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
ewestman@duke.edu

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 arent 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 dont 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 leafyou 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

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

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

mmHg

-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.

at 4 weeks
at 24 weeks
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

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

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 wasnt 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 Womens
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
ewestman@duke.edu