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Jeff S. Volek, Ph.D., R.D. Human Performance Laboratory Department of Kinesiology

Dietary Carbohydrate Restriction Uniquely Targets the Features of Metabolic Syndrome. Jeff S. Volek, Ph.D., R.D. Human Performance Laboratory Department of Kinesiology University of Connecticut Storrs, CT. Objectives.

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Jeff S. Volek, Ph.D., R.D. Human Performance Laboratory Department of Kinesiology

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  1. Dietary Carbohydrate Restriction Uniquely Targets the Features of Metabolic Syndrome Jeff S. Volek, Ph.D., R.D. Human Performance Laboratory Department of Kinesiology University of Connecticut Storrs, CT

  2. Objectives • Overview the function of dietary carbohydrate in the diet, its role as a macronutrient, and its connection to the metabolic syndrome. • Compare and contrast very low carbohydrate and low fat diets on metabolic syndrome markers and cardiovascular risk factors. • Provide evidence that the collection of metabolic syndrome markers responds in concert to carbohydrate restriction. • Provide evidence that dietary fat, even saturated fat, is not deleterious in the presence of low carbohydrate.

  3. Dietary Guidelines for Americans • KEY RECOMMENDATIONS • Consume <10% of calories from saturated fatty acids and less than 300 mg/day of cholesterol, and keep trans fatty acid consumption as low as possible. • Keep total fat intake between 20 to 35% of calories, with most fats coming from sources of polyunsaturated and monounsaturated fatty acids, such as fish, nuts, and vegetable oils. • When selecting and preparing meat, poultry, dry beans, and milk or milk products, make choices that are lean, low-fat, or fat-free. • Limit intake of fats and oils high in saturated and/or trans fatty acids, and choose products low in such fats and oils.

  4. Bethesda, we have a problem. 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.

  5. Replacing the average American fat content of the diet with carbohydrate has the most unfavorable effect on TC/HDL-C Mensink et al. AJCN. 77:1146-55, 2003.

  6. Effects of Decreasing SFA and Replacing it with Carbohydrate Replacing 5%en of SFA with carbohydrate increased coronary events (HR 1.07) Jakobsen et al. AJCN Feb 11 (Epub)

  7. Macronutrient Intake in Men 70 Carbohydrate 60 50 40 Grams 30 20 10 Protein 0 Fat -10 1976-1980 1988-1994 1999-2000 1971-1974

  8. Prevalence of Obesity in Adults (20 to 74 yr)

  9. Carbohydrate Glucose Insulin Sensitive Insulin Resistant Lipogenesis Hypertriglyceridemia Individuals with Insulin Resistance Abnormally Dispose of Carbohydrate Petersen et al. PNAS 104(31):12587-94, 2007

  10. Features of MetSyn •  Weight •  Fat •  TG •  HDL •  Glu •  Insulin •  BP •  Weight •  Fat •  TG •  HDL •  Glu •  Insulin •  BP Metabolic Syndrome Improved by CHO Restriction

  11. ↑Insulin ↑Carbs

  12. Macronutrients Protein Fat Carbohydrate Fuel (Energy) Roadblock to Burning Fat Essential Structural and Functional Roles Does carbohydrate have to be a macronutrient?

  13. 50:50 (RQ 0.85) Fuel Mix Low-Carb/High-Fat High-Carb/Low-Fat + Insulin - Insulin 100% Carbs (RQ 1.0) 100% Fat (RQ 0.7) ↓ Metabolic Syndrome & CVD Risk

  14. A New Paradigm Consistent with the idea that intolerance to carbohydrate is a fundamental feature of metabolic syndrome, we proposed that dietary restriction of carbohydrate would improve traditional and emerging aspects of the syndrome compared to a low fat diet. ↓ Carbohydrate ↓ Hyperinsulinemia/ Insulin Resistance ↓Glucose ↓Insulin ↓RBP-4 Improvement of Metabolic Syndrome Markers Dyslipidemia ↓ Fasting TG ↓ Postprandial TG ↑ HDL-C ↓ Small LDL Adiposity ↓ % body fat ↓ Abdominal fat Vascular Function ↑ Flow-mediated dilation ↑ NO bioavailability Inflammation ↓ Cytokines Fatty Acid Metabolism/ Composition ↓ SFA ↑ Fat Oxidation ↓Lipogenesis

  15. Lipids. 2008 Jan;43(1):65-77. Epub 2007 Nov 29. Lipids. 2008 Dec 12. [Epub ahead of print] Low Fat Low SFA Overweight Men and Women with AtherogenicDyslipidemia(n=40) VLCKD 12 wk

  16. Very Low Carbohydrate Diet

  17. Dietary Intake

  18. A CRD improves glucose, insulin & other traditional and emerging CVD risk factors Percent changes in glucose, insulin, RBP-4, and markers of atherogenic dyslipidemia after 12 wk of a CRD or low fat diet (LFD) (***P<0.001, **P<0.01, *P<0.05).

  19. Carbohydrate Restriction But Not Fat Restriction Reduces Retinol-Binding Protein 4 and Features of Metabolic Syndrome. T.E. GRAHAM, J.S. VOLEK, M.L FERNANDEZ, W.J. KRAEMER, R.J. WOOD, C.E. FORSYTHE, E.E. QUANN, B.B. KAHN. 5 0 -5 %Change RBP4 -10 -15 -20 VLCKD LFD

  20. -51% -19% Dyslipidemia: Triglycerides • Most reliable response to carbohydrate restriction • Carbohydrate induced triglyceridemia Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12

  21. A CRD dramatically improves the postprandial lipemic response to a high fat meal Postprandial lipemic responses to a high fat meal (908 kcal, 84% fat) before and after a CRD and LFD. Mean total AUC was significantly different between the CRD and LFD (P < 0.000). Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12

  22. 13% 1% Dyslipidemia: HDL-C • More effective than other lifestyle changes (exercise, smoking cessation, weight loss, n-3 PUFA) • Not dependent on starting levels • Stronger effect in women • Dependent on the cholesterol content of diet Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12

  23. A CRD improves qualitative features of LDL (increased particle size) Representative gels showing an abundance of larger LDL particles after a CRD and a predominance of smaller LDL particles after a LFD. CRD LFD Larger Particles Smaller Particles Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12

  24. Dyslipidemia: LDL Particle Size Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12 Krauss RM. Annu Rev Nutr. 21:283-95, 2001

  25. 0.4 0.4 CRD LFD 0.2 0.2 0 0 apoB/apoA1 (mg/dL) -0.2 -0.2 -0.4 -0.4 D -0.6 -0.6 -15% 8% -0.8 -0.8 apoB/apoA1 Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12

  26. Wk 12 Wk 12 Wk 0 Wk 0 0 0 -5 -5 -10 -10 Weight Loss (kg) -15 -15 -20 -20 VLCKD LFD -25 -25 A CRD enhances weight and fat loss Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12

  27. * Low-Fat Low-Fat * Low-CHO Low-CHO 0 -1 -2 -3 Whole Body Fat Loss (kg) -4 -5 -6 0 -1 -2 Trunk Fat Loss (kg) -3 -4 Mid Post Pre Volek et al. Nutr Metab. 2004 Nov 8;1(1):13.

  28. -2.0 -3.4 -3.5 -5.3 Improvements in body composition w/ CRD and weight training are additive LF+RE LC+RE LF LC 0 -1 -2 Change Percent Fat (%) -3 -4 -5 -6

  29. A CRD has a positive effect on fasting vascular function and in response to a high fat meal A Pre Occlusion Diameter Post Occlusion Diameter B Volek et al. Metabolism. In Press (A) Longitudinal image of the brachial artery before and after 5 min of arm cuff occlusion to induce reactive hyperemia. (B) Postprandial vascular responses to a high fat meal before and after 12 wk in subjects who consumed a CRD or LFD. Values represent the absolute difference (Wk 12 – Baseline) in peak %FMD of the brachial artery. Peak FMD = [(post occlusion diameter – pre occlusion diameter) / pre occlusion diameter]. **P < 0.01, *P < 0.05.

  30. Saturated Fat Saturated Fat Blood Saturated Fat Levels Low Fat Diet 12 g SFA/d 208 CHO/d High Fat Diet 36 g SFA/d 45 CHO/d

  31. Saturated Fat Burned as Fuel Saturated Fat Burned as Fuel Blood Saturated Fat Levels Saturated Fat Synthesis Low Fat Diet (208 g CHO/d) Saturated Fat Saturated Fat Intake (12 g/d) Saturated Fat Synthesis Low Carbohydrate Diet (45 g CHO/d) Saturated Fat Saturated Fat Intake (36 g/d)

  32. Despite being higher in saturated fat, a CRD decreases circulating levels of SFA Forsythe et al. Lipids. 43(1):65-77, 2008

  33. or…You are what you do with what you eat! Dietary carbohydrate has a significant influence on endogenous processing of SFA

  34. Inflammation EPA DHA PGI3 PGE3 TXA3 LTB5 Inflammatory Status AA PGI2 PGE2 TXA2 LTB4

  35. Forsythe et al. Lipids. 43(1):65-77, 2008

  36. A CRD has anit-inflammatory effects Forsythe et al. Lipids. 43(1):65-77, 2008

  37. Increased 20:4n-6, 20:4n-6/20:5n-3, and n-6/n-3 are commonly viewed as pro-inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory markers Change CE 20:4n-6/20:5n-3 VEGF V-CAM a TNF- P-sel PAI-1 MCP-1 L-sel IL-8 IL-6 g IFN- I-CAM E-sel EGF CRP -0.6 -0.4 -0.2 0 0.2 0.4 0.6 Correlation Coefficient Forsythe et al. Lipids. 43(1):65-77, 2008

  38. Does the quality of fat matter on a very low carbohydrate diet during iso-weight conditions? VLCKD High SFA Controlled Feeding VLCKD Low SFA/n-3 Controlled Feeding Habitual Diet Free-living Crossover washout VLCKD Free-living VLCKD Free-living 3 wk 6 wk 4 wk 3 wk 6 wk

  39. Diet Composition VLCKD Low-SFA/n-3 Controlled Feeding VLCKD High-SFA Controlled Feeding Habitual Diet Free Living Isocaloric

  40. The quality of fat on a CRD impacts the response in plasma levels of SFA

  41. A CRD regardless of fat quality decreases lipogenesis

  42. A CRD emphasing MUFA and n-3 PUFA decreases oxidative stress

  43. Impact of restricting dietary fat versus carbohydrate on risk factors

  44. Summary • Carbohydrate intake is intimately linked to metabolic syndrome • Properly implemented very low carbohydrate diets favorably impact a broad spectrum of metabolic syndrome markers and cardiovascular risk factors • Carbohydrate restriction targets all the markers of metabolic syndrome, whereas drugs target individual markers and have well known side effects What Level of Carbohydrate?

  45. Climbing the Carbohydrate Ladder Biomarkers: Weight loss TG 16:1n-7 High Athletes Naturally lean Moderate Overweight/obese Low Metabolically Compromised/obese Very Low

  46. Thank You

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