Atkins Nutritionals Scientific Advisory Board Meeting, July 9, 2010

Transcription

1 Atkins Nutritionals Scientific Advisory Board Meeting, July 9, 2010

2 Human Studies 1.Al-Sarraj T, Saadi H, Volek JS, Fernandez ML. Metabolic syndrome prevalence, dietary intake, and cardiovascular risk profile among overweight and obese adults years old from the United Arab Emirates. Metab Syndr Relat Disord Feb;8(1): Al-Sarraj T, Saadi H, Volek JS, Fernandez ML. Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome. Nutr Metab Cardiovasc Dis Sep Volek JS, Ballard KD, Silvestre R, Judelson DA, Quann EE, Forsythe CE, Fernandez ML, Kraemer WJ. Effects of dietary carbohydrate restriction versus low-fat diet on flow-mediated dilation. Metabolism Dec;58(12): Mutungi G, Waters D, Ratliff J, Puglisi M, Clark RM, Volek JS, Fernandez ML.Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet. J Nutr Biochem Apr;21(4): Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ, Kraemer WJ, Bibus DM, Fernandez ML, Feinman RD. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids Apr;44(4): Ratliff J, Mutungi G, Puglisi MJ, Volek JS, Fernandez ML. Carbohydrate restriction (with or without additional dietary choles terol provided by eggs) reduces insulin resistance and plasma leptin without modifying appetite hormones in adult men. Nutr Res Apr;29(4): Ratliff JC, Mutungi G, Puglisi MJ, Volek JS, Fernandez ML. Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men. Nutr Metab (Lond) Feb 20;5:6. 8.Seip RL, Volek JS, Windemuth A, Kocherla M, Fernandez ML, Kraemer WJ, Ruaño G. Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat. Nutr Metab (Lond) Feb 6;5:4. 9.Mutungi G, Ratliff J, Puglisi M, Torres-Gonzalez M, Vaishnav U, Leite JO, Quann E, Volek JS, Fernandez ML. Dietary cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming a carbohydrate-restricted diet. J Nutr Feb;138(2): Forsythe CE, Phinney SD, Fernandez ML, Quann EE, Wood RJ, Bibus DM, Kraemer WJ, Feinman RD, Volek JS. Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Lipids Jan;43(1): Mutungi G, Torres-Gonzalez M, McGrane MM, Volek JS, Fernandez ML. Carbohydrate restriction and dietary cholesterol modulate the expression of HMG-CoA reductase and the LDL receptor in mononuclear cells from adult men. Lipids Health Dis Nov 28;6: Torres-Gonzalez M, Shrestha S, Sharman M, Freake HC, Volek JS, Fernandez ML. Carbohydrate restriction alters hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet. J Nutr Oct;137(10): Wood RJ, Fernandez ML, Sharman MJ, Silvestre R, Greene CM, Zern TL, Shrestha S, Judelson DA, Gomez AL, Kraemer WJ, Volek JS. Effects of a carbohydrate-restricted diet with and without supplemental soluble fiber on plasma low-density lipoprotein cholesterol and other clinical markers of cardiovascular risk. Metabolism Jan;56(1): Ruaño G, Windemuth A, Kocherla M, Holford T, Fernandez ML, Forsythe CE, Wood RJ, Kraemer WJ, Volek JS. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction. Nutr Metab (Lond) May 15;3: Wood RJ, Volek JS, Davis SR, Dell'Ova C, Fernandez ML. Effects of a carbohydrate-restricted diet on emerging plasma markers for cardiovascular disease. Nutr Metab (Lond) May 4;3: Wood RJ, Volek JS, Liu Y, Shachter NS, Contois JH, Fernandez ML. Carbohydrate restriction alters lipoprotein metabolism by m odifying VLDL, LDL, and HDL subfraction distribution and size in overweight men. J Nutr Feb;136(2): Volek J, Sharman M, Gómez A, Judelson D, Rubin M, Watson G, Sokmen B, Silvestre R, French D, Kraemer W. Comparison of energyrestricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab (Lond) Nov 8;1(1):13 18.Sharman MJ, Volek JS. Weight loss leads to reductions in inflammatory biomarkers after a very-low-carbohydrate diet and a low-fat diet in overweight men. Clin Sci (Lond) Oct;107(4): Sharman MJ, Gómez AL, Kraemer WJ, Volek JS. Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. J Nutr Apr;134(4): Volek JS, Sharman MJ, Gómez AL, DiPasquale C, Roti M, Pumerantz A, Kraemer WJ. Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women. J Am Coll Nut r Apr;23(2): Volek JS, Sharman MJ, Gómez AL, Scheett TP, Kraemer WJ. An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr Sep;133(9): Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gómez AL, Scheett TP, Volek JS. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr Jul;132(7): Volek JS, Gómez AL, Kraemer WJ. Fasting lipoprotein and postprandial triacylglycerol responses to a low-carbohydrate diet supplemented with n-3 fatty acids. J Am Coll Nutr Jun;19(3): Animal Studies 1.Leite JO, DeOgburn R, Ratliff J, Su R, Smyth JA, Volek JS, McGrane MM, Dardik A, Fernandez ML. Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet. Atherosclerosis Apr;209(2): Fine EJ, Miao W, Koba W, Volek JS, Blaufox MD. Chronic effects of dietary carbohydrate variation on [18F]-2-fluoro-2- deoxyglucose uptake in rodent heart. Nucl Med Commun Sep;30(9): Leite JO, DeOgburn R, Ratliff JC, Su R, Volek JS, McGrane MM, Dardik A, Fernandez ML. Low-carbohydrate diet disrupts the association between insulin resistance and weight gain. Metabolism Aug;58(8): Sharman MJ, Fernandez ML, Zern TL, Torres-Gonzalez M, Kraemer WJ, Volek JS. Replacing dietary carbohydrate with protein and fat decreases the concentrations of small LDL and the inflammatory response induced by atherogenic diets in the guinea pig. J Nutr Biochem Nov;19(11): Torres-Gonzalez M, Volek JS, Leite JO, Fraser H, Luz Fernandez M. Carbohydrate restriction reduces lipids and inflammation and prevents atherosclerosis in Guinea pigs. J Atheroscler Thromb Oct;15(5): Torres-Gonzalez M, Leite JO, Volek JS, Contois JH, Fernandez ML. Carbohydrate restriction and dietary cholesterol distinctly affect plasma lipids and lipoprotein subfractions in adult guinea pigs. J Nutr Biochem Dec;19(12): Torres-Gonzalez M, Volek JS, Sharman M, Contois JH, Fernandez ML. Dietary carbohydrate and cholesterol influence the number of particles and distributions of lipoprotein subfractions in guinea pigs. J Nutr Biochem Nov;17(11): Reviews 1.Feinman RD, Volek JS. Carbohydrate restriction as the default treatment for type 2 diabetes and metabolic syndrome. Scand Cardiovasc J Aug;42(4): Accurso A, Bernstein RK, Dahlqvist A, Draznin B, Feinman RD, Fine EJ, Gleed A, Jacobs DB, Larson G, Lustig RH, Manninen AH, McFarlane SI, Morrison K, Nielsen JV, Ravnskov U, Roth KS, Silvestre R, Sowers JR, Sundberg R, Volek JS, Westman EC, Wood RJ, Wortman J, Vernon MC. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal. Nutr Metab (Lond) Apr 8;5:9. 3.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 Sep;47(5): Westman EC, Yancy WS, Haub MD, Volek JS. Insulin resistance from a low carbohydrate, high fat diet perspective. Metab Syndr Relat Disord. 2005;3(1): Westman EC, Feinman RD, Mavropoulos JC, Vernon MC, Volek JS, Wortman JA, Yancy WS, Phinney SD. Lowcarbohydrate nutrition and metabolism. Am J Clin Nutr Aug;86(2): Feinman RD, Volek JS. Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of weight loss. Nutr Metab (Lond) Jun 21;3:24. 7.Fernandez ML, Volek JS. Guinea pigs: a suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation. Nutr Metab (Lond) Mar 27;3:17. 8.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 (Lond) Nov 16;2:31. 9.Volek JS, Forsythe CE. The case for not restricting saturated fat on a low carbohydrate diet. Nutr Metab (Lond) Aug 31;2: Volek JS, Sharman MJ, Forsythe CE. Modification of lipoproteins by very low-carbohydrate diets. J Nutr Jun;135(6): Volek JS, Vanheest JL, Forsythe CE. Diet and exercise for weight loss: a review of current issues. Sports Med. 2005;35(1): Volek JS, Sharman MJ. Cardiovascular and hormonal aspects of very-low-carbohydrate ketogenic diets. Obes Res Nov;12 Suppl 2:115S-23S. 13.Westman EC, Mavropoulos J, Yancy WS, Volek JS. A review of low-carbohydrate ketogenic diets. Curr Atheroscler Rep Nov;5(6): Volek JS, Westman EC. Very-low-carbohydrate weight-loss diets revisited. Cleve Clin J Med Nov;69(11):849, 853, passim.

3 Prevalence (%) Overweight BMI Obese BMI That only a relatively small subset of adults has maintained a healthy weight in the context of current low fat guidelines implies that a majority 33.9 of 32.2 Americans may be metabolically and genetically programmed to benefit from alternative approaches

4 The increase in calories during the obesity epidemic was due largely to carbohydrate intake CARBOHYDRATE PROTEIN FAT

5 Ingest Carbohydrate Blood Sugar ( 20 g) Road to Health Road to Metabolic Syndrome Glycogen ( g) Oxidation Glycogen ( 100 g) Lipogenesis (fat synthesis)

6 84 hr of fasting or lipid infusion to meet REE Changes in plasma glucose, fatty acids, glycerol, ketones, insulin, epinephrine, as well as rates of lipolysis were similar Carbohydrate restriction, not the presence of a negative energy balance, is responsible for initiating the metabolic response to fasting. Am J Physiol. 262:E631-36, 1992

7 Maximum Fat Breakdown Decreases in insulin that occur on the Atkins diet result in large increases in fat breakdown and oxidation High Carbohydrate Diet Minimum Low Insulin Concentration High

8 Carbs Excessive carb intake is a slippery slope to diabetes Obesity Insulin Resistance Hyperinsulinemia Progression from Insulin Resistance to Diabetes is not inevitable Obesity (BMI 30) 2006 to 2008: 24% Non-Hispanic white 36% Non-Hispanic blacks 29% Black Pre-Diabetes (2003 to 2006): IFG = 100 to 125 mg/dl 25.9% of adults 20 yr 35.4% of adults 60 yr Impaired Glucose Tolerance b-cell Defect ( insulin secretion) Early Diabetes b -Cell Failure Diabetes (2007): 23.5 million (10.7%) adults Estimated Costs = $174 billion Late Diabetes

9 Insulin Signaling Lipolysis Insulin Function Nitric Oxide Glucose Uptake Glucose Secretion VLDL Secretion

10 Metabolic syndrome, insulin resistance, diabetes, and even many forms of obesity are all manifestations of carbohydrate intolerance How do we management other food intolerances (lactose, gluten)?

11 Features of MetS Weight Fat TG HDL Glu Insulin BP Improved by CHO Restriction Weight Fat TG HDL Glu Insulin BP

12 Low carbohydrate diets are more likely than low fat diets to effect global improvement in markers associated with insulin resistance

13 D Triglycerides (mg/dl) A 50 CRD 50 LFD Most reliable response to carbohydrate restriction % -19% -250 Volek et al. Lipids Apr;44(4): Epub 2008 Dec 12

14 Triglycerides (mg/dl) 400 CRD Wk Low Fat Diet Wk CRD Wk Low Fat Diet Wk Pre Occlusion Diameter Post Occlusion Diameter Volek et al. Metabolism July 24 0 Pre IP Time (hours) 0.0 Pre IP Time (hours) Volek et al. Lipids. 44: , 2009

15 D HDL-C (mg/dl) More effective than other lifestyle changes (exercise, smoking cessation, weight loss, n-3 PUFA) B CRD LFD Not dependent on starting levels 5 5 Stronger effect in women Dependent on the cholesterol content of diet % 1% 0 Volek et al. Lipids Apr;44(4): Epub 2008 Dec 12

16 CRD Larger Particles LFD Smaller Particles High Carbohydrate/Low-Fat Low Carbohydrate/High-Fat Volek et al. Lipids Apr;44(4): Epub 2008 Dec 12

17 D Small LDL3+ (%) D 10 8 CRD 10 8 LFD Krauss RM. Annu Rev Nutr. 21:283-95, 2001 Volek et al. Lipids Apr;44(4): Epub 2008 Dec 12

18 Percent Change 10 5 VLCKD LFD 0-5 IL-6 IL-8 TNF-a MCP-1 I-CAM E- Selectin PAI Forsythe et al. Lipids. 43(1):65-77, 2008

19 Treating any of the individual MetSyn markers w/ carbohydrate restriction holds promise to benefit the others. Low carbohydrate diets preferred primary intervention when >1 sign of insulin resistance is observed.

20 Limit your intake of saturated fat to <7% of energy.

21 SFA Intake Plasma LDL Heart Disease? Renowned science writer Gary Taubes What if It s All Been a Big Fat Lie? Good Calories, Bad Calories Provocative articles exposing the lack of quality science behind low-fat diets.

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23 Conclusions Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.

24 Replacing 5%en of SFA w/ carbs coronary events (HR 1.07) Jakobsen et al. AJCN Feb 11 (Epub)

25 Low Fat Low SFA Low Carbohydrate Diet 12 wk Low Fat Diet ~1500 kcal/day Low Carb Diet ~1500 kcal/day PRO CHO PRO CHO FAT Saturated Fat = 12 g FAT Saturated Fat = 36 g

26 Change Plasma SFA (%wt) in TAG Low Fat Low Carb Change Plasma SFA (mg/dl) in TAG Low Fat Low Carb 0 Despite eating 3 times more SFA compared to low-fat, subjects showed significantly greater reductions in plasma SFA on a low carbohydrate diet Forsythe et al. Lipids. 43(1):65-77, 2008

27 Metabolic Processing of Saturated Fat Low Fat Diet (208 g CHO/d) Saturated Fat Synthesis Saturated Fat Intake (12 g/d) Processing of dietary SFA is more efficient Saturated Fat when carbohydrate intake is low 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

28 Habitual CRD-SFA CRD-UFA PRO (%) CHO (%) Fat (%) Fat (g) SFA (g) MUFA (g) PUFA (g) n-3 (%) n-6 (%) Chol (mg)

29 Plasma SFA (%wt) in TAG Baseline CRD-SFA CRD-UFA 26.8 Plasma SFA (mg/dl) in TAG Low carbohydrate is a profound stimulus impacting the metabolic processing of ingested SFA Baseline CRD-SFA CRD-UFA

30 A CRD decreases fat synthesis regardless of fat quality Plasma 16:1 (%wt) in TAG Baseline CRD-SFA CRD-UFA

31 or you are what you do with what you eat!

32 Dietary Matrix SFA Carbs Saturated fat has a totally different metabolic behavior when consumed in the context of a low carbohydrate diet Path Dependence on Ambient Carbohydrate Carbohydrate Plasma SFA Insulin Sensitivity Normolipidemia Dietary Carbohydrate Metabolic Health Continuum Carbohydrate Plasma SFA Insulin Resistance Dyslipidema

33 Recent research showing rapid clearing of saturated fats, reduced inflammation and improvements in other biomarkers when consuming well-formulated low carbohydrate diets (Atkins Diet) should encourage us to re-examine their therapeutic value Immediate opportunity is to harness these benefits in the management of insulin resistance