New Twist on Low Carb vs. Low Fat for Weight Loss BOTH appropriate, but not for everyone

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1 New Twst on Low vs. Low for Weght Loss BOTH approprate, but not for everyone Sponsored by the Unversty of Arzona College of Medcne at the Arzona Health Scences Center Chrstopher Gardner, PhD Stanford Preventon Research Center Stanford Unversty, Department of Medcne Clncal Gudelnes on the Identfcaton, Evaluaton, and Treatment of Overweght and Obesty n Adults The Evdence Report. Natonal Insttutes of Health. Obes Res 1998;6(Suppl):1S9S. No dsclosures ~1% >% <3% % energy from carbohydrate 3% energy from fat and approxmately 1% energy from proten Obesty Trends* Among U.S. Adults BRFSS, 199, 199, (*BMI 3, or about 3 lbs overweght for 4 person) No Data <1% 1% 14% 1% 19% % 4% % 9% 3% Centers for Dsease Control & Preventon Low carb Hgh carb 1

2 Outlne Low- vs. Low : General Conclusons Insuln Resstance: Effect Moderator Detary Adherence Dfferences Det X Genotype Interacton Practcal Lmtatons of the Terms Low- and Low- Summary Recent Trals: 36 Foster GD, N Engl J Med. 3;348:8-9. Samaha FF, N Engl J Med. 3;348:741. Brehm BJ, J Cln Endocrnol Metab. 3;88: Aude Y, Arch Intern Med. 4;164:141. Stern L, Ann Intern Med. 4;14: Yancy W, Ann Intern Med. 4;14: Dansnger ML, JAMA. ;93:433. McAuley KA, Dabetologa. ;48:8-16. McMllan-Prce J, Arch Intern Med. 6;166: Truby H, BMJ. 6;33: LIMITATIONS: Small sample szes, short duraton (3 months for most), hgh drop-out rates, nadequate det assessment Work-Ste Study: Israel Months weght Change n Low- Medterranean Low- Sha et al, NEJM 8;39: Sample sze Low- Low- p< Medter- ranean Reten -ton 9% 8% 78% The NEW ENGLAND JOURNAL of MEDICINE ESTABLISHED IN 181 February 6, 9 VOL. 36 NO. 9 Comparson of Weght-Loss Dets wth Dfferent Compostons of, and ohydrates Frank M. Sacks, George A. Bray, Vncent J. Carey, Steven R. Smth, Donna H. Ryan, Stephen D. Anton, et al. DESIGN: Study Populaton: n=811 overweght men and women Four Dets: Dfferng n fat, proten, carbohydrate Duraton: years Prmary Outcome: -year weght change Change n body weght % energy C/ F/ P a a r r t ot b e n Months //1 (n=4) Low-, Ave // (n=) Low-, Hgh 4/4/1 (n=4) Hgh-, Ave 3/4/ (n=1) Hgh-, Hgh Sacks et al, NEJM 9;36(9): /811 (8%) completed the 4-month protocol

3 Change n body weght -1 Months Sacks et al, NEJM 9;36(9):89-73 CONCLUSION: Reduced calore dets result n -3 clncally meanngful weght loss regardless of whch -7 macronutrents they 6//1 (n=4) Low-, Ave emphasze. // (n=) Low-, Hgh 4/4/1 (n=4) Hgh-, Ave 3/4/ (n=1) Hgh-, Hgh 64/811 (8%) completed the 4-month protocol Sacks et al, NEJM 9;36(9):89-73 % energy //1 // 4/4/1 3/4/ % energy 1 6//1 // 4/4/1 3/4/ If macronutrent targets of study dets are not met, can the study hypothess be tested? Hgh Target Mean reported ntakes at 6 months and years dd not reach 6 the target levels for macronutrents. month Low- Low ohydrate Hgh ohydrate Average Hgh- If macronutrent targets of study dets are not met, can the study hypothess be tested? Pennngton Bomedcal Research Center If the feld s top scentsts are unsuccessful n achevng detary targets among partcpants. can t be done? A tkns T radtonal (L.E.A.R.N.) 7;97: O rnsh A Weght Loss Det Study Z one 7;97:

4 From Low- to Hgh n= overweght (BMI 7) women, years old % Energy ohydrate 7;97: Zone n=79 LEARN n=79 n=76 7;97: weeks Weekly Classes 6 months Prmary outcome: Weght Change 1 year Secondary outcomes: Lpds, blood pressure, body composton, nsuln, glucose Behavoral / psychosocal measures Appette / food preference measures Zone LEARN 8 weeks 17% 8% 16% % 6 months 18% 1% 63% 3% 9% 1 year 19% 9% % A TO Z Study Det Data NDS 3-day unannounced 4-hr recalls (3,137 recalls) 3% 3% 47% % 3% 46% -1 Weght -3 change as % of Data not presented baselne -7 7;97: Percent weght change across tme, by group -9 Zone LEARN Baselne Baselne weeks months 1 year Partcpants wth avalable data Zone LEARN ;97: A vs. Z p<.3 (Tukey s studentzed range test) % Retenton 1-year 88% 77% 76% 78% Low-ohydrate 1 year % 3% 46% Clncal Gudelnes on the Identfcaton, Evaluaton, and Treatment of Overweght and Obesty n Adults The Evdence Report. Natonal Insttutes of Health. Obes Res 1998;6(Suppl):1S9S. pp) ~1% <3% >% Favored Low WEIGHT p=.3 HDL-C p=.4 SBP p=.1 DBP p=.4 (not adjusted for multple testng) Zone LEARN 8 weeks 17% 8% % 4% 4% 34% % % 3% NOTE: The det of those assgned to wasn t just low carb, t was also hgh proten and hgh fat Natonal Gudelnes 19% % 9% 7;97: % 1% 63% 7;97:

5 Benefts of Hgh PROTEIN? Hgh PROTEIN long term rsk? WEIGHT LOSS, AND RELATED RISK FACTORS Hgh vs. Hgh ohydrate (holdng fat constant) Due, Int J Obes Relat Metab Dsord. 4;8: Farnsworth, Am J Cln Nutr. 3;78: Layman, JNutr;13: Nutr.;13: Noakes, Am J Cln Nutr. ;81: Hgh vs. Hgh (holdng carbohydrate constant) Luscombe-Marsh, Am J Cln Nutr. ;81: Wegle, Am J Cln Nutr. ;8:418. BLOOD PRESSURE AND OTHER RISK FACTORS, WEIGHT STABLE Appel, OMNI-HEART, JAMA. ;94(19):4464 There s no place n your body where extra proten can be stored. All proten that s absorbed s ether used for functonal purposes, or broken down nto fat or carbohydrate. Breakng down and/or elmnatng excess proten nvolves elmnatng ntrogen, whch wll ncrease demands on the kdney, and may leech calcum from bones. 1-month net weght change : Indvdual results ;97: month net weght change : Indvdual results Weght loss s feasble on a wde range of dets, from very-low, to ntermedate, to very-hgh carbohydrate 7;97: Evdence for role of carbohydrate, fat and proten Low- NOT proven to be superor n recent trals Low- has been consstently as or more effectve for weght loss Low- s typcally also Hgh and Hgh Average weght loss s modest after 1 years (~ kg) Long-term adherence to dets s typcally poor Studes are all relatvely short, often too short for weght restablzaton Many nherent challenges nvolved n conductng successful weght loss studes Outlne Evdence for Role of ohydrate, and Insuln Resstance: Effect Moderator Det X Genotype Interacton Practcal Lmtatons of the Terms Low- and Low- Summary

6 Overweght Heterogenety among those who are overweght and obese Heterogenety of CVD & TD Rsk Factors by Insuln Resstance Status (11 apparently healthy volunteers for weght loss study: BMI ) 7 6 Odds Rato 4 3 Tertles of SSPG Most Ins Sens Intermedate Most Ins Res Reference 1 (6-fold dff n SSPG for low vs. hgh tertle) p<.1 for all low vs. hgh tertle Hypertenson (JNC 7 th ) Hypertrglycerdema (ATP III) Low HDL-C (ATP III) Impared Fastng Glucose (ADA) McLaughln et. al. Arch Int Med 7;167:6448 kg BMI 9-36, generally healthy, n top tertle of SSPG (nsuln resstance) Lo H n=3 n=7 p=.3 : : 41 : 41 : 18 7 : : 18 Baselne 16- week ~6 kg Favors Lo Daylong Insuln (AUC)** Daylong TG (AUC)* Favors H LDL-C* Trglycerde* HDL-C** HDL 3-C** LDL-sze* E-selectn* *p<., ** p<.1 Not sgnf. SSPG SBP DBP Daylong glucose (AUC) Total-C Non-HDL-C Apo-B HDL -C ICAM-1 VCAM-1 McLaughln, Am J Cln Nutr, 6;84:8131 selne Change from bas -1 Low-glycemc load det (4:3: carb:fat:proten) Low-fat det (:: carb:fat:proten) All Low-GL n=36 Low-fat n=37 ~Insuln senstve Insuln concentraton <7. µlu/ml at 3 mn after 7-g dose of oral glucose Low-GL n=1 Low-fat n=13 p=.99 p=.9 p=. ~Insuln resstant Insuln concentraton >7. µlu/ml at 3 mn after 7-g dose of oral glucose Low-GL n=13 Low-fat n= Tme (months) CONCLUSION: Reducng glycemc load may be especally mportant to acheve weght loss among ndvduals wth hgh nsuln secreton. Ebbelng, JAMA 7;

7 Insuln senstvty/resstance Moderator of success wth hgh-carb vs. low-carb weght loss Obese, non-dabetc women 4-month feedng study Hypocalorc det H-/Lo- = 6: Lo-/H- = 4:4 CONCLUSIONS: H-/Lo- more effectve for nsuln senstve women Lo-/H- more effectve for nsuln resstant women Dfferences not explaned by changes n ntake, actvty or restng metabolc rate ) Weght Loss Insuln Senstve Fastng Insuln <1uIU/mL H- Lo-fat Lo- H-fat n=6 n=6 P<.1 P<. for fastng nsuln effect Insuln Resstant Fastng Insuln >1uIU/mL H- Lo-fat Lo- H-fat n=4 n= P<. Corner M-A et al. Obesty Research ;13(4):73-9 Insuln senstvty/resstance Moderator of success wth hgh-carb vs. low-carb weght loss Overweght (BMI -3) w & m 6-month feedng study Hypocalorc det (3% restrcton) Hgh GL = 6:: (carb:pro:fat) Low GL = 4:3:3 (carb:pro:fat) CONCLUSIONS: Low GL more effectve than Hgh GL for nsuln resstant adults, but not for nsuln senstve adults. Weght Loss Insuln Senstve INS-3 <66 mu/l Hgh GL Low GL Insuln Resstant INS-3 > 66 mu/l Hgh GL Low GL n=8 n=8 n=8 n=8 p=.3 p=.3 p=.47 p=.7 Pttas al. Dabetes Care ;8: Percent weght change across tme, by group Weght change as % of baselne Baselne weeks months 1 year Partcpants wth avalable data % Retenton 1-year 88% 78% Fastng Insuln Tertles Most Insuln Senstve (<7 µiu/ml) Most Insuln Resstant (>1 µiu/ml) Mean, SEM A TO Z Study: Exploratory analyses Weght loss Det (very low fat, hgh carb) (very low carb, unrestrcted fat and proten) -1-1 n=19 n=4 6 1 Months n=3 n=1 Success wth ether det for those who are relatvely nsuln senstve For those who are nsuln resstant, tradtonal low-fat det neffectve compared to low-carb det Weght Loss by Adherence Tertle (A TO Z Study) 1-Month Weght Change p=.6 n= 3 n= 3 p=.1 n= 19 n= 19 p=.6 n= 19 n= 19 Adherence tertles Hghest Lowest -1 Zone Alhassan, Intl J Obesty, 8; 7:496 7

8 Change n % s +% +1% -1% % -3% % 6 1 Months Fastng Insuln Tertles Lowest (most Ins Sens) Hghest (most Ins Res) +% +% +1% +1% +% % -1% -1% % Assgned to (Lowest ) Change n % s 6 1 Months Assgned to (Lowest ) Effect Moderator: Insuln Resstance Tradtonal Low- det may be partcularly neffectve for weght loss for those wth nsuln resstance Estmate of metabolc syndrome n US ~3% (Ford, JAMA, ) Insuln resstant ndvduals may fnd t nherently more dffcult to adhere to a lower-fat/hgher-carb det 1-month net weght change : Indvdual results ;97: Mult-Locus Genotype Patterns 3 Selecton crtera Genotype assocaton wth obesty/weght management valdated n 3 clncal studes Gene varant functonal, alters bologcal mechansms assocated wth body weght Clncal evdence of gene-det nteracton + genes revewed, 3 selected FABP rs PPARG rs 1818 ADRB rs

9 Mult-Locus Genotype Patterns 3 Selecton crtera Genotype assocaton wth obesty/weght management valdated n 3 clncal studes Gene varant functonal, alters bologcal mechansms assocated wth body weght Clncal evdence of gene-det nteracton 6 months pror to + genes revewed, 3 selected start of study. FABP rs PPARG rs 1818 Ths was a test of ADRB rs PREDEFINED genotype patterns Mult Locus Genotype Patterns Det Category Low- Low- Balanced FABP rs */* G/G A/* G/G Genotypes PPARG rs1818 G/* */* C/C C/C ADRB rs14714 */* G/* */* C/C Expected freq of mult-locus pattern Frequences calculated for Caucasans from Quebec Famly Study A TO Z Frequency Hypothess Overweght/obese women assgned to genotype approprate dets wll lose more weght over 1 months than women assgned to genotype napproprate dets Low ohydrate Genotype (LCG, n=) (n = 19) Zone (n = 9) LEARN (n = 1) (n = 1) Orgnal A TO Z partcpants (n = 311) 173 Not Genotyped Declned future contact (n = 34) Unable to locate (n = 16) Non-responders (n = 74) Contacted, declned (n = ) Swabs not returned (n = 6) Genotyped DNA nsuffcent for analyss (n = 3) (n = 138) 17 Lost to follow-up between: to months (n=) to 6 months (n = 6) 6 to1 months (n = 6) Completed 1-month protocol (n = 11) Low Genotype (LFG, n=48) (n = 11) Zone (n = 13) LEARN (n = 16) (n = 8) Nether Genotype (NG, n=3) (n = 3) Zone (n = 7) LEARN (n = 6) (n = 7) nge Weght Chan at 1 months By Det Group Assgnment 1 Month Weght Loss Zone LEARN n=33 n=9 n=3 n=7 p=.79 Wthout takng genotype pattern nto consderaton nge Weght Chan at 1 months By Genotype Pattern Low Low Nether Genotype Genotype Genotype n= n=48 n=3 p=.8 Wthout takng det group assgnment nto consderaton 1 month weght change Det Group X Genotype Low ohydrate Genotype (n=) A Z L O tk on EA rn n s e R N s h Low Genotype (n=48) A tk n s Z on e L EA R N O rn s h Nether Genotype (n=3) n=19 n=9 n=1 n=1 n=11 n=13 n=16 n=8 n=3 n=7 n=6 n=7 4-1 p-value for nteracton (LCG vs. LFG only) =. A tk n s Z on e L EA R N O rn s h 9

10 *Combnng all matched (n=7) and msmatched (n=33) mean ± sem weght change was.4 ± 1.6 kg vs. -1. ± 1. kg, respectvely (>6-fold dfference) 1 month weght change -1 Approprateness of Det Group X Genotype Match Genotype Assgned to n=19 n=14 p=.4 Matched vs. Msmatched* n=19 LCG & NG n=8 Matched Msmatched LCG LFG & NG Msmatched Matched LFG Gene-Det Interacton Prelmnary evdence suggests smple DNA test could help deters predct lkelhood of greater weght loss success wth a low carb vs. low fat det. Example may help to explan the substantal varablty n weght loss success among dfferent ndvduals tryng to follow the same det. Outlne Evdence for Role of ohydrate, and Effect Moderators: Insuln Resstance and Genetc Predsposton Practcal Lmtatons of the Terms Low- and Low- Summary Detary Macronutrents Low vs. Hgh Overly smplstc Detary Macronutrents Glycemc Index / Load Complex vs. Refned Fber-rch Monounsaturates/Polyunsaturates /Saturated Omega-3 vs. Omega Marne vs. Plant Omega-3 Plant, Marne, Anmal ~1% <3% Low- >% NIH Gudelnes Obes Res 1998;6 (Suppl):1S9S. 1%?? %?? 3%?? 4%?? A TO Z Baselne Det 19% 3% 46% 7;97: Lower than Natonal Gudelnes? Lower than Current Det? 1

11 ohydrates Polysacchardes Dsacchardes How Low? Fber Low Glycemc Hgh Glycemc Sucrose (Table Sugar) Lactose Glucose Fructose Galactose All s? Feces Corn syrup = 1% glucose Hgh fructose corn syrup = % fructose, 4% glucose Or, manly added sugars? ~1% <3% >% Low- 1%?? %?? 3%?? Saturated s Unsaturated C18:1 C16 and C18 C1 and C14 Polyunsaturated Monounsaturated Omega-3 C18: Omega NIH Gudelnes Obes Res 1998;6 (Suppl):1S9S. Natonal Gudelnes? / Prtkn / McDougall? Butter and beef also have a lot of 18:1 (monounsaturated) Coconut Fsh EPA DHA C: C:6 Flax C18:3 Walnuts Sunflower Ol Almonds Olve Ol How Low? Low fat yogurt All s? Manly saturated? All saturated? Plan Raspberry 11

12 Cultured certfed organc low fat pasteurzed mlk Pectn Cultures Cultured certfed organc low fat pasteurzed mlk Organc evaporated cane juce Organc raspberres Pectn Natural flavors Elderberry juce concentrate (for color) Locust bean gum Cultures Calores 9 Cal. % Daly Values Total. g 4% Sat 1. g 8% Cholest. 1 mg 4% Sodum 11 mg 4% Total. 11 g 4% Detary Fber g % Sugars 11 g 7 g 1% Calores 13 Cal. % Daly Values Total. g 3% Sat 1. g 7% Cholest. 1 mg 3% Sodum 9 mg 4% Total. 3 g 8% Detary Fber g % Sugars g 6 g 1% Cultured certfed organc low fat pasteurzed mlk Raspberres (1/ c) Pectn Cultures Cultured certfed organc low fat pasteurzed mlk Organc evaporated cane juce Organc raspberres Pectn Natural flavors Elderberry juce concentrate (for color) Locust bean gum Cultures Calores 1 Cal. % Daly Values Total 3. g 4% Sat 1. g 8% Cholest. 1 mg 4% Sodum 11 mg 4% Total. 18 g 4% Detary Fber 4 g 16% Sugars 14 g 8 g 1% Calores 13 Cal. % Daly Values Total. g 3% Sat 1. g 7% Cholest. 1 mg 3% Sodum 9 mg 4% Total. 3 g 8% Detary Fber g % Sugars g 6 g 1% Practcal Lmtatons of the Terms Low- and Low- How Low (what percentage)? Gen l publc dffculty achevng specfc percentages All types, or specfc types? Packaged food manpulatons Healthy Junk Food? LowER & LowER fat, choose low energy densty / hgh nutrent densty FOODS Overall Summary For average overweght/obese ndvdual, selected at random: Low- s not superor to Low- for weght loss Success wth ether approach s mnmal to neglgble Insuln Resstance: LowER- more approprate Adherence to LowER- better than LowER- Genetc Predsposton: May be ~6-fold dfference n success when approprately matched vs. msmatched Low s relatve, and can be deceptve Thresholds have not been establshed try lower Don t oversmplfy, Low needs to nclude: hgh nutrent densty low energy densty 1