Low Carb Dietary Treatment of Obesity and Metabolic Syndrome
Transcription
Low Carb Dietary Treatment of Obesity and Metabolic Syndrome
Low Carb Dietary Treatment of Obesity and Metabolic Syndrome Eric C. Westman, M.D. M.H.S. Director, Lifestyle Medicine Clinic Associate Professor of Medicine Department of Medicine Duke University Medical Center Durham NC Course Director, Medical Management of Obesity President, American Society of Bariatric Physicians Fellow, The Obesity Society Author, The New Atkins for a New You [email protected] Why am I still hungry if I have all of this extra stored energy? Hormonal Theory of Obesity • • Insulin partitions energy into the fat stores. Insulin “locks in” the energy in the fat store. Energy In Energy Locked In Why am I still hungry if I have all of this extra stored energy? • Inability to access stored fat energy • Carbohydrate ingestion raises insulin levels inhibits fat burning promotes fat storage Carbohydrate Restriction Lowers Serum Insulin Levels and Enhances Lipolysis • Sugar raises the serum glucose • Starches, like bread and pasta, are digested to glucose and raise the serum glucose • A carbohydrate restricted diet reduces the diet contribution to serum glucose, which then lowers insulin levels • Because insulin is a potent stimulator of lipogenesis (fat storage), and inhibitor of lipolysis, lowering insulin levels allows an individual to use their stored body fat Assumptions About Diets • • Humans must eat 120 grams of carbohydrate daily • • • • Low carb diets are “high protein” diets A low carb ketogenic diet (LCKD) cannot lead to weight loss because calories aren’t restricted LCKDs cause “harmful ketosis” Low carb diets are “hard to maintain” LCKDs diets increase cardiometabolic risk 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 3-10. 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 (100-140 g glucose/d).” • After ketoadaptation, 80% of the CNS energy can be derived from ketones, leaving 20-28 g glucose/d. • “Endogenous glucose production rate: 2-2.5 mg/kg/min ~ 2.8 – 3.6 g/kg/day. In a 70 kg man, this represents 210270 g/day.” Institute of Medicine, Dietary Reference Intakes, 2008 Assumptions About Diets • • Humans must eat 120 grams of carbohydrate daily • • • • Low carb diets are “high protein” diets Low carb diets cannot lead to weight loss because they don’t explicitly restrict calories LCKDs cause “harmful ketosis” Low carb diets are “hard to maintain” LCKDs diets increase cardiometabolic risk Diets, Carbohydrates and Calories Carb grams/day 300 Typical American Diet Very Low Fat Diet Low Glycemic Index Diet 200 Mediterranean Diet Zone Diet Atkins Maintenance 100 Low Carbohydrate Ketogenic Diet 50 20 0 (Ketonuria) Diabetes Solution Atkins Induction Protein Power 1000 Calories/day 2000 “Good” Carbs (low-glycemic) “Bad” Carbs (high-glycemic) What Do You Eat on a Low Carb Diet? Low Carbohydrate Ketogenic Diet (< 20 grams carbohydrate per day) • Eggs, bacon (or Sugar-free yogurt with berry slices) • Chicken Caesar salad (or Fast Food burger without the bun) • Snack: olives, cheese stick (or pepperoni slices, chicarrones) • Steak with bleu cheese, broccoli (or salmon with cream sauce) • Drinks: water, sugar-free drinks, coffee w/cream Individuals choose foods that they like from a list of low glycemic foods. Low Carbohydrate Ketogenic Diet EAT AS MUCH AS YOU WISH OF THE FOLLOWING FOODS: Meat: beef, lamb, veal, pork, ham, bacon or any game meat (rabbit, moose, venison) Poultry: chicken, turkey, duck, pheasant or other game birds Seafood: any fish or shellfish including but not limited to salmon, halibut, cod, oolichan, crab, prawns, clams, oysters, mussels, squid, octopus, any smoked, dried or plain canned fish or seafood (not cured with sugar), roe and roe-on-kelp Eggs: whole eggs (do not eat whites without yolks) LIMIT THESE FOODS UNTIL THE DIABETES IS IMPROVED OR ELIMINATED: Salad Greens: __2__ cups a day. Any leafy vegetable including lettuce or other salad greens, parsley, spinach, the tops of green onions, sprouts, fiddleheads, seaweed. (If it is a leaf—you can eat it.) Vegetables: __1__ cup (measured uncooked) a day. Vegetables that grow above the ground, including asparagus, beet greens, bokchoy, broccoli, brussel sprouts, cabbage, cauliflower, celery, chard, Chinese cabbage, cucumber, eggplant, green beans, kale, leeks, mushrooms, peppers, spinach, string beans, squash, tomatoes, turnips, wax beans and zucchini. YOU MUST EAT VEGETABLES EVERY DAY. Cheese: __4__ ounces a day. Includes hard, aged cheeses such as Swiss, cheddar, mozzarella, Monterey jack, Gruyere, goat cheese, bleu, feta and soft cheeses such as cream cheese, brie and camembert. Avoid processed cheeses, cheese spreads or cheese foods such as Velveeta. Levels of Low Carbohydrate Diets • Phase 1, Induction – 20 grams of Net Carbs (total carbs minus fiber) per day • Phase 2, Ongoing Weight Loss (OWL) – Each week or several weeks, add 5 daily grams of Net Carbs, as long as weight loss continues • Phase 3, Pre-Maintenance – Every week or several weeks, add 10 daily grams of Net Carbs, as long as weight loss continues • Phase 4, Lifetime Maintenance – Continue to consume the number of grams of Net Carbs that enables weight maintenance and appetite control Westman EC, Phinney SD, Volek JS. The New Atkins for a New You, 2010. 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, then @ 6mo Samaha 2003 Stern 2004 RCT Clinic Outpt adults 6m 12m qWk x 4, then monthly 12m then Wk 26, 34, 42, 52 q2Wk x 2, q4Wk x 4, Foster 2003 RCT Clinic Healthy adults Yancy 2004 RCT Clinic Healthy adults 6m q2Wks x 6, then monthly Brinkworth 2009 RCT Clinic Healthy adults 12 m q2Wks x 4, then monthly Nordmann et al. Arch Intern Med 2006;166:285-293. Outpatient LCKD RCTs: Weight Loss and Serum Lipids Low Fat Ref Low Carbohydrate Duration Weight LDL Trig HDL Weight LDL Sondike n=30 3 mo -4.1kg -17%* -6% +2% -9.9kg* +4% -48%* +4% Brehm n=42 6 mo -3.9kg† -5% +2% +8% -8.5kg*† 0% Samaha/ 6 mo Stern 12 mo n=132 -1.9kg† +3% -4% -2% -3.1kg -3% +2% -12% -5.8kg*† -5.1kg +4% -20%* 0% +6% -29% -2% Foster 6 mo -5.3kg† -3% -13% +4% -9.7kg*† +4% n=63 12 mo -4.5kg† -6% +1% +3% -7.3kg† +1% -28%* +18%* Yancy n=119 6 mo -6.5kg -3% -15% -1% -12.0kg* +2% -42%* +13%* -14.5kg +3% Brinkworth 12 mos -11.5kg +3% -12% N=40 * p<0.05 for between-groups comparison 0% Trig HDL -23%* +13% -21% +20%* -35% +21% Examples of Diet Programs DASH: Dietary Approaches to Stop Hypertension A diet with no extreme percentages of macronutrients; low in sugar, salt, alcohol and saturated fat, with moderate levels of total fat, and a high level of mono-unsaturated fats. It emphasizes helpful minerals and antioxidants to lower blood pressure. Ornish Very high carbohydrate vegetarian diet, extremely low fat, moderate protein. It advises: unlimited quantities of low-fat, high-fiber, complex CHO foods, such as beans, legumes, fruits, vegetables, and grains. Low fat dairy products are allowed in moderation. The following are prohibited: meats, eggs, nuts, oils, seeds, alcohol, and high fat fruits and vegetables. The Zone Diet 40% C, 30% P, 30% F; focuses on lean meats (especially poultry), avoids high-fat animal products (fatty meats, dairy products, eggs), as well as most grain products, starchy vegetables, and some fruits. South Beach Diet 28% C, 33%P, 39% F; emphasizes healthy carbs, such as whole grains and certain fruits and vegetables; mono-unsaturated fats, such as olive and canola oil and nuts; and lean sources of protein. Atkins • 6% C, 35% P, 59% F; carbohydrate-restricted, adequate protein, high-fat diet; 1 cup of nonstarchy vegetables, 2 cups of leafy greens at early, during most restrictive phase. Mediterranean 40% C, 17% P, 43% F; high amount of mono-unsaturated fats. The diet contains: vegetables, fruits, cereals, dairy products, meats and poultry, fish, wine, legumes, and olive oil – in that order. Workplace Diet Trial 322 workers at Israeli research center, BMI >27 kg/m2 R Low Fat Diet Mediterranean Diet Low Carb Diet • <30% fat • Calorie- • <35% fat • Calorie- • <20 g/day carbs restricted • Grains, vegies, fruits, legumes restricted • Add fish, nuts, olive oil initially • Increase to max of 120 g/day • No calorie restriction Shai I et al. New Engl J Med 2008;359:229-41. A Comparison of Three Diets Shai I. N Engl J Med 2008;359:229-41. Workplace Diet Trial: Serum Tests Test Low Fat Mediterranean Low Carb Systolic BP, mm Hg -4.3 -5.5 -3.9 Diastolic BP, mm Hg -0.9 -2.2 -0.8 LDL-C, mg/dl -0.05 -5.6 -3.0 HDL-C, mg/dl 6.3 6.4 8.4 Triglyceride, mg/dl -2.8 -21.8 -23.7 T Chol : HDL ratio -0.6 -0.9 -1.1 Hemoglobin A1c, % -0.4 -0.5 -0.9 C-reactive protein, mg/l -0.6 -0.9 -1.3 Yellow denotes p<0.05 for within-group change from baseline. Blue denotes p<0.05 for comparison of Low Carb vs Low Fat. Circulation. 2010;121:1200-1208. A Comparison of Four Diets Dansinger ML. JAMA 2005;293:43--53. A Comparison of Four Diets Gardner C. JAMA 2007;297:969-77. Insulin Resistance and Diet Success Re-examination of the A to Z Study [Gardner 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 Validates the concept that insulin resistance is essentially an expression of carbohydrate intolerance Low Carb Low Fat Insulin Resistant -11.9 lbs -3.3 lbs Insulin Sensitive -9.0 lbs -11.7 lbs Gardner, C.D., et al., Insulin Resistance - An Effect Moderator of Weight Loss Success on High vs. Low Carbohydrate Diets. Obesity, 2008. 16: p. S82. Low Fat Diet Reduces LDL-C Low Carb Diet Targets Trig/HDL Serum LDL-C: Serum Triglyceride: Nordmann et al. Arch Intern Med. 2006;166(3):285-293. Meta-analysis of RCTs Comparing Low-carb to Low-fat Diets • “Low-carbohydrate/high-protein diets are more effective at 6 months and are as effective, if not more, as low-fat diets in reducing weight and cardiovascular disease risk up to 1 year.” Hession M, Rolland C, Kulkami U, Wise A, Broom J. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obes Rev 2009;10:36-50. Mediterranean Diet Whole grains, fruits, vegetables, legumes, nuts, monounsaturated oil (olive oil, avocados, etc) Fish and seafood, moderate alcohol Limited poultry, dairy, red meat infrequent PREDIMED Study 30% lower risk of first cardiovascular event Lyon Heart Study - 50%-70% lower risk of recurrent CHD - . Estruch R et al. NEJM 2013;368:1279-190 de Lorgeril M et al. Circulation 1999;99:779-85. Low Carb vs. Low Fat Diet + Orlistat Study Design 146 overweight VA outpatient volunteers R Low Fat Diet + Orlistat Low Carb Ketogenic Diet • • • • • group meetings for 48 wks • exercise recommendation • multivitamin daily group meetings for 48 wks exercise recommendation multivitamin daily Orlistat (Xenical™) 120 mg three times a day Yancy WS Jr. et al. Arch Int Med 2010;170:136-45. Mean % Weight Change Over Time* Orlistat + Low Fat Diet Low Carbohydrate Diet n= 65 n= 57 74 71 66 65 60 61 69 61 52 53 46 54 72 64 58 58 51 50 57 48 43 54 41 40 Change in Blood Pressures at 3 Time points Change in Blood Pressure by Treatment Arm 2 1 0 -1 ΔmmHg -2 -3 P B D P B S LCKD P B D P B S O+LFD -4 -5 -6 -7 Yancy WS Jr. et al. Arch Int Med 2010;170:136-45. 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) Low Carbohydrate Diet Program and Triglycerides/HDL Before Diet After Low Carb Pgm Age Sex Duration Weight A1C Trig HDL 35 37 50 57 33 57 37 74 50 48 F F M M M M F M M F 5 mos 7 mos 13 mos 14 mos 21 mos 21 mos 22 mos 25 mos 26 mos 28 mos (lb) 188 154 245 245 290 231 168 250 275 156 11.3 4.8 10.9 6.2 8.9 9.8 5.1 9.0 - 503 1368 735 370 646 510 651 522 6500 2407 27 29 31 51 36 42 19 40 20 Weight A1C Trig HDL (lb) 175 215 227 293 212 140 198 215 156 6.3 5.3 5.3 6 5.2 5.8 5.3 5.3 - 145 243 329 114 166 48 172 60 329 84 41 60 37 60 38 69 31 66 37 37 Diabetic Diet in the Pre-Insulin Era 1914-1921 “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 Alcohol 15 grams 1,350 105 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., 1923. Allen FM. Protein diets and undernutrition in treatment of diabetes. JAMA 1920;74:571-577. Newburgh LH, Marsh PL. The use of a high fat diet in the treatment of diabetes mellitus. Arch Int Med 1921;27:699-705. “Spoonful of sugar in entire human bloodstream” Glucose meter = 100 mg/dL 5-7 liters of blood in the body 4 g/tsp sugar so 5-7g = “heaping spoonful” 100 mg 10 dL 1 grams ----------- * ----------- * -------- * 7 L blood = 7 grams dL L 1000 mg Glucose meter = 100 mg/dL 5-7 liters of blood in the body 4 g/tsp sugar so 5-7g = “heaping spoonful” // / / // / 100 mg 10 dL 1 grams ----------- * ----------- * -------- * 7 L blood = 7 grams dL L 1000 mg // / / / 5-7 grams of glucose in human bloodstream The Effect of a Low-carbohydrate, Ketogenic Diet Versus a Lowglycemic Diet on Glycemic Control in Type 2 Diabetes Mellitus Overweight or obese volunteers with type 2 diabetes R Low Glycemic Index Diet (LGI) instruction + group meetings + exercise recommendation + nutritional supplements Low Carbohydrate Ketogenic Diet (LCKD) instruction + group meetings + exercise recommendation + nutritional supplements Westman et al. Nutrition & Metabolism 2008;5:36. Primary Outcome: Hemoglobin A1c LCKD LGI 13 12 Hemoglobin A1c, % Hemoglobin A1c, % 13 11 10 9 8 7 12 11 10 9 8 7 6 6 5 5 Baseline 12 Weeks LGI (n=29) HgbA1c, % 24 Weeks Baseline 12 Weeks 24 Weeks Baseline 12 Weeks 24 Weeks Base24 mean (sd) mean (sd) mean (sd) change, % 8.3 (1.9) 7.5 (1.7) 7.8 (2.1) -0.5 (-6.0%)* 8.8 (1.8) 7.2 (1.2) 7.3 (1.5) -1.5 (-17.0%)* LCKD (n=21) HgbA1c, % *p <0.05 between groups Westman et al. Nutrition & Metabolism 2008;5:36. Effect of Diet Programs on Metabolic Syndrome Parameters LGI (n=29) LCKD (n=21) Week 0 Week 24 Change Week 0 Week 24 Change mean mean mean mean mean mean Fasting glucose, mg/dL 166.8 150.8 -16.0* 178.1 158.2 -19.9* Waist circumference, in. 47.0 42.4 -4.6 * 47.1 41.8 -5.3 * Triglycerides, mg/dL 167.1 147.8 -19.3 210.4 142.9 -67.5 * HDL cholesterol, mg/dL 48.7 48.7 -0 † 44.0 49.6 +5.6 * † Systolic blood pressure, mmHg 140.8 130.1 -10.7 * 144.4 127.8 -16.6 * Diastolic blood pressure, mmHg 84.1 78.5 -5.6 * 83.9 75.8 -8.1 * Body mass index, kg/m2 37.9 35.2 -2.7 * † 37.8 33.9 -3.9 * † * p < 0.05 for within-group change from Week 0 to Week 24. † p < 0.05, for between groups change from Week 0 to Week 24. Facts About Low Carbohydrate, High Fat Diets • • Carbohydrate is not an essential nutrient • • • • Low carb diets are adequate protein diets Low carb diets lead to weight loss because abnormal hunger/appetite goes away 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 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 mice. Am J Physiol Endocrinol Metab 2007, February 13. Saturated Fat is Processed Differently Under Different Metabolic Conditions Low Fat Diet (208 g CHO/d) Saturated Fat Synthesis Saturated Fat Saturated Fat Intake (12 g/d) Saturated Fat Burned as Fuel Low Carbohydrate 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, 2008 Fat Diet: Triglycerides Lipids Observed Very Low Carb Diet Liver Large LDL Chylomicrons Lymphatics Thoracic Duct Superior Vena Cava Triglyceride Atherosclerosis? Cells Diet: Carbohydrate Lipids Observed Mixed Diet Fat Simple sugars Triglycerides Portal Vein Chylomicrons Sugar Liver Lymphatics Triglyceride LDL VLDL LDL Small LDL Atherosclerosis Thoracic Duct Superior Vena Cava Triglyceride Cells 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 6/10 31.3 178 245 247 141 54 92 81 88 Initiation of Carbohydrate Restricted Diet 8/10 29.1 164 2/11 24.5 141 5/11 23.5 138 209 46 119 She asks, “Why wasn’t I given this option before? I was just given the options of medications.” Reduction in Belief in the Low-fat Diet • Low-fat diet recommendations started in a political subcommittee and then were never proven useful in subsequent studies • Dietary intervention study of 48,000 women using a low-fat had no effect on breast cancer, colorectal cancer, or heart disease Taubes, G. Good Calories, Bad Calories. Anchor, 2008. Prentice et al. Low-fat dietary pattern and risk of invasive breast cancer. The Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:629642. Beresford et al. JAMA 2006;295:643-654. Howard et al. JAMA 2006;295:655-666. 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 Low Carb Dietary Treatment of Obesity and Metabolic Syndrome Eric C. Westman, M.D. M.H.S. Director, Lifestyle Medicine Clinic Associate Professor of Medicine Department of Medicine Duke University Medical Center Durham NC Course Director, Medical Management of Obesity President, American Society of Bariatric Physicians Fellow, The Obesity Society Author, The New Atkins for a New You [email protected]