Part 3:  Carbohydrates:  types, tables, role in MeS   /rh/id3.html   (8/13/15)

The first side of the healthy-diet coin is to know what to avoid (foods which cause oxidative damage, glycation,  insulin resistance, fatty liver disease, metabolic syndrome, and atherogenesis)?    In exposing the cholesterol and the fat myths, you will find that dietary and serum cholesterol is not a causal factor for cardiovascular disease (CVD) nor saturated fats, but rather that pathogens in the artery walls is the main cause, and that trans-fats and polyunsaturated fats promote cardiovascular disease (CVD).   Also promoting[1] CVD is the combination of quantity of carbs plus sugars.  Special mention in the class of villains is fructose, one half of table sugar, sucrose, it starts the process by damaging the liver, which leads to insulin resistance (IR) a condition of diminished response by fat and muscle cells to insulin and thus elevated blood (serum) glucose which in response elevates insulin. Slowly with a high carbs diet IR develops into metabolic syndrome,[2] (MeS), which is a family of conditions that includes, obesity, type-2 diabetes (T2D) atherosclerosis (AS) and CVD.  Fructose is metabolized only in the liver where it is turned into fat, as the fat accumulates in hepatic (liver) cells and insulin resistance in the liver develops.  Fructose also promotes in the brain sugar addiction.  Over the decades the effects from the liver damage is exacerbated by a high carb diet that causes high serum insulin.  Insulin tells the body to store fat and burn glucose (carbs), which when chronic causes weight gain.  Muscle and fat cells (myocytes and adipocytes) become gradually resistant to the high insulin, thereby requiring even more insulin to lower serum glucose.  The high insulin high glucose compromises immune functions thereby promoting the development AS—the cause of hypertension and myocardial infarction (MI)—heart attack.  In time instead of producing even more insulin, the beta cells in the pancreas produce less, and with this decline T2D develops which is treated with drugs.   At this point the patient has developed MeS.  The recommended low in fat diet entails a high-carb diet to supply ATP that was once derived burning fats.   ATP is the energy molecule used by the body.  This is why the Western diet with low-fat increases the risk for CVD, and causes weight gain by affects upon the body’s fat-regulatory system (a topic developed at part 8).  Bodily systems are not simple in the body; if you wish an answer without the details go to diet.  All of these assertions above are developed in length below. 

Basics common sugars:  glucose, fructose, sucrose, galactose, starches, glycogen, and ATP.   Carbohydrates (saccharides) are divided into chemical groups based on the number of 6-carbon sugar molecules mono,   di and polysaccharides.   “Glucose [a monosaccharide] is a primary food source of energy for the body cells—with a few exceptions.  [Fatty acids, proteins (amino acids), galactose, and fructose are the other primary sources of energy which are converted to glucose in the energy producing (ATP) Krebs cycle (also called citric acid cycle)].  Glucose is transported from the intestines or liver to body cells via the bloodstream, and is made available for cell absorption via the hormone insulin, produced by the body primarily in the pancreas.  The body's homeostatic  mechanism keeps blood glucose levels within a narrow range.  It is composed of several interacting systems, of which hormone regulation is the most important.  Insulin decreases blood glucose.  If blood sugar levels remain too high the body suppresses appetite over the short term.  Long-term hyperglycemia causes many health problems including heart disease, eye, kidney, and nerve damage [through the process of glycation]” Wiki.  Glucose creates alertness through increase in level of norepinephrine—a reinforcer.  “Glucose intake was found to significantly increase plasma NE levels. In contrast, protein and fat intake was found to have no effect” Wiki, and, 1981.  This mechanism operates less efficiently in the obese, thus requiring great consumption of glucose for the response--1983.  As Dr. Lustig observed, obese children have a much lower response to glucose in soda.  Glycogen is the storage form of glucose. It is stored in the liver and muscles--total amount under 1 lb. It functions as a quick source for production of ATP (energy).  Glycogen is a multi-branched glucose polysaccharide of glucose and is analogous to starch a glucose polymer in plants.  Because of a 6 fold greater bulk than fat per unit of ATP energy derived, it is storage is limited.  However is it a quickly available reserve, of which up to 2 lbs. is stored. “Starch or amylum is a carbohydrate consisting of a large number of glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants as an energy store. It is the most common carbohydrate in human diets and is contained in large amounts in such staple foods as potatoes, wheat, maize (corn), rice, and cassava” Wiki.   Fructose (fruit sugar) stimulates only 1/5^th the product of insulin that glucose dose,[3] and its blood serum level is not  subject to insulin control and thus remains higher longer when compared to a like amount of glucose, at.  This longer serum clearance results further increase insulin response.  “Fructose given alone increased the blood glucose almost as much as a similar amount of glucose (78% of the glucose-alone area)” Wiki.  The catabolism of fructose (fructolysis) is different from glycolysis, though it can enter into the pathway that yields glycogen. Fructose is 70% sweeter than glucose, thus driving its commercial use, and it costs less than sucrose.  A very important point, missed by most, is that the regulation of food consumption, fructose has a lower satiety rating.[4]    Sucrose (table sugar) is a disaccharide consisting of glucose and fructose, and is readily hydrolyzed in the digestive system prior to absorption into a molecule of glucose and fructose.  It is found in plants, and is commercially concentrated from sugar beets and sugar cane and used as molasses and table sugar.  In 2010 US sugar added consumption averaged yearly 158 lbs. per person.  Starches consist of multiple long chains of glucose.  Galactose is a monosaccharide found in the milk disaccharide lactose, which in metabolism is converted to glucose.  Moreover its main dietary source milk sugar is lactose a disaccharide consisting of glucose and galactose.  Thus the For most people it is a minor carbohydrate in diet.   High fructose corn sweetener consists of 43% glucose and 55% fructose.  “Catabolism of carbohydrates and fats yield Adenosine triphosphate (ATP) the principle energy source, often called the “molecular currency of intercellular transfer.  It is recycled (reduced then oxidized) at such a high rate that a 150 lb. person will use his ½ lb. supply 300 times in 1 day” Wiki. 

Glycation Exogenous and Endogenous:  glycation consists of the covalent bonding of a protein or lipid (fat) molecule with a sugar molecule, most commonly fructose and glucose which are reducing molecules.  Glycation inside the body is endogenous, and outside the body is exogenous.  Endogenous glycation is in most cases the major contributing factor for age related diseases.   This topic is developed in the section on fructose, which is over 10 times more reactive than glucose.  Exogenous is dietary glycation.   Advanced Glycation End-products (AEGs) are formed when sugars are cooked with proteins and fats at a temperature over 120°C (249°F), but lower temperatures with longer cooking times also promote their formation.  “These compounds are absorbed by the body during digestion with about 10% efficiency.^{[citation needed]} Browning reactions (usually Maillard type reactions) are evidence of pre-formed glycations. Indeed, sugar is often added to products such asfrench fries and baked goods to enhance browning.^{[citation needed]} Glycation may also contribute to the formation of acrylamide,^[2] a potential carcinogen, during cooking. Until recently, it was thought that exogenous glycations and AGEs were negligible contributors to inflammation and disease states, but recent work has shown that they are important.^[3]  Food manufacturers have added AGEs to foods, especially in the last 50 years, as flavor enhancers and colorants to improve appearance.^[4] Foods with significant browning, caramelization, or directly added preformed AGEs can be high in these compounds.^{[citation needed]} A very partial listing of foods with very high exogenous AGEs includes donuts, barbecued meats, cake, and dark colored soda pop.^[5]” Wiki  Sugars (especially fructose) and starches pose significant health risks which make a saturated and monounsaturated fats a safer food source for energy—see Fats.

Sugar Alcohols (Polyol)

A sugar alcohol is a kind of alcohol prepared from sugar.^[1] These organic compounds are a class of polyols, also called polyhydric alcohol, polyalcohol, or glycitol. They are white, water-soluble solids that occur naturally and are used widely in the food industry as thickeners and sweeteners. In commercial foodstuffs, sugar alcohols are commonly used in place of table sugar (sucrose), often in combination with high intensity artificial sweeteners to counter the low sweetness. Unlike sugars, sugar alcohols do not contribute to the formation of tooth cavities.  Sugar alcohols have the general formula HOCH₂(CHOH)_nCH₂OH. In contrast, sugars have two fewer hydrogen atoms. Sugar alcohols occur naturally and at one time, mannitol was obtained from natural sources. Today, they are often obtained by hydrogenation of sugars, using Raney nickel catalysts.  Of these, xylitol is perhaps the most popular due to its similarity to sucrose in visual appearance and sweetness [of which there are 19 listed in Wikipedia].   As a group, sugar alcohols are not as sweet as sucrose, and they have less food energy than sucrose. Their flavor is like sucrose, and they can be used to mask the unpleasant aftertastes of some high intensity sweeteners and some sugar alcohols can produce a noticeable cooling sensation in the mouth when highly concentrated, for instance in sugar-free hard candy or chewing gum. Sugar alcohols are usually incompletely absorbed into the blood stream from the small intestines which generally results in a smaller change in blood glucose than "regular" sugar (sucrose). This property makes them popular sweeteners among diabetics and people on low-carbohydrate diets.  Wiki.  These sweeteners have minor affect if any upon insulin index and little upon glucose index—1997.  There is some evidence that their effect upon appetite regulation could be comparable to that of sucrose.  Unfortunate it is not in the interest of corporations to do studies to expose side effects or other effects that would adversely affect sales.  Given unknown health risks moderation in use is advisable. 

Hormone weight regulatory system: ghrelin and leptin, insulin and Glucagon systems 

Ghrelin (pr. GREL-in), the "hunger hormone", is a peptide produced by ghrelin cells in the gastrointestinal tract, which functions as a neuropeptide in the central nervous system. Beyond regulating hunger, ghrelin also plays a significant role in regulating the distribution and rate of use of energy…. The receptor for ghrelin is found on the same cells in the brain as the receptor for leptin, the satiety hormone that has opposite effects from ghrelin….   Injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner.  Studies have shown that ghrelin levels are negatively correlated with weight. This data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain…. When a person loses weight their ghrelin levels increase, which causes increased food consumption and weight gain. On the other hand, when a person gains weight, ghrelin levels drop, leading to a decrease in food consumption and weight loss. This suggests that ghrelin acts as a body weight regulator,   Ghrelin acts on its receptor in the pancreas to inhibit glucose-stimulated insulin secretion” Wiki.  The appetite-hormone system is complex, and certain conditions don’t follow the simple hunger-serum level paradigm. The same for the other hormone is the fat, glucose, appetite, activity regulatory processes. 

Leptin (Greek λεπτός (leptos) meaning "thin") is a 16-kDaadipokine that plays a key role in regulating energy intake and expenditure, including appetite and hunger, metabolism, and behavior. It is one of the most important adipose-derived hormones.   Leptin functions by binding to the leptin receptor. The Ob(Lep) gene (Ob for obese, Lep for leptin) is located on chromosome 7 in humans. Human leptin is a protein of 167 amino acids… the level of circulating leptin is proportional to the total amount of fat in the body.  This hormone circulates in blood and acts on the hypothalamus to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. Leptin acts on receptors in the hypothalamus of the brain, where it inhibits appetite.  This appetite inhibition is long-term, in contrast to the rapid inhibition of eating by cholecystokinin (CCK) and the slower suppression of hunger between meals mediated by PYY3-36.   Leptin signals the brain that the body has had enough to eat, producing a feeling of satiety. In humans, low circulating plasma leptin has been associated with cognitive changes associated with anorexia, depression, HIV, and the development of Alzheimer's disease.  Leptin modulates the immune response to atherosclerosis, of which obesity is a predisposing factor” Wiki.  That fructose bypasses the leptin-insulin regulatory system is a secondary behind elevated insulin as a cause for the rise in obesity since 1970.  It also causes a rise in ghrelin which is the slip-side of leptin, it increase appetite. 

Insulin and glucagon in glucose regulation:  The Isle of Langerhans in the pancreas produces the hormones glucagon, insulin and amylin, somatostatin, and pancreatic polypetides, all of which play a role in the regulation of blood glucose-glycogen levels.  Glucagon and insulin play major roles in the regulation of cellular glucose-glycogen levels.  “Glucagon raises blood glucose levels by promoting gluconeogensis and  glycogenolysis.   Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored  glycogen  polymers into glucose, which is released into the bloodstream. As these stores become depleted, glucagon then encourages the liver and kidney to synthesize additional glucose by gluconeogenesis.  Glucagon turns off glycolysis in the liver [the production of ATP], causing glycolytic intermediates to be shuttled to gluconeogenesis.  High blood glucose levels stimulate the release of insulin” Wiki.  Insulin causes cells in the skeletal muscles, and fat tissue to absorb glucose from the blood.  Insulin stops the use of fat as an energy source by inhibiting the release of glucagon.  Insulin is provided within the body in a constant proportion to remove excess glucose from the blood, which otherwise would be toxic. When blood glucose levels fall below a certain level, the body begins to use stored sugar as an energy source through glycogenolysis, which breaks down the glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source.[5]  When control of insulin levels fails, diabetes mellitus can result.  Patients with type 2 diabetes are insulin resistant.  Over 40% of those with Type 2 diabetes require insulin as part of their diabetes management plan” Wiki.   “Insulin causes esterification of fatty acids–-forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters and thereby forces its storage and its lack the reverse” Wiki.

Insulin resistance (IR):  Insulin resistance promotes glycation through the higher level of plasma (blood) sugars for a longer period of time.  Glycation² damages LDL and thus when in excess causes the formation of plaque.  “Higher concentrations of glycated LDL are present in diabetic than non-diabetic individuals, but even in the latter, there is generally more circulated glycated than oxidatively modified LDL… [glycation[6] damaged LDL] prevents LDL receptor-mediated uptake and promotes macrophage scavenger receptor uptake. The recognition that LDL glycation is at least as important as oxidation in atherogenesis… ” 2008 journal, and.  This increase in damaged LDL is associated  (but not causal) with a lower active transport of LDL into cells to fulfill the bodily needs and thereby causes a higher signaling to the liver for the production of more LDL.  Thus higher level of blood LDL is associated with IR.  IR is a cause of AS by promoting damaged LDL through high blood sugar and thus glycation of LDL.  “Leptin resistance can be triggered in rats by ad libitum [at ones pleasure] consumption of energy-dense, highly palatable foods over a period of several days…. IR stimulates the formation of new fatty tissue and accelerates weight gain.  Obesity should therefore not be regarded as a pathology or disease, but rather as the normal, physiologic response to sustained caloric surplus…  Sedentary lifestyle increases the likelihood of development of insulin resistance.  It's been estimated that each 500 kcal/week increment in physical activity related energy expenditure reduces the lifetime risk of type 2 diabetes by 6%.  A different study found that vigorous exercise at least once a week reduced the risk of type 2 diabetes in women by 33%” Wiki. Exercise lowers blood sugar.   In Science 2003 a study confirmed an age  association with IR in that there is among the elderly a ~40% reduction in oxidative and phosphorylation activity in the mitochondria; viz., the person with IR, their mitochondria clears glucose at a much lower rate.

High sugar diet:  A chain of interconnected conditions arise from decades-long elevation in blood glucose and fructose.  Metabolic syndrome, insulin resistance, obesity, and fatty live are results of sugar-initiated damage to the liver.  The liver synthesizes glucose from certain amino acids, lactate, and glycerol; breaks down g1lycogen into glucose, and convert glucose to glycogen which it can store.   Sugars cause oxidative and glycation damage to the liver which diminish its functions.  It appears that both glucose and fructose contribute to the damage, with probably fructose being the more important of the two.   In Hippocampus 2008:  “Here, we used functional and structural assays to characterize the effects of excessive caloric intake on the hippocampus, a brain region important for learning and memory.  We conclude that a high-calorie diet reduces hippocampal synaptic plasticity and impairs cognitive function, possibly through BDNF-mediated effects on dendritic spines.”  High sugar diet causing fatty liver and metabolic syndrome is supported both by population studies and laboratory research (topics developed below).  High sugar diet is linked to tooth decay insulin intolerance, gout obesity, diabetes, atherosclerosis, CVD, Alzheimer’s disease, cognitive decline, and many other age-related chronic conditions.   Fructose is 7.5 fold more reactive that glucose in pathogenic glycation, (actually 15 fold because of slower clearance), thus its role in chronic diseases is much greater than glucose. 

Fructose, the differences from glucose:  “Unlike glucose, which is metabolized widely in the body, fructose is metabolized almost completely in the liver in humans, where it is directed toward replenishment of liver glycogen and triglyceride synthesis.   Fructose is also not metabolized in insulin-sensitive peripheral tissues. Fructose is selectively taken up and almost completely metabolized by liver hepatocytes, while much of dietary glucose passes through the liver where it is metabolized in skeletal muscle to CO₂, H₂O and ATP” Wiki. “Fructose is often recommended for diabetics because it does not trigger the production of insulin by pancreatic β cells, probably because β cells have low levels of GLUT5 [transport system into pancreas] although its net effect is debated.  Fructose has a very low glycemic index of 19 ± 2, compared with 100 for glucose and 68 ± 5 for sucrose [discussed at end of this article].  Fructose is also seventy-three percent sweeter than sucrose.  Compared with consumption of high glucose beverages, drinking high-fructose beverages with meals results in lower circulating insulin and leptin levels, and higher ghrelin levels after the meal.  Since leptin and insulin decrease appetite and ghrelin increases appetite, some researchers suspect that eating large amounts of fructose increases the likelihood of weight gain” Wiki, this calls to question the advice for diabetics on the safety of fructose as it promotes obesity a key health issue for three-fourths of those with type 2 diabetes, and through a 15 fold higher rate of glycation per bolus.  However there are 2 metabolic pathways in fructolysis:  one produces triglycerides from DHAP and glyceraldehyde 3- phosphate; the other converts DHAP into glucose and glycogen.  “Since fructose consumption has been hypothesized to be a cause of insulin resistance, obesity, … and, leading to metabolic syndrome. In preliminary research, fructose consumption was correlated with obesity.  A study in mice showed that a high fructose intake may increase adiposity.  While a few other tissues (e.g., sperm  cells and some intestinal cells) do use fructose directly, fructose is metabolized primarily in the liver.  Since leptin and insulin decrease appetite and ghrelin increases appetite, some researchers suspect that eating large amounts of fructose increases the likelihood of weight gain.  A preliminary human study indicated that fructose may not influence  metabolic activity or blood flow in brain regions regulating satiety ("fullness"), and so may promote overeating.  Excessive fructose consumption may contribute to the development of non-alcoholic fatty liver disease [describe below}” Wiki.  Typical findings for effects of high fructose diet include:  “Fructose is more lipogenic[fat producing] than glucose or starches, and usually causes greater elevations in triglycerides and sometimes cholesterol than other carbohydrates.   Dietary fructose has resulted in increases in blood pressure, uric acid, and lactic acid.  People who are hypertensive, hyperinsulinemic, hypertriglyceridemic[7], non-insulin-dependent diabetes, or postmenopausal, they are more susceptible to these adverse effects of dietary fructose than healthy young subjects.”  In Fructose, weight gain and insulin resistance syndrome, 2002 journal article states:  “Because leptin production is regulated by insulin responses to meals [and fructose doesn’t stimulate insulin production], fructose consumption also reduces circulating leptin concentrations. The combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae [injury].”  Corresponding with the rise in CVD and obesity has been fructose’s dietary increase.  USDA chart:  The per-capita yearly consumption of sweeteners was 109 lbs. in 1950 and 152 lbs. in 2000.  The USDA states: “The food consumption in 1970 was 2275 calories and in 2000 was 2,750 calories per person per day, 475 calories above the 1970 level.”  Though both glucose and fructose are about equally efficient at producing ATP (the body’s energy source), fructose rate of glycation is 7.5 fold greater [actually 15 fold because of slower clearance than glucose].  In addition fructose has a greater role than glucose in obesity, IR, MeS, fatty liver disease, and numerous chronic conditions.  Though I have relied upon Wikipedia as a source, those with a financial interest spin their articles; thus other sources than the fructose article to place fructose in the spot light as the leading cause for the plethora of conditions that are currently epidemic. 

Sugar addiction:  “The hedonic pathway comprises a neural conduit between two brain areas:  the ventral tegmental area bv (VTA) and the nucleus accumbens (NA also known as the reward center),… Pleasure occurs when the VTA signals the NA to release dopamine, a neurotransmitter…. When the released dopamine binds to its specific dopamine D­₃ receptor in the NA, the sense of pleasure is experienced.  [Sugars] are also key players in the hedonic pathway, modulating reward to response to meals.  In normal circumstances, after you’ve eaten a sufficient amount, leptin sends a signal to the VTA to suppress the release of dopamine, thereby reducing the reward of food…. If you feed a rodent a palatable food (e.g., a high-fat, high-sugar food such as cookie dough), the animal experiences reward because dopamine is released from VTA and binds to D­­₃ receptor in the NA…. Dopamine stimulation in the NA reinforces the intake of drugs or alcohol and also of food…. After you’ve eaten a sufficient amount, leptin sends a signal to the VTA to suppress the release of dopamine, thereby reducing the reward of food.  That’s what obesity is:  leptin resistance.   What about insulin, leptin’s accomplice?  Normally, people are sufficiently sensitive to insulin.  Insulin’s job is to clear dopamine from the synapses…. Thus the rise in insulin that occurs during a meal blunts the reward of further food intake.  This acts as a servo-mechanism built into the hedonic pathway to prevent overfeeding.  Insulin resistance leads to leptin resistance in the VTA, contributing to increased caloric intake by preventing dopamine clearance from the NA.  Increase pleasure is then derived from food when energy stores are full…. Thus, the combination of high fat along with high sugar is likely to be more addictive than high fat alone.  All the criteria for sugar addiction have been demonstrated in rodent models.   Evolutionary, sweetness was the signal to our ancestors that something was safe to eat“, Prof. Robert Lustig, Fat Chance 2013, p 50-56.  If you doubt the sugar addiction theory, try cutting your sugar intake to 24 grams a day (6 teaspoons).  Use the food labels to determine sugar content and USDA Handbook for the bulk foods (mainly fruits, vegetables).  I tried it, and though fairly good at eliminating sugar added products, I keep nibbling on fruits.  I have eliminated the sugar added foods at the source, the grocery store.  They simply aren’t getting replaced, and the worse of them have been trashed.  Secondly observe the behavior of children between the ages of 3 and 6, most crave sugar added products, and let their parents know it.  Loaded on sugar they become hyperactive.    Another mechanism for this addiction is through the stimulation caused by the neurotransmitter norepinephrine.  Glucose creates alertness through increase in level of norepinephrine—a reinforcer.  “Glucose intake was found to significantly increase plasma NE levels. In contrast, protein and fat intake was found to have no effect” Wiki, and, 1981.  This mechanism operates less efficiently in the obese, thus requiring great consumption of glucose for the response--1983.  As Dr. Lustig observed, obese children have a much lower response to glucose in soda.  Sugar & refined carbs are highly addictive through multiple mechanisms.       

Stress, Cortisol and Food Comfort:   “It is released in response to stress and a low level of blood glucose. Its primary functions are to increase blood sugar through gluconeogenesis, suppress the immune system, and aid the metabolism of fat, protein, and carbohydrate” Wiki.

Metabolic syndrome and sugar:  “metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose,…. Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes. Some studies have shown the prevalence in the USA to be an estimated 34% of the adult population, and the prevalence increases with age” Wiki.  “A randomized, controlled trial of 74 adult men who were administered 200 g fructose daily for 2 weeks with or without allopurinol. Primary measures included changes in ambulatory blood pressure, fasting lipids, glucose and insulin, homeostatic model assessment (HOMA) index, body mass index and criteria for metabolic syndrome…  High doses of fructose raise the blood pressure and cause the features of metabolic syndrome” at journal.  Sugar, especially fructose diet has been demonstrated in both human and animal experiments to cause metabolic syndrome—estrogen has been shown to be protective.[8]  Metabolic syndrome affects 44% of the U.S. population older than age 50” Wiki.  Note this is inflated by including dyslipidemia in the list of conditions that qualify for the condition—another way for pharma to sell Statins and Part 2  on the cholesterol myth.  Thus one more drug, a statin, is added to chemical soup:  one for diabetes, the 3 for hypertension, one for weight loss, and a protein pump inhibitor to reduce the risk of an ulcer from this polypharmacy.  The benefits of treating hypertension go to pharma, not the patient—except for malignant hypertension. And it gets worse, since pharma’s drugs don’t fix the problem, which isn’t hypertension, but atherosclerosis.  Hypertension is to atherosclerosis, as fever is to bronchitis; both are signs of an illness.  And it get even worse, over 80% of MI, result from young-unstable plaque, which occludes blood vessels under 20% and isn’t a cause of hypertension.  The cause of hypertension is the mature, encapsulated hard plaque doesn’t leak. This explains why lowering blood pressure doesn’t work.  Thus when Cochrane Review looked at pharma’s better studies, they found they weren’t worth the side effects—but pharma is very good at marketing.  The effective treatment for metabolic syndrome is diet and lifestyle changes.  

Fructose and non-alcoholic fatty liver disease (NAFLD):  Fructose brings about NAFLD in the same way as alcohol:  ethanol is metabolized in the liver and used in the production of fatty acids, the same from fructose.[9]  Liver cells as they accumulate fat become deformed, the degree of which affects performance.   Moreover, glycation in the liver causes additional damage.   This condition can progress to a point where it shows up on liver function tests in “75% of obese people.  “Fatty livers occur in 33% of European-Americans, 45% of Hispanic-Americans, and 24% of African-Americans” Wiki.  “Non-alcoholic fatty liver disease (NAFLD) is the term for a wide range of conditions caused by a build-up of fat within the liver cells. It is usually seen in people who are overweight or obese.  NAFLD is related to insulin resistance and the metabolic syndrome and may respond to exercise, diet change, and weight loss.   It is a spectrum disease, and at the low end of NAFLD, few have symptoms.  Some patients complain of fatigue and malaise.  A healthy liver should contain little or no fat. Most people with NAFLD only carry small amounts of fat in their liver, which doesn't usually cause any symptoms. This early form of the disease is known as simple fatty liver, or steatosis.  Simple fatty liver is very common in the UK, reflecting the number of people who are obese or overweight.  It is one of the most common forms of liver disease, with an estimated 25-30% people in the UK having early forms of NAFLD” NHS.   “It is difficult to distinguish alcoholic FLD from nonalcoholic FLD, and both show micro-vesicular and macro-vesicular fatty changes at different stages.  Fatty change represents the intra-cytoplasmatic accumulation of triglycerides (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus (micro-vesicular fatty change). In this stage, liver cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving characteristic signet ring appearance (macro-vesicular fatty change). Large vacuoles may coalesce and produce fatty cysts, which are irreversible lesions.  Defects in fatty acid metabolism are responsible for pathogenesis of FLD, which may be due to imbalance in energy consumption and its combustion, resulting in lipid storage, or can be a consequence of peripheral resistance to insulin, whereby the transport of fatty acids from adipose tissue to the liver is increased.  Impairment or inhibition of receptor molecules (PPAR-α, PPAR-γ and SREBP1) that control the enzymes responsible for the oxidation and synthesis of fatty acids appears to contribute to fat accumulation. On the other hand, nonalcoholic FLD may begin as excess of unmetabolised energy in liver cells.  Hepatic steatosis [fat build up in liver] is considered reversible and to some extent non-progressive if the underlying cause is reduced or removed.  FLD is observed in up to 75% of obese people, 35% of whom progressing to NAFLD”   Wiki.   A high fructose diet affects metabolism in the liver through NAFLD that promotes insulin resistance throughout the body.  “The degradation of the metabolic processes in the liver entails a decrease in energy and subsequent related emotional problems such as depression.  The close parallel in fructose metabolism results in metabolic consequences which resemble those from alcoholism.  Given the many functions of the liver, a healthy liver has numerous varied benefits.”  In Gastroenterology “soft drink consumption is the most common risk factor for fatty infiltration of the liver in patients without classic risk factors” like finding, and.   The role of sugar is found in hundreds of journal article on NAFLD. 

Role of glucose, fructose in glycation and CVD and other conditions:  “Excess fructose consumption has been hypothesized to be a cause of insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic syndrome [and NAFLD].  In preliminary research, fructose consumption was correlated with obesity.  A study in mice showed that a high fructose intake may increase adiposity [body fat]” Wiki. “Why glucose — and not another monosaccharide such as fructose — is so widely used in organisms is not clearly understood.  One reason might be that glucose has a lower tendency than other hexose sugars to react non-specifically with the amino groups of proteins [glycation]. This reaction - (glycation) - reduces or destroys the function of many enzymes. The low rate of glycation is due to glucose's preference for the less reactive cyclic isomer. Nevertheless, many of the long-term complications of diabetes (e.g., blindness, renal failure, and peripheral neuropathy) are probably due to the glycation of proteins or lipids” Wiki.  The standard theory is that the process which causes other age related chronic conditions, glycation,  is the main vector in atherogenesis:  “they produce reactive chemicals that can oxidize small dense type-B LDL, and cause in a variety of complex ways through the accumulation of glycation end products (AGEs) affect a number of cellular process of which some are atherogenic, and also contribute significantly to the conditions associated with old age” (Mo. 2009).[10]  The process centers around glycation, ”which is the result of typically covalent bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme.  All blood sugars  are reducing molecules.  Endogenous glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars:  glucose, fructose, and galactose.  It appears that fructose and galactose[11] have approximately ten times the glycation activity of glucose, the primary body fuel.  Some glycations are benign, but others are more reactive than the sugars they are derived from, and are implicated in many age-related chronic diseases such as cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged), Alzheimer's disease  (amyloid proteins are side-products of the reactions progressing to AGEs), cancer (acrylamide and other side-products are released), peripheral neuropathy  (the myelin is attacked), and other sensory losses such as  deafness (due to demyelination).  This range of diseases is the result of the very basic level at which [1] glycations interfere with molecular and cellular functioning throughout the body and [2] the release of highly oxidizing side-products such as hydrogen peroxide.  Long-lived cells (such as nerves and different types of brain cell), long-lasting proteins (such as crystallins of the lens and cornea), and DNA may accumulate substantial damage over time.  Cells such as the retina cells in the eyes, and beta cells (insulin-producing) in the pancreas are also at high risk of damage. Damage by glycation causes stiffening of the collagen in the blood vessel walls, leading to high blood pressure, especially in diabetes.  Glycations also cause weakening of the collagen in the blood vessel walls which may lead to micro- or macro-aneurisms; this may cause strokes if in the brain” Wiki.  (Note fructose only modestly stimulates insulin production and thus its contribution in tables of glycemic index, insulin index and glycemic load is small.)[12]  Pharma has slipped in atherogenesis to the list of conditions in which glycation is a main causal force.  But there are critics and strong evidence that the main culprit in atherogenesis is pathogens living in the artery walls that cause the immune response by leukocytes.  Microphages and macrophages within the artery wall are responding to the presence of the pathogens, so too is the LDL.   Besides the function of transport of triglycerides and cholesterol, LDL has a second function that of neutralizing toxins secreted by the pathogens.  LDL has been shown to have toxins from infection attach to it.   The putative key role of oxidized LDL is another part of pharma’s cholesterol myth.  The actual importance of glycation and reactive oxygen species (ROS) has been muddled by the cholesterol myth and the believers interpreting every bit of evidence in atherogenesis as examples of that fits the cholesterol myth.   Pharma has framed the dialogue on atherogenesis, and the evidence for pathogen has been essentially ignored as also the failure to find a strong relationship between elevated cholesterol and ischemic events.   The role of glycation and ROS is minor.  Thus what is an inflammatory response by the immune system is of the typical type, namely in response to pathogens, not to ROS that damage LDL as promoted by pharma.  For your acceptance of the infective-agent theory, you must examine the links provided above and review the research.  I did this in the winter of 2014-15 and was convinced, and thus I had to revise all of my earlier published materials on CVD and diet.  This is part of an all too common pattern of business using their tobacco science to frame the discussion. 

Corn syrup (glucose syrup) “is a food syrup, which is made from the starch of corn and contains varying amounts of maltose  and higher oligosaccharides, depending on the grade. Corn syrup is distinct from high-fructose corn syrup (HFCS), which is manufactured from corn syrup by converting a large proportion of its glucose  into  fructose using the enzyme xylose isomerase, thus producing a sweeter compound due to higher levels of fructose.  [Unlike sucrose, HFCS is 2 monosaccharides, thus it is not hydrolyzed in the stomach.]  A bushel (25 kg) of corn will yield an average of 31.5 pounds (14.3 kg) of starch, which in turn will yield about 33.3 pounds (15.1 kg) of syrup.  Glucose syrup was the primary corn sweetener in the United States prior to the expanded use of high fructose corn syrup production.  HFCS is a variant in which other enzymes are used to convert some of the glucose into fructose.  Corn syrup is available as a retail product. The best-known brand in the U.S. is Karo” Wiki.  The causes for CVD & obesity epidemics rest with the food industry: they replaced corn syrup with HFCS, increased the amount of sugars in manufactured foods, changed dietary practices through a huge advertising campaign, and promoted the low fat diet high carb diet with the use of vegetable oils instead of saturated fats.  Their lobbying and use of marketing science resulted in the change in dietary recommendation established through the McGovern United States Senate Select Committee on Nutrition and Human Needs, also called the McGovern committee after its only chairperson. It met from 1968 to 1977 and issued in January 1977 ”a new set of nutritional guidelines for Americans that sought to combat leading killer conditions such as heart disease, certain cancers, stroke, high blood pressure, obesity, diabetes, and atherosclerosis…. They suggested that Americans eat less fat, less cholesterol, less refined and processed sugars, and more carbohydrates and fiber” Wiki.   This led to the birth of the Western diet with its disastrous health consequence. 

Maltose, malt sugar, “is a disaccharide formed from two units of glucose joined with an α(1→4) bond.   Maltose is the disaccharide produced when amylase breaks down starch. It is found in germinating seeds such as barley as they break down their starch stores to use for food. It is also produced when glucose is caramelized.  In humans, maltose is broken down by the enzyme maltase so that there are two glucose molecules from which the glucose metabolism obtains energy” Wiki.  Since Maltose and Karo are without fructose, they are the preferred sweeteners. 

In summary:  Fructose because of its failure to stimulate insulin-leptin brain control of appetite is the primary cause of obesity in those on a high sugar diet.  Fructose because of its 10 fold greater rate of glycation causes more damage than glucose.  The increase in sugar in the diet has caused a rapid rise in the rate of diabetes, metabolic syndrome, fatty liver, and insulin resistance.  Given that Oriental traditional diet is high in polished white rice and low in sugar (15 gm/day, Japan) and various experiments upon the effect of high fructose drinks, the evidence indicates that the combination of starches and sugars is the main culprit in the obesity and CVD dramatic increase.  Japan’s rate of Alzheimer’s and CVD are about one third and obesity even less when compared to those who eat a carb-fructose rich Western diet.  Japan is first on the longevity list.  Similar rates are found in those societies that eat a low sugar diet.  Strenuous exercise diminishes the effect of sugar overload by burning off the excess glucose in the muscles.  Thus it would seem that a low sugar diet high starch diet would provide a safer source of ATP (energy).  But one of the indicators of metabolic syndrome is high blood glucose.  Could glucose play a greater role and are all starches equal?

Paleolithic (hunter-gatherer) diet. There is a chorus of critics of the western diet; they extol the Paleolithic diet (Stone Age, stone tools and without metal), the prehistoric period from 2.6 million to 10,000 years ago which is without processed grains, trans-fats, and the liberal consumption of  high sugar foods.  “Modern humans are said to be maladapted to eating foods such as grain, legumes, and dairy, and in particular the high-calorie processed foods that are a staple part of most modern diets.  The evolutionary discordance hypothesis states that ‘many chronic diseases and degenerative conditions evident in modern  Western populations have arisen because of a mismatch between Stone Age genes and recently adopted lifestyles’” Wiki.  Our Western diet is violating our genetic heritage.  Are they right?  In Part 2  I laid to rest the misconceptions about the Mediterranean diet, the same here for parts of the Paleolithic diet.  Though there are exceptions, what stated here applies to the majority of Paleolithic societies.  On the face of it, the argument is flawed.  Paleolithic humans, more than any other animal, have adopted to eating a wide variety of foods, just consider the differences in diet of the Eskimo, the Yanomamo of the Amazon jungle, the Lapps of northern Europe, the Polynesians Islanders[13], and the Bush People of the Kalahari Desert.  The maladaptation argument is right only about high sugar diet, transfats, and polyunsaturated fats, but not dairy, legumes, carbs, and grains.  What follows, I am relying upon Gary Taube, Why We Get Fat, 164-168 and the article he relied upon the work of Cordan.  Corban’s 2000 article analyzies the diet analyzed the diet of 229 Paleolithic societies, short, long.  High amounts of animal products were consumed (73% > 50% of calories) which amounts at the high end to over 85% of their calories from meat and fish.  Only 14% got more than 50% of their calories from plant foods.  Fat averages over 40%, the Inuit 80%.  To prevent health consequences such as gout from high-protein diet, more fat is need for the liver to eliminate nitrogen as urea (Cordan 689).  Thus the fatty portion of meat is prized.  The caution of critics concerning dairy again is without merit since several society such as the Lapps of Scandinavia relied heavily upon dairy as did Mongolian and some African tribes.  It is further clouded by the fact that those Neolithic societies which practiced farming were equally free of modern diseases associated with the Western diet.  Wild sources of grain had small kernels, thus few of these societies consumed grains, and those that did ground the kernel, such as the Indians of central Mexico.   The main changes are the introduction in the Western diet of corn, grains, potatoes, and sugar.  Current fruits have higher-sugar content than the wild varieties.  The Western diet is unique with its recommended 15% of calories from protein, 33% from fat with 7% being saturated, and the remainder from carbohydrates (USDA).  Beside the high carbs and sugars, the Western diet is high in unhealthful fructose, omega-6 fatty acids, and other polyunsaturated fats subject to rancidification (see Part 4).  Native peoples consumed mostly saturated fats, and moderate at most fructose.  Food science supports the Paleolithic-Neolithic diet. 

Whole grain wheat compared to white flour. 

Inositol    Upon inositol is bonded to each OH group a phosphate (PO₄) bonds with the removal of the hydrogen to form phytic acid that consists of 6 H₂PO₄ around a benzene core.  The most prominent form of inositol, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol (former names meso-inositol or i-inositol). Inositol is a carbohydrate, though not a classical sugar.  Its taste has been assayed at half the sweetness of table sugar (sucrose).  It plays an important role as the structural basis for a number of secondary messengers in eukaryotic cells, and was once considered a B vitamin, but since it is synthesized from glucose-6- phosphate (G-6-P) in sufficient amounts, thus it is not an essential nutrient. Various health benefits have been independently tested, including cancer when administered with phytic acid.  Unfortunately pharma is not going to fund definitive studies.  Myo-inositol is naturally present in beans, grains, fruits, and nuts mostly in the unavailable phytate form rather than the bioavailable lecithin form.  Beans and grains, being nuts, they contain large amounts of phytic acid.  Since wheat is the main source of starch in the Western diet, is whole grain wheat superior to refined white flour?  The affirmative answer has become a truism, but white flour remains far more popular because it tastes better.  Since few people grind and make their own breads, I will consider the commercial whole grain breads and brown flour--using US regulations.  The major issue with whole-wheat breads arises from phytic acid[14], which prevents the absorption of most of the micronutrients.   While epidemiological studies support benefits, there are so many contravening variables that a biological mechanistic answer is required. Whole grain wheat has 14% bran and 3% germ, thus only 83% endosperm, while white refined flour is all endosperm.  A number of nutrients are found in the germ:  “Whole-grain foods are rich sources of antioxidants, including vitamins, trace minerals, phenolic acids, ligands, and phytoestrogens. Vitamin E and selenium are particularly concentrated in whole grains. Other trace minerals such as copper, zinc, and manganese are also found in the outer layer of grains. In addition, phytic acid, traditionally considered an anti-nutrient, may also function as an antioxidant. In particular, phytic acid has the ability to form chelates with a variety of metals [prevents their absorption from foods], it also suppresses the damaging iron-catalyzed redox reactions.[15]  Overall, whole grains are a potent source of numerous antioxidant compounds that may help to inhibit oxidative damage.[16]  Whole grains are also important dietary sources of water-soluble, fat-soluble, and insoluble antioxidants. The long list of cereal antioxidants includes vitamin E, tocotrieonols, selenium, phenolic acids, and phytic acid” AJCN 1999.  But merely listing potential beneficial chemicals in wheat germ and bran doesn’t prove that they are of value in whole grain commercial breads, or that they are bioavailable.  Per 100 gm of whole wheat flour, the germ portion is 3 gm.  The table in Wiki shows that of FDA minimum daily requirements a portion of 100 gm of whole wheat grain flour, the germ contributes 28% of magnesium and 5% of zinc. Phytic acid in the gut bonds to mineral to form insoluble salts, and thus is not absorbed from the gut.  Unfortunately, the content in nut and legumes varies greatly based on soil and plant genetics, which makes quantification over a wide range.  For general guidance assume that the absorption rate has been lowered by 50% when the meal includes a sizeable portion of nut products. Nut products include nut oil such as soy bean, legumes, nuts, and whole grains.  As for mineral absorption from nuts legumes, and whole grains assume that they is less than 25%. Given this negative effect of phytic acid in wholegrains, white bread is preferred.  (For more on phytic acid go to the Weston Price Foundation site.) The literature critical of processed foods praises whole wheat for its lower glycemic index (slower rate of absorption over measured during the 2 hours from ingestion).  Because sugar is added to mask the bitter taste, and the use of softeners, the popular whole wheat bread has nearly the same ratings as white bread.  “However, most breads made with 100% whole wheat or wholemeal flour have a GI not very different than endosperm only (white) bread.  Many brown breads are treated with enzymes to soften the crust, which makes the starch more accessible (high GI)” Wiki.  Given the loss of calcium in whole-wheat bread from phytic acid, Consumer Report  be added, for both are essential and frequent Americans are deficient of.  As for nuts and legumes and nut oils, their benefits as sources of proteins and slower absorption (resistant starches, next section) of carbs entails that they make up for the lower bioavailability of minerals.  Nut oils are preferred for a much different reason, they are high in monounsaturated fats, and thus are far more healthful that the polyunsaturated fats that are subject to rancidification in the body and are high in the omega-6 fatty acids.     

1.  Rye bread containing 47% kibbled rye, Holt et al.  Breads with grain berries also rate similar. 

2.  Bread made from whole-meal wheat flour—Source Wikipedia Insulin Index.

Dietary Fiber is the indigestible portion of polysaccharides derived from plants.  It is divided into 2 classes:  Soluble fiber which dissolves in water and is fermented by bacterial in the colon into gases and physiologically active byproducts and can be prebiotic[17] and insoluble fiber which is metabolically inert and provides bulking and thereby promote intestinal peristalsis.  Some insoluble fibers are metabolically fermented by bacteria in the large intestine and are prebiotic.  “Generally, however, it is assumed that a prebiotic should increase the number and/or activity of bifidobacteria and lactic acid bacteria. The importance of the bifidobacteria and the lactic acid bacteria (LABs) is that these groups of bacteria may have several beneficial effects on the host, especially in terms of improving digestion (including enhancing mineral absorption^[10]) and the effectiveness and intrinsic strength of the immune system” Wiki.   Major sources typical amounts cooked grams per cup:  beans 15, whole grains 4, hulled grains 2.5, fruits 4, vegetables 6.  All is not positive, for along with phytic acid “dietary fiber may bind metallic cations in both in vitro and in vivo studies” 1991.  Two large epidemiological studies have failed to find a reduction in colon tumors or cancer with a high fiber diet.  Given its minor role in promoting health, it is near the bottom of my list of dietary concerns.  .  Fiber promotes satiation thus lowers calories per meal and it contributes on an average just 2 calories per gram.  Other groups of compounds not digestible include waxes and lignans which are polyphenolic substances derived from the amino acid phenylalanine via dimerization or cinamic acid.   “Both obesity and Type 2 Diabetes are diseases caused by excessive insulin. Insulin resistance develops over time, with persistently high insulin. If fibre can protect against elevated insulin, then it should protect against Type 2 Diabetes” 2015 Dr. Fung. Dietary recommended amount is 25 grams per day.  Rather focus on healthful meals as to quantity of fiber, focus on the amount of sugar and keeping insulin response low.  Low insulin response is promoted by small meals and frequent healthful snacks (low in carbs).  Other factors include exercise prior to and subsequent a meal, fiber, fats, and to a lesser extent protein, and of course eating foods with a low insulin index.  A healthful diet has many ingredients.

Starch, resistant starch (RS) and metabolic syndrome   “Glucose is absorbed at a higher rate from white flour products than whole wheat products, thus white rice, potatoes,  and white bread have a higher glycemic index (blood-sugar level will become high and remain their longer).  Thus whole wheat is beneficial for those with metabolic syndrome and type 2 diabetes—but not whole wheat bread because of processing which makes its glycemic index just 3% lower than white bread.  Since there are many different chemical structures of starch and the digestive enzymes vary as to their ability to hydrolyze them their glycemic index, glycemic load, and insulin index scores varies.  There is strong evidence that cooked starch affects insulin more than resistant starch[18] (RS).  Fibers, mostly cellulose are partially digested hours later by intestinal flora and absorbed in the small and large intestines and thus contribute to the 2 hour window in which the 3 above named indexes are measured.    

Resistant starch has been categorized into four types:

• RS1 Physically inaccessible or digestible resistant starch, such as that found in seeds or legumes and unprocessed whole grains.  [Partially absorbed through digestion by bacteria in the intestines that split the long chains of sugar molecules into monosaccharides.]

• RS2 Resistant starch that occurs in its natural granular form, such as uncooked potato, green banana flour and high amylose corn

• RS3 Resistant starch that is formed when starch-containing foods are cooked and cooled such as in legumes, breads, cornflakes, and cooked-and-chilled potatoes, pasta salad or sushi rice. Occurs due to retrogradation, which refers to the collective processes of dissolved starch becoming less soluble after being heated and dissolved in water and then cooled.

• RS4 Starches that have been chemically modified to resist digestion. This type of resistant starches can have a wide variety of structures and are not found in nature. 

  “Research of RS2 resistant starches from high amylose corn indicates benefits in intestinal/colonic health as well as metabolic benefits in glycemic management, satiety and hunger, and eye health.  Different types of source of resistant starch are digested and/or fermented differently and thus must be considered individually” Resistant starch reduces glycemic response … R2 increases insulin sensitivity” Wiki. In Journal 2004:  “RS intake is associated with several changes in metabolism which may confer some health benefits. RS intake seems to decrease postprandial glycemic and insulinemic responses, lower plasma cholesterol and triglyceride concentrations, improve whole body insulin sensitivity, increase satiety, and reduce fat storage.” Positive effects have also been found for RS in the large bowel.  In journal 2005: “Several indices of large-bowel function, including short-chain fatty acids, were improved relative to standard whole meal wheat. These results indicate that this high-amylose wheat has a significant potential to improve human health.”  The next section on glycemic index (GI) & table is instructive as to RS in that it measures the extracted carbohydrates minus fiber from different foods and gives a comparative rating as to the total blood-glucose level over a 2-hour period with pure glucose powder rated as 100.