Richard Johnson - The Origins of Obesity and the Fattening of

The Origins of Obesity and the Fattening of
Man (Science Talk, 50 min)
Richard J Johnson, MD, University of
Colorado
Dr Johnson has a laybook (Fat Switch, mercola.com) and patents and
patent applications related to this work. He also has shares with XORT
therapeutics.
Obesity and Diabetes: The Twin Epidemics
One in three
adults are obese
One in 30 adults
are obese
One in nine adults
are diabetic
One in 50,000
adults are
diabetic
Johnson et al
Am J Clin Nutr 2007
Obesity is Affecting our Children
Children in the USA
% Obesity
First graders in Chile
Nearly one in five first
graders are obese
One in six children
are obese
Source: Albala, 2001
Obesity has Partners: Diabetes, High Blood
Pressure and Heart Disease
The Metabolic Syndrome
•Abdominal obesity
•Elevated Fasting glucose (insulin resistance)
•Elevated triglycerides
•Low HDL cholesterol
•Elevated blood pressure
Diabetes
High Blood
Pressure
Fatty Liver
Cirrhosis
Stroke and Heart Disease
Chronic Kidney
Disease
Sugar Intake Linked to Diabetes
Diabetes increased in New York City from
3 cases/100,000 in 1880 to 20 cases per
100,000 in 1920
Risk Factors
Wealthy
Over age 45
Sedentary
Caucasian
Merchants in the Food Industry
Haven Emerson (1874-1957)
Sugar consumption
New York City Health Commissioner
Arch Int Med
1924; 34:585-630
Sugar Intake and Diabetes
Sugar
consumption in
New York city
(Emerson, 1924)
Yemenites in
Israel (Cohen,
1961)
20% of diet was sugar vs 0% in Yemen
Sugar consumption in Manila
(Concepcion 1922)
Ceylon and
Egypt (1907)
Wealthy Hindu in Bengal
(Charles 1907)
Natal Indians of S
Africa (Campbell
1963)
77 lbs/yr intake vs 12 lbs/yr in India
‘Overnutrition’ and Lack of Exercise
Is to Blame
Too Many
Calories
Too little
energy used
Cars, TV,
Internet,
Elevators
Obesity: Is it from Bad Habits?
Appetite is Regulated:
Leptin, the appetite hormone
A Mouse Lacking LEPTIN
weighs more than two
control mice
Many Obese People appear to become Resistant to Leptin
Friedman Nature 1994; 372:425
Increased Food Intake due to Food Addiction:
Simulation of Dopamine in the Brain
Similarities between
Obesity AND Addiction
Lean
Dopamine creates a pleasure
response
Control
Obese
Abuser
Dopamine D2 receptor imaging
Gaining Weight is an Active Process
We eat large portions
since we cannot
control our appetite
We produce less
energy since we have
a defect burning Fat
Leptin Resistance
Dopamine Pleasure
Response
Reduced ATP
Biology is Driving Culture, not Culture Driving Biology
BUT WHAT IS ACTIVATING THIS PROCESS IN HUMANS?
Revisiting the Role of Sugar and its Partner,
Fructose
•Sugar (sucrose): fructose/glucose
•High fructose corn syrup (HFCS)fructose/glucose
•Fructose is in honey and fruit
Soft Drinks are the Major Source:
•One third of sugar intake is from soft
drinks.
Role of Fructose in Obesity
*
Control Mouse
Fructose-fed Mouse
Ishimoto T, PNAS 2012; 109:4320-5
Fructose stimulates Weight Gain
Am J Physiol Regul Integr Comp Physiol 2008;295:R1370-5; Eur J Clin Nutr 2012;66:201-8
Fructose Stimulates Fat Production and Insulin
Resistance
Rats were fed the same number of calories for 5 months
Sirirat Reungjui et al JASN 2007; 18:2624
High Sugar Diets Make the Liver Fatty Despite
Caloric Restriction
Oil Red O Stain for Fat
Starch Fed
Rat
Sugar Fed
Rat
Sprague Dawley rats fed sucrose or starch diet for 4 months at 90% of
normal intake
Roncal -Jimenez et al Metabolism 2011; 60: 1259-1270
Fructose Causes Metabolic Syndrome in
Animals
Johnson et al, End Rev 2009;30:96-116
The Stanhope Study: Fructose Increases Fat
Overweight Adults
were given 25% of
calories as either
glucose or fructose
for 10 weeks
Total
Subcut Visceral Total Subcut Visceral
Glucose
Fructose
Stanhope et al, J Clin Invest 2009; 119: 1322-1334
Effect of Fructose (200 g/d) for 2 weeks on
Metabolic syndrome in Men: Menorca Study
Metabolic Syndrome (NCEP-ATPIII)(%)
Triglycerides
HDL Cholesterol
Insulin resistance (HOMA)
Weight
(kg)
BMI (kg/m2)
24 hr Systolic BP (mm Hg)
24 hr Diastolic BP (mm Hg)
Baseline
19%
Change
44%
136 ± 15
46.5 ± 1.5
1.7 ± 0.2
84.3 ± 2.3
29.0 ± 0.6
126±2
75 ± 2
55±20
-2.5 ± 0.7
0.57 ± 0.16
0.6 ± 0.2
0.2 ± 0.1
7±2
5 ±3
P Value
<0.001
<0.001
<0.005
<0.003
<0.003
<0.001
<0.001
Perez-Pozo et al Int J Obes
2010
Fructose can be Produced from Carbs
(Glucose)
Glucose
Polylol Pathway
Fructose
Rice can be converted to Sugar in the Body
Lanaspa, Ishimoto et al, Nature Comm 2013
High Glucose Diet Stimulates Fructose
Production in the Liver
Fructose Level in the Liver
Normal diet Glucose-rich diet
Lanaspa and Ishimoto, Nature Com, 2013
Carbohydrates cause Fatty Liver and PreDiabetes from Fructose
3000
Insulin ###
Levels###
3000
Normal
Mouse
Fed Glucose
(Carbs)
Mouse
Fed Glucose
that cannot
metabolize
Fructose
2000
1000
0
Insulin (pg/ml)
Insulin (pg/ml)
*** ***
2000
1000
0
Water
Glucose
Water Glucose
Water Glucose
Water Glucose
WT
W T KHK-A/CKHK-A/C
KO
KO
Normal
Mouse
Mouse cannot
metabolize fructose
Mice That cannot Metabolize Fructose are Protected
Lanaspa, Nature Com 2013
HFHSD
KO
Sugar and Fat Work Together
##
##
##
#
##
***
*
1 .5
8
1 .06
4
*
* *
0 .5
2
0 .00
**
1 .5
1 .0
0 .5
WWT
T
KHK-A/C
KO
KHK
- A /C KO
#
*
1 .0
Sugar
and Fat
0 .5
LFD
H FD H FH SD LFD
WT
HFD HFHSD
KHK - A /C KO
10
5
0
0 .0
0 .0
LLFD
F D HHFD
F D HHFHSD
F H S D LLFD
F D HHFD
F D HHFHSD
FHSD
15
#
1 .5
C O L 1 A 1 / -a c ti n r a ti o
10
Liver Fibrosis
###
2 .0
C D 6 8 / -a c ti n r a ti o
Intrahepatic triglyceride
M C P -1 / -a c ti n r a ti o
(mg/mg protein)
Liver Inflammation
T im p 1 / -a c ti n ra ti o
Liver Fat
12
2 .0
LFD
H FD H FH SD LFD
WT
HFD HFHSD
KHK - A /C KO
High Fat
Ishimoto et al Hepatology 2013
LFD
Sugar Intake in the United States
•Sugar and HFCS Intake Represents 15% of all Calories in the average adult
•Minority populations (African-American and Mexican American) are eating more
JAMA Intern Med. 2014;:.
Cardiovascular Mortality Increases with Sugar
Intake
Risk for
Heart Attack
or Stroke
100%
50%
JAMA Intern Med. 2014;:.
Is There Historical Evidence Supporting a Role
for Sugar in Obesity?
Egypt and Obesity Among the Pharaohs and
Wealthy of the Old Kingdom
Obesity first appeared in Egypt among Pharaohs and
the wealthy of the Old Kingdom
Apiaries also date to this time, as does the
appearance of dental cavities among the Pharaohs
and wealthy
Queen Hatshepsut, who became Pharaoh, was
recently discovered to have been both obese and
probably diabetic based on studies of her mummyshe also had carious teeth
Queen Hatshepsut
The Discovery of Sugar Cane and the
Rise of Sugar
Sushruta Describes Diabetes in the Ganges
Valley of India
Diabetes develops in the
individual who “is in the habit
of taking sweet liquids”
Sushruta
The Spread of Sugarcane
1400 A.D
700 A.D
1500 A.D
950 A.D
500 A.D
500 A.D
600 A.D
500 B.C
Sugar and Royalty– The Adipose Rex
Syndrome
King Edward I of England ordered 1877 pounds
of sugar for the royal household in 1287 and
6,258 pounds of sugar in 1288
One pound of sugar equaled 28 pounds of cheese or 34 dozen eggs
Sugar as a Medicine
St Thomas Aquinas was an
Italian Priest
in the 13th
Century who liked sugar so
much that he argued it was a
medicine and could be eaten
during the fast
He went on to become very
obese
King Manuel and his Gift of Sugar
Sugar is Introduced to the Americas by
Christopher Columbus
On his second voyage
in 1493, Columbus
stopped in La Gomera
in the Canary Islands
where he had a
romance with Beatriz
de Bobadilla.
Christopher
Columbus
Beatriz de Bobadilla
On leaving, she gave
sugar cane cuttings to
Columbus to bring to
America
Increased Production in Sugar Plantations
makes Sugar Affordable
The Triangle Trade
Sugar: The Perfect Additive
1610-asia
1650-mexico
1550Caribbean
1615-africa
Sugar Intake increases in England and Holland
First
“For one fat person in
France or Spain, there are
a hundred in England”
William Wadd 1816
The Emergence of Morbid Obesity
Daniel Lambert died at age 40
with a weight of 732 pounds.
“His waistcoat could easily
enclose 7 persons of ordinary
size.”
Encyclopedia Brittanica, 1809
The Fat Switch, 2012, Mercola.com
The Rise of Sugar
Sugar intake per
year
Johnson et al
1700
4 lbs
1800
18 lbs
1900
90 lbs
2000
155 lbs
Am J Clin Nutr 86:899-906, 2007
Sugar Intake Correlates with Obesity Rates
HFCS
introduced
60
50
60
WWI and II
40
20
40
30
20
Sugar
intake
Obesity
rate
10
0
0
1700 1750 1800 1850 1900 1950 2000
Obesity Prevalence %
Sugar Consumption
Kilograms/Individual
80
Based on
Disappearance
Data
Year
Johnson et al
Am J Clin Nutr 86:899-906, 2007
Sugar Intake Correlates with Diabetes Rates
WWI and II
Annual Per Capita Intake of Soft Drinks (12
oz) in the USA
Anderson TA. Annu Rev Nutr 1982;2:113-32
Sweetened Beverage Intake in the USA, 19782000
Nielsen and Popkin.J Prev Med 2004;27:205-10
Sugar and the Maori
James Cook’s Voyage 1769
“The men are of the size of the larger European Stout,
clean, limber, active, and fleshy but never fat” Joseph Banks
Julien-Marie Crozet’s Voyage, 1791
“The men were great eaters…. They were partial to sugar;
they drank tea and coffee with us…they show repugnance for wine..
.and they do not eat salt”
Dietary Survey 1945. Sugar represents 15% of total dietary
(calorie) intake in Maori
Wright St Clair. New Zealand Medical Journal 1969; McLaughlin and Wilson New Zealand Med J 1945
Western Diet and Obesity in Nauru
Jared Diamond, Nature 2003
What about Fruits????


Relatively Lower Content of Fructose
Have other good components (vitamin C, antioxidants,
flavonols, fiber, potassium, etc)
Summary
•The storing of FAT is a biological process
•Sugar contains Fructose that activates this process
•Eating Sugar increases Body FAT
•Eating Sugar causes the Metabolic Syndrome
(prediabetes) and increases the risk for Diabetes, Heart
Disease, Liver and Kidney Disease
•Sugar intake has Increased over the Centuries and intake is
highest in minority populations. One of the major causes is
SOFT DRINKS
•IT IS TIME TO CAMPAIGN AGAINST SOFT DRINKS!!!!!
Special Thanks
Miguel
Lanaspa PhD
Takuji Ishimoto
MD, PhD
Gaby SanchezLozada, PhD
Yuri Sautin
PhD
And to all of my collaborators, past and present
Type of Sugary Beverage Changes During
Childhood
Age 2-5
Daily intake of sugary beverages
10-12 tsp added sugars/day
Age 6-11
Age 12-19
Miller et al Am J Prev Med 2013; 45: 416-421
The Problem with Soft Drinks