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1. Overview the function of dietary carbohydrate in the diet, its role as a macronutrient, and its connection to the metabolic syndrome.
2. Compare and contrast very low carbohydrate and low fat diets on metabolic syndrome markers and cardiovascular risk factors.
3. Provide evidence that the collection of metabolic syndrome markers responds in concert to carbohydrate restriction.
4. Provide evidence that dietary fat, even saturated fat, is not deleterious in the presence of low carbohydrate.
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KEY RECOMMENDATIONSConsume <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.
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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.
Bethesda, we have a problem.
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Mensink et al. AJCN. 77:1146-55, 2003.
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Jakobsen et al. AJCN Feb 11 (Epub)
Replacing 5%en of SFA with
carbohydrate increased coronary events (HR 1.07)
Replacing 5%en of SFA with
carbohydrate increased coronary events (HR 1.07)
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Glucose
Carbohydrate
Insulin Sensitive
Insulin Resistant
Lipogenesis
Hypertriglyceridemia
Petersen et al. PNAS 104(31):12587-94, 2007
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Weight
Fat
TG
HDL
Glu
Insulin
BP
Features of MetSyn
Weight
Fat
TG
HDL
Glu
Insulin
BP
Improved by CHO Restriction
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↑Insulin
↑Carbs
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Essential Structural and
Functional Roles
Fuel (Energy)
Roadblock to Burning
Fat
Does carbohydrate have to be a macronutrient?
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100% Carbs (RQ 1.0)
100% Fat(RQ 0.7)
Fuel Mix
↓ Metabolic Syndrome &CVD Risk
↓ Metabolic Syndrome &CVD Risk
50:50(RQ 0.85)
+ Insulin- Insulin
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Improvement of Metabolic Syndrome Markers
↓ Hyperinsulinemia/Insulin Resistance
↓ Glucose↓ Insulin↓ RBP-4
Dyslipidemia↓ Fasting TG↓ Postprandial TG↑ HDL-C↓ Small LDL
Adiposity↓ % body fat↓ Abdominal fat
Inflammation↓ Cytokines
Vascular Function
↑ Flow-mediated dilation↑ NO bioavailability
Fatty AcidMetabolism/Composition↓ SFA↑ Fat Oxidation↓ Lipogenesis
↓ Carbohydrate
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.
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Lipids. 2008 Jan;43(1):65-77. Epub 2007 Nov 29.
Lipids. 2008 Dec 12. [Epub ahead of print]
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-50
-40
-30
-20
-10
0
10
Glucose Insulin RBP-4 TG HDL-C ApoB/ApoA-1
CRD LFD
Perc
ent
Chan
ge
**
******
******
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).
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Low Fat
R2 = 0.08
Low Carbohydrate
R2 = 0.29
-40
-30
-20
-10
0
10
20
30
40
-350 -300 -250 -200 -150 -100 -50 0 50
Change in Dietary Carbohydrate (g)
Ch
ang
e in
RB
P4
(mg
/mL
)
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.
VLCKD LFD-20
-15
-10
-5
5
0
%C
hang
e R
BP
4
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Most reliable response to carbohydrate restriction
Carbohydrate induced triglyceridemia
-250
-200
-150
-100
-50
0
50
D T
rig
lyce
rid
es (
mg
/dL
)
A CRD
-250
-200
-150
-100
-50
0
50LFD
-51% -19%
Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12
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0.0
50.0
100.0
150.0
200.0
250.0
300.0
350.0
400.0
Pre IP 1 2 3 4 5 6
Low Fat Diet Wk 0
Low Fat Diet Wk 12
Time (hours)
0
50
100
150
200
250
300
350
400
Pre IP 1 2 3 4 5 6
CRD Wk 0
CRD Wk 12
Time (hours)
Trig
lyce
rides
(mg/
dL)
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
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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
-5
0
5
10
15
D H
DL-
C (m
g/d
L)
B CRD
-5
0
5
10
15LFD
13% 1%
Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12
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CRD CRD LFD LFDLarger
ParticlesSmallerParticles
Representative gels showing an abundance of larger LDL particles after a CRD and a predominance of smaller LDL particles after a LFD.
Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12
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-22
-20
-18
-16
-14
-12
-10
-8
-6
-4
-2
0
2
4
6
8
10
D S
mal
l LD
L3+
(%
)
D CRD
-22
-20
-18
-16
-14
-12
-10
-8
-6
-4
-2
0
2
4
6
8
10LFD
Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12Krauss RM. Annu Rev Nutr. 21:283-95, 2001
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-0.8
-0.6
-0.4
-0.2
0
0.2
0.4LFD
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
D ap
oB
/ap
oA
1 (
mg
/dL
)
CRD
-15% 8%
Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12
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-12
-10
-8
-6
-4
-2
0
0 1 2 3 4 5 6 7 8 9 10 11 12Week
Wei
gh
t L
oss
(kg
)
VLCKDLow Fat
A
-25
-20
-15
-10
-5
0
LFD
Wk 0 Wk 12
-25
-20
-15
-10
-5
0
Wei
gh
t L
oss
(kg
)
VLCKD
Wk 0 Wk 12
Volek et al. Lipids. 2009 Apr;44(4):297-309. Epub 2008 Dec 12
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-6
-5
-4
-3
-2
-1
0
Whole Body Fat Loss (kg)
*Low-CHO
Low-Fat
-4
-3
-2
-1
0
Pre Mid Post
Trunk Fat Loss (kg)
Low-Fat
Low-CHO
*
Volek et al. Nutr Metab. 2004 Nov 8;1(1):13.
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-2.0
-3.4
-6
-5
-4
-3
-2
-1
0
Ch
an
ge P
erc
en
t Fa
t (%
)
LF
-3.5
-5.3
LF+RE LC+RELC
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(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.
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
Pre 1.5 3 4.5
CRD LFD
Abso
lute
Cha
nge
in P
eak
%FM
D
*
**
Time (hours)
A Pre Occlusion Diameter Post Occlusion Diameter
B
Volek et al. Metabolism. In Press
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Blood Saturated Fat Levels
High Fat Diet 36 g SFA/d
Low Fat Diet 12 g SFA/d
Saturated Fat
Saturated Fat
208 CHO/d
45 CHO/d
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Saturated Fat
Saturated Fat
Blood Saturated Fat Levels
Saturated Fat Burned as
Fuel
Saturated Fat Burned as
Fuel
Low Carbohydrate
Diet (45 g CHO/d)
Low Fat Diet
(208 g CHO/d)
Saturated Fat Synthesis
Saturated Fat Intake (12 g/d)
Saturated Fat Synthesis
Saturated Fat Intake (36 g/d)
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-4
-3
-2
-1
0
1
TG CE
CRD (36 g SFA/d)LFD (12 g SFA/d)
Chan
ge in
Ser
um S
FA (%
)
* *
-4
-3
-2
-1
0
1
TG CE
CRD (36 g SFA/d)LFD (12 g SFA/d)
Chan
ge in
Ser
um 1
6:1n
-7 (%
)
*** ***
Forsythe et al. Lipids. 43(1):65-77, 2008
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Forsythe et al. Lipids. 43(1):65-77, 2008
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-40
-35
-30
-25
-20
-15
-10
-5
0
5
10
IL-6 IL-8 TNF-a MCP-1 I-CAM E-Selectin
PAI-1
Pe
rce
nt
Ch
an
ge
VLCKD LFD
Forsythe et al. Lipids. 43(1):65-77, 2008
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CRP
EGF
E-sel
I-CAM
IL-6
IL-8
L-sel
MCP-1
PAI-1
P-sel
V-CAM
VEGF
TNF-
IFN-
-0.6 -0.4 -0.2 0 0.2 0.4 0.6
Change CE 20:4n-6/20:5n-3
Correlation Coefficient Forsythe et al. Lipids. 43(1):65-77, 2008
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0
5
10
15
20
25
30
35
Serum TG Fraction
LFD (40 g SFA/d)CRD (86 g SFA/d)CRD (47 g SFA/d)
Plas
ma
SFA
(%) *
0
50
100
150
200
250
300
Serum TG Fraction
LFD (40 g SFA/d)CRD (86 g SFA/d)CRD (47 g SFA/d)
Plas
ma
SFA
(mg/
mL)
**
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0
1
2
3
4
Serum TG Fraction
LFD (40 g SFA/d)CRD (86 g SFA/d)CRD (47 g SFA/d)
Plas
ma
16:1
n-7
(%)
* *
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0
200
400
600
800
1000
1200
1400
0 1 2 3 4 5 6 7 8
8-is
o PG
F2α
pg/
mg
crea
tinin
e
Subjects
Baseline
CRD-SFA
CRD-UFA
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Low Fat
Low Carbohydrate
LDL Concentration
Small LDL (Pattern B)
Fasting & Postprandial TG
HDL (concentration and size)
TC/HDL or apoB/apoA-1
Fasting & Postprandial Glucose
Fasting & Postprandial Insulin
Insulin Sensitivity (HOMA, Clamp, TG/HDL, RBP-4)
CRP (Inflammation)
Vascular Function
Serum SFA (Fatty Acid Composition)
Oxidative Stress
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1. Carbohydrate intake is intimately linked to metabolic syndrome
2. Properly implemented very low carbohydrate diets favorably impact a broad spectrum of metabolic syndrome markers and cardiovascular risk factors
3. Carbohydrate restriction targets all the markers of metabolic syndrome, whereas drugs target individual markers and have well known side effects
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Metabolically Compromised/obese
Athletes
Naturally lean
Overweight/obese
Biomarkers: Weight lossTG16:1n-7
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