Anne-Marie Kaulfers, MDPediatric Endocrinology

University of South Alabama

Disclosureswww.INRseminars.comInstitute 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

ObjectivesUnderstand 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 schoolGroup 1: cornflakes, milk, 2 spoonfuls of

sugar, waffle, and maple syrupGroup 2: egg, bread, jam, butter, yogurtGroup 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 behaviorAnd also did memory tests 2-3 hours after

breakfastWhen students ate breakfast #3 they had

better scores on memory and ability to sustain attention

Other studies that show relationship of food to brain function70-90 yr olds:

highest carbs: 2 x risk of mild cognitive impairment

Rats fed excessive fructose for 6 weeksmoved slower and forgot how to get out of a maze

2003: 815 elderly patients with no dementiaHigh fat intake = higher chance of Alzheimer’sHigh omega 3 fatty acid intake = less chance

2008: 1,049 people in CABiggest waist = 3 x increased risk of dementia

Relationship of food and brainPeople at age 60

Overwt in young age: poorer memory at age 60Followed 30-60 yr olds for 5 years.

High BMI: lower test scores of mental statusMRI 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 BrainSummary: 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 brainIn 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

Cells of the Body

Insulin = the key that unlocks the door, lets sugar into the cell

I

Type 1 DiabetesAutoimmune destruction of the insulin-

making cellsUsually starts in childhoodCompletely dependent on insulin injections

Blood Sugar

Pancreas

Body

Beta cell

Insulin

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Pancreas

Body

Blood Sugar

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Pancreas

Body

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Body

I

Body

I

Body

I

Body

Blood SugarBlood SugarBlood SugarBlood SugarBlood Sugar

ii

Pancreas

Body

ii

Body

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Body

ii

Body

ii

Body

Blood SugarBlood SugarBlood SugarBlood SugarBlood Sugar

Pre-Diabetes/Insulin Resistance

ii

Pancreas

Body

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Body

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BodyBodyBody

Blood SugarBlood Sugar

Type 2 Diabetes

Blood SugarBlood SugarBlood Sugar

Diabetes and DementiaDiabetes 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 dementiaIt is a severe, age-related decline in memory

and cognitive functioning1 in 8 people over age 65 have ADNearly half of people over age 85 have ADThe 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 Amyloid-beta (AB) plaques

Too many “Tau” proteins

Alzheimer’s Disease: Physical brain changes

AD and insulin: the connectionTau is controlled by insulin signalsBrain 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 startsThe 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 barrierWithout enough insulin in the brain, bad things

start happening.Lower brain insulin signaling increases tau and

AB plaques in miceToo 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 BrainParts of the brain that use

insulin:Cerebral cortexHippocampusHypothalamusAmygdala

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 BrainGlut-4 dysfunctionOxidative stressThe insulin resistance in the brain can

damage the blood vessels, leading to strokesWhite matter of the brain starts to disappear

Consequences of Diet in the BrainBrain-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

LeptinGhrelinCortisolDopamine

Bad fat vs Good FatSaturated Fat Mono/Polyunsaturated

FatButterGheeLardCoconut oilCottonseed OilPalm kernel OilDairy: Creams/cheeseFatty Meats

Vegetable OilOlive, Canola, Soybean

AvocadoOily fishNutsSeeds

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: CortisolWhen 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: DopamineWhen 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 HormonesThese 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 HormonesNormal State Insulin Resistance/Type

2 If your stomach is

empty:

Ghrelin

LeptinAfter you eat:

Ghrelin

Leptin

If your stomach is empty:

Ghrelin

LeptinAfter you eat:

Ghrelin

Leptin

Appetite: Food AddictionEat healthy carbs Eat high sugar foods

that taste REALLY sweetMake some insulinInsulin 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.

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” foodsDiet 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 high-fructose corn syrup will lead you down this same road to being addicted to high sugar foods.

Dopamine and ObesityOver 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 modelsB vitamins? – some positive effects on memoryVitamin D? – important for preserving cognitionVitamin E? – shown to delay progression of AD,

but high doses can be harmfulVitamin A and C? – antioxidant vitamins, but no

proven benefit and can be toxicGinseng? - not studied well enough to knowGinkgo biloba? – lots of bad medication

interactions

Foods that protect the brainProven to be beneficial:Antioxidant rich foodsAlcohol/WineFiber: Improves alertness and decreases perceived

stressOmega-3 fatty acids (DHA)

Major building structures of the membranes in the brain

Fish, salmon, flax seeds, krill, chia, kiwi, butternuts, walnuts, baby formula

FlavanoidsCocoa, green tea, Ginkgo tree, citrus fruits, red wine,

dark chocolate

AntioxidantsNo formal recommendation on the amount per

dayNo proven benefit in supplements, and high

doses can be toxicExperts think these foods have a wide range of

functions besides reducing “oxidative stress”Foods that naturally contain antioxidants:

Fruits, veggies, nuts, seeds, grains, olive oilFresh spices: oregano, cinnamon, turmeric,

parsley, basil, ginger black pepper

Alcohol/WineLight and moderate drinking = protective

effect against cognitive impairment and dementia

Heavy drinking = no protective effectWine 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

FlavonoidsReduce oxidative stress, improve insulin

sensitivity, protects heart and blood vessels2012: 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 BewareMost 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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Physiology. 2012 May 15; 590:2485-2499. Benon D et al. 1999. The Effects of Nutrients on Mood. Public Health

Nutrition. 2(3A):403-9.5). Benton D, et al. The influence of the glycaemic load of breakfast on the

behavior of children in school. Physiology and Behavior. 92 (2007) 717-724.

Bourre JM. Effects of nutrients in food on the structure and function of the nervous system. Part 2. J Nutr Health Aging. 2006 Sep-Oct;10(5):386-99.

Burkhalter TM et al. A Narrative Review of Physical Activity, Nutrition, and Obeisty to Cognition and Scholastic Performance across the Human Lifespan. Adv Nutr vol 2:201S-206S, 2011.

Cizza G et al. Was Feuerbach right: are we what we eat? J Clin Invest.2011 Aug;121(8):2969-71.

Craft S. Insulin resistance and Alzheimer’s disease. Curr Alzheimer Res 2007 Apr;4(2):147-52. Review.

References (2) Craft S. The role of metabolic disorders in Alzheimer’s disease and

vascular dementia. Arch Neurol. 2009;66(3):300-305. DeLaMonte SM. Brain Insulin Resistance and Deficiency as

Therapeutic Targets in Alzheimer’s Disease. Curr Alzheimer Res 2012; 9(1): 35-66.

Desideri G et al. CoCoA Study. Hypertension. 2012. Flint A. et al. Associations between postprandial insulin and blood

glucose responses, appetite sensations and energy intake in normal weight and overweight individuals. Br J Nutr. 2007 Jul; 98(1):17-25.

Gestuvo MK Hung WW Common dietary supplements for cognitive health. Aging Health. 2012;8(1):89-97.

Gomez-Pinilla F. Brain Foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008; 9(7):568-578.

Jacka FN et al. A prospective study of diet quality & mental health in adolescents. PLoS One. 2011;6(9);e24805.

References (3) Kanoski SE et al. Western Diet Consumption and Cognitive

Impairment: Links to Hippocampal and Obesity. Physiol Behav. 2011 April 18; 103(1):59-68.

Mietus-Synder ML. Lustig RH. Childhood obesity: adrift in the “limbic triangle” 2008. Ann Rev Med. 59:147-162.

Morris MC. et al. Dietary Fats and the risk of incident Alzheimer disease. Arch Neurol. 2003;60:194-200.

Raji CA et al. Brain structure and obesity. Hum Brain Mapp. 2010;31:353-64.

Whitmer RA wt al. Central obesity and increased risk of dementia more than three decades later. Neurology 2008;71(14):1057-1064.

The EndQuestions?