The Brain is What You Feed It: Effects of Nutrition on the Brain

1. The Brain is What You Feed It: Effects of Nutrition on the Brain Anne-Marie Kaulfers, MD Pediatric Endocrinology University of South Alabama

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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!

9. 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.

10. Carbohydrates Blood Sugar Cells of the Body

11. Carbs Blood Sugar Insulin = the key that unlocks the door, lets sugar into the cell I Cells of the Body

12. Type 1 Diabetes • Autoimmune destruction of the insulin-making cells • Usually starts in childhood • Completely dependent on insulin injections

13. Pancreas Beta cell Blood Sugar Insulin Body

14. Pancreas Blood Sugar I Body

15. Pancreas I I I I I Blood Sugar Blood Sugar Blood Sugar Blood Sugar Blood Sugar Body Body Body Body Body

16. 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

17. Type 2 Diabetes Pancreas ii ii ii Blood Sugar Blood Sugar Blood Sugar Blood Sugar Blood Sugar Body Body Body Body Body

18. 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.

19. 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.

20. 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

21. AD: Physical brain changes Too many “Tau” proteins Too many Amyloid-beta (AB) plaques

22. Alzheimer’s Disease: Physical brain changes

23. 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.

24. 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.

25. The Blood Brain Barrier “I’m the Blood Brain Barrier. You wanna get into the brain, you gotta go through me”

26. 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.”

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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.

34. 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

35. Bad fat vs Good Fat Saturated Fat Mono/Polyunsaturated Fat • Butter • Ghee • Lard • Coconut oil • Cottonseed Oil • Palm kernel Oil • Dairy: Creams/cheese • Fatty Meats • Vegetable Oil • Olive, Canola, Soybean • Avocado • Oily fish • Nuts • Seeds

36. Foods high in Simple Sugars ?

37. 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

38. 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.

39. 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.

40. 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.

41. 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

42. Appetite Hormones Normal State Insulin Resistance/Type 2 • If your stomach is empty: • Ghrelin Leptin • After you eat: • Ghrelin Leptin • If your stomach is empty: • Ghrelin Leptin • After you eat: • Ghrelin Leptin

43. Appetite: Food Addiction Eat healthy carbs Eat high sugar foods that taste REALLY sweet • 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. • 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.

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

45. 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.

46. 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

47. 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

48. 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

49. 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.

50. 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