Anne-Marie Kaulfers, MD
Pediatric Endocrinology
University of South Alabama
Disclosures
 www.INRseminars.com
 Institute for Natural Resources
 “Food, Mood, and Cognition” seminar is where most of
the references came from, seminar given by Gina M.
Willett, PhD, RD
 This talk and the topics presented are my own and not
endorsed or supported by that organization
Objectives
 Understand how what we eat influences how we think
and learn, and how it affects our memory
 Examine the relationship of Alzheimer’s disease to
diabetes
 Explore how the hormones in our body actually
promote weight gain and food addiction
 Learn about which foods are good for our brain
How different breakfast foods
affect kid’s behavior (2007)
 5-7 year olds who ate breakfast at school
 Group 1: cornflakes, milk, 2 spoonfuls of sugar, waffle,
and maple syrup
 Group 2: egg, bread, jam, butter, yogurt
 Group 3: ham, cheese, bread, and butter
How different breakfast foods
affect kid’s behavior (2007)
 Then they watched with a video camera to assess
ability to focus, and behavior
 And also did memory tests 2-3 hours after breakfast
 When students ate breakfast #3 they had better scores
on memory and ability to sustain attention
Other studies that show relationship of food
to brain function
 70-90 yr olds:
 highest carbs: 2 x risk of mild cognitive impairment
 Rats fed excessive fructose for 6 weeks
 moved slower and forgot how to get out of a maze
 2003: 815 elderly patients with no dementia
 High fat intake = higher chance of Alzheimer’s
 High omega 3 fatty acid intake = less chance
 2008: 1,049 people in CA
 Biggest waist = 3 x increased risk of dementia
Relationship of food and brain
 People at age 60
 Overwt in young age: poorer memory at age 60
 Followed 30-60 yr olds for 5 years.
 High BMI: lower test scores of mental status
 MRI on 94 elderly adults
 High BMI: atrophy of parts of brain, smaller brain volume
 CA Dept of Ed: 885,000 middle school kids.
 Better fitness level = better academic test scores
 Adults with Type 2 diabetes.
 High sugar meal = poorer memory 2 hours later
Relationship of Food and Brain
 Summary: Overconsumption of energy and high BMI
suggest poorer academic performance when you are a
child and more decay of the brain structure as an
adult. Increased physical activity improves brain
health and function.
 Conclusion: Poor diets can lead to brain dysfunction.
 Why?
 It’s all insulin’s fault!
Insulin and it’s action on the brain
 In 2005, researchers looked at the brains of people
with Alzheimer’s disease.
 They found that their brains had very low levels of
insulin and insulin receptors, and that all the signal
pathways that control energy metabolism, memory,
cognition were all functioning poorly.
Carbohydrates
Blood Sugar
Cells of
the Body
Carbs
Blood Sugar
Insulin = the key that
unlocks the door, lets
sugar into the cell
I
Cells of
the Body
Type 1 Diabetes
 Autoimmune destruction of the insulin-making cells
 Usually starts in childhood
 Completely dependent on insulin injections
Pancreas
Beta cell
Blood Sugar
Insulin
Body
Pancreas
Blood Sugar
I
Body
Pancreas
I I I I I
Blood Sugar
Blood Sugar
Blood Sugar
Blood Sugar
Blood Sugar
Body
Body
Body
Body
Body
Pre-Diabetes/Insulin Resistance
Pancreas
ii ii ii ii ii
Blood Sugar
Blood Sugar
Blood Sugar
Blood Sugar
Blood Sugar
Body
Body
Body
Body
Body
Type 2 Diabetes
Pancreas
ii ii ii
Blood Sugar
Blood Sugar
Blood Sugar
Blood Sugar
Blood Sugar
Body
Body
Body
Body
Body
Diabetes and Dementia
 Diabetes increases risk of mild cognitive impariment,
dementia and AD, either due to lack of insulin or
insulin resistance or both
 Overweight people who are not considered obese have
a 2-fold increased risk of getting Alzheimer’s disease.
Obese has a 3-fold risk.
 There is also mild cognitive impairment in animal
models of Type 2 diabetes and obesity.
Alzheimer’s disease: Type 3 diabetes?
 Famous study from 2005:
 Rats were ingested with a drug that can cause type 2
diabetes (streptozocin).
 When this drug was given by mouth or by IV, they got
type 2 diabetes.
 When they injected this drug directly into their brain,
it caused brain insulin deficiency, brain insulin
resistance, impairment in learning and memory, and
the identical brain lesions that are seen in AD.
Alzheimer’s Disease (AD)
 The most common cause of dementia
 It is a severe, age-related decline in memory and
cognitive functioning
 1 in 8 people over age 65 have AD
 Nearly half of people over age 85 have AD
 The difference between age-related cognitive decline
and AD is that AD had actual physical damage to brain
cells, which also causes behavioral changes
AD: Physical brain changes
Too many “Tau” proteins
Too many Amyloid-beta (AB) plaques
Alzheimer’s Disease:
Physical brain changes
AD and insulin: the connection
 Tau is controlled by insulin signals
 Brain insulin resistance leads to disruption of the
insulin signals that control nerve cell survival. It
messes up the systems that control neuron plasticity
(storing and creating memories) and cognition.
 Turning off insulin signaling in the brain causes
“oxidative stress” which damages proteins and DNA,
promotes inflammation, causes brain cell death, and
increases both tau and AB plaques.
AD and insulin: how it starts
 The Blood-Brain Barrier (BBB)
 This BBB keeps bad stuff from our body from getting
into our brains. It protects us from toxins.
 So anything we eat or make in our body, if we need it
to go to the brain, it has to cross the BBB first.
The Blood Brain Barrier
“I’m
the Blood Brain Barrier.
You wanna get into the brain,
you gotta go through me”
The Blood Brain Barrier:
Normal State
1st up: Sugar.
“Yep go right in, we
need you”
Next: Insulin.
“Sure, come on in,
we need you too.”
Blood Brain Barrier: In a patient
with pre-diabetes/insulin resistance
or Type 2 Diabetes
“Insulin! Again! I am
sick of seeing you.
You come around too
much. Go away, I am
tired of letting you in”
Obesity and high-fat diets decrease the ability of
insulin to get across the blood brain barrier
AD: Insulin can’t get through
the Blood brain barrier
 Without enough insulin in the brain, bad things start
happening.
 Lower brain insulin signaling increases tau and AB
plaques in mice
 Too much insulin in the body also interferes with the
body’s ability to get rid of the AB plaques once they are
made
 People with AD have reduced levels of insulin in their
brain and lower levels of insulin signaling too
Insulin Effects in the Brain
 Parts of the brain that use insulin:
 Cerebral cortex
 Hippocampus
 Hypothalamus
 Amygdala
How we think
Controls our memory
Controls our appetite,
energy level, weight
gain or loss
Controls stress
Without enough insulin in the brain, all of these systems suffer
Consequences of Insulin Problems in the Brain
 Glut-4 dysfunction
 Oxidative stress
 The insulin resistance in the brain can damage the
blood vessels, leading to strokes
 White matter of the brain starts to disappear
Consequences of Diet in the Brain
 Brain-derived neurotrophic factor (BDNF) plays an
important role in the survival, maintenance, and
growth of brain cells, especially in the hippocampus
and hypothalamus.
 Interference with BDNF reduces synaptic plasticity,
which is important for learning and memory.
 Diets high in saturated fats and simple sugars have
been shown to reduce BDNF levels and to interfere
with synaptic plasticity and making new nerve cells
Alzheimer’s Disease is a Metabolic Disorder
 MRI of patients with AD show decrease in sugar
metabolism in the hippocampus (learning and
memory)
 The neurodegeneration seen in AD can be produced
by experiments that cause brain insulin resistance and
deficiency
 Brain insulin deficiency and resistance could account
for the structural , molecular, and biochemical lesions
that correlate with the cognitive decline and dementia
in AD
Alzheimer’s Disease:
Is metabolism really to blame?
 Conclusions:
 Type 2 diabetes can enhance progression but is not
sufficient to cause AD by itself.
 Obesity, insulin resistance, and Type 2 diabetes and all
of these processes that result from it contribute to AD
and mild cognitive impairment, but they are not
proven to “cause” it yet.
 Insulin resistance is just a co-factor, contributing to
the problem.
Why are we going to keep
eating foods high in sugar and
fats even though we know how
harmful it is?
 It is all insulin’s fault
 Leptin
 Ghrelin
 Cortisol
 Dopamine
Bad fat
vs
Good Fat
Saturated Fat
Mono/Polyunsaturated Fat
 Butter
 Lard
 Vegetable Oil
 Olive, Canola, Soybean
 Avocado
 Coconut oil
 Oily fish
 Cottonseed Oil
 Nuts
 Palm kernel Oil
 Seeds
 Ghee
 Dairy: Creams/cheese
 Fatty Meats
Foods high in Simple Sugars
Appetite Hormones: Ghrelin
When there is no
food in your belly,
and your body
needs the energy,
you make Ghrelin,
which tells you that
you are hungry
Appetite Hormones: Leptin
When you have eaten
enough food, you make
Leptin. Leptin tells you
that you are full, and
that you should stop
eating.
Appetite Hormones: Cortisol
When you are stressed out,
anxious, or depressed, you make
Cortisol, which tells you to go
eat high sugar and high fat
food.
Cortisol also tells you to make
Ghrelin, so you get super hungry
for all the wrong foods.
Cortisol also turns off Leptin, so
you never feel full.
Cortisol also tells you to store
everything you eat as fat.
Appetite Hormones: Dopamine
When we eat high fat,
high sugar foods, we
make lots of
Dopamine, which
gives us the reward
from food. It turns on
the pleasure center of
the brain – the same
part of the brain that
responds to morphine,
nicotine, and alcohol.
Appetite Hormones
 These are all supposed to work together and play nice,
but when you have insulin resistance, these hormones
get all of their signals crossed
 2007: Gave obese and normal weight people a meal,
then they asked about their appetite after lunch. The
normal weight people were not hungry after they ate.
The obese group still reported that they felt hungry.
 Obese people may not respond correctly to hormone
signals after eating, correlating with insulin levels
Appetite Hormones
Normal State
Insulin Resistance/Type 2
 If your stomach is empty:
 If your stomach is empty:
Ghrelin
Ghrelin
 After you eat:
 Ghrelin
Leptin
Leptin
 After you eat:
Leptin Ghrelin
Leptin
Appetite: Food Addiction
Eat healthy carbs
 Make some insulin
 Insulin makes sure that the
“pleasure center” of the brain
never gets told anything, so
you don’t crave food. You just
eat till you are full and then
stop eating.
Eat high sugar foods that
taste REALLY sweet
 The excessive sugar goes right
to the “pleasure center” of the
brain and causes tons of
Dopamine to be released.
 This causes an exaggerated
emotional response, reduced
ability to stay away from that
food, leading to compulsive
eating.
“Diet” Drinks and “Low fat” foods
 Diet Drinks, made with artificial sweetners, taste
REALLY sweet, maybe too sweet. This causes excessive
releases of Dopamine also, causing us to crave real
sugar. Eating the real sugar causes the weight gain.
 Low fat foods add in extra sugar or artificial
sweeteners, making it taste REALLY sweet, leading to
the same process.
 Fructose also tastes REALLY sweet, so foods with highfructose corn syrup will lead you down this same road
to being addicted to high sugar foods.
Dopamine and Obesity
 Over time, our body can become resistant to these
excessive dopamine surges (the same way you get
resistant to insulin).
 Our body “panics” without Dopamine, causing us to go
try to find it again, so we eat even higher and higher
amounts of high sugar/high fat foods to try to turn on
Dopamine again.
 Drugs that cause weight gain are the ones that turn off
Dopamine in our brains.
What foods should we eat to
protect our brain?
Hopeful but unproven yet:
 Curry? – improves cognitive decay in rat models
 B vitamins? – some positive effects on memory
 Vitamin D? – important for preserving cognition
 Vitamin E? – shown to delay progression of AD, but
high doses can be harmful
 Vitamin A and C? – antioxidant vitamins, but no
proven benefit and can be toxic
 Ginseng? - not studied well enough to know
 Ginkgo biloba? – lots of bad medication interactions
Foods that protect the brain
 Proven to be beneficial:
 Antioxidant rich foods
 Alcohol/Wine
 Fiber: Improves alertness and decreases perceived stress
 Omega-3 fatty acids (DHA)
 Major building structures of the membranes in the brain
 Fish, salmon, flax seeds, krill, chia, kiwi, butternuts,
walnuts, baby formula
 Flavanoids
 Cocoa, green tea, Ginkgo tree, citrus fruits, red wine,
dark chocolate
Antioxidants
 No formal recommendation on the amount per day
 No proven benefit in supplements, and high doses can
be toxic
 Experts think these foods have a wide range of
functions besides reducing “oxidative stress”
 Foods that naturally contain antioxidants:
 Fruits, veggies, nuts, seeds, grains, olive oil
 Fresh spices: oregano, cinnamon, turmeric, parsley,
basil, ginger black pepper
Alcohol/Wine
 Light and moderate drinking = protective effect
against cognitive impairment and dementia
 Heavy drinking = no protective effect
 Wine is better than beer or hard liquor, since wine has
natural antioxidants.
Omega – 3 fatty acids (FA)
 2012: Rats with cognitive decline and a high-fructose
diet. They started giving them omega-3 FA and the
brain problems/memory improved.
 Dietary deficiency can prevent the renewal of the
brain structures and accelerate brain aging
 Most common dietary supplement is DHA
Flavonoids
 Reduce oxidative stress, improve insulin sensitivity,
protects heart and blood vessels
 2012: 90 elderly patients with mild cognitive
impairment.
 Gave them a drink once a day with different amounts
of flavanols, then did cognitive brain tests before and
after
 Test scores were higher in the high flavanol groups
after 8 weeks and the high flavanol group also had
improved insulin resistance and blood pressure.
Chocolate: Buyer Beware
 Most chocolates bought in a grocery store and so
processed and full of sugar that the harm is more than
the benefit
 White chocolate: no cocoa (Flavonoids)
 Milk chocolate: 20% cocoa
 Dark chocolate: 1 ounce of 70-85% cocoa is beneficial
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The End
Questions?