How Low Can You Go? Evidence Update For Low- Carb Eating

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How Low Can You Go?Evidence Update For LowCarb EatingWilliam S. Yancy, Jr, MD MHS FTOSDirector, Duke Diet and Fitness CenterAssociate Professor of MedicineDuke UniversityDisclosures Consultant for Consultant for Guideline CentralLearning Objectives Describe the low-carbohydrate eatingpattern and the rationale behind it Summarize weight loss effects of lowcarbohydrate eating plans Describe potential mechanisms of weightloss during low-carbohydrate eating Describe the effects of low-carbohydrateeating on health and risk factors

Client SB67 yo WM with diabetes, high cholesterol, hypertensionInsulin Units per ContinueMetforminDecreaseatorvastatin0Week 0WeightGlucoseWeek 1Week 2252Week 3236Week 4231190-30084-110TG28468HDL3442LDL533610.58.4Hb A1cOutline Background on low-carbohydrate eatingpattern Weight loss effects How weight loss occurs Health effects5Nutritional Therapy for ObesityE nergy consum ption intended to cause negative calorie balance and lossof fat m assLow -calorie diets:1,200-1,800 kcal/dayR estricted fat dietLow-fat diet:V ery low -calorie diets:Less than 800 kcal/dayP hysiciansupervisionrecom m endedR estrictedcarbohydrate dietLow-glycemic diet:R ecom m endedfor shorterdurationsLow-carbohydratediet50-150 grams/dayFull m ealreplacem entprogram s 30% fat caloriesVery low-fat diet: 10% fat caloriesVery lowcarbohydrate diet 50 grams/day(with or withoutnutritional ketosis)Reference/s: [91] [92] [94] [95] [96] [97] [509]Obesity Algorithm . 2015-2016 Obesity Medicine Association.6

Diets, Carbohydrates, and Calories300Carbohydrate (g/day)Typical U.S. DietLow Glycemic DASHIndex DietDiet200Mediterranean DietRice Diet10050200VLCD(Ketonuria)Duke MCD Zone DietSo. Beach Phase 2Atkins MaintenanceProtein Power, Paleo,So. Beach Phase 1, Duke LCDAtkins Induction, Keto10002000Calories/dayLow Carbohydrate Ketogenic Diet(LCKD) Initially, 20 g of carbohydrates per day––––Unrestricted amounts of meat and eggsFour oz. hard cheeseTwo cups salad vegetablesOne cup low-carbohydrate vegetables Calories not restricted Carbohydrate intake slowly increased asweight goal approached Daily multivitamin, copious liquids, broth

Low Carb / High Fat Diet Rationale:The Role of Insulin Dietary carbohydrate (sugar or starch) raisesserum glucose and insulin A carbohydrate restricted (high fat) diet reducesthe diet contribution to serum glucose, which thenlowers insulin levels Insulin is a potent stimulator of lipogenesis (fatstorage) and a potent inhibitor of lipolysis (fatburning) Lowering insulin levels leads to burning of storedbody fat, raising serum ketones and loweringbody weightHow Low Can You Go?(Or Are Carbohydrates Essential in Humans?)What is known: Humans can endogenously synthesizecarbohydrates Humans do not show signs of deficiency in theabsence of dietary carbohydrates No reports of micronutrient deficiency syndromesin clinical trials of low carbohydrate ketogenic diets RDA for carbohydrates is 130g /day to ensuresufficient glucose for the brain– However, when intake is 130g /day, the body meetsenergy needs of brain with endogenously producedglucose and ketonesTondt J, Nutr Res Rev, In Press.Outpatient Low Carb Trials: Weight LossNDuration(mo)Low-fat(kg)Brehm 2003 †426-3.9-8.5*Yancy 2004‡1196-6.5-12.0*Samaha 2003 †ReferenceLow-carb(kg)1326-1.9-5.8*Foster 2003†636-5.3-9.7*Foster 2003†6312-4.5-7.3Stern 2004 ‡13212-3.1-5.1Dansinger 2005 §16012-3.0-2.1Gardner 2007 §31112-1.6-4.7** p 0.05 for between-groups comparison.For Gardner, comparison was the Zone diet.

RCTs 12 months: Low Carb vs Low Fat-0.91 kg (-1.65, -0.17)Bueno NB, Br J Nutr, 2013.2-Year Low Carbohydrate Diet StudiesFoster G, Ann Intern Med, 2010.Shai I, NEJM, 2008.How Weight Loss Occurs:Calories, Calories, Calories!Bas el ine DietStud y DietMean Calories per day25002000150010005000Low Carb ParticipantsLow Fat ParticipantsYancy WS, Arch Intern Med, 2010.

Calories are Reduced b/c Hunger is LessGibson AA, Obes Rev, 2015.How Weight Loss Occurs: A Little Bit ofWater LossLow Carb (n 59)43Low Fat (n 60)4241-2.4 kg†40-1.8 kg†3924k20Wkk16W12kWkWW8106kWWk42kWkWk038WMean Total Body Water, kg44Duration of Intervention† p 0.05, for comparison between diet groups.Yancy WS, Ann Intern Med, 2004.How Weight Loss Occurs:What About Metabolism?Low carb dietModerate carb dietHigh carb dietEbbeling CB, BMJ, 2018.

Health Effects: Symptomatic EffectsLow fatSymptom(n 60)Constipation35%Headache40%Bad breath8%Muscle cramps 7%Diarrhea7%Weakness8%Rash0%Low carb(n 59)68%60%38%35%23%25%13%P value .001.03 .001 . WS, Ann Intern Med, 2004.Comparison of Participant CompletionRates of Low-Fat vs Low-Carb Diet StudiesEach pointrepresents acomparisonfrom one of19 studies.Feinman RD,Nutrition, 2015.Meta-Analysis: Low Carb vs Low FatNo. ofTrialsNet DifferenceLow Carb – Low Fat95% CIWeight, kg22-1.0 2.2, 0.2Systolic BP, mmHg18-1.0 3.5, 1.5Diastolic BP,mmHg18-0.7 1.6, 0.2HDL-C, mg/dL193.3*1.9, 4.7LDL-C, mg/dL193.7*1.0, 6.4TG, mg/dL20-14.0* 19.4, 8.7Variable*p 0.05 for net change.Hu T, Am J Epidemiol, 2012.

DIRECT (PI-Iris Shai) Study – 6 yearsSchwarzfuchs D,N Engl J Med,2012.Glucose and Insulin Response to 300kcal Meal After 10 days on DietHigh-carb dietIntermediate-carb dietLow-carb diet(n 6)*Glucose AUC lowest for low-carbdiet (p .001).*Insulin AUC different for eachdiet (p .001)Bisschop, J ClinEndocrinol Metab, 2003.Network Meta-analysis Comparing DietEffects on Glycemia in Type 2 DM 56 trials enrolling 4937 participantscomparing 9 diets:– Low-fat, Vegetarian, Mediterranean, high-protein,moderate-carbohydrate, low-carbohydrate,control, low GI/GL, Paleolithic “For reducing HbA1c, the low-carbohydratediet was ranked as the best dietary approach(SUCRA: 84%), followed by theMediterranean diet (80%) and Paleolithic diet(76%) compared to a control diet.”Schwingshackl L, Eur J Epidemiol, 2018.

Other Benefits in Patients with DiabetesRCT using group medical visits (GMVs)– Low-carbohydrate weight loss program vs medicationintensification to improve glycemia Both improved HbA1c by 1% Additionally, low-carbohydrate program led to:– Greater weight loss by 3.7 kg– Reduction in diabetes medication vs increase incomparison arm– Transient greater improvement (during greatestweight differences) in diabetes-related distress– 50% reduction in hypoglycemia eventsYancy WS Jr, JAMA Intern Med, 2019.Client RJT64 yo WF with sleep apnea, diabetes, fatty liver,hypertension, mild 201320162018Weight200199182151144138BP rilCarvedilolLisinoprilLisinoprilDM acinFish oilsPitavastatinFish oilsFish oilsFish oilsHb 56984CRP1.341.081.040.42Low Carb Take Home Points Low carbohydrate intake leads to spontaneousreduction in calorie intake and lower insulin levels Body fat breaks down into ketonesà used for energy Early diuresis requires adequate intake of fluid and salt Weight loss mildly better on average than comparison If carbohydrate is added back, do it gradually Blood pressure and triglycerides decrease, HDLincreases LDL does not typically increase BUT it does at times Blood sugar decreases profoundly--reduce medicationsat diet start!

Duke Diet and Fitness Center28Extra Slides29Active Learning Question #1Compared with low-fat eating patterns, lowcarbohydrate eating patterns typically lead towhich of the following changes in serum lipidprofiles?A. Lower HDL cholesterol levelB. Higher HDL cholesterol levelC. Lower LDL cholesterol levelD. Higher triglyceride levelE. Higher triglyceride: HDL ratio30

Active Learning Question #1Compared with low-fat eating patterns, low-carbohydrate eatingpatterns typically lead to which of the following changes in serum lipidprofiles?A. Lower HDL cholesterol levelB. Higher HDL cholesterol levelC. Lower LDL cholesterol levelD. Higher triglyceride levelE. Higher triglyceride: HDL ratioRationale: Multiple randomized clinical trials in various populations andmeta-analyses of these trials have shown that low-carbohydrate eatingpatterns lead to higher HDL cholesterol and lower serum triglycerideswhereas low-fat eating patterns lead to lower LDL cholesterol.Ref: Hu T et al. Am J Epidemiol. 2012;176 Suppl 7:S44-54.31Active Learning Question #2There are data to support that weight lossfrom a low-carbohydrate eating pattern isrelated to which of the following?A. Water loss from use of glycogen storesB. Water loss related to lower insulin levelsC. Reduced calorie intakeD. Increased energy expenditureE. All of the above32Active Learning Question #2There are data to support that weight loss from a low-carbohydrate eating pattern is related to which ofthe following?A.Water loss from use of glycogen storesB.Water loss related to lower insulin levelsC.Reduced calorie intakeD.Increased energy expenditureE.All of the aboveRationale: Water loss occurs particularly in the early phase of a low-carbohydrate eating pattern and isthought to be due to a combination of water release that occurs as glycogen stores are used andchanges that occur in the kidney when insulin levels are lower resulting in greater release of sodiumand water. Multiple studies have shown that low-carbohydrate eating leads to reduced appetite andcalorie intake. Studies by Ebbeling show increased energy expenditure measured by doubly labelledwater occurs on a low-carbohydrate eating plan.Ref:Yancy W S JR et al. Ann Intern Med 2004;140(10):769-77.Yancy W S JR et al. Arch Intern Med 2010;170(2):136-145.Ebbeling CB et al. BMJ. 2018;363.33

Current Treatment Options for ObesitySurgery(In order of lowest risk/costand potency):LAGB VSG RNYVery Low Calorie DietPotency*Lifestyle MedicationIncludes lifestyle, and antiobesity medicationsLifestyleIncludes nutrition, physicalactivity, and behavioralprogramsRisk/Cost*Potency includes many factors, such as the amount, rate, and sustainability of weight loss, and the long-term resolution of adiposopathy and fat mass disease.Potency varies greatly for each individual (i.e., long-term adherence to a lifestyle program can be as potent as gastric bypass surgery).Obesity Algorithm . 2015-2016 Obesity Medicine Association.34The Role of Ketones Ketone bodies: molecules that deliver energy Ketones can be used by all cells excepterythrocytes, cornea, lens, retina Ketone levels increase when dieting–––––Fed stateOvernight fastLow-carb diet—induction 20 days fastingDiabetic ketoacidosis0.1 mmol/L0.3 mmol/L1–3 mmol/L10 mmol/L25 mmol/L Serum pH did not decrease below 7.37 in astudy performing arterial blood gas analysesMeckling KA, Can J Physiol Pharmacol, 2002; Coleman MD,J Am Diet Assoc, 2005; Yancy WS, Eur J Clin Nutr, 2007.Are Carbohydrates Essential in Humans?Definitions: Physiological essentiality- substance that is indispensablefor life (eg, cholesterol) Nutritional essentiality- substance that is indispensable inthe diet (eg, leucine, linoleic acid, vitamin A, calcium, copper)– required in the diet for growth, health, and survival– inadequate intake results in characteristic signs of a deficiencydisease– signs of deficiency are prevented only by the nutrient or aspecific precursor of it, not by other substances– substance is not synthesized in the body and is thereforerequired to be obtained from the diet Nutrients that can be removed from the diet without causinggrowth failure or disease are classified as nonessentialTondt J, Nutr Res Rev, In Press,

RCTs Comparing LC vs LF DietsPublic Health CollaborationFind out more at: Before/After Low Carb EffectsNo. ofReportsNet Change95% CIWeight, kg28-7.0*-7.2, -6.9Systolic BP,mmHg22-4.8*-5.3, -4.3Diastolic BP,mmHg22-3.1*-3.5, -2.7HDL-C, mg/dL221.7*1.4, 2.0LDL-C, mg/dL22-0.5-1.5, 0.6TG, mg/dL19-29.7*-32.0, -27.4Variable*p 0.05 for net change.Santos FL, Obes Rev, 2013.Variability of Change in WeightOrlistat Low Fat DietLow Carbohydrate DietYancy WS Jr, Arch Intern Med, 2010.

Heart Disease Risk for Types of Fat% Change in CHD10080Trans(p 0.001)6040200-20-40Saturated(p 0.1)1%E2%E3%E4%E5%EMonounsaturated(p 0.05)Polyunsaturated(p 0.003)Risk for replacement of X% of energy from carbohydrate by fat.Hu et al. NEJM, 1997. (Nurses’ Health Study)Meta-analysis:Associationof SaturatedFat with HeartDisease andStrokeSiri-Tarino PW,Amer J ClinNutr2009Meta-analyses: Saturated Fat Intake and Heart DiseaseSkeaff CM, Ann Nutr Metab, 2009 (Cohort studies: 28 studies, N 280,000, f/u 4-25y) Total fat intake and CHD mortality 0.94 (95% CI 0.74 to 1.18) Saturated fat intake and CHD mortality RR 1.14 (95% CI 0.82 to 1.60)Schwingshackl L, BMJ Open, 2014 (RCTs of secondary prevention: 12 trials, N 7150) Reduced fat or modified fat diets did not reduce all-cause mortality, CHD mortality, or CV eventsSiri-Tarino, Amer J Clin Nutr, 2010 (Prospective cohort studies: 16 studies, N 347,747) Saturated fat and CHD RR 1.07 (95% CI 0.96 to 1.19)Chowdhury R, Ann Intern Med, 2014 (Prospective cohort studies: 32 studies, N 530,525) Saturated fat and CHD RR 1.02 (95% CI 0.97 to 1.07)de Souza, BMJ, 2015 (Prospective cohort studies: 12 studies, N 339,090) Saturated fat and all cause mortality RR 0.99 (95% CI 0.91 to 1.09)Saturated fat and CVD mortality RR 0.97 (95% CI 0.84 to 1.12) Saturated fat and ischemic stroke RR 1.02 (95% CI 0.90 to 1.15) Saturated fat and type 2 diabetes RR 0.95 (95% CI 0.88 to 1.03)Hooper L, Cochrane, 2015 (RCTs of primary or secondary prevention: 12 trials: N 54,000 ) Saturated fat and all-cause mortality RR 0.97 (95% CI 0.90 to 1.05)Saturated fat and CV mortality RR 0.95 (95% CI 0.80 to 1.12)Harcombe Z, Open Heart, 2016 (RCTs of primary or secondary prevention: 10 trials, N 62,421, mean f/u 5.4y) Mean serum total cholesterol lowered Total/saturated fat and all-cause mortality RR 0.99 (95% CI 0.94 to 1.05)Total/saturated fat and CHD mortality RR 0.98 (95% CI 0.88 to 1.08)Harcombe Z, Br J Sports Med, 2017 (Cohorts 7 studies; N 89,801; mean f/u 11.9y) Total fat intake and CHD mortality RR 1.04 (95% CI 0.98 to 1.10) Saturated fat intake and CHD mortality RR 1.08 (95% CI 0.94 to 1.25)

Predicted Changes in Blood Cholesterolbasedon Types of Fat Intake8Saturated fat6Mono unsaturated fatPol yunsaturated fat4% Change20-2-4-6-8-10H DL-CLDL-CLDL-C /HD L-CTGBased on replacement of 5% of energy as carbohydrate with fatty acid.Mensink RP, Arterioscler Thromb, 1992; Hu FB, Willet WC. JAMA 2002.SystematicReviewOf Diabetes% change in HbA1c by% dietary carbohydrate13 trials metcriteria: 45%carbohydrate 2 to 26 weekdurationKirk JK, JADA, 2008.Network Meta-analysis Comparing DietEffects on Glycemia in Type 2 DM Size of nodes:proportionalto total Nallocated toeach diet Thickness oflines:proportionalto number ofstudies ofeach directcomparisonSchwingshackl L, Eur J Epidemiol, 2018.

Zone Diet Typical U.S. Diet Rice Diet) Duke MCD 20 0 50 100 200 300 Calories/day 1000 (Ketonuria) Low Glycemic Index Diet Mediterranean Diet Protein Power, Paleo, So. Beach Phase 1, Duke LCD Atkins Induction, Keto So. Beach Phase 2 Atkins Maintenance DASH Diet VLCD Low Carbohydrate Ketogenic Diet

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