40

60

80

100

0 2 4 6 8 10 12 14

Fats

% of Fat

0

20

40

60

80

100

0 2 4 6 8 10 12 14

Protein

% of Protein

USA MEX AUS BRAZIL S. AFR GER RUS CUBA JAP S.ARAB INDIA CAN ESP U.K.

USA MEX AUS BRAZIL S. AFR GER RUS CUBA JAP S.ARAB INDIA CAN ESP U.K.

USA MEX AUS BRAZIL S. AFR GER RUS CUBA JAP S.ARAB INDIA CAN ESP U.K.http://chartsbin.com/view/1160

•FAO Statistics Division 2010, Food Balance Sheets, Food and Agriculture Organization of the United Nations, Rome, Italy, viewed 17th March, 2011, <http://faostat.fao.org/>.

Simpson & RaubenheimerObes Rev 2005;6:133-142

Simpson & Raubenheimer Obes Rev 2005;6:133-142

Protein Leveraging Hypothesis

Gosby et al., PLoS ONE 2011;6:e25929

Total energy and nutrient intakes over the 4-day 10%, 15% and 25% protein ad-libitum study periods

Gosby AK, Conigrave AD, Lau NS, Iglesias MA, et al. (2011) Testing Protein Leverage in Lean Humans: A Randomized Controlled Experimental Study. PLoS ONE 6(10): e25929. doi:10.1371/journal.pone.0025929http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025929

Martens et al., AJCN 2013;97:86-93

5%en Protein15%en Protein

30%en Protein

Martens et al., Am J ClinNutr 2013;97:86-93

40 male, 39 female adultsNormal weight12 day RCT

Martens et al;, Am J Clin Nutr 2014;99:1397-1406.

Protein Appetite

SpecificNon-Specific

Hypothesis

• Quantity per meal• Daily amount• Pattern of use• Food source• Food form • Mode of action

Protein is a modifiable dietary constituent that may aid in weight management while contributing

positively to diet quality• Appetitive Sensations

• Food Choice

• Post-Prandial Thermogenesis

• Resting Energy Expenditure

• Substrate Oxidation

Appetite• Hunger – Initiation of ingestive event –

energy-based• Desire to Eat - Initiation of ingestive event –

cognitive/sensory-based• Fullness – Termination of ingestive event• Prospective Consumption – Projected portion

size

High Protein Diets & Weight Loss

mo Atkins Zone LEARN Ornish p

2 1381 1455 1476 1408 .526 1538 1503 1598 1553 .64

mo Atkins Zone LEARN Ornish p

2 34.6 34.5 34.8 34.7 .88

6 34.3 34.4 34.8 34.6 .65

Energy Intake (Kcals/d)

Energy Expenditure (Kcals/kg/d)

“The greater satiety from the higher protein content of the Atkins diet may have contributed to the benefits observed for that group”

Gardner et al., JAMA 2007;297:969-977.

Weigle et al., AJCN 2005;82:41-48

Santesso et al., Eur j Clin Nutr 2012;66:780-788

(38 studies)

Belza et al., Am J Clin Nutr2013;97:980-989

N = 25 MalesNP = 14%enPMP = 25%enPHP = 50%enP

Brennan et al., Am J Physiol2011;303:G129-G140

N = 16 Lean, 16 Obese Adults

HF = 6.2gP (~12%en)HC = 9.8gP (~17%en)HP = 23.3gP (~44%en)

LP = 6.2gP (~12%en)AP = 15.2gP (~29%en)HP = 23.3gP (~44%en)

Brennan et al., Am J Physiol2011;303:G129-G140

N = 16 Lean, 16 Obese AdultsHF = 6.2gP (~12%en)HC = 9.8gP (~17%en)HP = 23.3gP (~44%en)

Brennan et al., Am J Physiol2011;303:G129-G140

N = 16 Lean, 16 Obese AdultsLP = 6.2gP (~12%en)AP = 15.2gP (~29%en)HP = 23.3gP (~44%en)

Energy Intake

Recent ReviewLeidy et al., AJCN – Protein Summit 2

• Acute feeding trial >120 minutes• Low and high protein isoenergetic meals• Protein differential >10g• <40% of meal as fat• Outcomes of: appetite ratings, food intake, or

measured hormones • 24 Studies

Percent Favoring High ProteinOutcome Percent of Studies

Hunger (reduction) 35%

Fullness (increase) 55%

Ghrelin (reduction) 37%

GLP-1 (increase) 47%

PYY (increase) 47%

Food Intake (reduction) 18%

Authors Duration Effects on Satiety Effect on Food Intake

Johnson, 1993Poppitt, 1998Porrini, 1995Rolls, 1988Stubbs, 1996Stubbs, 1999Johnstone, 1996Barkling, 1990DeGraaf, 1992Geliebter, 1978Long, 2000Hill, 1986Holt, 1995Vanderwater, 1994Westerterp-Plantenga, 1999Booth, 1970Ludwig, 1999Araya, 2000Porrini, 1997Teff, 1989

90m90m2h2h5h24h15d4hday70m13h/13d1h2h2m24h2.5h5h3.5h2h3h

IncreaseIncreaseIncreaseIncreaseIncreaseIncreaseIncrease

NSNSNS

I (acute) D (chronic)IncreaseIncreaseIncreaseIncrease

-----

DecreaseDecreaseDecreaseDecrease

NSNSNS

DecreaseNSNS-----

DecreaseDecreaseDecrease

NSNS

Summary of Protein Appetite Research

Eisenstein et al., Nutr Rev 2002; 60:189-20036

Authors Form Effect on Hunger Effect on Food Intake

Booth et al.

Hill & Blundell

Hill & Blundell

Rolls et al.

Barkeling et al.

Stubbs et al.

Vanderwater & Vickers

Johnson & Vickers

Poppitt et al.

Lambert et al.

Latner & Schwarts

Driver

de Graaf et al.

Stockley et al.

Sunkin & Garrow

Geilebter

Rumpler et al.

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Solid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid

Liquid (34g)

Decrease

Decrease

Decrease

=

Decrease

Decrease

Decrease

Decrease

Decrease

Decrease

=

=

=

Decrease

Decrease

Decrease

Decrease

=

Decrease

Decrease

Decrease

Decrease

=

=

=

=

=

Summary of Protein Appetite Research

Eisenstein et al., Nutr Rev 2002; 60:189-20037

0

500

1000

1500

2000

2500

3000

3500

4000

Kca

lsEnergy Intake

(N=40)

Liquid

Solid

Liquid

Solid

Liquid

Solid

Carbohydrate Fat Protein

**

*

(Watermellon) (Coconut) (Dairy)

Body Weight

Rate of Weight Loss is Unaffected by Dietary Macronutrient Content

Kinsell, et al Metabolism 13:195, 1964.

160

180

200

220

240

260

280

0 10 20 30 40 50 60 70 80

Days

Fat 12-83%en

Protein 14-36%en

Carbohydrate 3-64%en

In Energy Balance, Weight is Unaffected by Diet Composition

Leibel, et al Am J Clin Nutr 55:350, 1992.

N=16: 13 adults, 3 children

Intervention:15-56 days

Protein: 15%en

Energy Intake of Trappist Nuns Unaffected by Diet Composition

Van Stratum Am J Clin Nutr 31:206, 1978

N=22

Fat: 24 vs 47%en

Protein: 18%en

Dansinger et al., JAMA 2005;293:43-53

Sacks et al., NEJM 2009;360:859-873

Sacks et al., NEJM 2009;360:859-873

Wycherley et al., Am J Clin Nutr 2012; 96:1281-1298

Wycherley et al., Am J Clin Nutr 2012; 96:1281-1298

Fat Mass

Wycherley et al., Am J Clin Nutr 2012; 96:1281-1298

Fat-Free Mass

Dong et al. Br J Nutr 2013; 110:781-189

Patients with Type 2 Diabetes

Santesso et al., Eur JClin Nutr2012;66:780-788

Schwingshackl & Hoffman Nutr J 2013;12:48

Long-Term RCT’s (>12 months)

Clifton et al., Nutr Metab & Cardiovasc Dis 2014;24:224-235

Clifton et al., Nutr Metab 7 Cardiovassc Dis 2014;24:224-235

Long-Term Weight Maintenance ( Follow-up >12 months)

ThermogenicEffect of Feeding

Ravn et al., Food Nutr Res 2013;57: 19676

TEF and Appetite

Weigle et al., AJCN 2005;82:41-48

Table 3. Thermic Effect of Feeding (TEF)____________________________________________________________________________

Author Duration (hours) Diet TEF %____________________________________________________________________________Crovetti10 7.0 68% P, 19% F, 12% C 11.0

69% C, 21% F, 10% P 4.070% F, 21% C, 9% P 4.2

Swaminathan20 1.5 100% P 6.3100% C 3.3100% F 1.012% P, 33% F, 55% C 5.4

Welle21 4.0 100% P 10.3100% C 7.3100% F 6.5

Schutz22 4.0 14% P, 59% C, 27% F 6.55% P, 64% C, 31% F 3.5

Robinson23 9.0 77% P, 7% F, 16% C 11.577% C, 7% F, 16% P 8.0

Karst24 6.0 100% P 20.7100% C 4.7

Nair25 2.6 100% P 15.0100% C 6.0100% F 7.0

Westerterp26 24.0 29% P, 61% C, 10% F 14.69% P, 30% C, 61% F 10.5

Hendler27 3.0 95% P, 2% C, 3% F 4.041% P, 55% C, 4% F 5.8

Steiniger28 6.0 100% P 22.0100% C 5.7

P = protein, F = fat, C = carbohydrate

Eisenstein et al., Nutr Rev 2002;60:189-200

Thermogenic Contribution to Energy Balance

2000 Diet Kcal (15%P; 30%F; 55%F) 130 Kcals2000 Diet Kcal (30%P; 30%F; 40%F) 153 Kcals

TEF = 0.132P(g) + 0.051F(g) + 0.054C(g)

*Requires ~2-fold increase in Energy from Protein

REE

Wycherley et al., Am J Clin Nutr 2012; 96:1281-1298

Resting Energy Expenditure

Leidy et al., Obesity 2007;15:421-429

46 overweight-obese f adult females

12 week 750kcal deficit diet

18%en or 30%en Protein

Contribution of Lean Body Mass To Energy Balance

Mean Muscle mass of young, male

Mean muscle mass of elderly female

35 – 50Kg

<13kg

2 kg differences of lean mass ~20 kcal/d

Wolfe RR. AJCN 2006;84:475-482.

Summary• Higher protein diets:• May enhance fullness under selected conditions• Have higher thermogenic properties that may modestly

aid weight loss or maintenance• Are associated with greater retention of lean body

mass and higher resting energy expenditure• May be associated with lower energy intake acutely• May promote modest reduction of body weight and fat

mass • May aid weight maintenance

Small Changes:

Are They Meaningful?

Future Directions:Leveraging Protein for Weight management

Quantify the contributions from:– Each mode of action– Satiety, palatability, and protein balance– Protein sources, food form, pattern of intake– Individual differences