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    Nutrition and the Effects of Macronutrients
    "From Fructose to Trans Fats"

    Timothy D. Bilash MD MS OBG
    Northern Inyo Hospital, Bishop, California
    December 27, 2006

    <Presentation Outline and References>
    >>>> to slide presentation (pdf file)
    >>>> to Macronutrients main page
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    Directly based on:
    Nutritional Implications of Macronutrient Substitutes
    Anals of the New York Academy of Sciences Vol 819 (1997)
    G. Anderson, B. Rolls, D. Steffen, Eds.

  1. Nutrients

    1. What are Macronutrients (Major Food Groups that provide Energy) [11]

        1. Total Body Water (TBW) = 60 Liters in man
        2. Intracellular Fluid (ICF) = 40 Liters
        3. Extracellular Fluid (ECF) = 20 Liters
        1. Contains nitrogen
        2. Body components
        3. Increase protein Intake by 50% under Stress
      3. FAT (REQUIRED)
        1. Energy Storage (long-term)
        1. Small Carbohydrates (Simple Sugars and Starches)
        2. Big carbohydrates (Complex Starches)
        3. Obtainable from Protein
        4. Energy source

    2. What are Micronutrients
      1. Vitamins
      2. Minerals
      3. Special fats
      4. Metabolic Cofactors

    3. Vitamins
      1. Vitamin D
      2. Vitamin B Complex
        1. Thiamine (B1)
        2. Riboflavin (B2)
        3. Niacin (B3)
        4. Pantothenic Acid (B5)
        5. Biotin (B7)
        6. Folate (B9)
        7. Cobalamin (B12)
      3. Vitamin C (Yellow, Tangy Taste)
      4. Vitamin A (Beta Carotene, Orange Color)
      5. Green, Red, Yellow Colors

    4. Minerals
      1. Potassium (K) Rich Foods :
        Tomatoes, Broccoli, Dried fruits, Figs, Whole Nuts, Bran cereals,
        Cauliflower, Carrots, Bananas, Oranges, Spinach, Seaweed,
        Beef steak, Pork, Lamb
      2. Magnesium (Mg), Calcium (Ca)
      3. Iron (Fe), Zinc (Zn), Selenium (Se), Copper (Cu)
      4. N Engl J Med 1998;339:451-8, ACOG Clin Rev Jan/2000 p3

  2. Historical Changes in Nutrition and Health

    1. Dietary changes over 12 years from 1977 to 1990 (Canada) [3] (North America, US) [4, 70, 89]
      1. (+)120% increase in Low-Fat and Skim Milk, Fat modified products
        66% of the U.S. population is using a Lower Fat Milk product
      2. (+) 40% increase in Dark Green Vegetables
      3. (+) 20% increase in Grains and Carbonated Soft drinks,
        Heavy Cream, Cheese, Frozen Deserts, Full-Fat Yogurts
      4. (-) 34% decrease in Fat Consumption , Total Fat and Saturated Fat
        (as a percentage of Calories NHANES III)
      5. (-) 40% decrease in Milk, Pork and Beef (Red Meat, Butter, Whole Milk, Eggs)
      6. (-) 05% decrease in Total Calories (we consume fewer Calories today than in 1900)

    2. US Obesity rate has doubled or more
      1. Less sensitive to Exercise Cues (don't adjust intake to activity)

    3. Specific Food Shifts [123]

      1. Before 1492
        1. New World Foods Available before 1492 (but not available in the Old World)
          1. Amaranth, Artichoke, Avocado, Kidney Bean, Lima Bean, Blackberry, Blueberry, Cacao (Chocolate), Cassava, Black Cherry, Cranberry, Concord Grape, Guava, Huckleberry, Maize, Papaya, Peanut, Pecan, Chili Pepper, Pineapple, Popcorn, Potato, Pumpkin, Quinoa, Raspberry, Wild Rice, Sassafra, Sunflower, Tomato, Turkey
        2. New World Foods that were Imported before 1492 (from the Old World)
          1. Almond, Apple, Apricot, Asparagus, Barley, Cabbage, Cattle (Beef, Milk and Dairy Products), Cucumber, Eggplant, Garlic, Goat (Meat, Millk and Dairy products), Grapes (Wines), Lemon, Lettuce, Lime, Oats (and Oatmeal), Olive, Onion, Orange, Pig (pork and Lard), Rice, Rye, Sheep (Lamb, Milk and Dairy products), Sugar Cane, Turnip, Wheat

      2. After 1492
        1. New World Staples and Foods no longer available
          1. Agouti, Anus, Calabash, Caiman, Chunu, Coracon, Duck Potato, Golden Club, Guanaco, Iguana, Jicama, Manatee, Muskrat, Oca, Pemmican, Pithaya, Sacqwuenummener Berry, Tapir, Zapote
          2. Improved food diversity and diet in some places, but disasters in others
        2. Old World (Europe)
          1. Old World Wheat was replaced with New World Potatoes
          2. New World Maize brought to Europe by Colombus dispersed throughout Europe, Africa and Asia
          3. Maize consumed alone, without its culturally protective mix of legumes, led to Pellagra in Europe (Nicain/Vitamin B3 deficiency).
            1. Legumes, as in Alfalfa, Clover, Peas, Beans, Lupins, Peanuts, fix nitrogen

      3. There is no evidence that Pellagra (Niacin Deficiency) existed before 1492.

  3. Normal Metabolic Values

    1. Calorie comparisons (1 kcal/g - kilocalories per gram = 4.2 kJ - kilojoules) [11,142]

      9 kcal/g Fat
      4 kcal/g Protein**
      3 kcal/g Protein (available)**
      4 kcal/g Carbohydrate (if oxidized)
      3 kcal/g Carbohydrate (if stored as Fat)*
      1.5 kcal/g Oligo-Fructose
      1 kcal/g Polydextrose
      *Carb fuel value is 4kcal/g, but 25% of Carbohydrate energy is expended if stored as Fat
      *Protein fuel value is 4kcal/g, but 25% of Protein energy is expended to metabolize

    2. Energy Consumption (Energy Intake, non-obese) [70]
      1. Energy Intake regulation is very precise for most individuals
        1. We adjust Intake according to Energy Content, resisting change [3]
        2. Lean persons tend to remain lean even when their Intake of Fat increases.
        3. Increase Fat Oxidation (burning) when increase Fat intake (non-Obese)
        4. [Pietro Antonio Tatranni-1xii]
        5. 34% of Energy is consumed as Fat
        6. Resting Muscle burns Fat
        7. Working Muscle burns Sugar
      2. Men Consume an average of 2600 calories/ day (2.6 kcal/day)
      3. Women Consume an average of 1800 calories (1.8 kcal/day)
      4. Resting Fat metabolism is lower in women than in Men, leading to Fat Storage in Women
      5. One problem may be that women are eating men portions?

    3. Energy Expenditure (Energy Use)
      1. Basal Metablic Rate (BMR) = 20 kcal/kg of Body Weight
        1. Energy expended that is sufficient only for the functioning of the vital organs, such as the heart, lungs, brain and the rest of the nervous system, liver, kidneys, sex organs, muscles and skin.
        2. At rest, in a neutrally temperate environment, in the post-absorptive state (digestive system is inactive, which requires about twelve hours of fasting), with no Sympathetic stimulation.
        3. The more common and closely related measurement, under less strict conditions, is Resting Metabolic Rate (RMR).
      2. Resting Metabolic Rate (RMR) is the minimum number of calories your body needs to support its basic physiological functions, including breathing, circulating blood and all of the numerous biochemical reactions required to keep you alive.
        1. RMR is generally 60-75% of Total Daily Caloric Expenditure, higher than the baseline BMR
        2. Calculator at
      3. Relative contribution to Energy Use
        1. Resting Metabolic Rate (60-70%)
        2. Physical Activity (15-30%)
        3. Thermogenesis (5-10%)
        4. Physical Activity correlates with Sympathetic activity, Family Membership
        5. [Pietro Antonio Tatranni-1 xii]

  4. Dietary Issues

    1. Satiety dependent more on Mass than Calories (inhibition of further intake after consumption)
      1. [Barbara J. Rolls xiv]
    2. Consider Total calories vs Macronutrient distribution of Calories
      1. Fat substitution reduces Fat Intake, but does not reduce Energy Intake
      2. Lower limit of >15% of calories from Fat set by the American Heart Association
    3. Have to restrict Calories to burn Fat [38]
      1. It's the Calories, stupid! (not the source)
    4. There are ages differences in responsiveness to Energy Density of Food [201]
    5. Factors that increase diet induced thermogenesis
      1. Dietary fiber (digestion)
      2. High protein diets
      3. Nutrient imbalance

  5. Glucose Utilization by Tissues

    1. Brain needs ~ 120gms Glucose (0.120 kg, 360 kcal) per day (can use Acetoacetate in starvation)
      1. Acetoacetate is water soluble transportable form of Acetyl-CoA
      2. Fatty acids cannot enter nerve tissue
    2. RBC's need Glucose for Energy
    3. WBC's need Glucose to remake Cell Membranes (used in phagocytosis, for cell skeleton)
    4. Muscle :
      1. 30 kg of Muscle in man, 10% = Glycogen (3 kg, 12,000 kcal)
      2. 1.5 kg of Glycogen (1500 gms, 6000 kcal, 5%) in Muscle is non-essential,
        Body converts Glycogen to Glucose to meet Brain starvation need for 30 days
        before starts breaking down essential proteins
      3. Muscle Energy Source
        1. Fatty Acids account for 80% of Muscle Energy at rest
        2. Glucose accounts for 75% of Muscle Energy at activity

        3. Fitness raises the set point switchover to Glucose (longer use of Fatty Acids)
      4. Muscle can shift to burn Ketone Bodies directly (in starvation)
      5. Protein is the only source of Glucose after Glycogen stores gone
        1. F.A. go to Pyruvate in TCA, but no new Glucose is made
    5. Liver :
      1. 1.5 kg of Liver, 5% Glycogen = 75gms (0.075 kg, 300kcal)
      2. Liver, Fat, Muscle need Insulin to get the Glucose into cells
      3. Glucose can enter Muscle cells directly in excercise without Insulin
    6. Heart
      1. Heart burns Fatty Acids exclusively
      2. In Ketoacidosis Heart muscle and Renal Cortex use Acetoacetate in preference to Glucose
    7. Adipose :
      1. Fat oxidation increases as Fat Mass increases to reach new equilibrium [39]
        1. Hi Free Fatty Acids, Hi Triglycerides, Insulin Resistance
    8. Problems with Hi Glucose
      1. Hi glucose in cells is turned into Sorbitol- which remains hyperosmotic after serum
        glucose levels are reduced. Therefore get eye lens swelling after give Insulin.
      2. 1% Glucosuria (~3+) does not cause polyuria
      3. Diabetic Neuropathy- Quinine or Elavil helps with pain

  6. Formal Recommendation Examples

    1. 1988 Surgeon's General Report on Nutrition and Health [138]
      1. Decrease Hi-Fat, Saturated Fat and Cholesterol Foods
      2. Increase Vegetables, Fruits, Whole Grain Foods
    2. 1989 Diet and Health Report of the National Academy of Sciences [138]
      1. Increase Carbohydrates to 55% of Total Calories
      2. Double the Intake of Vegetables and Fruits
      3. Neutral with respect to Sugars
    3. 1995 USDA and HHS Dietary Recommendations [138]
      1. Eat a variety of Foods
      2. Balance the Food you eat with Physical Activity
      3. Choose a diet low in Fat, Saturated Fat, and Cholesterol
      4. Choose a diet with plenty of Grain products, Vegetables, and Fruits
      5. Choose a diet moderate in Sugar
      6. Choose a diet moderate in Sodium
      7. Drink Alcoholic Beverages only in moderation
    4. 1990 American Heart Asociation/ American Diabetes Association [142]
      1. Reduce Fat to 30% of Calories

  7. "Poison" Foods

    1. Fructose Sugar
      1. When Table Sugar (Sucrose) is digested, it breaks down into equal amounts of Fructose and Glucose (Dextrose).
      2. Fructose is a little sweeter than table Sugar (Sucrose).
      3. Modest amounts of Fructose occur naturally in fruits and vegetables, with other Sugars.
      4. Modest amounts of Fructose are safe and do not boost blood Glucose levels, making the sweetener attractive for diabetics.
      5. Large amounts of Fructose increase Triglyceride (Fat) levels in blood, thereby increasing the risk of heart disease .
      6. Fructose affects Thyroid, Liver and Paraventricular Nuclear function , conversion of T4 to T3
      7. Fructose is metabolized only in the Liver
      8. Fructose mimics a magnesium deficiency , and may worsen Copper deficiency ( )

    2. High Fructose Corn Syrup (HFCS)
      1. Corn Syrup is treated with enzymes to convert some of its Glucose (Dextrose) to Fructose,
        which results in High Fructose Corn Syrup (HFCS).
      2. Hi-Fructose Corn Syrup (HFCS) is a major source of Fructose in the typical diet.
      3. HFCS typically contains about half Fructose and half Glucose.
      4. HFCS has largely replaced ordinary Sugar used in soft drinks and many other foods, because it is cheaper.
      5. Americans consume about 59 pounds per year of HFCS (a total of 150 pounds per year of all refined sugars).
      7. High Fuctose Corn Sugar (HFCS) was introduced in 1906, escaping safety evaluation by the FDA

    3. Corn Protein, Oil, Products (Maize)

      1. Corn Protein is low in Tryptophan
        1. Associated with Pellagra (Niacin/Nicotinic Acid)
          1. Niacin Deficiency (B3)
            1. Essential for tissue respiration , Citric acid cycle (Carbohydrate Metabolism)
            2. Nicotine Adenine Dinucelotide (NAD) contains Niacin, is synthesized from Tryptophan [G&G6th p1568]
            3. Chronic Alcohol ETOH causes Vit B3 deficiency
            4. Niacin deficiency associated with Obesity
              1. Pima Indians (Eat Corn)
            5. Dermatitis, Diarrhea, Nausea, Vomiting, Mental confusion, Agitation, Dementia, Delusions, Hallucinations, Loss of Appetite
            6. Flour is supplemented with Niacin
          2. Needs to be balanced with Beans to avoid deficiency

      2. When Cornmeal was fed as virtually the sole source of protein to ten male volunteers during a 100-day study, at an intake of 6g of nitrogen per day (approx. 36g protein), not all the subjects were in positive nitrogen balance. Yet all the essential amino acids met or exceeded standard requirements, with the exception of Tryptophan - of which 91% was provided. These results suggest that on a Corn Protein diet, non specific nitrogen is the first limiting factor , not lack of esssential Amino Acids.
        1. Corn-fed Cattle appear to have increased Bovine flatulence, may contribute to global warming.
        2. Kies, C., Williams, E. and Fox, H.M. (1965). 'Determination of first limiting nitrogenous factor in corn protein for nitrogen retention in human adults', J. Nutr., 86, 350-356.

      3. Corn-Fed Beef looks better than Grass-Fed, because of the added Fat marbling, but the marbling is a result of indigestible Saturated Fats. We're better off without them.
        1. Statements from Advocates of Grass-Fed over Corn Fed Beef (Milk Cattle also?)
          1. It is leaner (about 1/3 the Fat)
          2. It is higher in Conjugated Linoleic acid (3-5 times as much)
          3. It is higher in Omega-3 Fatty acids (2-6 times as much)
          4. It is higher in Vitamin E (2-4 times as much)
          5. It is higher in Beta-Carotene
          6. When cattle are “finished” on Corn or Grain, the meat changes dramatically. The ratio of omega-6 fatty acids to omega-3 Fatty Acids goes from about 1:1 to greater than 10:1 , and levels of the other beneficial nutrients drop dramatically. This change occurs very quickly, being complete within 30 days on grain. This is why when purchasing grass-fed beef you need to ask for 100% grass-fed.
      4. Corn Oil - the Problem Oil
        1. A study at the San Fransisco VA (2005) has demonstrated that Omega-6 Fatty Acids such as the Fat found in Corn Oil promotes the growth of Prostate tumor cells in the laboratory (see Corn-fed Cattle) .

    4. Polyunsaturated/Monunsaturated Natural Oils

      1. Vegetable (Natural) Oils are Polyunsaturated (Safflower, Sesame, Sunflower, Corn, Soybean) and Monounsaturated (Canola, Olive, Peanut, Avocados)
      2. Vegetable (Liquid) Oils are meant to be consumed in dilute forms (nuts, grains)
      3. Polyunsaturated Oils may inhibit Thyroid Function
      4. Un- saturated Fats/Oils oxidize easily, which may produce Free Radicals in vivo, a health risk increasing cell damage
        1. Polyunsaturated Fats especially may increase Damage from Free Radicals
        2. Saturated Fat does not produce Free Radicals
      5. But Liquid Oils are better than Solid Fats (best if mono - or un - saturated)

    5. "Industrial Waste By-products" ( "Plastic Fat" and "Artifical Sugars" )

      1. Hydrogenation is the addition of hydrogen to Unsaturated (Partially Saturated) Carbon Chains (have one or more double bonds) creating more Saturated (less Unsaturated) or totally Saturated compounds (no double bonds).

      2. Hydrogenated Fat and Oils ( Artificial Partially Saturated Fats are NOT OK )
        1. Vegetable Oil (Natural, Polyunsaturated, usually liquid ) is processed into
          semi-solid shortening by reacting it with Hydrogen . Partial Hydrogenation reduces
          the levels of Polyunsaturated (Natural) Oils, and also creates Trans (artificial) Fats,
          which promotes heart disease. Hyrogenated Fats are Partially Saturated or Totally Saturated.
        2. Crisco, introduced in 1906 , is Partially Hydrogenated Vegetable Fat used for baking
          and frying in place of Lard. Crisco escaped safety evaluation by the FDA and Contains
          Trans Fat
        3. Fully Hydrogenated Vegetable Fat (Totally Saturated) does not have any Trans Fat or
          Polyunsaturated (Natural) Oils. It is sometimes mixed (physically or chemically)
          with Liquid Oils to create Trans-free Shortening. When it is chemically combined
          with Liquid Oil, the ingredient is called Inter-Esterified Vegetable Oil.

      3. Trans Fat (Not OK) vs Cis Fat (OK)
        1. Double bonds bind carbon atoms tightly and prevent rotation of the carbon atoms along the bond axis. This gives rise to configurational isomers which are arrangements of atoms that can only be changed by breaking the bonds.
        2. Trans Fatty Acids are so named because the carbon atoms adjacent to the double bond is on opposite sides, resulting in a straight configuration and solid at room temperature. In contrast, naturally occuring Cis Fatty Acids contain have adjacent carbon atoms on the same side, resulting in a bent shape and a liquid.

        3. A committee of the U.S. Food and Drug Administration (FDA) concluded that
          on a gram-for-gram basis, Trans Fat is even more harmful than Saturated Fat .
        4. The Institute of Medicine has advised consumers to limit Trans Fat, ideally
          less than about 2 grams a day (what might come from naturally
          processed Trans Fat in Beef and Dairy products).
        5. Animal Fat (Lard) has very low levels of Trans Fat
        6. Saturated Fat lowers Heart Disease compared to Trans Fat
        7. Because the Fats in Margerine are partially hydrogenated (not fully saturated),
          manufacturers can claim it is "polyunsaturated" and market it as health food.
        8. Trans Fat was first introduced 75 years ago, escaping safety evaluation by the FDA (until now)
          Because of the known and unknown health effects of these hydrogenation by-products,
          government health regulations would not allow the process to be used for making edible
          products if it were introduced today.
          The Margerine Hoax Roubos, from Nexus Magazine,

      4. In 2004, the Center for Science in the Public Interest petitioned the FDA to immediately
        require restaurants to disclose when they use Partially Hydrogenated Oil and to begin
        the process of eliminating Partially Hydrogenated Oil from the food supply.

      5. Most large chains and many smaller independent restaurants continue to fry in
        Partially Hydrogenated Oil and their French Fries, Fried Chicken, Fried Fish, and Pot Pies
        contain substantial amounts of Trans Fat.

      6. Oil processors are improving the Hydrogenation process so that less Trans Fat
        forms (new Trans-Free Crisco is all Saturated Fat)

      7. In Denmark, the government has virtually banned partially Hydrogenated Oil.
        In that country, as well as Australia and Israel, McDonald's fries in Trans-Free
        Liquid Vegetable Oil.

  8. Goverment and Food Industry has fed us "Garbage" for over 75 years:

    1. "Plastic Fat" ( Hydrogenated Oils ) and "Cardboard" ( Corn/Soy Solids )
      that is sweetened with "Artificial Sugar" ( High Fructose Corn Syrup )

    2. Warning: What the the animals eat, you eat
      1. Artificial Fats
      2. Corn, Soybean feed
      3. Estrogens to fatten animals
      4. Growth Hormones
      5. Antibiotics

    3. Nutrition Challenge:
      1. Find a Loaf of Bread that does not contain Corn Sugar
      2. Find a package of Hot Dogs that does not contain Corn Sugar
      3. Find a Can of Soup that does not contain Corn Sugar
      4. Find Maple Syrup that contains Maple Syrup instead of Corn Sugar
      5. Find Butter at KFC or McDonald's Restaurants

  9. MacroNutrient Substitutes (Sugar replacers, Fat replacers) [142]

    1. Food Additive Regulation (FDA) [22]
      1. Common use in food prior to 1958 is grandfathered in
      2. Safety established by scientific procedures after 1958
      3. Burden is on petitioner to demonstrate safety

    2. Carbohydrate Replacement Bulking Agents
      1. Reduced Starch Hydrolysates
        1. Hydrogenated Simple Sugars
        2. Partial hydrolysis followed by Hydrogenation
        3. < 3.2kcal/g (13.4 kJ)
        4. Little reaches colon
      2. Polyols (ie, Mannitol, Xylitol)
        1. Variable Calories (0-70%)
        2. Poorly absorbed, fermented in colon by micro-flora
      3. Oligofructose (Root Sugars)
        1. Fructo-oligosaccarides occur naturally in Onion, Asparagus, Wheat, Rye
        2. Oligofructose, which is produced from Chicory Roots, consists of up to several dozen Fructose molecules linked end to end. It is not absorbed in the small intestine, but is partly digested in the large intestine. This slightly sweet ingredient provides less than about half as many calories per gram as Fructose or other Sugar. Oligofructose promotes the growth of "good" bifidus bacteria.
        3. Not digested by the brush border enzymes of the small intestine
        4. Fermented in the Colon by micro-flora
        5. 1/3 as sweet as sucrose (table suger)
        6. 1.0-1.5 kcal/g (4.2-6.3 kJ)
        7. Also artificially produced from Sucrose
          1. Up to several dozen Fructose ch ained together
      4. Dietary Plant Fiber (Complex Carbohydrate Bulking Agents) [142]
        1. Dietary Fiber is not one material, but a broad classification that encompasses a wide range of substantially different chemical structures
        2. Dietary Fiber is a mixture of Soluble (disperses in Water) and Insoluble Fiber
          1. Fruits contain 38% soluble
          2. Cereals and Vegetables contain 32% soluble
          3. Legumes 25% contain soluble
        3. Some Fiber sources
          1. Apple
          2. Sugar Beet
          3. Pea Fiber
          4. Bran
          5. Toasted Ceral Defatted Germ
          6. Fruit Pastes
        4. Soluble Fiber
          1. Gums
            1. Ancient Gums are still being used in food preparation
            2. Plant Exudates (Gum Arabic, Gum Tragacanth)
            3. Plant Extracts (Pectin)
            4. Seed Gums (Quince, Psyllium, Okra, Locust Bean)
            5. Seaweed Gums
            6. Have a wide range of viscosity, solubility, and taste
            7. Not digested in the small intestine, partially digested by colonic bacteria to Short Chain Fatty Acids and absorbed in the colon
            8. 4.2 kJ (1kcal.g) to 13.9 kJ (3.4 kcal/g)
          2. Pectins (Apples, Citrus Friuts, Sunflower Seeds, Sugar Beets)
            1. Slowly degraded in Large Intestine
            2. Lowers cholesterol
          3. Beta-Glucans (cereal bran, barley, oats)
            1. Glucose polymers (beta linkages)
            2. Improved bowel activity, lower Cholesterol
          4. Galactomannas (Guar Gum, Locust Bean Gum)
            1. Emulate texture of fat
          5. Amylose and Resistant Starch [16, 147]
            1. Heat processing becomes resistant to digestion
            2. Absorbed in small intestine, also fermented in colon to FFA and absorbed
          6. Lignans
            1. Rye bread is the best source of Lignans (3x higher than white bread)
          7. Mucilages
        5. Fiber may contribute many health benefits [150]
          1. Dilutes fecal material
          2. Shortens bowel transit time (alters resorption)
          3. Modifies Bile Acid metabolism
            1. Produces Butyric Acid, which is used as the main energy source of Colonocytes during Colonic fermentation of soluble fibers [150]
            2. Butyrate, Acetate and Proprionate have healing benefits in the Colon
          4. Soluble Fiber reduces Postprandial Glucose and Insulin response [149]
            1. Guar Gum, high-Amylose Starch in crackers or muffins as part of a meal (50-75%)
          5. Insoluble fiber, such as Wheat Bran, does not decrease Postprandial Glucose or Insulin response [148]
            1. Hemicelluloses
            2. Cellulose (Fibrous Vegetables)
              1. Non-caloric, Insoluble Bulking Agent
          6. High Intake of Fiber may produce Bloating, Flatulance and Intestinal Gas, Diarrhea, and Mineral Loss [151]
            1. Fiber and Starches increases the amount of fermentable material reaching the Colon, used as Energy by the Colonocytes

    3. Fat Substitutes
      1. Lower Calorie Fats (fewer than 9 kcal/g)
        1. Small Chain Triglycerides (SCT)
          1. 5 kcal/gm (21kJ)
          2. poorly absorbed
        2. Medium Chain Triglycerides (MCT)
          1. 7-8 kcal/gm
          2. metabolic advantage (absorbed through the portal blood and rapidly absorbe for energy )
        3. Long Chain Triglycerides (LCT)
          1. 5 kcal/gm
          2. Hydrogenation of Vegetable Oils (Canola, Soy)
          3. Salatrim
            1. long and short chain fatty acid mixture
            2. converts Oleic, Linoleic Acids to Stearic Acid, then converted to Oleic Acid when absorbed
          4. poorly absorbed
      2. Proteins and Carbohydrates
        1. Starch, Dextrins, Protein
        2. Provide the feel of fat when hydrated
        3. 4 kcal/gm (16.8kJ)
      3. Polydextrose
        1. Only partially digested by humans
        2. Not fermented in colon
        3. Laxative at greater than 90gms/day
        4. 1.0kcal/g (4.2 kJ)
      4. Sucrose Polyester (Olestra)
        1. Not digested by the Small Intestine or Colon [158]
        2. Requires Fat-souble Vitamin Supplement

  10. Genetics, Activity, Diet

    1. 30 - 40% Weight Variance is Genetic [30]
      1. Twin studies show a genetic component
      2. 30 genetic loci for Weight
      3. Many loci for Body Fat Distribution
      4. Gene expression is modified by Nutrients [133]

    2. Pima Indians in Arizona [29]
      1. 19th century - Normal Weight
        1. Diet High in Complex Carbohydrates , Low in Fat and Alcohol
        2. Diet High In Corn, Beans
        3. Physical labor
      2. 20th century - Obesity and Diabetes common
        1. Diet high in Sugar, Fat, Alcohol
        2. Diet High In Corn, Beans
        3. Sedentary existence
        4. Lo RMR individuals gained more weight [32]
        5. Muscle LPL accounts for individual differences in weight gain
      3. High Corn Diet maintains weight, less protein turnover/GH ?
        1. ?good if calorie poor diet ?
        2. ?protein needs

    3. Excess Calories
      1. Obesity Prisoner Study
        1. Prisoners asked to gain weight by eating more
        2. They became lethargic, less proficient, had poor perceptions of their body at higher weights
        3. External behavioral stimuli found to be more important
        4. Sims, E.A.H. (1976). Experimental obesity, dietary-induced thermogenesis and their clinical implications.
          Clinics in Endocrinology and Metabolism, 5, 377–395.
        5. Residency Lectures: 9/92
        6. .pdf
      2. Selective Overconsumption
        1. Overconsumption of Carbohydrates is associated with preferential Oxidation of Carbohydrates with increased ( Storage of Fat )
        2. Overconsumption of Fat is associated with increased ( Storage of Fat)
        3. Assumption that reduction of dietary fat will automatically cause weight loss is incorrect
        4. [John C. Peters xiv]

    4. Restricted Calories
      1. Subjects placed on semi-starvation diets have lost up to 25% of their body weight, but
        regained that weight within months of returning to a normal diet.
        1. Keys, A., Brozek, J., Henschel, A., Mickelsen, O., & Taylor, H.L. (1950). The Biology of Human Starvation.
          Minneapolis: University of Minnesota Press.
        2. .pdf

  11. Food Choice

    1. Lo-Fat Diet
      1. Low-Fat diet reduces Fat Intake
        1. Reduction in Fat Intake from 40% to 30% reduces Fat and Total Energy Intake
        2. Reduction in Fat Intake below 30% is associated with Caloric compensation for the decrease[184]
        3. Carbohydrate replaces Fat
      2. Fat subsitution with Olestra reduces Fat and Energy Intake
        1. Olestra substitution for Regular Fat reduces Fat and Energy Intake when Fat Snacks are limited
          1. Lo-Fat Olestra Meals did not affect daily Energy Intake
            1. Subjects compensated for the reduction of Fat by eating more Carbohydrates [183]
          2. Lo-Fat Olestra Chip Snacks decreased Fat and Energy Intake compared to regular Chip Snacks
            1. Only if Fat Snacks are limited
        2. Male rats fed Fat-free margerine consumed more Food than rats fed Vegetable Oil Spread, but not Female Rats
      3. Shift to Complex Carbohydrates from animal products (Fat) reduces Micronutrient Intake
        1. Diets with less than 15 percent energy from Fat have decreased Zinc and Vitamin E intakes
        2. [David J. Mela xiii]
        3. Corn and Soybean Oil are lower in Vitamin E [243]
      4. Cut out the Hi-Fat Snacks! (causes to eat less)

    2. Hi-Carb Diet
      1. Carbohydrate decreases Fat oxidation and promote Fat storage, and even increases new Fat
      2. Carbohydrate increases T3, by increasing T4 -> T3 (p 668 speroff 5th edition, Danforth)
        1. T3 is the active thyroid hormone, converted from T4
        2. Carbohydrate is the primary determinant of T3
        3. During the weight-maintenance phases of long-term overfeeding studies, T3 was increased when Carbohydrate was isocalorically substituted for Fat in the diet.
      3. Shift from Animal Products (Fat) to Complex Carbohydrates (Carbs) reduces intakes of required nutrients [4]
        1. Calcium, Iron, Zinc, Copper, Vitamin A & D, other trace minerals
        2. [Penny Kris-Etherton xii]
      4. Carbohydrate is burned according to its Intake (Limited Storage, as for Proteins)
        1. Hi Carbohydrate or Hi Protein decreases Fat Oxidation (but only in Energy Surplus )
      5. There is little evidence that a CHO-rich diet, or intense sweeteners, promotes spontaneous Weight Loss [66]
        1. Intense Sweeteners actually cause Men to eat more ( but not women ) [David J. Mela xiii]
      6. Many successive days of Carbohydrate overfeeding can lead to an net conversion of Carbohydrate into Fat, but this does not
        occur on the typical Western Diet (Hi-Fat)

    3. Hi-Fat Diet
      1. Lean subjects tended to increase Lipid Oxidation on a Hi-Fat Diet
      2. Obese and Previously Obese subjects did not increase Lipid Oxidation on a Hi-Fat Diet
        1. Post-Obese subjects also increased Storage of Fat on a Hi-Fat Diet after weight loss
      3. Subjects informed of the Fat content of Premeal Snack ate more when labeled as "Lo-Fat" than when labeled "Hi-Fat". [185]
      4. Subjects not informed of the Fat content of Premeal Snacks ate more after a Hi-Fat/Hi-Calorie load than after a Lo-Fat/Hi-Calorie Load.
      5. Hi-Fat Soup at meals increased Total Calorie Intake over no soup, Fat-Free and Oleastra Soups [185]
        1. Consider Low-Fat Soup at meals

    4. Hi-Protein Diet
      1. Affluence (GNP) is associated with a shift from Plant Protein sources to Animal Protein sources
      2. [Adam Drewnowski xiii]
      3. Protein Stores increase from Growth Hormones, Androgens, Physical Training, Weight Gain [39]
      4. Protein Stores do not increase with dietary Protein Intake
      5. Protein is burned in proportion to its Intake (Limited Storage, as for Carbohydrates)
        1. Hi Carbohydrate or Protein decreases Fat Oxidation (if Energy Surplus)

    5. Combination Fat, Sugar, Protein [134]
      1. Mixtures of Cream (20% Fat) with Sugar (10% wt/wt) have a synergystic effect, and are most preferred
        1. Sweetened Milk and Cream, Milk Shakes, Cream Cheese, Cake Frosting, Ice Cream
      2. Preference for Fat over Sugar is linked to the degree of Overweight
      3. Obese patients select Food that is Low in Sugar and High in Fat
        1. Obese Men preferred Protein/Fat mixtures (Meats)
        2. Obese Women preferred Sweet Carb/Fat mixtures (Fat, Sugar or both)
      4. Formerly Obese individuals showed preferences for Intense Sweet and Hi-Fat Foods
      5. Lean subjects do not select Hi-Fat Foods
      6. Women with Eating Disorders sometimes liked Sweets, but were averse to the oral sensation of Dietary Fat

    6. Kool Aid for Children [204]
      1. Aspartame and Low Glucose Maltodextrin (LGM) sweetened Kool Aid supressed Calorie Intake compared to water
      2. Sucrose sweetened Kool Aid supressed Intake compared to Aspartame
      3. Water prior to a meal might actually increase Food Intake
      4. So Sucrose sweetened Kool Aid supresses Calorie Intake, as does LGM
        1. LGM Kool Aid < Sucrose Kool Aid < Aspartame Kool Aid = Water
        2. Supression was equivalent at 60, 30 or 0 minutes prior to meal
        3. Table 3,4 [204]
      5. Children's ability to regulate Energy Intake is fragile, and can be easily disrupted by parental child-feeding practices [209]
        1. Early experiences, including child-feeding practices imposed by parents, are major factors in Food Intake control [218]

  12. Lifestyle Issues

    1. Alcohol and Drugs
      1. Poor Nutrition
      2. Liver, Brain damage
    2. Smoking
      1. Nicotine (oxygen poison)
      2. Carbon monoxide (oxygen blocker)
    3. Exercise
      1. Aerobic excercise burns more Sugar than Fat (sweating, huffing and puffing)
      2. Most likely mechanism for the reduction in Fat oxidation during high-intensity exercise is a downregulation of carnitine palmitoyltransferase I, either by a marked decline in free carnitine availability, or by a decrease in intracellular pH.
      3. At high exercise intensities (usually sustainable only by highly trained athletes), muscle Glycogen can be depleted within 2 hours, and this can represent 300-400 grams of total carbohydrate or so.
      4. Increasing Calories burned to 10-25% of daily calories causes Weight Loss in Obese patients [33]
      5. The majority of research shows that Women derive a greater proportion of their Energy Expenditure from Fats during low to moderate intensity excercise relative to Men.
      6. Low intensity exercise uses majority of Energy from Fat as a percentage. Low intensity Cardio workout for longer duration is recommended (Slow-twitch). However, a higher Total Energy Expenditure does come from more intense excercise levels (absolute Calories), so shorter durations of higher intensity can be added.
      7. Total Activity Level and Toning is important
    4. Diabetes
      1. Insulin inhibits Lipolysis, so Fat is stored instead of being used.
      2. Metabolic Androgen Syndrome
    5. Coffee, Tea (Caffeine, Theophylline) blocks Phosphodiestersae, increasing cAMP and productions of Fatty Acids from Adipose
      1. Green Tea increases Fat Oxidation
        1. Inhibits CPMT, increasing NE, prolonging effect of NE (without increase)
        2. 36 to 41%
    6. Hunger
      1. Well fed rats had no preference for 30% Corn Oil Emulsion (nutritive) versus 30% Mineral Oil Emulsion (nonnutritive ) [158, 160]
      2. Hungry rats select Food that has more Calories
        1. Food-deprived rats had an 85% preference for the nutritive Corn Oil Emulsion over nonnutritive Mineral Oil emulsion
      3. Energy Intake did not change with reduction in Fat percentage [160]
        1. Fat-modified foods did not change Preference for Hi-Fat Foods in human subjects, even if Fat intake was significantly reduced
        2. 51% vs 30% Fat Diets and (Plateuas at 21% Calories as Fat)
        3. 63% Calories as Fat increased Energy Intake, however
    7. Snacks [160, 163, 165]
      1. Hi-Fat Snacks
        1. Rats fed ad-lib Hi-Fat Snack Foods ate more Calories (4354 vs 3983 kcal), gained more Body Fat
        2. Rats feed a 40% kcal Hi-Fat Diet for 10 weeks had Higher Insulin and Higher Insulin Resistance with a Glucose load
          1. left upper figure p162 insulin levels [ ]
          2. Reversed within 3 days of switching to a 30% kcal Fat Diet.
      2. Lo-Fat Snacks
        1. Rats fed Lo-Fat Snack food consumed a greater percentage of Energy as Carbohydrate
        2. Rats on Lo-Fat Diets had more Lean Body mass than Control or Hi-Fat Diets, but also more Fat Mass and Weight Gain (for same Calorie Intake)
        3. This degree of Fat replacement could not be replicated in a Human Diet
      3. May indicate differences in Activity
    8. Weight Control versus Health Risks
      1. Weight Loss alone decreases Total Cholesterol by 50%, LDL by 60%, and Triglycerides by 70% [149]
    9. Denial

  13. Respiratory Quotient RQ (volume CO2 produced/volume O2 consumed, a molar ratio)

    1. Food is burned to CO2 and H2O
      1. C x H y O z + ( w-z)O2 -> C02 + H20 (Carbs)
        CxHy + ( w) O2 -> C02 + H20 (Fat)
    2. RQ
      1. RQ = CO 2 exhaled / O 2 inhaled
      2. Reflects Ratio of Carbon to Oxygen in burned food
      3. Reflects Carb Oxidation to Fat Oxidation
    3. Normal RQ is 0.7 -1.0 (usually about 0.8)
      1. RQ of Foods
        1. Lipogenesis 1.0-1.2 ( conversion of Carbohydrates and Organic Acids to Fat)
        2. Glucose oxidation 1.0
        3. Protein oxidation 0.82
        4. Fat oxidation 0.70
        5. Ethanol 0.67
      2. Burning Carbs means Hi RQ (1.0)
        1. HI RQ Associated with Weight Gain
        2. Sugar uses less O2 ( carbs have OH groups)
        3. Less Oxygen needed when burn carbs (altitude effects)??
        4. Burning more Sugar means less Sugar available, so get hungrier???
      3. Burning Fat means Lo RQ (0.7)
        1. Fat uses more O2, lowers ratio
        2. Fat produces more H2O ??

  14. Body Weight Regulation Mechanisms [30]

    1. A Majority of nutrition studies in Animals involve a single dietary manipulation. [156]
      1. Purified laboratory diets do not represent human diets with more limited food choices.
      2. Non-Human Primate studies have more limited cost and subject numbers than rodents and take longer (decades)
    2. Short-term Regulation
      1. Gut Peptides signal the brain through vagus a fferent nerve
      2. Cholecystekinin, Bombesin, Neurotensin, Glucagon-like Peptide
      3. Modulate duration and amount of a single meal
    3. Long-term Regulation
      1. Hypothalamus regulation (complex process)
        1. Lesions of ventro medial hypothalamus cause obesity
        2. Lesions of ventro lateral hypothalamus cause weight loss
        3. Thought to be a feedback signal from body mass or body fat mass
      2. Leptin
        1. Expressed in Adipose tissue
        2. Correlates with body mass index and body fat
        3. Injections of Leptin increases energy expenditure and decreases appetite
        4. Leptin resistance in obese people (probable signal transduction pathway, beyond receptor level)
      3. Other Hormones
        1. Galanin, Polypeptide y (PPY), Corticotropin-Releasing Hormone (CRH), Opioids, Insulin
    4. Hypotheses for Regulation
      1. Leptin
        1. increased Leptin --> diminished Neuropeptide Y --> diminished Food Intake
      2. Cortisol
        1. Cortisol Releasing Hormone (CRH) --> diminished Food Intake
        2. Hi Stress, Hi Cortisol, Lo CRH, Lo ACTH situations --> ?

  15. Three metabolic Predictors of Weight Gain [32]

    1. Low Resting Energy Expenditure (REE)
      1. Family members tend to be similar
      2. How much Food burned at rest
    2. Elevated Respiratory Quotient (RQ) (Hi RQ = Hi Carb Oxidation)
      1. Individuals with higher RQ were more likely to gain weight over a five year period [32]
        1. Hi RQ = Hi Carb Oxidation, Lo Fat Oxidation
        2. Hi RQ = less Oxygen used
      2. Hi RQ will preferentially oxidize Carbohydrate , depositing Fat
        1. Carbohydrate deposited as Glycogen signals satiety , inhibits further intake
        2. Fat deposited easily, directly into Fat cells, which creates no signals of satiety
      3. How much Oxygen is used to burn that Food
    3. Insulin Sensitivity
      1. Insulin shifts to preferentially use Carbohydrate for fuel in Muscle (Burn Carbs)
      2. Insulin shifts to promote Fatty Acid Entry into Fat cells (Store Fat)
      3. Insulin augments Lipoprotein Lipase (LPL) actions in Adipose (Store Fat)
      4. Insulin inhibits Lipolysis, Fat Release (No Release)
      5. Adipose in Obese very sensitive to Insulin
        1. Hi Carbs induce Hi Insulin Induces above (Hi Carb Diet)?
        2. Insulin Resistance limits further Fat gain ? [39] [ ]
      6. How much Fat is burned by Muscles (versus Stored in Adipose)

  16. Diet versus Exercise for Weight Loss

    1. Diet only (-500kcal/day)
      1. body weight decreased
      2. loss of Lean mass
      3. less loss in Fat mass
    2. Activity only (-500 kcal/day)
      1. body weight decreased
      2. gain in lean mass
      3. more loss in fat mass
    3. Diet plus Activity (-250 kcal/day, -250 kcal/day)
      1. body weight decreased
      2. gain in lean mass
      3. more loss in fat mass with combined approach
    4. Zuti, W.B., & Gelding, L.A. (1976). Comparing diet and exercise as weight reduction tools. Physician and
      Sportsmedicine, 4, 49–53.

  17. Energy Balance [p44]

    1. Metabolic Regulation
      1. Metabolic fuels used by the body changes with the Energy requirements, Composition of the diet, Nutrient and Energy Intakes.
        1. Balance of each Macronutrient appears to be regulated separately
        2. There is little new Lipogenesis (newly made Fat that gets Stored)
      2. Approximate Energy Values for Food (kcal/g)
        1. Food Fats 37
        2. Ethanol 29
        3. Food Protein 17
        4. Food Small Carbohydrate 16
        5. Food Carbohydrate/UCC 8 (Undigestible Complex Carbohydrates ~50% available)
      3. Fuel sources are burned in a specific order depending on availability:
        1. ETOH (29) > Protein (17) > CHO (16) > Fat (37) in kcals
        2. All macronutrients are metabolized completely to CO 2 and H 2 0, (except Protein)
          1. Protein is incompletely metabolized, due to deamination and ureogenesis
        3. ETOH cannot be stored and must be oxidized, ultimately at the expensive of fat oxidation, which promotes fat storage
          1. however, liver converts amino acids, glucose and alcohol to fat [p48]
        4. Excess Protein or Carbohydrate is preferentially burned next
          1. Positive balance of Protein leads to a rapid increase in the Protein oxidation, depending on the
            bodies requirements for Amino Acids, and induction of the enzymes for Protein metabolism.
          2. Same for positive intake of CHO
        5. No mechanism to convert Fatty Acids to Glucose in animals
      4. Additional Energy is used to Store CHO or Fat [p51]
        1. The cost of converting ingested Carbohydrate to New Fat is about 24% per calorie of ingested Carbohydrate
        2. The cost of converting ingested Carbohydrate to Glycogen is about 5% per calorie of ingested Carbohydrate
        3. The cost of converting ingested Fat to Stored Fat is about 2%
        4. Protein to Stored Fat - goes thru Carbohydrates First
        5. ETOH cannot be stored and is disposed of by obligatory oxidation, ultimately at the expense of fat oxidation
          1. Promotes Fat Storage of Dietary Fat. [49]
        6. Storage as a percentage of available Energy
          1. CHO to Stored Fat ~26%
          2. Protein to Stored Glycogen ~25%
          3. CHO to Stored Glycogen ~5%
          4. Fat to Stored Fat ~2%
        7. Does this mean that only half of the protein calories ingested ever gets stored as fat???

    2. Energy Intake - Effect of Diet Composition for Weight Reduction Diets
      1. Weight and Volume are important factors in Food Intake. Perception of Weight and Food Volume cues changes only gradually [61]
      2. Carbohydrate Intake determines the food oxidation ratio
        1. CHO, not Fat, is preferentially oxidized on Hi-Fat/Hi-Carb diets
          1. CHO becomes the preferred metabolic fuel as Carbohydrate intake increases [50]
        2. Dietary CHO is spared to meet demand on Hi-Fat/Lo-Carb diets
          1. Fat oxidation will increase to meet the energy requirements, conserving CHO when Intake and Stores decrease
          2. Requirements for Glucose oxidation is satisfied under all but the most extreme conditions of Carbohydrate deprivation.
          3. Glucose-Alanine and Cori Cycles insure supply of Glucose
        3. Physical state of Carbohydrate may be important in reducing Total Calorie Intake.
          1. Starches may produce a more blunted , yet prolonged influence on satiety than mono- and di- saccharides, but it is relatively modest.
          2. Undigestable Carbohydrates (UCC) decrease Fat absorption , enhance satiation and limit meal sizes.
          3. Calories in drinks appear to be poorly compensated for compared to solid food [62].
            1. Calories in drinks do not caused an aadjusted decreased intake to compensate
        4. Alcohol (cannot be stored) or high loads of Protein (converted into Carbs) blocks CHO oxidation
      3. (HP), (HF), (HC) Weight Reducing Diets showed no difference in Total Weight Loss over two weeks.
        1. CHO and Fat are equivalent with the same Calorie Intake (Iso-Energetic) [p57, 50]
          1. Hi Fat (HF) and Lo Fat (LF) diets are equivalent for effect on how much you eat
          2. Excess CHO or Fat leads to Stored Fat .
            1. Hi Fat diet (Fatty Acid increase) spares Carbs, Hi Carb diet spares Fat
              1. Hi dietary CHO leads to storage of dietary Fat [p66].
              2. Hi dietary Fat leads to storage of dietary Fat
        2. No difference between Hi-Fat (HF) and Lo-Fat (LF) diets as to Total Pounds lost (for the same amounts of Food and Calories)
          1. Reductions in Fat or CHO Intake are compensated for by increased Intake .
          2. Decreasing the Fat content decreases dietary Energy Density , can lead to a modest but prolonged decrease in Energy Intake .
        3. (HC) and (HF) dieters lose a higher percentage of Body Water Weight , so lose less Fat for given Weight Loss compared to (HP). [ ]
        4. Little difference between types of Carbohydrates for Weight Loss
          1. No difference between Hi-Carb (HC) and Hi-Fat (HF) diets as to Lean Body pounds loss
          2. Supplementing the diet with UCC appears to have modest effects .
          3. Low energy density diet with fiber rich bulk may have more favorable effects
      4. Whole body new Lipogenesis can take place only under conditions of very High Carbohydrate (HC) diets
        1. Lipid synthesis takes 3 days to induce with overfeeding of CHO
          1. Builds up Glycogen stores first.
          2. Little new Fat is made in that period.
        2. Unless there is massive CHO feeding, new Fat is not made .
        3. Speaks against high Carbohydrate diets
      5. Hi Protein Diet (HP) Weight Reducing Diet limits Protein wasting during dieting , preserves lean body mass
        1. HP diet limits the decrease in Energy Expenditure due to loss of Lean Body mass during dieting
        2. Protein Intake or oxidation reduces subsequent Intake Calories more than CHO or Fat Intake.
          1. The previous days cumulative stores and the oxidation of Protein and CHO stores were negatively correlated to following days Energy Intake .
          2. fig3b [p56]
        3. (HP) diets lose more Fat calories
      6. Lo-Carb (LC) Weight Reducing Diet
        1. Covert removal of 2.1MJ/d of Sugar from the diet initially decreased Energy Intake
        2. Followed by a later increased Fat Intake from 3.57 to 3.97 MJ/d
        3. Maintained a net Energy deficit of 1.7MJ/d.
        4. (MJ = Million Joules = Kilo KiloJoules = Kilo kiloCalories = Kcal ) [65]
        5. A Fat-Sugar "Seesaw" is commonly seen. Diets low in Sugar are found to be High in Fat
      7. Paradoxical effects of Sugar Intake
        1. The views of the early 1970's were wrong that sweetness provided in the form of Calories stimulates Feeding and Obesity
          1. Epidemiological data suggest consumption of sugars is actually associated with thinness
          2. This may not be causative: physically active people may select more sugars which they burn off (immediate burn)
          3. Also, effects may be due to cognitive cues
          4. Time of Day may alter the effect of Sugar loads [DrTim]
          5. Low Calorie Breakfast is associated with a decrease in daily Energy Intake [182]
      8. Drinks with or prior to Meals[181]
        1. Hunger ratings were the same for different drinks
        2. Men
          1. In Lean Men , Aspartame-sweetened Non-Carbonated Water leads to a short-term increase in appetite .
          2. In Men , Aspartame-sweetened Carbonated Drinks induced a transient suppression of appetite .
          3. In Men , Sucrose-sweetened lemonade with meals increased overall Calorie Intake , and trended but was not significant 30-60mins before meals
        3. Women
          1. In Women, Aspartame-sweetened lemonade increased intake the next day. [181]
          2. In Women, Sucrose-sweeetend drinks supressed appetite and was compensated for. [64]
      9. Soda [188]
        1. Consumption of Hi-Fructose Corn Syrup-sweetened Soda increased Calorie Intake and Weight Gain.
        2. Consumption of Aspartame-sweetened Soda decreased Calorie Intake in both sexes compared to no drink
          1. Decreased Weight in Males
          2. No Weight change in Females however
          3. Compensate with decreased Sugar Intake from other sources, so no overall increase in Sugar
      10. Artificial Sweeteners [163]
        1. Aspartame 1 g/kg body weight, caused hypothalamic lesions in neonatal rats
          1. Aspartame 2g/kg did not produce this lesion in NonHuman Primates
          2. Aspartame Ester is metabolized in the same way as natural food in Rodents, Rabbits and Monkeys
            1. Hydrolyzed in the Intestine to di-peptide that is split into free amino acids and absorbed.
        2. There was a trend for subjects who knew they had consumed Aspartame to eat more during the rest of the day.
        3. Bulk Artificial Sweeteners (Inversion Sugars) may reduce Fat Gain compared to Sucrose, and increase Intestinal biobacterias, which may reduce the risk of Colon Cancer. [165]
      11. Appetite Satiation
        1. Those nutrients most readily oxidized (most thermogenic) are the most satisfying [61]
          1. Protein is more satiating than CHO
            1. High Protein (HP) diet most satiating at the same Energy Density by far [56, 60]
            2. Amino Acid Infusions decrease Caloric Intake 100%, Glucose Infusions decrease 70%, and Fat infusions 50% [60]
          2. Carbohydrate is more satiating than Fat, but only in the short term
            1. HC diet more satiating than HF , but only for the first hour after ingestion
            2. Glycogen deposits help Satiety (Carbohydrate Stores exert a negative feedback on Energy Intake)
          3. A drop in plasma Glucose predicts meal initiation
            1. Small infusion of Glucose blocks this drop, and delays feeding by up to three hours
            2. Use small Carbohydrate Snack, Protein soup prior to Meal?
        2. Negative Energy Balance (dieting) while CHO is depleted increases hunger above normal . [p58]
          1. Subjects felt significantly more hunger on Low Energy Density Diets than High Energy Density Diets when CHO was kept low
          2. CHO depletion + Diet restriction = Hunger
        3. Alcohol completely bypasses appetite control, and may actually increase Energy Intake
      12. Carbohydrate inhibits Fat oxidation
        1. Fat oxidation during exercise is very sensitive to the interval between eating Carbohydrate and the onset of exercise and the duration of the exercise. This is due in part to the elevation of plasma Insulin in response to the Carbohydrate meal and the resultant inhibition of Lipolysis in Adipose tissue, thus reducing the mobilization of Free Fatty Acids (FFA) into the plasma. The effect is evident for at least 4 hours after eating 120g of Carbohydrate that has a high Glycemic Index. Under these conditions, the Carbohydrate reduces both Total Fat Oxidation and plasma FFA concentration (less Fat available to burn) during the first 50 minutes of moderate-intensity exercise. However, this suppression of Fat oxidation is reversed as the duration of exercise is increased; after 100 minutes of exeercise, the rate of Fat oxidation is similar, whether or not Carbohydrate was eaten before exercise. It appears that the body relies heavily on Carbohydrate and less on Fat when Carbohydrate is eaten during the previous few hours, and therefor Carbohydrate is preferred when it is available. It is likely that Insulin plays a role in regulating the mixture of Carbohydrate and Fat oxidized during exercise.
          Sports Science Exchange, Fat Metabolism During Exercise #59,

        2. Glycemic Index of Foods

    3. Energy Expenditure [51]
      1. Amount and composition of Diet consumed has little impact of Total Energy Expenditure in the short term
      2. There is little ability to dissipate excess Energy Intake by increasing the rate of metabolism (Energy Expenditure).
      3. Excess energy, taken in the form of any nutrient, ultimately promotes fat storage .
        1. An increase in the oxidation of Protein or CHO leads to decreased oxidation of Fat, and promotes Fat storage
        2. What becomes important is the effects of nutrients on appetite.
      4. Fat to CHO ratio of the diet had no detectable effect on Energy Expenditure
        1. Storage capacity for Protein and CHO is limited (has to be burned)
        2. Converting CHO to Fat is energetically expensive though, so the body avoids Fat synthesis
      5. CHO contributes more than Fat to immediate postprandial Energy Expenditure (EE)
        1. CHO is the major fuel being oxidized and stored immediately postprandial
        2. Little energy is used for fat absorption during this period.
        3. Beyond that time, Fat oxidation contributes more to the Energy Expenditure (because no carbs around)
      6. CHO to Fat storage is important only in CHO overfeeding (not on Normal or Hi Fat diet).
        1. CHO overfeeding increases CHO oxidation and Energy Expenditure by 15-25% [52]
        2. Fat overfeeding increases CHO oxidation or Energy Expenditure only by 50-10%
        3. The body would rather burn the Carbohydrate and store the Fat.
      7. Protein ingestion induces the largest obligatory metabolic rise in EE due to metabolism, costs of protein synthesis, gluconeogenesis, and ureogenesis. This is 25% per calorie of ingested Protein.
      8. What becomes important is the effects of nutrients on appetite .
      9. Preparation (Microwave increases b linkages , more resistant to digestion)
      10. After weight loss, Fat Oxidation drops significantly [175]
        1. Fig 5 [176]

  18. Fat

    1. Fat Intake
      1. Obesity is less prevalent in countries with a low Fat to Energy ratio (China, Japan)
        1. Also have a lower Total Energy Intake
      2. There is a positive association between Fat Intake and Baseline Body Mass Index
        1. Baseline Fat Intake not associated with subsequent weight gain .
          1. Little evidence for an effect of Fat Intake on daily Energy Expenditure
          2. Fat Intake may not cause Weight Gain
        2. **Pima Indians had the same Energy Expenditure on a Hi-Fat or Hi-Carbohydrate diet
          1. Fat oxidation depends on Total Calorie balance, not Fat Intake (fills out the energy needs- use vs storage, see below)
        3. Hi-Fat diets tend to promote Overeating and Weight Gain
          1. Fat has minimal appetite-suppressant effects
          2. Eat more of everything then
      3. Short- and Medium- term Energy Balance
        1. Protein and Carbohydrate are oxidized in proportion to their intakes.
          1. The body has limited capacity for carbohydrate storage, and tightly regulates Protein balance.
          2. Increased oxidation of CHO and Protein leads to diminished Fat Oxidation under Energy Surplus
          3. Dietary Fat is oxidized to match the energy needs after Protein and Carbohydrate Food has been oxidized.
          4. Excess Fat Intake is stored as Fat [174]
        2. 9 hours after a Lo Fat breakfast in one example, Carbohydrate and Protein intakes were completely Oxidized, but Fat Balance was negative .
          1. When additional fat was added in this Fasting State, it was Stored as Fat, not utilized as Energy [38 Flatt et al.]
          2. Support for avoiding Hi Fat snacks
        3. "Fat takes up the slack" in Energy needs
      4. Long-Term Energy Balance
        1. Fat Oxidation rate increases as Fat mass increases, to reach a new equilibrium
        2. 10kg gain in fat mass increased Fat oxidation by 180 kcal (20g/day) [Shutz et al. 39]
        3. Probably due to increased Insulin Resistance (less insulin sensitivity) ??? [ ]
        4. Reduction of Fat in Margarine, Mayonanaise and Salad Dressing have the greatest impact on Dietary Energy Intake [82]
        5. "Fat sticks"
        6. No change in the caloric requirement to maintain weight or concentrations of T3 was found after long-term (3 mo) of Fat overfeeding . (Danforth)

    2. Fat Storage
      1. High levels of Lipoprotein Lipase (LPL) in Adipose deposits Fat
      2. Fatty acids are transported attached to the major Protein in the circulation, Albumin
      3. Free Fatty Acid created from the breakdown of circulating Triglycerides enters cells and is stored .
      4. Fatty Acid synthesis occurs in the Cytosol of Liver, Adipose and Mammary Glands (humans)
      5. Half-life of Lipoprotein Lipase (LPL, deposits Fat in adipose)
        1. 2 vs 4 hrs non-fasting (for white vs brown Adipose)
        2. 24 vs 40 hrs fasting is down regulated (for White vs Brown Adipose)
      6. Gene that regulates LPL activity in adipose tissue may be abnormal (Obesity, Insulin resistance, and related metabolic disorders)
        1. For Obese subjects, LPL-specific activity was unresponsive to a meal (re-feeding)
        2. For Obese subjects, LPL activity failed to be down-regulated on fasting (higher in obese subjects than in lean controls)
      8. If all the Energy Stored as Fat in the body (50,000 kcal) were stored as Glycogen (Carbohydrate), it would add 100 pounds

    3. Fatty Acid Beta Oxidation Enzyme Systems
      1. b Oxidation of Fats [40]
        1. Occurs in LIver and MuscleMitochondria.
        2. Fatty oxidation also occurs in Peroxisomes yielding Hydrogen Peroxidase, not ATP
        3. Lipoprotein-bound Triglycerides are hydrolyzed to Glycerol and Free (unesterified) Fatty Acids by Lipoprotein Lipase (LPL)
        4. Fatty Acids enter the cell
        5. Fatty Acids picked up by CoA to Acyl CoA
        6. Acyl CoA picked up by Carnitine Palmitoyl Transferase (CPT)
        7. Acyl CoA-CPT enters Mitochondria ( inhibited by Malonyl CoA)
        8. Acyl CoA oxidzed to Acetyl CoA in Mitochondria, and transported to the Cytosl for burning as Citrate
        9. Slow-twitch muscles use b Oxidation as main source of ATP (sustained excercise)
        10. Estrogen may mobilize Fat from Adipose. It enhances epinephrine, which increases lipolysis in Adipose tissue thru HSL
        11. Estrogen stimulates the production of Growth Hormone (GH), inhibiting Glucose uptake and mobilizing FFA from Adipose. GH also inhibits Insulin produstion from the Pancreas and stimulating HSL promoting Lipolysis in Adipose
      2. Lipoprotein Lipase (LPL)
        1. Hydrolyzes Free Fatty Acids from Triglycerides at Cell Membrane
        2. Partitions Triglycerides into Adipose (Storage) and Muscle (Oxidation) Cells
        3. Muscle LPL
          1. Muscle LPL is a rate limiting step
          2. At rest, Fatty Acid oxidation accounts for 80% of Muscle substrate oxidation
          3. Inverse correlation between muscle LPL activity and RQ (Muscle Tone Lowers RQ)
      3. b Hydroxyl Acyl CoA Dehydrogenase ( b OAC)
        1. Related to whole body fat utilization
        2. Inverse correlation between Muscle b OAC activity and RQ
      4. Acyl CoA Hydroxylase (ACC)
        1. Synthesizes Malonyl CoA
      5. Malonyl CoA
        1. Controls entry of Acyl CoA into Mitochondria
        2. Competitive inhibitor for Acyl CoA
        3. Signals fuel availability (Storage vs Burn)
        4. Inhibited by Carbs? [ ]
      6. Chains with an odd number of carbons are oxidized as even numbered, but final products are Prioprionyl CoA and Acetyls Coa. Propionyl CoA is converted to Methylmalonyl CoA and then to Methylmalonyl CoA, Succinyl CoA, and goes into the TCA cycle. It requires enzyme methylmalonyl mutase and Vitamin B12.
      7. Lipolysis is inhibited by insulin . It leads to decreased cAMP thru Phosphodiesterase

    4. Reduced Fat strategies
      1. Dramatic decreases in total Fat can result in marked decreases in Saturated Fat
      2. A diet higher in Total Fat (~35% of calories), yet low in Saturated Fat, may be preferable for certain individuals, such as with Diabetes
      3. Peanuts and Olive Oil are rich sources of mono-unsaturated fat, and Peanuts are a source of Protein as well. [87]
        1. Substitution of Olive Oil reduces Calories
        2. Substitution of Peanuts reduces Fat and increases Protein Calories
      4. Fat reduction strategies (Modified Milk, Meat, and Fat products) did not significantly alter the nutrient quality of the diets
        1. With the exception of two nutrients ( Vitamin E and Zinc ) .
        2. Other Micronutrient content continue to be greater than two-thirds of RDA.
        3. Table 2 [p88]
      5. Using all NonFat products can result in 16% Energy from Fat (as compared to average 34%).
        1. If all fat reduction strategies are applied, dietary Fat is reduced to possibly dangerously low levels of 7 to 8% energy .
        2. These are 50 percent lower than the 15 percent recommended, making nutrient deficiencies likely .
      6. Reduced Fat foods reduce the intakes of Fat, but not the Intake of Calories in the MSFAT trial [p103]
        1. Those who use three or more Reduced Fat foods ate higher Total Caloric Intake than did those who consumed none
        2. No changes in body weight over a study period of six-months. [103]
        3. Vitamin A intake was higher
        4. Zinc intake was higher
        5. Ion intake was higher

  19. Metabolic Changes with Diet Calorie Restriction

    1. BMR decreases 20% at beginning of a Calorie Restricted Diet
    2. Ketosis (Liver)
      1. Glycoysis Pyruvate goes to Acetone [ ]
      2. Acetone goes to Acetic Acid and Lactic Acid, probably thru Acetaldehyde intermediate
      3. Especially in ketoacidosis,
      4. Ketone bodies may also be generated in the periphery in addition to Liver
    3. Thyroid Hormones T3 and T4 go down with Calorie Restriction
      1. TSH does not go up
      2. Less T4 to T3
      3. How about Free T4?
      4. Suppression of Pituitary vs Thyroid Stimulation?
    4. Body weight does not parallel CHO Energy Balance under certain circumstances
      1. Weight Density for Carbohydrate forms vary (different from Fat)
      2. Glycogen contains less water than equivalent Sugars that comprise it
        1. Hydrolysis of Polysaccharides requires adding Water [46]
          1. For every Glycosidic Starch bond lysed, a water molecule is used
          2. 100g of Starch gives 110g of Monosaccharide (more energy)
          3. Glycogen weighs less than the equivalent Food Calories (more Energy Dense)
      3. Initial Weight loss in Diet is Water when use Glycogen Stores
        1. Loss of water at beginning of diet
        2. 10% increase in water weight loss from Carb Stores per Calorie [ ]
        3. Glucagon effect to maintain Glucose
      4. CHO is also Stored as Glycogen with additional H 2 O in 1:3 ratio ( Hydrated ) [52]
        1. A net change in CHO of 330g gives a 1kg weight change
        2. The burning of Glycogen loses 4 times as much weight when burned, the storing of Glycogen gains 4 times as much weight when stored, as the equivalent Fat per Calorie.
      5. Burning Carbs loses more Weight than burning Glycogen (over two weeks)
        1. When subjects overfed with 40% more CHO Calories, weight increased by 1.35 kg
        2. When subjects underfed by 40% less CHO Calories, weight decreased by 1.70kg
        3. When subjects overfed with 40% more Fat Calories, weight increased by by 0.84kg
        4. When subjects underfed by 40% less Fat Calories, weight decreased by 0.72kg

  20. Endocrinology Issues

    1. Hyperinsulin, high Carbohydrates increases Glucose transport into fat cells [p747]
    2. Cortisol increases glucose output from liver and decreases use in periphery
    3. Arginine is a powerful stimulator of Insulin secretion (and proportional to glucose concentration) [p287] [ ]
      1. what foods to avoid? [ ]
    4. Amino acids induce Glucagon
      1. low sugar, hi protein --> increased glucagon, decreased insulin??
    5. Exercise increases Glucagon
    6. Hi Glucose, Hi Insulin, Hi FFA inhibit Glucagon
      1. Glucose or Carbohydrate rich meal
    7. Duodenal stimulation of CCK suppresses feeding
    8. Thyroid hormone, Glucagon increases cAMP
      1. cAMP [p749,750]
        1. Effects of increased cAMP
          1. Increases Glucose level in fasting state (from Glycogen, and new in liver)
          2. increases Malonyl CoA (used to make Triglycerides)
          3. increases Lipolysis
        2. Somatostatin inhibits cAMP.
          1. ?after a meal, D cells of pancreas, tryptophan load
        3. Progesterone increases MAO
          1. Decreases synaptic NE
          2. www.drumlib/com
    9. Williams Endocrinology, 6th edition

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