Update on Low Carbohydrate Diets: Research and Clinical...

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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 [email protected] 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

Transcript of Update on Low Carbohydrate Diets: Research and Clinical...

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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

[email protected]

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

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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

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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. 3

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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 210-

270 g/day.”

Institute of Medicine, Dietary Reference Intakes, 2008

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Food

Lipids Carbohydrates Proteins

Fatty acids + glycerol Amino acids

Acetyl coA

Pyruvate

Energy Processing With Carbohydrate

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Food

Lipids Proteins

Fatty acids + glycerol Amino acids

Acetyl coA

Pyruvate

Energy Processing Without Carbohydrate

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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 - 0.07 86 10.7

1983 Lean 30-50 kcal/kg Post 1.6 74 9.0

Langfort 8 < 5% 3d Pre - 0.28 23.0

1996 Lean 32 kcal/kg Post 1.9 10.5

Sharman 20 46g 56d Pre 0.08 90 23.7

2002 Lean 2400 kcal Post 0.28 90 15.6

Atkinson 7 0.5g 42d Pre - - 105 29.2

1985 Obese 1800 kcal Post 85 15.4

Hall 10 Starvation 12d Pre 0.15 0.27 90

1964 Obese Post 1.04 3.97 69

Westman EC. Journal of Clinical Outcomes Management 1999;6:36-40.

Sharman MJ et al. J Nutr 2002;132:1879-1885. 7

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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 203.9 205 138 127

1980 Obese Post 187.0 217 93 151

Golay 22 40g/1000 6 wk Pre 235.4 220 150.5 -

1996 Obese Post 173.7 123.9 34.9

Willi 6 25g/675 2 mo Pre 147.8 162 100

1998 Obese Post 121 90

Young 3 30g/3666 9 wk Pre 102.2

1971 Obese Post 86.0

Rabast 14 40g/1340 4 wk Pre 240.5

1981 Obese Post 214.1

Rabast 25 25g/1000 1 mo Pre 245 230

1978 Obese Post 204 134

Westman EC. Journal of Clinical Outcomes Management 1999;6:36-40. 8

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Effect of Very Low Carbohydrate Diets on Weight and Lipids

Ref Subjects CHO/Kcal Duration Weight Chol Trig LDL

Rickman 12 7g/1400 7-17d Pre 139.5 215 131 -

1974 Lean Post 131.6 248 116

Azar 6 1g/2000 4d Pre 150.0 245.2 - -

1963 Lean Post 143.5 284.3

Phinney 9 20g/? 4 wk Pre - 169 91 -

1983 Lean Post 208 79

Newbold 7 ?/? 3-18 mo Pre 263.0 113.0

1988 ? Post 189.3 74.7

Westman EC. Journal of Clinical Outcomes Management 1999;6:36-40.

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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

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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;113:30-36. 11

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Pilot Low Carb Study:

Weight loss over 6 months

-14

-12

-10

-8

-6

-4

-2

0

Wk 0 Wk 2 Wk 4 Wk 6 Wk 8 Wk

10

Wk

12

Wk

16

Wk

20

Wk

24

Duration of Intervention

Me

an

Pe

rce

nt

Ch

an

ge

in

Bo

dy

We

igh

t (s

em

)

* p < 0.001 comparing Week 0 to Week 24 (n=41).

Change = - 10.3%

Westman et al. Am J Med 2002;113:30-36. 12

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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;140:769-777. 13

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Percent Change In Body Weight

* p < 0.0001, for within-group change from Baseline to Week 24 for each diet group.

† p = 0.0002, for comparison between diet groups at Week 24.

-16

-14

-12

-10

-8

-6

-4

-2

0

Wk

0

Wk

2

Wk

4

Wk

6

Wk

8

Wk

10

Wk

12

Wk

16

Wk

20

Wk

24

Duration of Intervention

Mean

(S

EM

) %

Ch

an

ge i

n B

od

y W

t

Low Fat

Low Carb

-9.3%*

-14.2%*†

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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

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Diets, Carbohydrates and Calories

Atkins Induction

Zone Diet

Typical American Diet

Protein Power

CHO Grams/day

20

0

50

100

200

300

Calories/day

2000 1000

(Ketonuria)

Mediterranean Diet

Atkins Maintenance

Very Low Fat Diet

Low Glycemic Index Diet

Diabetes Solution Low Carbohydrate Ketogenic Diet

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Six-month Pilot Study:

Diet Composition

Composition

Mean Daily Intake

% of Daily Caloric Intake

Protein 113.8 g 32.1

Fat 95.5 g 59.6

Carbohydrate 22.3 g 6.5

Calories 1427.3 kcal

Westman et al. Am J Med 2002;113:30-36.

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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

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Low Carbohydrate Diet Composition

0

50

100

150

200

250

300

350

net carb fiber protein fat

gm/d

Usual Diet (3111 kcal/d)

Low Carb (2164 kcal/d)

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;142:403-411. 19

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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

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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, 2007

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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

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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

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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

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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, www.kostdoktorn.se) 25

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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

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Effect on Serum Lipids

Variable Baseline Wk8 Wk16 Wk24 Change

mg/dl mean mean mean mean

Cholesterol 214 201 201 203 -6%*

Triglycerides 130 82 75 74 -43%*

LDL 136 136 128 126 -7%*

HDL 52 49 58 62 +16%*

Chol/HDL 4.3 4.3 3.6 3.4 -21%*

Westman et al. Am J Med 2002;113:30-36. 27

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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 233.8 220.7 -6%* 245.4 236.0 -4%

Triglyceride 184.0 144.4 -22%* 167.3 86.0 -49%*†

LDL-C 144.9 139.8 -4% 157.3 158.4 +1%

HDL-C 54.1 52.8 -2% 54.3 60.0 +11%*†

Chol/HDL 4.4 4.3 -5% 4.8 4.1 -15%*†

Trig/HDL 3.6 2.9 -18% 3.3 1.7 -49%†

* p < 0.01, for within-group changes from Baseline. † p < 0.05 for between-groups comparisons.

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Effect on Fasting Lipid Subclasses

0

20

40

60

80

100

120

140

Larg

e VLD

L

Interm

ed V

LDL

Small V

LDL

IDL

Larg

e LD

L

Interm

ed LDL

Small L

DL

Larg

e HDL

Small H

DL

mg

/dl

Baseline (n=36)

Week 6 (n=36)

Week 12 (n=36)

Week 24 (n=36)

0

20

40

60

80

100

120

140

Larg

e VLD

L

Inte

rmed

VLD

L

Sm

all V

LDL

IDL

Larg

e LD

L

Inte

rmed

LDL

Sm

all L

DL

Larg

e HDL

Sm

all H

DL

mg

/dl

Baseline (n=27)

Week 6 (n=27)

Week 12 (n=27)

Week 24 (n=27)

LOW CARBOHYDRATE DIET PGM LOW FAT DIET GROUP

*

*

*

*

* p < 0.05 for comparison between groups

Westman et al. Int J Cardiol 2006;110:212-216. 29

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Effect on Fasting Lipid Subclasses

0

0.5

1

1.5

2

2.5

3

Larg

e VLD

L

Interm

ed V

LDL

Small V

LDL

Larg

e LD

L

Small L

DL

Larg

e HDL*

10

Small H

DL*

10

LDLP

*100

Baseline (n=43)

Week 24 (n=43)

0

0.5

1

1.5

2

2.5

3

Larg

e VLD

L

Inte

rmed

VLD

L

Sm

all V

LDL

Larg

e LD

L

Sm

all L

DL

Larg

e HDL*

10

Sm

all H

DL*

10

LDLP

*100

mg

/dl

Baseline (n=35)

Week 24 (n=35)

LOW CARBOHYDRATE DIET PGM LOW FAT DIET GROUP

*

*

*

*

Seshadri et al. Am J Med 2004;117:398-405.(Subanalysis of Samaha, Stern papers) * p < 0.05 for comparison between groups

*

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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

Foster 2003 RCT Clinic Healthy

adults 12m

q2Wk x 2, q4Wk x 4, then Wk 26, 34, 42, 52

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. 31

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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

Outpatient LCKD RCTs: Weight Loss and Serum Lipids

* p<0.05 for between-groups comparison

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2 months (“efficacy”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL L/H

Atkins 40 1736 137g 93.5 89.5 -3.6 kg +1.3 -32.3 +3.2 -0.18

Zone 40 1434 157 90.4 54.5 -3.8 kg -9.7 -54.1 +1.8 -0.33

WWatchers 40 1615 191 80.5 54.5 -3.5 kg -12.1 -9.2 -0.2 -0.42

Ornish 40 1393 230 70.0 27.5 -3.6 kg -16.5 -0.4 -3.6 -0.21

Popular Diet Effects on Weight Loss and Cardiac Risk Factors

Dansinger ML et al. JAMA 2005;293:43-53.

12 months (“effectiveness”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL L/H

Atkins 40 1886 190g 86.0 80.5 -2.1 kg -7.1 -1.2 +3.4 -0.39

Zone 40 1757 173 90.4 71.5 -3.2 kg -11.8 -2.5 +3.3 -0.52

WWatchers 40 1832 208 82.5 64.0 -3.0 kg -9.3 -12.7 -3.4 -0.55

Ornish 40 1819 218 76.5 64.0 -3.3 kg -12.6 +5.6 -0.5 -0.31

“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 self-

determined interest level.”

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2 months (“efficacy”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL DBP

Atkins 77 1381 ~62g 97 84 -4.3 kg +2.3 -52.3 -0.4 -2.9

Zone 79 1455 152 87 57 -2.0 kg -5.3 -24.8 -0.5 -2.1

LEARN 79 1476 180 73 49 -2.8 kg -7.3 -17.2 -3.8 -1.4

Ornish 76 1408 220 60 33 -2.8 kg -10.1 -10.9 -5.3 -0.4

Popular Diet Effects on Weight Cardiac Risk Among Women

Gardner CD et al. JAMA 2007;297:969-977.

12 months (“effectiveness”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL DBP

Atkins 77 1599 ~140g 84 78 -4.5 kg +0.8 -29.3 +4.9 -4.4

Zone 79 1594 179 80 62 -1.5 kg 0 -4.2 +2.2 -2.1

LEARN 79 1654 194 79 61 -2.5 kg +0.6 -14.6 -2.8 -2.2

Ornish 76 1505 195 68 50 -2.4 kg -3.8 -14.9 0 -0.7

“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 email and telephone reminders…and incentive payments.”

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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/m2 -1.65 -0.53 -0.92 -0.77 .01

Waist-hip ratio -0.019 -0.013 -0.009 -0.012 .10

HDL-C, mg/dL +4.9 +2.2 +2.8 0.0 0.002

Triglycerides, mg/dL -29.3 -4.2 -14.6 -14.9 0.01

Non-HDL-C, mg/dL -5.1 -0.5 -4.0 -6.8 0.36

Insulin, mU/mL -1.8 -1.5 -1.8 -0.2 0.17

Glucose, mg/dL -1.8 -1.6 +0.5 -0.8 0.54

Diastolic b.p., mmHg -4.4 -2.1 -2.2 -0.7 0.009

Systolic b.p., mmHg -7.6 -3.3 -3.1 -1.9 <0.001

Gardner CD et al. JAMA 2007;297:969-977. 35

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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:

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 Carb Low Fat

Insulin

Resistant

Insulin

Sensitive -11.7 lbs

-11.9 lbs -3.3 lbs

-9.0 lbs

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

36

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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;42:256-63.

• 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;47:307-18.

• Volek JS et al. Carbohydrate restriction has a more favorable impact on

the metabolic syndrome than a low fat diet. Lipids 2009;44:297-309.

37

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Low Carb vs. Low Fat Diet + Orlistat

Study Design

146 overweight VA outpatient volunteers

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

R

Yancy, Arch Int Med, 2009. 38

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Mean % Weight Change Over Time*

n= 74 71 66 65 60 61 69 61 52 53 46 54

65

n= 72 64 58 58 51 50 57 48 43 54 41 40

57

Low Carbohydrate Diet

Orlistat + Low Fat Diet

39

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Change in Blood Pressures at 3 Time points

Change in Blood Pressure by Treatment Arm

-7

-6

-5

-4

-3

-2

-1

0

1

2

SBPDBP

SBPDBP

LCKD O+LFDΔmmHg

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

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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

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Saturated Fat

Saturated Fat

Metabolic Processing of Saturated Fat

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)

Forsythe et al. Lipids. 43(1):65-77, 2008 42

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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. 43

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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 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., 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. 44

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Fat

Liver

Large LDL

Chylomicrons

Cells Atherosclerosis?

Thoracic Duct Superior Vena Cava

Triglycerides

Lymphatics

Triglyceride

Diet: Lipids

Observed Very Low Carb Diet

45

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Fat

Small LDL

Carbohydrate

VLDL

Liver

LDL

Chylomicrons

Cells Atherosclerosis

Thoracic Duct Superior Vena Cava

Simple sugars

Portal Vein

Triglyceride

Sugar

Triglycerides

Lymphatics

Triglyceride

Diet: Lipids

Observed Mixed Diet

LDL

46

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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

Initiation of Carbohydrate Restricted Diet

8/10 29.1 164

2/11 24.5 141

5/11 23.5 138 209 46 119 81 88

She asks, “Why wasn’t I given this option before? I was just given the

options of medications.” 47

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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