Body Functions DIMS Summer 2013

1. Body Functions DIMS Summer 2013

2. Modern Food Overview • Industrial agriculture • GMOs • Pesticides/chemicals • Other environmental effects • Sweatshops and hierarchy/slavery • Factory farming and animal treatment • Environmental effects • Food addiction • Institutional reality • Corporations • Governments • Domestication and the energy of food • Waste- 25%

3. Conventional Wisdom • How does nutrition affect health? Here’s the mainstream version: • The Fat-Cholesterol Hypothesis (aka Diet-Heart Hypothesis) • Fat and cholesterol are the dietary causes of heart disease (CVD) • Later, saturated fat and LDL cholesterol are singled out • And, dietary fat raises blood cholesterol, leading again to CVD • Lowering these reduces CVD and prolongs life- “heart-healthy foods” • And obesity • Surgeon General: “Overweight and obesity result from excess calorie consumptionand/or inadequate physical activity.” • And fat has the most calories per gram, so it’s the most fattening • Fat makes you fat, and it turns the blood to milky sludge, which creates atherosclerotic plaques

4. The Official Story • The nation turned away from grains and cereals and toward fat and red meat and paid the price • The “great epidemic” of heart disease • CVD was rare a century ago, and now it’s the #1 killer in the US • Coincided with the “changing American diet” • An increase in meat and fat consumption paralleling the rise in CVD • But the surge in heart disease, obesity, and diabetes came along with the message that fat is bad and carbs are good • In the US, average fat intake has dropped from 45% of total calories to 35% in the last 30 years, and cholesterol has fallen- people are following the message • Without improvements in health- quite the opposite! • 2,500 deaths each day from CVD- still the #1 killer • Obesity 12-14% of population from 1960’s thru 1980, but in 2004, 1 in 3 Americans obese, another 1 in 3 overweight • Diabetes has more than doubled since 1980 • From WWII, during the supposed “epidemic,” through the 1960’s, the American diet increased in total fat • But mainly vegetable fats, considered “heart-healthy” • And increase in vegetables and citrus fruits • Decrease in animal fats • Increase in cancer incidence also during this period • Inflammation? Toxins? Carbohydrates? Maybe any or all, or something else, but evidence against dietary fat as the cause

5. Diseases of Civilization • Tribal and indigenous populations tend to have low levels of the “diseases of civilization” • When exposed to Western diet- including sugar, molasses, white flour, white rice- these diseases appear • Obesity, diabetes, CVD, HTN, stroke, CA, cavities, periodontal dz, appendicitis, ulcers, diverticulitis, gallstones, hemorrhoids, varicose veins, constipation • When any of them appear, they eventually all do • Stress, other factors also important • The Carb Hypothesis: The dietary cause of these diseases is the consumption of refined carbohydrates • Rejected in the 1970’s- incompatible with fat-chol idea

6. Metabolic Syndrome • Imbalances common to obesity, DM, CVD • Abdominal obesity • Elevated triglycerides and free fatty acids • Low HDL, high LDL (small, dense LDL) • Hypertension • Hyperinsulinemia • Insulin resistance/glucose intolerance • Prothrombotic state • Proinflammatory state- elevated C-reactive protein • Elevated uric acid- precursor of gout • Also- endothelial dysfunction, oxidative stress, inflammation • Related- polycystic ovary syndrome, fatty liver disease, erectile dysfunction • These predict each other and major disease outcomes • Many worsened by refined carbsand stress • CA also- same incidence patterns, but not part of syndrome • Also stress- elevated GC’s, epi, norepi in syndrome • 24% of US adult population

7. Glycemic Index • Insulin-the dominant hormone in energy metabolism • Regulates fat, carb, and protein metabolism • Chronically high in obesity • Type I DM- emaciation, lack of insulin • Type II DM- obesity, hyperinsulinemia, insulin resistance- impaired ability to use blood sugar, but not to store it as fat • Glycemic index- rate of digestion, absorption, and conversion of carbs to blood sugar • The higher the GI, the higher the blood sugar spike • And the higher the resulting insulin rise • Glucose = 100 • Fat and protein decrease GI, refined carbs raise it • Glycemic load- GI per portion • Recent studies- diets high in GI, GL, starch assoc with increased DM risk • Low-GI diets assoc with improved glycemic control, insulin sensitivity • Total dietary fat not a risk factor for type 2 DM • So carbs, especially refined carbs, cause more rapid blood sugar spikes, leading to more rapid and pronounced elevations of blood insulin

8. Sugar Toxicity • Reactive oxygen species- burning glucose transforms oxygen into free radicals and other oxidants – oxidative stress • Free radicals- assoc with CVD, CA, others • Change cell membrane permeability • Harm mitochondria • Inhibit DNA coding • Distort RNA communication • Neutralized by antioxidants • Advanced glycation end-products (AGE’s) • Glycation-sugar attaches to protein without enzyme • Random reaction, leading to more of same • The sugar disengages in low blood sugar • In high blood sugar, continuing process = AGE’s • AGE’s cross-link with each other and other proteins • Accumulate in eye, kidney, arterial lining, nerve endings • All of which are damaged in DM • Collagen- most abundant protein, structural • AGE version ages skin- diabetics look older • Also stiffening of joints, arteries, heart, lungs- leather • LDL particularly susceptible to glycation • As is HDL, making them both more atherogenic • LDL also susceptible to oxidation • Trapped in artery wall more effectively, along with its cholesterol, and more resistant to removal from blood • Elevated in CVD patients, particularly in the plaques

9. Diabetes • High blood glucose • Glycosuria, frequent urination • Constant hunger for sugar and refined carbs • Urine smells and tastes like sugar (DM aka “sugar sickness”) • Absent in isolated populations eating traditional diets • Rise in type 2 DM in Western societies coincides with rise in consumption of sugar and white flour • Death rate from DM up 400% btw 1900 and 1920 in US, up 15X since Civil War, similar in Britain and France • “Rises and falls in the sugar consumption are followed with fair regularity within a few months by similar rises and falls in the death rates from diabetes.” • -H. Emerson, Columbia U, 1924 • Of the 13 countries highest in consumption of sugar, 11 are found among the 13 highest in death rate from diabetes • DM found in 0.1% of US population 100 years ago • Now 7%, a 70-fold increase • Mainstream view- DM from obesity, inactivity, and fat-rich low-carb diet • Obesity and diabetes • Fat cells distend and respond less to insulin • Less glucose and fat taken up- CV damage • Hormones then trigger fat and muscle to become more insulin-resistant • Pancreas secretes more insulin • Vicious circle, leading to beta cell burnout and type I DM

10. Hypertension • BP greater than 140/90 • Moves together with CVD, stroke, obesity, DM, high triglycerides • Mainstream- saltas the dietary cause of HTN • Water retained along with the salt, blood volume up • But effect small- cutting salt intake in half lowers BP by <5 mm Hg- the body normally just excretes the salt • Insulin elevated in HTN • Encourages the kidneys to hold on to sodium • Stimulates the SNS, stress response • Increases HR, constricts blood vessels = higher BP • Joslin’s DM: chronically elevated insulin “the major pathogenetic defect initiating the hypertensive process”in type 2 DM • High blood glucose inhibits salt excretion, so we retain water • And is itself a solute helping to retain water, just like salt • Carb Hypothesis- carbs raise insulin levels, leading to HTN, obesity, other diseases of civilization

11. Building the Official Truth • Ancel Keys- physiologist at U Minnesota- starting 1940’s • Naples (and Madrid)- rich more HD than poor, and rich ate more fat • Therefore, dietary fat raises blood cholesterol leads to HD • Study of six countries- the more dietary fat, the more HD mortality- but data available for 22 countries, and the effect vanishes when all are included • Selection (or confirmation) bias- choosing evidence that supports conclusion • Everything else “misinterpreted, irrelevant, or bad data”- like studies of Navajos, Irish immigrants, African nomads, monks, etc, showing no relation btw dietary fat and HD • Masai nomadic herders live on milk, blood, and meat, and have blood cholesterol levels among the lowest ever measured • Extensive atherosclerosis, but no HD • Cholesterol up when they then ate Western diet • Keys: “The peculiarities of those primitive nomads have no relevance to diet-cholesterol-CHD relationships in other populations.” • Debate • Skeptics- “show us the science” • Proponents- obligation to help patients- need to act- urgency • Press fed the fire also- positive feedback loop • Manufacturing stress and fear to manufacture consent

12. Tale of the Tape- The Evidence • 1950- Framingham Heart Study- 5100 residents given physicals, the examined every two years to see who got HD • Risk factors- HTN, abnormal EKG, obesity, smoking, family history- these have proven accurate over time • Cholesterol- blood levels over 260 assoc with 5x greater HD risk than chol under 200- compelling evidence • But- the men who died of HD more likely to have low chol, and little association for women at all • And (despite NIH preventing publication) men with very high (>300) and very low (<170) chol have same amount and types of dietary fat • No correlation btw dietary fat and either blood chol or HD- true in virtually every study comparing these within a single population

13. Tale of the Tape • 1957- Western Electric Study • 5400 male employees- looking at HD among those who ate the most and the least fat • 88 cases of HD- 14 in high-fat group, 16 in low-fat • Dietary fat not assoc with death from CHD • “If viewed in isolation, the conclusions that can be drawn from a single epidemiologic study are limited. Within the context of the total literature, however, the present observations support the conclusion that the [fat] composition of the diet affects the level of serum cholesterol and the long-term risk of death [from CHD] in middle-aged American men.” • This analysis then cited in AHA and NHLBI (Nat’l Heart, Lung, and Blood Institute) report The Cholesterol Factsas one of seven “epidemiologic studies showing the link btw diet and CHD [that] have produced particularly impressive results,”… “showing a correlation btw saturated fatty acids and CHD.” • 1956- Seven Countries Study- Ancel Keys again • And once again picking the countries in advance that he knew would support the hypothesis

14. The OfficialStory Advances • AHA-now everyone recommended low-fat diet- 1970 • Not just high-risk men with past MI, high chol, or smoking hx • And AHA seen as main source of expert info • 1970’s- polyunsaturated fats assoc with CA in animals • So advice to eat less fat and less saturated fat • 1977- Dietary Goals for the US- now government says eating less fat helps health • Staff director Marshall Metz: “We really were totally naïve, a bunch of kids who just thought, Hell, we should say something on this subject before we go out of business.” • 55-60% carbs, fats from 40% to 30%, only 1/3 saturated- the official diet • They admit there’s no evidence that lowering dietary fat lowers blood chol, but justify it with weight loss • “Fat supplies 9 calories per gram, whereas protein and carbohydrates … supply only 4 calories per gram. … Consequently, … the consumption of a diet deriving 40 percent of its calories from fat may result in a continual struggle to lose weight.” • So… USDA Dietary Guidelines for Americans • “Avoid Too Much Fat, Saturated, Fat, and Cholesterol” • And (in NEJM), “To be a dissenter was to be unfunded because the peer-review system rewards conformity and excludes criticism.”

15. NHLBIstudies • Multiple Risk Factor Intervention Trial (MRFIT) • 12K men with chol >290 • Half advised to quit smoking, take BP meds, eat low-fat, low-chol diet • 7 years later, more deaths in experimental group • Lipid Research Clinics (LRC) Coronary Primary Prevention Trial • 3800 men with chol >265 • All told to eat chol-lowering diet, half given chol med • 71 deaths in control group, 68 in experimental • “It is now indisputable that lowering cholesterol with diet and drugs can actually cut the risk of developing heart disease and having a heart attack.” • But- extrapolation from drug study to diet • Now- massive health campaign • The LRC results “strongly indicate that the more you lower cholesterol and fat in your diet, the more you reduce your risk of heart disease.” • AHA president: “If everyone ate chol-lowering diet, “we will have [atherosclerosis] conquered”by the year 2000 • 4 other studies, 1980-84, trying to establish a relationship btw dietary fat and health- none succeeded • And low cholesterol levels found to be associated with higher risk of CA- many studies (p. 54 GCBC) • NHLBI: “Surprise and chagrin” • But- NIH“consensus conference” to establish unanimity • Held in 1984, interestingly… Note: All page references are to Gary Taubes’Good Calories, Bad Calories

16. Getting the Word Out • 1988- Surgeon General’s Report on Nutrition and Health • The “disproportionate consumption of food high in fats” now responsible for 2/3of the 2.1 M US deaths in 1988 • “The depth of the science base… is even more impressive than that for tobacco and health in 1964.” • National Academy of Sciences- Diet and Health • “Highest priority is given to reducing fat intake, because the scientific evidence concerning dietary fats and other lipids and human health is strongest and the likely impact on public health the greatest.” • The media reports it, and now the debate is about low-fat vs. very low-fat • How much fat do we need to cut out in order to be healthy?

17. Carbs and CVD • 1955- Ahrens- carbohydrate-induced lipemia • Test tubes- “The lipemic plasma was obtained during the high-carbohydrate period, and the clear plasma during the high-fat regimen.” • Joslin: “The percent of fat (in the blood) rises with the severity of the disease (diabetes)… and is especially related to the quantity of carbohydrate, … rather than with the fat administered.” • Dietary carbs elevate TG’s, lower HDL, and, although they lower total LDL, raise the small, dense LDLthat’s associated with CVD • Insulin- the higher the levels, the greater the CVD • Stimulates TG synthesis and secretion to fat cells • Insulin resistance exacerbates this • Enhances transport of cholesterol and fat into the arterial wall • Stimulates chol and fat synthesis in artery wall • Enhances smooth muscle cell proliferation in artery walls

18. LDL Subtypes • 1980- LDL in the population in two patterns • Pattern A- large, fluffy LDL, low CVD risk • Pattern B-small, dense LDL, high CVD risk • High TG’s, low HDL (not in pattern A) • This pattern (the atherogenic profile) also found in DM • Small, dense LDL- Elevated in CVD • Strong negative correlation with HDL • Squeezes more easily through damaged artery walls • Structural changes in protein facilitatingadhesion • Remains in bloodstream longer • Oxidizes more easily • The higher the dietary carbs • The smaller and denser the LDL • The more likely the appearance of pattern B • The greater the CVD risk • The more saturated fat in the diet, the larger and fluffier the LDL!

19. Cancer • Increasing CA incidence • GI-colon, rectal, gall bladder • Endocrine-breast, endometrial, ovarian, prostate • These are the cancers related to diet and lifestyle • At least 75-80% preventable with diet and lifestyle • Some role for pollution and chemicals, genetics • Diet the largest role • Incidence patterns similar to CVD, DM, obesity • Another disease of civilization • Sugar intakecorrelated with incidence and mortality • In colon, rectal, breast, ovarian, prostate, kidney, nervous system, and testicular CA • 5 countries with highest sugar intake also the 5 countries with the highest breast CA mortality • 5 lowest = 5 with least mortality • Tumors burn much more sugar than normal cells • CA linked to glucose intolerance

20. Cancer • Insulin • Acts a growth promoter, normally and in CA • Fuel and growth signals to cells, including CA cells • Breast CA tumors- more receptors for insulin • IGF- insulin-like growth factor • Prominent hormone in growth regulation • Also elevated in high-carb diet • Can mimic effects of insulin, and vice versa • Levels of both tend to move together over time • IGF enhances tumor growth • IGF receptors necessary for tumor growth • Particularly with estrogen • Tumors can secrete their own IGF • Tumor cells have more IGF receptors • Insulin unbinds IGF to enter cells • IGF also overrides the cell suicide (apoptosis) program • Insulin and IGF both cause benign tumors to metastasize • They accelerate the process of the cell becoming cancerous, and keep it alive and multiplying • Hyperinsulinemia and elevated IGF in breast, prostate, colorectal, and endometrial CA • So the carbs lead to extra insulin and extra blood sugar along with extra IGF and extra signals to proliferate • They may not cause the CA, but they encourage the transformation into malignancy • An ideal environment for CA growth

21. Alzheimer Disease • Most common form of dementia • Progressive and fatal brain disease • Plaques-beta-amyloid protein between cells • Tangles-protein inside dying nerve cells • Both disrupt nerve cell communication • Both accumulate in most people • Risk factors- age, genetics, family history, smoking • Also- HTN, CVD, stroke, DM, metabolic syndrome, hyperinsulinemia • Another disease of civilization • Incidence patterns similar to CVD, DM, obesity • 2x increased risk in diabetics, 4x if on insulin

22. Alzheimer Disease • Insulin-degrading enzyme (IDE) • Clears both amyloid and insulin • Insulin can monopolize it • In animals- the less IDE available, the more amyloid • Mice without IDE gene get AD and type 2 DM • Insulin given to healthy elderly volunteers • Amyloid increased proportionately • The older the person, the greater the increase • Decreasing insulin increases amount of IDE • Amyloid- normal protein in brain • Healthy brains clear it out, but not in AD • AGE’s found in plaques and tangles • Nobody knows for sure what causes AD • Theory- AD starts with glycation • Proteins stick to themselves and each other • Disposal mechanisms don’t work, so they accumulate • Cross-linking leads to AGE’s • Glycation also generates ROS (free radicals) • Damaging neurons further

23. Obesity • The Official Story- weight gain comes from taking in too many calories and/or expending too few • Surgeon General: “Overweight and obesity result from excess calorie consumption and/or inadequate physical activity.” • US, 1970’s to 1990’s: increased caloric intake • NHANES- 1971 to 2000- 150 calories per day in men, 350 in women • USDA- 1971 to 1982: 3300 calories per day per person • 1993-1997: 3800 calories • 90% of the 500 calories from carbs • The rise in obesity also coincides with increasing exercise

24. Reports • F.P. Fouche, South Africa, 1925, British Medical Journal • “I never saw a single case of gastric or duodenal ulcer, colitis, appendicitis, or cancer in any form in a native, although these diseases were frequently seen among the white or European population.” • Smithsonian Institution, 1908 • “Malignant diseases, if they exist at all… must be exceedingly rare.” • As were CVD, appendicitis, peritonitis, ulcer, etc. • The Native Americans (SW US and Mexico) lived as long as or longer than local whites • Isaac Levin, Columbia U, 1910- survey of 107 physicians • Buchanan- 15 yr practice, 2000 Indians, avg lifespan 55-60, one case of CA • Goodrich- 13 years, 3500 Indians, zero cases of CA • Total- 115,000 Indians, treated for a few months to 20 years, 29 total cases of malignant tumor • Low levels of CA, CVD, etc., among: • Inuit eating all-meat diet • Masai eating blood, milk, and meat • The Natural History of Cancer, 1908 • Many continents and regions • Fiji- 120,000 tribal people, 2 deaths from CA • Borneo- Dr. Pagel- 10 years, zero cases of CA • In NYC, 32 deaths per 1000 people in 1864, 67 in 1900 • Philly- 31 in 1861, 70 in 1904 • “The negative evidence is convincing that in the opinion of qualified medical observers cancer is exceptionally rare among primitive peoples” • Fredrick Hoffmann, later a founder of the ACS

25. The Pima Indians • Highest rates of obesity and diabetes in the US • Is it their genes? • NIH: “If the Pima Indians could return to some of their traditions, including a high degree of physical activity and a diet with less fat and more starch,we might be able to reduce the rate, and surely the severity, of unhealthy weight in most of the population.” • Early 19th century and before • Game, fish, clams, corn, beans, cattle, poultry, wheat, melons, figs, cactus • 1846: “Sprightly… in fine health… the greatest abundance of food” • 1860’s: “Years of famine”as white and Mexican settlers came in • Game hunted nearly to extinction, water taken by the whites • 1890’s: government rations to avoid starvation • 1900’s: “Real obesity is found almost exclusively among the Indians on reservations” • The rations- 50% of calories from sugar and flour • 1950’s: “large quantities of refined flour, sugar, and canned fruits high in sugar,” also soda, candy, chips, cakes • 1962: “soda pop is used in immense amounts”

26. The Official Story • Energy Balance and the First Law of Thermodynamics • A calorie is a calorie is a calorie • Change in energy stores = energy intake – expenditure • Weight gain accompanied by positive energy balance- eat more than you burn, and you get fat • Obesity causes or worsens the conditions of metabolic syndrome and the diseases of civilization • And obesity caused by overeating, particularly a high-fat diet, and inactivity, so low-fat diet and exercise to fix • “Willful descent into self-gratification” • The obese responsible for their condition • Character defect- they overeat and won’t change • Willpoweris the cure • Assumption- intake and expenditure are independent variables • We can change one without changing the other • USDA- “For most adults a reduction of 50 to 100 calories per day may prevent gradual weight gain.” • Calorie-restricted, low-fat, high-carb diets and exerciserecommended for weight loss • Fats fatten us the most effectively (in this view)

27. Tale of the Tape-Low Calorie Diet • Low-calorie semi-starvation diets • “Balanced” diets with fewer calories- calorie restriction • Benedict 1917 • 2 groups of 12 men, 1400-2100 calories per day, 3 mos • Weight loss • Constant hunger, feeling cold • Metabolism slowed 30% • Anemia, weakness, loss of concentration, loss of libido • Weight gain on any more than 2100 cals • Binge eating after study, all weight regained in 2 weeks • And another 8 lbs extra in the next 3 weeks • In general- 25% lost 20 lbs, 5% lost 40 lbs • Almost all gained it back • Keys 1944 • 32 male conscientious objectors • 24 weeks on “semi-starvation” diet- 1570 calories • 400 cals protein, 270 fat, 900 carbs • Also 5-6 mile walk each day • 12 lbs lost in 12 weeks • Another 3 the next 12 weeks • Slow nail growth, hair loss, increased wound healing time, metabolism down, slowed reflexes, depression,irritability, feeling cold • Constant hunger, fixation on food, cheating on diet • When allowed to eat, 8000 cals per day • Total weight gain 10 lbs • Subjects weighed 5% more at the end, 50% more body fat

28. Tale of the Tape • Cochrane 2002 review 0f low-fat and calorie-restricted diets: Weight loss “so small as to be clinically insignificant.” • 2001 USDA review- 28 trials of low-fat diets, 20 calorie-restricted • Average- 1700 calories per day, weight loss 9# at 6 mos, overall gain of 1# • Women’s Health Initiative- 1991 NIH • 49K women age 50-79, 29K usual diet, 20K low-fat diet, 8 years • 20% calories from fat • More veggies, fruits, whole grains • 120 fewer calories per day in experimental group • No less breast CA, CVD, colon CA, or stroke in experimental group • 2 pounds average weight loss • Waist circumference, which measures abdominal fat, increased • NHLBI: “The results of this study do not change established recommendations on disease prevention.” • Exercise • Björntorp 1973- 7 subjects, 6 months of exercise three times a week, no change in weight • Pi-Sunyer 1989- weights can go up, down, or remain steady • Denmark 1989- sedentary people trained to run marathons for 18 months • 18 men lost 5 lbs, 9 women lost no weight • Randomized trials show less effect • Somewhere between 3 ounces a month gained and 2 ounces a month lost • Animal experiments- the more the rats run, the more they eat, weights unchanged • Hunger and intake increase in proportion to the calories expended • “Working up an appetite”

29. Tale of the Tape- Low-Carb Diet • Denmark 1936 • 21 obese patients, 2 years • 1850 calories/day, 25% carbs, 60% fat • Cream, butter, olive oil, eggs, cheese, meat • 2 lbs weight loss per week, no chronic hunger or fatigue • Donaldson 1920’s: 6 oz meat, 2 oz fat, at each meal, no sugar, flour, alcohol, starch, ½ hour walk • 17K patients, 2-3 lbs/wk loss, no hunger • Alfred Pennington- DuPont 1949: 20 execs, 9-54 lbs loss, 2 lbs/wk, no hunger, increased physical energy and sense of well-being • No calorie restriction- min 2400, avg 3000 • Carbs restricted to 80 cal/meal • Thorpe 1957- rapid weight loss (6-8 lbs/mo), no hunger, weakness, lethargy, or constipation • Ohlson and Young 1952: 14-1500 cals/day, 24% protein, 54% fat, 22% carbs • 7 women, overweight to obese, 16 weeks, 19-37 lbs lost • No hunger, addition of muscle mass • 16 overweight women, 9-26 lbs lost in 10 weeks, no hunger, “unexpectedly healthy,”sense of well-being • 8 overweight male students, 1800 cals/day, 9 weeks, 13-28 lbs lost, almost 3 lbs/week • Leith 1961: 48 patients who had tried and failed with low-cal diets, 28 lost btw 10 and 40 lbs • “The patients ingested protein and fat as desired”

30. The Low-Carb Diet • Wilder 1930’s: a few hundred cals/day, meat, fish, egg white, 80-100 cals of green veggies- weight loss without hunger • Bistrian 1970’s: 700 patients, 50% fat, 50% protein, 650-800 cals/day, weight loss without hunger • 1000, 1200, 1320, 1400, 1800, 2200, 2700, or no calorie restriction at all- weight loss without hunger • Kemp 1956: low-carb diet, no calorie restriction • 1450 overweight and obese patients • 49% lost at least 60% of excess weight- 25# after 1 year • 38% defaulted, 13% didn’t lose weight • 6 recent trials- weight loss after 3-6 mos was 2-3x greater on low-carb, calorie-unrestricted diet than on calorie-restricted, low-fat diet • JAMA 2003 review: “Of the 34 0f 38 lower-carbohydrate diets for which weight change after diet was calculated, these lower-carbohydrate diets were found to produce greater weight loss than higher-carbohydrate diets.”

31. So What’s Going On Here? • Official story- obesity from too many calories in, too few calories out • So eat fewer calories or exercise more to lose weight • These are independent variables- you can change one without affecting the other • Obesity is a character defect- driven by the brain- and losing weight is a matter of willpower, of overcoming the body • But restrict calories, and activity and metabolism decrease • Exercise more, and work up an appetite! • “Consistently high or low energy expenditures result in consistently high or low levels of appetite.” -Hugo Rony, 1940 • 1998: “Energy intake can be interpreted as a crude measure of physical activity.” • Carb Hypothesis- calories in and calories out are dependent, linked variables determined by a set point • Any increase in energy expenditure induces hunger and increase in intake • Any decrease in intake induces decrease in expenditure • Slower metabolism or reduced activity • Homeostasis-our bodies minimize long-term fluctuations in energy reserves and maintain a stable weight, unless the set point is changed

32. Two Situations • So here’s how the high-carb situation looks: • Carbs raise blood sugar raises insulin • The insulin tells the body to store nutrition as fat • There’s a burst of energy after a high-carb meal as the muscles and organs get sugar • But then, as the insulin tells the body to store energy, and as the sugar runs out, the fat that could power the cells can’t be released • The muscle and organ cells become depleted • Creating hunger and carb cravings (and sayings about being hungry an hour after eating Chinese food, not that Western high-carb meals don’t do the same) • And another round of carb intake • This vicious cycle continues until the fat cells are full • A new steady state at a higher weight • Weight only plateaus when • The fat tissue becomes insulin-resistant • Or the increased concentration of FFA’s in the fat cells or other forces balance out the insulin • This is determined by individual variation in carbohydrate sensitivity

33. Two Situations • And here’s the low-carb situation: • Blood glucose and insulin are not chronically elevated • So after a low-carb meal, they stay low • The muscle cells fill with energy, and the rest is stored as fat • Because the insulin is low between meals, the stored fat is easily accessible and freely released • The cells draw on this reserve to stay well nourished • When the reserves run low (several hours later, not an hour), the body (not the brain, the cells!) signals hunger • Eat another low-carb meal and start the process again • At no point does fat accumulate in the fat cells, so at no point do weight gain and obesity develop • And because glucose and insulin stay low, they aren’t able to drive the other diseases of civilization either

34. Inflammation • Pro-inflammatory state associated with obesity • Chronic inflammation in adipose tissue- obesity stimulates macrophage infiltration, leading to inflammatory cascade • Theories- adipose tissue hypoxia; altered adipose signaling; fatty-acid activation of innate immunity; metabolic endotoxemia • Inflammation and adiposity cause insulin resistance by interfering with insulin signaling • Systemic inflammatory, insulin-resistant, atherogenic state; metabolic dyslipidemia  type 2 DM and CVD • Component of metabolic syndrome • Associated with endothelial dysfunction • All of which increases CVD risk • 2012- metabolic endotoxemia- bacterial lipopolysaccaride- low-grade inflammation • Increased intestinal permeability- from high sugar diet, leads to increased plasma endotoxin, activation of systemic inflammation • Transplant of gut microbiota in mice transferred metabolic syndrome • Circ Res 2012: dietary fat lipoprotective • Rodent studies- replacing refined carbs with fat (polyunsaturated, saturated, monounsaturated) “can attenuate or prevent ventricular expansion and contractile dysfunction in response to hypertension, infarction, or genetic cardiomyopathy. … alters cardiac membrane phospholipid fatty acid composition, decreases the onset of new heart failure, and slows the progression of established heart failure. This effect is associated with decreased inflammation.” • JAMA 2004: Mediterranean diet (more whole grains, fruits, vegetables, nuts, olive oil) decreases inflammation • 180 patients with metabolic syndrome over two years • Experimental group lower CRP, decreased insulin resistance, improved endothelial function • Compared with “prudent diet” of 50-60% carbs, 15-20% protein, <30% fat

35. Inflammatory Foods • Inflammation and specific foods- more research needed in general • Trans-fatty acids/partially hydrogenated oils- endothelial damage, raise LDL, lower HDL • Omega-6 fatty acids- trigger pro-inflammatory signals • Nuts, seeds, vegetable oils • Sugar/refined carbs- cytokine release, increases in inflammatory PAI-1 (plasminogen activator inhibitor) • Factory-farmed animal fat- saturated fat assoc with reduced HDL anti-inflammatory activity (endothelial adhesion) • Grain-fed diet high in omega-6, low in omega-3 • Contains pro-inflammatory arachidonic acid- less improves rheumatoid arthritis symptoms • Also Neu5Gc- body makes antibodies • Processed meats (smoked, cured, salted, chemically preserved)- inflamm, colon CA • Alcohol- increases intestinal permeability, GI inflammation • Dairy products- casein and lactose stimulate inflammation • Milk- lactase persistence in only 40% worldwide • Monosodium glutamate (MSG)- inflammation, central obesity, type 2 DM in animals • Aspartame, many other additives • Gluten- celiac disease, wheat allergy, gluten intolerance • Wheat is acid-forming and inflammatory • Protective foods • Omega-3 fatty acids- fish, flaxseed, walnuts, grass-fed animals • Olive oil- contains natural anti-inflammatory • Antioxidants- non-citrus fruits, vegetables • Spices- ginger, garlic, cinnamon, turmeric • Green tea- anti-inflammatory phytochemicals

36. Dean Ornish • Demonstrated reversal of heart disease • Also- prostate CA, telomerase length, gene expression, diabetes (decreased HbA1c and medication), BMI, lipid profile (LDL down 40%, also TG’s, total cholesterol), blood pressure, depression • Comprehensive lifestyle changes • Very low-fat diet- natural, unrefined- fruits, veggies, whole grains, legumes, soy • Moderate exercise- walking • Stress management- yoga, breathing, meditation, imagery • Social support- support groups, improved relationships • http://www.ornishspectrum.com/proven-program/

37. Stress and Diabetes • More glucose and fat in the blood • Stress promotes insulin resistance • Glucocorticoids make fat cells less sensitive to insulin • In order to shunt energy to muscles • Stress can encourage the immune system to attack the pancreas • Higher rates of major stressors in the three years before onset (of type I)- trigger events? • Stress increases the chances of getting DM, accelerates its development, and encourages the major complications

38. Stress Effects • Stress and Nutrition • GC’s stimulate appetite • And preferentially for starch, sugar, and fat • Make brain less sensitive to satiety signal (leptin) • Particularly in the case of frequent intermittent stressors (also known as normal days in modern culture!) • Synthesis of cortisol depletes nutrients- vitamins and minerals • Caused/exacerbated by simple sugars • Increased cortisol increases neuropeptide Y • Carb cravings • Stress hormones shunt energy into the blood • TG breakdown, FFA and glycerol flood the circulation • Proteins to amino acids to glucose • Increased LDL, decreased HDL • Caffeine, processed sugar, processed flour, and salt elevate the stress response • Stress and Addiction • Using the drug decreases stress during the buzz • The stress comes in as the effects wear off • Increases likelihood of addiction • Increases extent of addiction • Increases difficulty of withdrawal • Increases likelihood of relapse • Sugar and refined carbs stimulate the same dopamine pathways as addictive drugs • Grains contain exorphins • Opioidslike morphine or heroin, and also addictive

39. Apples and Pears • Pear shape- gluteal fat • Apple shape- abdominal fat- worsened by stress • Greater risk for CVD, DM, other dz of civ • GC’s promote apple obesity in the presence of high insulin • Abdominal fat cells more sensitive to GC’s • Abd fat released straight to liver • Converted to glucose, elevated blood sugar • Stress -> carb cravings -> apple obesity -> dz of civ • The carbs and the apple fat both reduce the stress response- they really do help you feel good, as addictions do • Until the insulin stores the carbs as fat, starving the muscle cells and creating stress, starting the cycle over again • Also, lower ranking humans are more likely to be obese and more likely to be apple obese

40. Stress and Hierarchy • Inverse relationship between health and socioeconomic status • Specific disease causes vary, but gradient remains • Synergy between stress, agriculture, and hierarchy • Robert Sapolsky: “Agriculture is a fairly recent human invention, and in many ways it was one of the great stupid moves of all time. Hunter-gatherers have thousands of wild sources of food to subsist on. Agriculture changed all that, generating an overwhelming reliance on a few dozen domesticated food sources, making you extremely vulnerable to the next famine, the next locust infestation, the next potato blight. Agriculture allowed for the stockpiling of surplus resources and thus, inevitably, the unequal stockpiling of them – stratification of society and the invention of classes. Thus, it allowed for the invention of poverty. I think that the punch line of the primate-human difference is that when humans invented poverty, they came up with a way of subjugating the low-ranking like nothing ever before seen in the primate world.”

41. Digging at Roots • Obesityis found only in humans and domesticates,not wild animals • And it’s associated with the Western diet • So what are we doing that the other animals aren’t? • Among other things, no other animals growgrains (or consume other species’ dairy) • As we changed our diet to first increase carbs (agriculture),then refine them (industrialization), did we disrupt our homeostasis? • Along with agriculture and the dawn of civilization, • Nutrition worsens • Lifespan and body stature decrease • Famine, anemia, rickets, epidemic infectious disease • The Diseases of Civilization (no surprise, right?) • Work increases sharply • As does environmental destruction • And social hierarchy • And chronic stress

42. Pyramid

43. Circle

44. Food Issues Revisited • Industrial agriculture • GMOs • Pesticides/chemicals • Other environmental effects • Sweatshops and hierarchy/slavery • Factory farming and animal treatment • Environmental effects • Food addiction • Institutional reality • Corporations • Governments • Domestication and the energy of food • Waste- 25% • In the end, no one right way to eat • Your body knows how to eat. Your Primal Matrix knows- listen! • What do these all have in common? What’s the underlying relationship?