Childhood
Obesity
2013
“Some dog I got.
We call him Egypt,
because in every room
he leaves a pyramid.”
The Childhood Obesity
Epidemic
Childhood obesity rates have tripled since 1980
and are now at 17 % of children and
adolescents between the ages of 2 and 19
causing:






Low self-esteem
Depression
Increased risk of Type II diabetes
Increased risk of high blood pressure
Trouble with bones and joints
Sleep Disorders
The Childhood Obesity
Epidemic
Several causes (to name a few)
 Lack of exercise (TV, VRC/DVD, computers/smart phones)
 Eating out of the home more often
 Over-consumption of calorie-rich foods
(especially sugar-sweetened drinks)
 Huge influx of sugar, especially fructose, into
the diet
 Redefining obesity (In 1998, the U.S. definitions were made
congruent with World Health Organization guidelines, redefining
approximately 29 million Americans, previously “healthy” to “overweight”)
The Childhood Obesity
Epidemic
Exercise?
 Lancet study in 2012 showing lack of exercise kills
as many people a year as smoking
 The figures add up to about 5.3 million deaths per
year from lack of exercise and its resultant health
complications, including obesity and heart
disease
 The CDC sites physical inactivity as the major
cause of childhood obesity
The Childhood Obesity
Epidemic
Exercise?
 The calories burned during housework and
general exercise in stay-at-home housewives
in 1952 was about 450 calories more than
females burn today
 The National Food Survey of 1952 found that
on average women consumed nearly 2,500
calories a day
 It’s estimated that women now consume
1,500 to 2000 calories a day
 Only 4% of women get 30 minutes of
moderate or vigorous exercise five days a
week
The Childhood Obesity
Epidemic
Exercise?
 As far back as 1960 President
Kennedy wrote an article for
Sports Illustrated entitled “The Soft
American”
 In 1966, when records of obesity
began, only 1.2 per cent of men
and 1.8 per cent of women had a
BMI of more than 30
 Today, for example, more people
work desk jobs compared to more
active jobs in the past
The Childhood Obesity
Epidemic
Eating out?




More sugar and fat
Less likely to have vegetables
Portion sizes larger and fixed
Fewer family dinners (less bonding)!
The Childhood Obesity
Epidemic
Sugar?
 Since the 1960's, when saturated fat was
demonized as the cause of heart disease,
processed foods have reduced the content
of fat while simultaneously increasing sugar
 In the year 2000, more than 30% of
carbohydrates consumed in the United
States came from added sugars (refined cane and
beet sugar, corn sweeteners, edible syrups, and honey)
The Childhood Obesity
Epidemic
Sugar?
There are three
MONOSACCHARIDES or
"simple sugars,“ glucose
(also known as dextrose),
fructose, and galactose.
Sugar commonly refers
to mono-, di-, oligo-, or
poly-saccharides.
There are three common
DISACCHARIDES, sucrose
(also known as table sugar),
maltose, and lactose.
GRAINS
VEGETABLES
FRUITS
OILS
MILK
MEAT & BEANS
Sugars
Biochemistry
 Sucrose (table, cane, raw, brown, granulated,
confectioner's, and turbinado or unrefined sugar)
= glucose + fructose
 Maltose (malt sugar) = glucose + glucose
 Lactose (milk sugar) = glucose + galactose
Fats Versus Sugars
Focus on the heart
 High glycemic load carbohydrates (e.g. refined
carbohydrates) impact cardiovascular disease
way more than saturated fatty acids
 Sugar associated with higher levels of LDL and
reduced HDL
 The amount of fat eaten did not affect the
level of blood fats (Lund University, Sweden study, N= 4301 people)
Fructose
 A moderate amount of fructose from fresh fruits
and vegetables has long been part of human
diets. However, abundant production of refined
sweeteners has dramatically increased fructose
intake
 Fructose "levulose" or "fruit sugar" is a sugar found
in fruit, honey and fruit juice
 Fructose with glucose make sucrose
 Fructose is much sweeter than sucrose
 Fructose does NOT cause a significant change in
blood sugar levels, as sucrose does
Fructose
 Table sugar is 50% fructose
 High-fructose corn syrup is about 55%
fructose
 Agave syrup is 90% fructose
The Food Pyramid
Steps to a healthier you involve avoiding
fructose
What do you get in a 5-star pyramid?
Fructose is isocaloric
but NOT isometabolic
to glucose. This means
you can have the same
amount of calories from
fructose or glucose, but
the metabolic effect will
be entirely different
despite the identical
calorie count.
GRAINS
A tomb with a view.
VEGETABLES
FRUITS
OILS
MILK
MEAT & BEANS
Fructose Metabolism
(Different than glucose metabolism)
Glucose
 Glucose is allowed to flow
freely in the blood out to the
tissues
 Inhibitory binding protein helps
regulate the first step of
glucose
 Glucose metabolism’s ratelimiting step is
phosphofructokinase (PFK)
Fructose
 Fructose or fruit sugar is
absorbed, then metabolize
mainly in the liver first-pass
 Inhibitory binding protein is itself
inhibited by the first product of
fructose metabolism, fructose 1
phosphate (F1P)
 Fructose enters the glycolytic
pathway at the triose level,
bypassing PFK
 Fructose induces up-regulation
of lipogenic gene expression
High Fructose Diets
(In rodents)
 Animals fed a fructose/water diet causes metabolic
syndrome
• Insulin resistance
• Impaired glucose tolerance
• Hyperinsulinemia
• Hypertension
• Hypertriglyceridemia
 Animals fed a glucose/water diet with the exact same
caloric content does NOT!
Fructose and Metabolic
Syndrome(dysfunction)
 Fructose in the liver bypasses the rate-limiting
enzyme controlled by insulin
 Fructose causes increases in carbohydrate
response element binding protein turning on
certain genes that trigger the production of
fat
Fructose and Metabolic
Syndrome(dysfunction)
 Comparing fructose to glucose, high
amounts of fructose in the diet contribute to
the development of risk factors that predict
heart disease and type 2 diabetes
• Central adiposity (visceral fat)
• Hypertension
• High triglycerides
• Fatty liver
Fructose and Oxidative Stress
 High amounts of fructose in the diet appears
to increase oxidative stress*
• Children given fructose beverages 3 times a day
with their meals show increased levels of oxidative
stress* and significantly increased triglycerides (this
oxidative stress stays up overnight)
• Children given glucose beverages 3 times a day
with their meals do not have increased oxidative
stress and triglyceride levels rise significantly less
• Therefore fructose may be pro-inflammatory
*oxidative stress as measured by the redox potential or
the oxidation of glutathione
Fructose and Oxidative Stress
 The redox potential directly measures the
level of oxidation of glutathione
(measurement of the oxidation response of
the body to a metabolite, in this case
fructose)
 It appears that oxidation leads to
inflammation and the cascade of metabolic
dysfunction
Non-nutritive Sweeteners
These sweeteners contain no calories
 Aspartame sold under the brand name
NutraSweet® and Equal®
 Sucralose brand name Splenda® (heatstable)
 Saccharin brand name Sweet’N Low®
 Acesulfame-K brand name Sweet One®
 Stevia brand name Truvia® and PureVia®
Non-nutritive Sweeteners
 Using rats, researchers found that animals given a
normal diet plus non-nutritive sweeteners in their
water gained weight while animals given a normal
diet and just plain water did NOT
 Rats use taste to determine how many calories
they consume, and non-nutritive sweeteners
appear to dysregulate their internal metabolism
Metabolic Dysfunction
(makes one prone to disease)
 About 80 percent of obese people suffer
from metabolic dysfunction
 About 40 percent of normal-weight people
also suffer from metabolic dysfunction
 Excessive sugar/fructose consumption is a
primary driver of metabolic dysfunction*
*It is difficult to avoid fructose even when glucose
ingredient of a processed food
sugar is the main
Metabolic Dysfunction
(Eight primary diseases related to M D)
 Type 2 diabetes (2010 meta-analysis of eleven studies involving 310,819
participants and 15,043 cases of type 2 diabetes noted that sugar-sweetened beverages
increase the risk of metabolic syndrome, type 2 diabetes, and obesity by increasing
dietary glycemic load, leading to insulin resistance, β-cell dysfunction, and inflammation)*
 Hypertension
 Lipid problems
 Heart disease (Switching from saturated fatty acids to carbohydrates with high
glycemic index values cause a statistically-significant increase in the risk of MI, and
fructose appears more damaging than glucose in terms of cardiovascular risk).





Non-alcoholic fatty liver disease
Polycystic ovarian syndrome
Cancer
Dementia
Tooth decay (lower rates of tooth decay have been seen in individuals with
hereditary fructose intolerance who typically self-select a diet low in fructose)
* Fructose appears to be the primary cause
Solutions?
 Read food labels and consume less
processed food (avoiding fructose contamination)
 Drink more milk and water, and consume
less artificially sweetened drinks (if consumption of
sugar-sweetened drinks are stopped, then taste receptors up-regulate and
become sensitive to “sweet” again)
 Eat at home
 Increase physical activity
 Ask your school if you can visit to teach facts
about food and health on an ongoing basis
Solutions?
Read food labels
• Ingredients are listed in descending order by
amount
• Does NOT distinguish between sugars that
naturally occur in food and those that are
added to the food
• Sucrose is listed by its common name, sugar
• Fructose, glucose, high-fructose corn syrup,
high-maltose corn syrup, and other sweeteners
are NOT put into the “sugar” category
Solutions?
Consume less processed food
• You can significantly reduce your fructose
intake by eliminating all sugar-containing foods,
including breakfast cereals, granola bars,
candies, desserts, snack foods and any other
foods listing sugar of any kind in their ingredient
list
• Avoid fruit juices
• Stick to low-fructose fruits, such as berries,
melons and citrus fruits
Solutions?
Drink more milk and water, and consume less
artificially sweetened drinks
 Drinking ice cold water 30 minutes before
meals is filling and limits food intake. Also
drink a glass of water every few hours to
keep hydrated
 Get large glasses for water with meals and
bottles in car and in room
 If consumption of sugar-sweetened drinks
are stopped, then taste receptors upregulate (and become sensitive to “sweet” again)
 Once taste-receptors are up-regulated, milk
becomes sweet again
Solutions?
Eat at home




Less sugar- and fat-enriched food
More likely to have vegetables
Portion sizes are NOT fixed
Family dinners promote bonding!
 What did the Pharaoh say when he saw the pyramid?
 Mummy’s home.
Solutions?
Exercise
 Encourage children to strive for 60 minutes or
more of physical activity every day
 Get the kids involved in team sports
 Kids learn best by example!
 What did the Pharaoh say when he saw the pyramid?
 Mummy’s home.
Solutions?
Teach
 Ask your local school if you can visit to share
facts about food and health on an ongoing
basis
 The word DOCTOR comes from the Latin verb
docēre “to teach.”
Need I say more?
The End
Fructose Metabolism
(Gene expression)
Glucose
 Glucose is allowed to flow
freely in the blood out to the
tissues
 Glucose metabolism’s ratelimiting step is
phosphofructokinase (PFK)
 inhibitory binding protein helps
regulate the first step of
glycolysis
Fructose
 Insulin: Fructose does NOT
stimulate insulin secretion, but
chronic fructose feeding
causes insulin resistance,
resulting in higher plasma
insulin
 Gluconeogenesis: Fructose
induces the regulatory enzymes
FBPase and G6Pase causing
the robust accumulation of
glycogen
 fructose diet increased G6PD
activity, a rate-limiting enzyme
of the pentose phosphate
pathway
Fructose Metabolism
(Gene expression)
 Carbohydrate and Lipid metabolism:
• Genes involved in carbohydrate metabolism are
strongly regulated by hormones such as insulin,
glucagon and glucocorticoids, and are sensitive to
nutritional status
• Carbohydrate response element binding protein
(ChREBP), a transcription factor , up regulated by
fructose, induces lipogenic genes such as PK, ACC,
and FAS, as well as the glycolytic enzymes KHK,
aldolase B, G6Pase, FBPase and PFK,
Fructose Metabolism
(Gene expression compared to glucose)
 Lipogenesis:
•
•
Fructose highly induces the lipogenic genes PK, ACC, and FAS
Fructose may cause a shift in the energy source for extra hepatic
tissues from triglycerides to glucose
 Gluconeogenesis:
•
Fructose induces the regulatory enzymes FBPase and G6Pase causing
the robust accumulation of glycogen in hepatocytes
 Pentose phosphate pathway:
•
Fructose increases G6PD activity, a rate-limiting enzyme
*It is difficult to avoid fructose even when glucose
ingredient of a processed food
sugar is the main
Fructose to Glucose
 Fructose is converted in the hepatocyte by KHK to
fructose1-phosphate, then by aldolaseB to dihydroxy
acetonephosphate asleep, then to glyceraldehyde 3phosphate, then to fructose 1, 6- biphosphate, then by
FBPase to fructose 6-phosphate, then by G6PD to
glucose 6-phosphate, then by G6Pace to glucose
where it is released into the plasma
Fructose to Lipid
 Fructose is converted in the hepatocyte by KHK to
fructose1-phosphate, then to glyceraldehyde, then to
glyceraldehyde 3-phosphate, then by pyruvate kinase
to pyruvate then by FAS and GPAT to triglyceride, and
then to VLDL where it is released to the plasma
Fructose Metabolism
 Fructose consumed in the diet (in the form of native
fructose or sucrose) is converted to fructose-1phosphate (F1P) in the liver
 F1P decreases the affinity of the inhibitory binding
protein for glucokinase causing the first step in glycolysis
to accelerate(so more glucose is phosphorylated – a
step that consumes ATP)
 The capacity of liver cells to phosphorylate fructose
(and make F1P) exceeds their capacity to metabolize
F1P. Consumption of excess fructose can cause an
imbalance in liver metabolism by indirectly depleting
liver cells of ATP.
 What did the Pharaoh say when he saw the pyramid?
 Mummy’s home.
Fructose Metabolism
 Fructose in the liver bypasses the rate-limiting
enzyme controlled by insulin
 Fructose causes increases in carbohydrate
response element binding protein turning on
certain genes that trigger the production of
fat
Amylose
Long chains of glucose molecules
 Bound together in long chains, glucose molecules
assembled into amylose do NOT taste sweet
• Brown rice or corn do NOT taste sweet for this reason
• Any grain is a source of amylose and also a source
of glucose
• Maltotriose is three glucose molecules connected to
one another
• Maltose is two glucose molecules connected
together
Sugars




Because most of the fructose increase seen in the American diet
is due to the use of sugar and high-fructose corn syrup, you
should first try to reduce your fructose intake by eliminating
processed foods
You can significantly reduce your fructose intake by eliminating
all sugar-containing foods, including breakfast cereals, granola
bars, candies, desserts, snack foods and any other foods listing
sugar of any kind in their ingredient list
Avoid fruit juices
stick to low-fructose fruits, such as berries, melons and citrus fruits
Nutritive Sweeteners
Processed

















Confectioner's/powdered sugar: finely ground sucrose
Corn syrup/corn sugars: liquid combination of maltose, glucose and dextrose, used often in sodas, baked goods,
and canned foods
Dextrose: glucose with water added
Invert sugar: sucrose that is divided into its two components--glucose and fructose, sweeter than sucrose, used in
candies and baked products, liquid
Sucrose: combination of glucose and fructose, often called "table sugar", produced from concentrated sugar
cane or sugar beet juice, includes raw sugar, brown sugar, granulated sugar, confectioner's sugar and turbinado
sugar (unrefined sugar)
Non-processed
Brown sugar: obtained from molasses syrup
Fructose: sugar found naturally in all fruits, sometimes referred to as "levulose" or "fruit sugar"
Glucose: syrup derived from corn starch, also found in small amounts in some fruits
Honey: sweetener produced by bees, made up of fructose, glucose, and water
Lactose: milk sugar, combination of glucose and galactose
Maltose: produced during fermentation, also called "malt sugar", found in beer and bread
Mannitol: byproduct from producing alcohol (doesn't actually contain any alcohol), only contains half the
calories of sugar because it's not well absorbed by the body, used in many diabetic foods
Maple sugar: comes from maple tree sap, combination of sucrose, fructose and glucose
Molasses: residue of processing sugar cane
Raw sugar: brown-colored sugar that can be granulated, coarse or solid, results from the evaporation of
moisture from sugar cane juice
Sorbitol: made from glucose, found naturally in some fruits (specifically berries), absorbed by the body much
more slowly than regular sugar, often used in diabetic foods
Non-Nutritive Sweeteners





Aspartame (brand names Equal and Nutrasweet): made from
phenylalanine and aspartic acid (two amino acids--the building
blocks of protein), 220 times sweeter than sugar
Acesulfame K (brand names Sunett and Sweet One): heat
stable (can be used in cooking and baking), 200 times sweeter
than sugar, often combined with other sweeteners including
saccharin and used in diet soda and other foods
Neotame: made from phenylalanine and aspartic acid, heat
stable, 7000-13,000 times sweeter than sugar, used in a variety of
foods and beverages
Saccharin (brand name Sweet 'N Low): 200-700 times sweeter
than sugar, used in numerous low-calorie foods and beverages
Sucralose (brand name Splenda): made from sugar, 600 times
sweeter than sugar, heat stable, widely used in food products,
popular tabletop sweetener
Glutathione





Small tripeptide protein composed of the three amino acids:
cysteine, glutamic acid and glycine
The sulfhydryl (thiol) group (SH) of the cysteine portion serves as
a proton donor
Antioxidant, preventing damage to cellular components by
reactive oxygen species such as free radicals and peroxides
Binds to toxins, such as heavy metals, solvents, and pesticides,
and transforms them into a form that can be excreted in urine or
bile
Serves as an electron donor, reduces disulfide bonds, and in the
process, glutathione is converted to its oxidized form glutathione
disulfide (GSSG), also called L-(-)-glutathione
Glutathione



The ratio of reduced glutathione to oxidized glutathione within
cells is often used as a measure of cellular toxicity
An increased GSSG-to-GSH ratio is considered indicative of
oxidative stress
In healthy cells and tissue, more than 90% of the total
glutathione pool is in the reduced form (GSH) and less than 10%
exists in the disulfide form (GSSG).
Glutathione
 Acetaminophen’s cytochrome P450-reactive
metabolite, N-acetyl-p-benzoquinone imine (NAPQI),
becomes toxic when the reduced form of glutathione
(GSH) is depleted by an overdose of acetaminophen
 When all GSH has been spent, NAPQI reacts with the
cellular proteins, killing the liver cells
 Glutathione taken orally is NOT well, so Mucomyst (Nacetyl-L-cysteine) is used for acetaminophen overdose
because it is metabolized by the liver cells to L-cysteine
and used in the de novo synthesis of GSH
Glutathione
Supplements that have also been shown to increase
glutathione content within the cell serve as GSH precursors







N-acetylcysteine, commonly referred to as NAC, is the most
bioavailable
S-adenosylmethionine (SAMe)
Whey protein
Vitamin C raises glutathione by helping the body manufacture it
Calcitriol, the active metabolite of vitamin D synthesized in the
kidney, increases glutathione levels in the brain and appears to
be a catalyst for glutathione production
Vitamin B6, riboflavin and selenium are required in the
manufacture of glutathione, but the extent to which any of
these nutrients effectively increase glutathione levels in
humans remains unclear
BMI
 The Body Mass Index was devised around 1840 by
Lambert Adolphe Quetelet, a Belgian statistician and
sociologist, and bore his name “the Quetelet Index” until
1972
 In 1998, the U.S. definitions were made congruent with
World Health Organization guidelines, redefining
approximately 29 million Americans, previously healthy
to overweight
 Assumptions about the distribution between lean mass
and adipose tissue are inexact, and generally
overestimates adiposity
 Error in the BMI is significant and so pervasive that it is
NOT generally useful in evaluation of health