Update on Low Carbohydrate Diets: Research and Clinical Implementation Part 1

Transcription

1 Update on Low Carbohydrate Diets: Research and Clinical Implementation Part 1 Eric C. Westman, M.D. M.H.S. Duke University Medical Center Durham, North Carolina ewestman@duke.edu Associate Professor of Medicine Course Director, Medical Management of Obesity Vice-president, American Society of Bariatric Physicians Fellow, The Obesity Society Co-author of The New Atkins for a New You 1

2 Assumptions About Diets Humans must eat 120 grams of carbohydrate daily Low carb diets cannot lead to weight loss because they don t explicitly restrict calories Low carb diets are high protein diets LCKDs cause harmful ketosis Low carb diets are hard to maintain LCKDs diets increase cardiometabolic risk 2

3 Human Essential Nutrients Water Energy Mineral elements Major: calcium, phosphorus, potassium, sulfur, sodium, chlorine, magnesium Trace: iron, iodine, copper, zinc, manganese, cobalt, chromium, selenium, molybdenum, fluorine, tin, silicon, vanadium Amino acids Isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, valine Fatty acids Linoleic, linolenic Vitamins Water soluble: thiamine (B1), riboflavin (B2), pyridoxine (B6), cobalamine (B12), niacin, pantothenic acid, folic acid, biotin, lipoic acid, vitamin C Fat-soluble: vitamins A, D, K, E Other Inositol, choline, carnitine Harper AE. Defining the essentiality of nutrients. In Shils ME et al, eds. Modern Nutrition in Health and Disease. Baltimore, William & Wilkins, 1999, pp

4 Daily Carbohydrate Requirements The lower limit of dietary carbohydrate compatible with life apparently is zero, provided that adequate amounts of protein and fat are consumed. The minimal amount of exogenous and endogenous carb is dependent upon the brain ( g glucose/d). After ketoadaptation, 80% of the CNS energy can be derived from ketones, leaving g glucose/d. Endogenous glucose production rate: mg/kg/min ~ g/kg/day. In a 70 kg man, this represents g/day. Institute of Medicine, Dietary Reference Intakes,

5 Energy Processing With Carbohydrate Food Lipids Carbohydrates Proteins Fatty acids + glycerol Amino acids Pyruvate Acetyl coa 5

6 Energy Processing Without Carbohydrate Food Lipids Proteins Fatty acids + glycerol Amino acids Pyruvate Acetyl coa 6

7 Effect of Very Low Carbohydrate Diets or Starvation on Carbohydrate Metabolism Ref Subjects CHO/Kcal Duration AcAc b-oh-b Glu Insulin mmol/l mmol/l mg/dl Phinney 9 20g 28d Pre Lean kcal/kg Post Langfort 8 < 5% 3d Pre Lean 32 kcal/kg Post Sharman 20 46g 56d Pre Lean 2400 kcal Post Atkinson 7 0.5g 42d Pre Obese 1800 kcal Post Hall 10 Starvation 12d Pre Obese Post Westman EC. Journal of Clinical Outcomes Management 1999;6: Sharman MJ et al. J Nutr 2002;132:

8 Effect of Very Low Carbohydrate Diets on Weight and Lipids Ref Subjects CHO/Kcal Duration Weight Chol Trig LDL Larosa 24 0g/? 2 mo. Pre Obese Post Golay 22 40g/ wk Pre Obese Post Willi 6 25g/675 2 mo Pre Obese Post Young 3 30g/ wk Pre Obese Post 86.0 Rabast 14 40g/ wk Pre Obese Post Rabast 25 25g/ mo Pre Obese Post Westman EC. Journal of Clinical Outcomes Management 1999;6:

9 Effect of Very Low Carbohydrate Diets on Weight and Lipids Ref Subjects CHO/Kcal Duration Weight Chol Trig LDL Rickman 12 7g/ d Pre Lean Post Azar 6 1g/2000 4d Pre Lean Post Phinney 9 20g/? 4 wk Pre Lean Post Newbold 7?/? 3-18 mo Pre ? Post Westman EC. Journal of Clinical Outcomes Management 1999;6:

10 Assumptions About Low Carbohydrate, High Fat Diets Humans must eat 120 grams of carbohydrate daily Low carb diets cannot lead to weight loss because they don t explicitly restrict calories Low carb diets are high protein diets LCKDs cause harmful ketosis Low carb diets are hard to maintain LCKDs diets increase cardiometabolic risk 10

11 Low Carbohydrate Ketogenic Diet Program Over Six Months: Pilot Study 51 overweight volunteers Low Carbohydrate Diet instruction + group meetings + exercise recommendation + nutritional supplements Westman et al. Am J Med 2002;113:

12 Mean Percent Change in Body Weight (sem) 0 Pilot Low Carb Study: Weight loss over 6 months Change = % Wk 0 Wk 2 Wk 4 Wk 6 Wk 8 Wk 10 Wk 12 Wk 16 Wk 20 Wk 24 Duration of Intervention * p < comparing Week 0 to Week 24 (n=41). Westman et al. Am J Med 2002;113:

13 Very Low Carb Diet Program vs. Low Fat Diet Randomized Controlled Trial 120 overweight, hyperlipidemic volunteers R Low Fat, Low Calorie Diet + group meetings + exercise recommendation Low Carbohydrate Diet (no mention of Calories) + group meetings + exercise recommendation + nutritional supplements Yancy et al. Ann Intern Med 2004;140:

14 Mean (SEM) % Change in Body Wt Percent Change In Body Weight Low Fat Low Carb %* %* Wk 0 Wk 2 Wk 4 Wk 6 Wk 8 Wk 10 Duration of Intervention * p < , for within-group change from Baseline to Week 24 for each diet group. Wk 12 Wk 16 Wk 20 Wk 24 p = , for comparison between diet groups at Week

15 Assumptions About Low Carbohydrate, High Fat Diets Humans must eat 120 grams of carbohydrate daily Low carb diets cannot lead to weight loss because they don t explicitly restrict calories Low carb diets are high protein diets LCKDs cause harmful ketosis Low carb diets are hard to maintain LCKDs diets increase cardiometabolic risk 15

16 Diets, Carbohydrates and Calories CHO Grams/day 300 Typical American Diet Low Carbohydrate Ketogenic Diet (Ketonuria) Very Low Fat Diet Low Glycemic Index Diet Mediterranean Diet Zone Diet Atkins Maintenance Diabetes Solution Atkins Induction Protein Power Calories/day 16

17 Six-month Pilot Study: Diet Composition Composition Mean Daily Intake % of Daily Caloric Intake Protein g 32.1 Fat 95.5 g 59.6 Carbohydrate 22.3 g 6.5 Calories kcal Westman et al. Am J Med 2002;113:

18 LCKD vs. LFD Diet Composition Diet Component Low Fat (n=7) Low Carb (n=13) Protein 73g (18%) 109g (30%) Fat 54g (31%) 98g (60%) Carbohydrate 201g (51%) 35g (10%) Energy 1588 kcal 1472 kcal * Food records are from the entire 6 months 18

19 Low Carbohydrate Diet Composition Usual Diet (3111 kcal/d) Low Carb (2164 kcal/d) gm/d net carb fiber protein fat Boden G et al. Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med 2005;142:

20 Assumptions About Low Carbohydrate, High Fat Diets Humans must eat 120 grams of carbohydrate daily Low carb diets cannot lead to weight loss because they don t explicitly restrict calories Low carb diets are high protein diets LCKDs cause harmful ketosis Low carb diets are hard to maintain LCKDs diets increase cardiometabolic risk 20

21 The Role of Ketones Ketone bodies: molecules that deliver energy Ketones can be used by all cells except erythrocytes, cornea, lens, retina, renal medulla Ketone levels increase when dieting Fed state 0.1 mmol/l Overnight fast 0.3 mmol/l Low-carb ketogenic diet 1 3 mmol/l > 20 days fasting 10 mmol/l Diabetic ketoacidosis 25 mmol/l Serum ph did not decrease below 7.37 in a study performing arterial blood gas analyses Meckling KA, Can J Physiol Pharmacol, 2002; Coleman MD, J Am Diet Assoc, 2005; Yancy WS, Eur J Clin Nutr,

22 Metabolism Society, Spring 2011 Conference on Ketone Bodies Review of Biochemistry of Ketone Bodies Ketone Body Effects on Cardiac Energetics and Glycolytic Flux Ketone Bodies and Cancer Human Keto-adaptation: Physiology and Function Anti-ketogenic Effect of Insulin and Dietary Carbohydrate Clinical Treatments using Nutritional Ketosis The Ketogenic Diet for Epilepsy 22

23 Assumptions About Low Carbohydrate, High Fat Diets Humans must eat 120 grams of carbohydrate daily Low carb diets cannot lead to weight loss because they don t explicitly restrict calories Low carb diets are high protein diets LCKDs cause harmful ketosis Low carb diets are hard to maintain LCKDs diets increase cardiometabolic risk 23

24 Low Carbohydrate Internet-based Support Group Survey Active Low-Carber Forum is an on-line support group started in 2000 and in 2008 had 86,000 An anonymous 2-item survey was posted to describe the attitudes and behaviors of people following low carbohydrate diets Survey respondents (n=2000) were predominantly female, overweight, and following the Atkins diet or some variation of it Over 1400 claimed to have used a low carb diet to lose and maintain at least a 30 pound weight loss 28% of respondents reported that their doctor was initially neutral but supportive after favorable results were obtained Feinman RD, Vernon M, Westman EC. Nutrition Journal 2006;5:26. 24

25 Low Carbohydrate Diet Are Very Popular in Sweden (Google Searches for Popular Diets in Sweden 2008-present) Low Carbohydrate High Fat Low Glycemic Index Weight Watchers (Andreas Eenfeldt, 25

26 Assumptions About Low Carbohydrate, High Fat Diets Humans must eat 120 grams of carbohydrate daily Low carb diets cannot lead to weight loss because they don t explicitly restrict calories Low carb diets are high protein diets LCKDs cause harmful ketosis Low carb diets are hard to maintain LCKDs diets increase cardiometabolic risk 26

27 Effect on Serum Lipids Variable Baseline Wk8 Wk16 Wk24 Change mg/dl mean mean mean mean Cholesterol %* Triglycerides %* LDL %* HDL %* Chol/HDL %* Westman et al. Am J Med 2002;113:

28 Effects on Serum Lipids Low Fat (n=32) Low Carb (n=44) Variable (mg/dl) Week 0 Week 24 Change Week 0 Week 24 Change Cholesterol %* % Triglyceride %* %* LDL-C % % HDL-C % %* Chol/HDL % %* Trig/HDL % % * p < 0.01, for within-group changes from Baseline. p < 0.05 for between-groups comparisons. 28

29 mg/dl mg/dl Effect on Fasting Lipid Subclasses LOW FAT DIET GROUP LOW CARBOHYDRATE DIET PGM * Baseline (n=27) Week 6 (n=27) Week 12 (n=27) Week 24 (n=27) * Baseline (n=36) Week 6 (n=36) Week 12 (n=36) Week 24 (n=36) * * 0 0 Large VLDL Intermed VLDL Small VLDL IDL Large LDL Intermed LDL Small LDL Large HDL Small HDL Large VLDL Intermed VLDL Small VLDL IDL Large LDL Intermed LDL Small LDL Large HDL Small HDL * p < 0.05 for comparison between groups Westman et al. Int J Cardiol 2006;110:

30 mg/dl Effect on Fasting Lipid Subclasses LOW FAT DIET GROUP LOW CARBOHYDRATE DIET PGM Baseline (n=35) Week 24 (n=35) Baseline (n=43) * Week 24 (n=43) * * * * 0 0 Large VLDL Intermed VLDL Small VLDL Large LDL Small LDL Large HDL*10 Small HDL*10 LDLP*100 Large VLDL Intermed VLDL Small VLDL Large LDL Small LDL Large HDL*10 Small HDL*10 LDLP*100 Seshadri et al. Am J Med 2004;117: (Subanalysis of Samaha, Stern papers) * p < 0.05 for comparison between groups 30

31 Outpatient LCKD Randomized Controlled Trials: Design Reference Design Setting Patients Duration Visits Sondike 2003 RCT Clinic Healthy teens 3m q2wk Brehm 2003 RCT Clinic Healthy adults 6m q2wk x 6, 6mo Samaha 2003 Stern 2004 RCT Clinic Outpt adults 6m 12m qwk x 4, then monthly Foster 2003 RCT Clinic Healthy adults 12m q2wk x 2, q4wk x 4, then Wk 26, 34, 42, 52 Yancy 2004 RCT Clinic Brinkworth 2009 RCT Clinic Healthy adults Healthy adults Nordmann et al. Arch Intern Med 2006;166: m 12 m q2wks x 6, then monthly q2wks x 4, then monthly 31

32 Outpatient LCKD RCTs: Weight Loss and Serum Lipids Low Fat Low Carbohydrate Ref Duration Weight LDL Trig HDL Weight LDL Trig HDL Sondike 3 mo -4.1kg -17%* -6% +2% -9.9kg* +4% -48%* +4% n=30 Brehm 6 mo -3.9kg -5% +2% +8% -8.5kg* 0% -23%* +13% n=42 Samaha/ 6 mo -1.9kg +3% -4% -2% -5.8kg* +4% -20%* 0% Stern 12 mo -3.1kg -3% +2% -12% -5.1kg +6% -29% -2% n=132 Foster 6 mo -5.3kg -3% -13% +4% -9.7kg* +4% -21% +20%* n=63 12 mo -4.5kg -6% +1% +3% -7.3kg +1% -28%* +18%* Yancy 6 mo -6.5kg -3% -15% -1% -12.0kg* +2% -42%* +13%* n=119 Brinkworth 12 mos -11.5kg +3% -12% 0% -14.5kg +3% -35% +21% N=40 * p<0.05 for between-groups comparison 32

33 Popular Diet Effects on Weight Loss and Cardiac Risk Factors To approximate the realistic long-term sustainability of each diet, we asked participants to follow their dietary assignment to the best of their ability to their 2 month assessment, after which time we encouraged them to follow their assigned diet according to their own selfdetermined interest level. 2 months ( efficacy ) Group n kcal/d CHO PRO FAT Weight LDL Trig HDL L/H Atkins g kg Zone kg WWatchers kg Ornish kg months ( effectiveness ) Group n kcal/d CHO PRO FAT Weight LDL Trig HDL L/H Atkins g kg Zone kg WWatchers kg Ornish kg Dansinger ML et al. JAMA 2005;293:

34 Popular Diet Effects on Weight Cardiac Risk Among Women Each diet group attended 1-hour classes led by a registered dietician once per week for 8 weeks and covered approximately one eighth of their respective books per class...efforts to maximize retention included and telephone reminders and incentive payments. 2 months ( efficacy ) Group n kcal/d CHO PRO FAT Weight LDL Trig HDL DBP Atkins ~62g kg Zone kg LEARN kg Ornish kg months ( effectiveness ) Group n kcal/d CHO PRO FAT Weight LDL Trig HDL DBP Atkins ~140g kg Zone kg LEARN kg Ornish kg Gardner CD et al. JAMA 2007;297:

35 Effect of Diet Programs on Metabolic Syndrome Parameters From Baseline to 12 Months Atkins Zone LEARN Ornish P (n=77) (n=79) (n=79) (n=76) value BMI, kg/m Waist-hip ratio HDL-C, mg/dl Triglycerides, mg/dl Non-HDL-C, mg/dl Insulin, mu/ml Glucose, mg/dl Diastolic b.p., mmhg Systolic b.p., mmhg <0.001 Gardner CD et al. JAMA 2007;297:

36 Re-examination of the A to Z Study [Gradner et al. JAMA 2007] Women divided into tertiles based on insulin resistance Weight loss at 12 mo: Simply put, insulin resistance strongly influences how we respond to different diets Insulin Resistant Low Carb Low Fat lbs -3.3 lbs Validates the concept that insulin resistance is essentially an expression of carbohydrate intolerance Insulin Sensitive lbs -9.0 lbs Gardner, C.D., et al., Insulin Resistance - An Effect Moderator of Weight Loss 36 Success on High vs. Low Carbohydrate Diets. Obesity, : p. S82.

37 Carbohydrate Restriction Treats Metabolic Syndrome Volek JS, Feinman RD. Carbohydrate restriction improves the features of Metabolic Syndrome: Metabolic syndrome may be defined by the response to carbohydrate restriction. Nutr Metab 2005;2:31. Feinman RD, Volek JS. Carbohydrate restriction as the default treatment for type 2 diabetes and metabolic syndrome. Scand Cardiovasc J 2008;42: Accurso A et al. Dietary carbohdyrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal. Nutr Metab 2008;5:9. Volek JS, Fernandez ML, Feinman RD, Phinney SD. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res 2008;47: Volek JS et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009;44:

38 Low Carb vs. Low Fat Diet + Orlistat Study Design 146 overweight VA outpatient volunteers R Low Fat Diet + Orlistat group meetings for 48 wks exercise recommendation multivitamin daily Orlistat 120 mg three times a day Low Carb Ketogenic Diet group meetings for 48 wks exercise recommendation multivitamin daily Yancy, Arch Int Med,

39 Mean % Weight Change Over Time* Orlistat + Low Fat Diet Low Carbohydrate Diet n= n=

40 Change in Blood Pressures at 3 Time points Change in Blood Pressure by Treatment Arm ΔmmHg SBP LCKD DBP SBP O+LFD DBP Δ at 4 weeks Δ at 24 weeks Δ at 48 weeks 4 wks (-0.5 v.+0.1; p<.001) 24 wks (-3.0 v.+0.7; p<.001) 48 wks (-5.9 v.+1.5; p<.001) 40

41 Facts About Low Carbohydrate, High Fat Diets Carbohydrate is not an essential nutrient Low carb diets lead to weight loss because abnormal hunger/appetite goes away Low carb diets are adequate protein diets Nutritional ketosis is a marker of burning fat For many people low carb diets are easy to follow LCKDs diets reduce cardiometabolic risk by addressing the metabolic syndrome 41

42 Metabolic Processing of Saturated Fat Low Fat Diet (208 g CHO/d) Saturated Fat Synthesis Saturated Fat Intake (12 g/d) Saturated Fat Saturated Fat Burned as Fuel Low arbohydrate Diet (45 g CHO/d) Saturated Fat Synthesis Saturated Fat Intake (36 g/d) Saturated Fat Saturated Fat Burned as Fuel Forsythe et al. Lipids. 43(1):65-77,

43 Does Insulin Reduction Explain the Lack of Rise in Serum Cholesterol? Kennedy AR et al. A high fat, ketogenic diet induces a unique metabolic state in 43 mice. Am J Physiol Endocrinol Metab 2007, February 13.

44 Diabetic Diet in the Pre-Insulin Era Quantity of food required by a severe diabetic patient weighing 60 kilograms * Food Calories Carbohydrate 10 grams 40 Protein 75 grams 300 Fat 150 grams 1,350 Alcohol 15 grams 105 1,795 Strict diet : Meats, poultry, game, fish, clear soups, gelatin, eggs, butter, olive oil, coffee, tea * Osler W, McCrae T. The Principles and Practice of Medicine. NY: Appleton and Co., Allen FM. Protein diets and undernutrition in treatment of diabetes. JAMA 1920;74: Newburgh LH, Marsh PL. The use of a high fat diet in the treatment of diabetes mellitus. Arch Int Med 1921;27:

45 Diet: Lipids Observed Very Low Carb Diet Liver Fat Triglycerides Chylomicrons Lymphatics Large LDL Thoracic Duct Superior Vena Cava Triglyceride Atherosclerosis? Cells 45

46 Diet: Lipids Observed Mixed Diet Carbohydrate Simple sugars Portal Vein Sugar Liver Fat Triglycerides Chylomicrons Lymphatics LDL Triglyceride Small LDL VLDL LDL Thoracic Duct Superior Vena Cava Triglyceride Atherosclerosis Cells 46

47 Weight Loss, Improvements in Lipids A 50 year old white female with obesity (BMI = 31.3) wants to lose weight. Fasting lab tests: Date BMI Wt (lbs) Chol Trig LDL HDL Glucose 6/ Initiation of Carbohydrate Restricted Diet 8/ / / She asks, Why wasn t I given this option before? I was just given the options of medications. 47

48 Summary Instructing people to limit carbohydrate grams leads to a spontaneous reduction in caloric intake (without explicitly limiting calories) and: Loss of body weight Improvements in fasting serum lipid profiles (triglyceride, HDL, chol/hdl ratio) Improvement in systolic blood pressure Reduction in waist circumference Low carbohydrate diets can be used in the clinical setting by trained practitioners A low carbohydrate diets is the preferred diet for metabolic syndrome 48