2013 “Some dog I got. We call him Egypt, because in every room he leaves a pyramid.”

1. Childhood Obesity 2013“Some dog I got. We call him Egypt, because in every room he leaves a pyramid.”

2. 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

3. The Childhood Obesity EpidemicSeveral 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”)

4. The Childhood Obesity EpidemicExercise? • 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

5. The Childhood Obesity EpidemicExercise? • The calories burned during housework and general exercise in stay-at-home housewives in 1952was about 450 calories more than females burn today • The National Food Survey of 1952found 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

6. The Childhood Obesity EpidemicExercise? • As far back as 1960President 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

7. The Childhood Obesity EpidemicEating out? • More sugar and fat • Less likely to have vegetables • Portion sizes larger and fixed • Fewer family dinners (less bonding)!

8. The Childhood Obesity EpidemicSugar? • 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)

9. The Childhood Obesity Epidemic Sugar? There are three MONOSACCHARIDESor "simple sugars,“ glucose (also known as dextrose), fructose, and galactose.   Sugarcommonly 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

10. SugarsBiochemistry • 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

11. Fats Versus SugarsFocus 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 LDLand reduced HDL • The amount of fat eaten did not affect the level of blood fats(Lund University, Sweden study, N= 4301 people)

12. 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 NOTcause a significant change in blood sugar levels, as sucrose does

13. Fructose • Table sugar is 50% fructose • High-fructose corn syrup is about 55% fructose • Agave syrup is 90% fructose

14. The Food PyramidSteps to a healthier you involve avoidingfructose What do you get in a 5-star pyramid? A tomb with a view. Fructose is isocaloricbut NOTisometabolic 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 VEGETABLES FRUITS OILS MILK MEAT & BEANS

15. Fructose Metabolism(Different than glucose metabolism) Glucose 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 oflipogenic gene expression • 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 rate- limiting step is phosphofructokinase (PFK)

16. 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!

17. Fructose and Metabolic Syndrome(dysfunction) • Fructose in the liver bypasses the rate-limiting enzymecontrolled by insulin • Fructose causes increases in carbohydrate response element binding protein turning on certain genes that trigger the production of fat

18. Fructose and Metabolic Syndrome(dysfunction) • Comparing fructose to glucose, high amounts of fructosein 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

19. Fructose and Oxidative Stress • High amounts of fructosein 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

20. 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

21. Non-nutritive Sweeteners These sweeteners contain no calories • Aspartamesold under the brand name NutraSweet® and Equal® • Sucralosebrand name Splenda® (heat-stable) • Saccharin brand name Sweet’N Low® • Acesulfame-K brand name Sweet One® • Stevia brand name Truvia® and PureVia®

22. 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

23. 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 sugar is the main ingredient of a processed food

24. 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

25. 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 toteach facts about food and health on an ongoing basis

26. Solutions?Read food labels • Ingredientsare listed in descending order by amount • Does NOTdistinguish between sugars that naturally occur in food and those that are added to the food • Sucroseis 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

27. 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

28. 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 up-regulate(and become sensitive to “sweet” again) • Once taste-receptors are up-regulated, milk becomes sweet again

29. Solutions?Eat at home • Less sugar- and fat-enriched food • More likely to have vegetables • Portion sizes are NOT fixed • Family dinnerspromote bonding! • What did the Pharaoh say when he saw the pyramid? • Mummy’s home.

30. 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.

31. 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 Latinverb docēre“to teach.” Need I say more?

32. The End

33. Fructose Metabolism(Gene expression) Glucose Fructose Insulin: Fructose does NOT stimulate insulin secretion, but chronic fructose feeding causes insulin resistance, resulting in higher plasma insulin Gluconeogenesis: Fructose inducesthe regulatory enzymes FBPaseand G6Pase causing the robust accumulation of glycogen fructose diet increased G6PD activity, a rate-limiting enzyme of the pentose phosphate pathway • Glucose is allowed to flow freely in the blood out to the tissues • Glucose metabolism’s rate- limiting step is phosphofructokinase (PFK) • inhibitory binding protein helps regulate the first step of glycolysis

34. Fructose Metabolism(Gene expression) • Carbohydrate and Lipid metabolism: • Genes involved in carbohydrate metabolism are strongly regulated by hormones such as insulin, glucagonand 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, FBPaseand PFK,

35. Fructose Metabolism(Gene expression compared to glucose) • Lipogenesis: • Fructose highly induces the lipogenicgenesPK, 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 sugar is the main ingredient of a processed food

36. Fructose to Glucose • Fructose is converted in the hepatocyte by KHK to fructose1-phosphate, then by aldolaseB to dihydroxyacetonephosphate asleep, then to glyceraldehyde 3-phosphate, 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

37. 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

38. Fructose Metabolism • Fructose consumed in the diet (in the form of native fructose or sucrose) is converted to fructose-1-phosphate (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.

39. Fructose Metabolism • Fructose in the liver bypasses the rate-limiting enzymecontrolled by insulin • Fructose causes increases in carbohydrate response element binding protein turning on certain genes that trigger the production of fat

40. Amylose Long chains of glucose molecules • Bound together in long chains, glucose molecules assembled into amylose do NOTtaste sweet • Brown rice or corn do NOTtaste 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

41. 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

42. Nutritive SweetenersProcessed • 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

43. 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

44. Glutathione • Small tripeptideprotein 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

45. 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).

46. 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 (N-acetyl-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

47. 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

48. BMI • The Body Mass Index was devised around 1840by Lambert AdolpheQuetelet, a Belgian statistician and sociologist, and bore his name “the QueteletIndex” 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 NOTgenerally useful in evaluation of health