Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
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Showing posts with label insulin resistance. Show all posts
Showing posts with label insulin resistance. Show all posts

Thursday, May 31, 2012

Dr. Oz on Sweeteners: Sugar, Fructose, Insulin/Resistance, AGE, FattyLiver



I was shocked when Dr. Oz recommended a snack made with agave syrup. I had seen a previous program by America's representative of the medical industry in which he revealed the hazards of agave syrup as a new source of fructose. Now he just skipped over the use of this fructose syrup as a "natural" sweetener, even though it is even less healthy than high fructose corn syrup, HFCS. There seems to be a lot of deliberate confusion about sweeteners and since I am trained as a carbohydrate chemist, I will try to tell it as I see it.

General Information 
  • Carbohydrates are not needed in your diet, since your liver can make all the blood sugar that you need from protein. Most diabetics can benefit from a low carbohydrate diet. 
  •  Glucose, the blood sugar, is primarily responsible for turning on insulin production, so sweeteners (glucose, sucrose, HFCS, corn syrup) or dietary carbohydrates (starch, e.g. cereal, rice, pasta, potatoes, bananas) that are readily converted to glucose, cause blood insulin levels to rise. 
  •  Fructose in any form (HFCS, sucrose, agave syrup) contributes to liver damage. Fructose is the most chemically reactive sugar. 
  •  Artificial sweeteners, especially in soft drinks, do not contribute dietary calories, but they apparently increase insulin production and contribute to hunger, eating and obesity. 
  •  Insulin production removes glucose from the blood, i.e. lowers blood sugar, by increasing glucose transport into fat cells. If glucose is in your blood, but insulin is not present, e.g. type I diabetes, then you get thin. If glucose is in your blood and insulin is present, then you get fat. If you are fat and glucose is still high in the blood and insulin is present, then the fat cells will die unless they shut off the insulin response, i.e. insulin resistance. Lowering the amount of carbohydrates, sweeteners/starch, in your diet makes it easier to control blood sugar levels and avoid hunger. 
  •  Decreasing dietary carbohydrates means that calories have to be present in some other form and the answer is saturated fat. Most polyunsaturated fats, e.g. vegetable oils, except olive oil, are not healthy. The fats in meat, butter, eggs and coconut oil are the healthy choices supported by the biomedical literature, and along with vegetables, form the foundation of a healthy, anti-inflammatory diet. 
Central Metabolism Started with Fructose not Glucose 
All organisms convert sugars through a common series of enzymatic steps, called central metabolism, to a simple, three-carbon compound called pyruvate. Pyruvate can be used as a source of energy in mitochondria in the presence of oxygen or converted into alcohol or acids in various forms of fermentation. No matter what sugars are used, e.g. glucose, galactose, mannose, they are all converted in cells into derivatives of fructose. Thus, fructose is common to all organisms and can be considered to be the most primitive. So why is glucose usually considered to be the the start of central metabolism and why is dietary fructose dangerous?

Fructose is too Reactive to Transport 
The first cells used fructose as the starting material to make the building block molecules of cells, e.g. carbs, proteins, fats, nucleic acids, and energy in the form of ATP. Multicellular organisms, such as animals and plants had to move sugars from cell to cell. It would be obvious to transport fructose, since all other molecules could be converted into fructose, but the problem is that fructose is too chemically reactive, i.e. it reacts with proteins to form AGE. It is for that reason that fructose is converted by cells into glucose, which is less than one tenth as chemically reactive. In plants, the reactive groups of glucose and fructose are bonded together to produce sucrose, table sugar, which is much less reactive and can be transported in plant vessels at very high concentrations.

High Blood Sugar is Bad, High Fructose is Worse (AGE-ing) 
High levels of blood sugar, glucose, react with proteins to produce advanced glycation end products, AGE. Fructose in the blood produces these inflammatory compounds more than ten times faster. That is why fructose is a bad sweetener for diabetics. Eating fructose, e.g. agave syrup or sucrose, doesn't directly raise blood sugar/glucose levels, since it raises blood fructose levels, which is worse.

Fructose Fattens Livers 
Fructose is rapidly absorbed in the intestines and transported to the liver. The blood vessels of the liver remove fructose from the blood and it is rapidly converted into fat. Fructose in sweeteners has now surpassed alcohol as the major source of liver disease.

Sweeteners
Fructose is ten times sweeter than glucose, and that is why cheap forms of glucose, such as corn syrup, are treated with enzymes to convert some of their glucose into fructose to produce high fructose corn syrup. Corn syrup is not as sweet as pure glucose, because the syrup contains a mixture of short chains of glucose of different lengths, and the chains decrease in sweetness with length. By changing some of the glucose into fructose, the HFCS can be made as sweet as table sugar, sucrose. Corn subsidies keep corn syrup cheap and make HFCS very profitable. Unfortunately, the HFCS contains fructose and therefore it has the liver toxicity and AGE-forming inflammation of fructose.  Agave syrup is like HFCS on steroids.

Agave Syrup is Fructose 
Agave syrup contains fructose produced by industrial processing of the fructose polysaccharides, inulin, in agave extracts. I cannot understand why anyone would use this commercially processed fructose as a sweetener. It doesn't raise blood sugar as much as sucrose, because there is much more fructose than sugar (like very high fructose corn syrup) it raises blood fructose levels instead, which is much, much worse.

Sugar Makes You Hungry 
The human body can only use simple sugars, e.g. glucose, fructose, sucrose, or starch. Body enzymes convert sucrose into fructose + glucose, and starch into glucose. Other carbs, such as soluble fiber, are only digested by gut bacteria in the colon. The conversion of starches to glucose begins with enzymes in saliva in the mouth and is completed in the upper part of the digestive tract. Starch should be considered as a simple sugar, because it causes a rapid rise in blood sugar, just like glucose. It may actually be faster than table sugar. The rapid rise of blood sugar causes a rapid increase in blood insulin, which in turn rapidly removes sugar into fat cells. The rapid rise and fall of blood sugar provides the experience of hunger. That is why cereal, e.g. oat meal, in the morning produces intense hunger just a few hours later. Actually, oat meal is not quite as unhealthy as most cereals, because it also has some soluble fiber to feed gut flora. A protein and fat breakfast, e.g. bacon and eggs, does not produce rapid hunger, because it does not produce a large insulin rise and glucose fall.

Insulin Resistance is Better than Death by Glucose 
As fat cells accumulate glucose as a result of blood sugar transported into the cells in response to insulin, more and more of the glucose is converted into fructose and on to pyruvate. The pyruvate accumulates in mitochondria and ATP production is saturated. This is potentially lethal for the cells, because the conversion of pyruvate into ATP is accomplished by removing high energy electrons as the pyruvate is converted to carbon dioxide. The high energy electrons accumulate in the inner membranes of the mitochondria and if they are not systematically converted to low energy electrons and dumped onto oxygen to produce water, reactive oxygen species, ROS are produced and the result is inflammatory oxidative stress. Antioxidants would be needed to protect from major cellular and organ damage. The cells protect themselves by responding to the accumulation of high energy electrons on the mitochondria by shutting down the response to insulin and blocking further intracellular glucose accumulation. This is insulin resistance.

Carbs: Never too Low 
Dietary carbs, such as sugars and starches are not needed, because the liver can convert protein into glucose. Thus, diabetics, who have a hard time balancing their dietary intake of carbs with the insulin that they inject, can simplify the process by routinely eating less carbs spread through many meals and triggering some glucose production by the liver. Craving for carbohydrates/sweets can be dramatically reduced simply by eating fewer carbs and avoiding insulin production that can lead to more dramatic swings of blood sugars and hunger. Using this strategy, I am hungry less than once a week.

Healthfulness of Sweeteners 
 --from Most Healthy....
  • Stevia - is a diterpene glycoside (I previously made the silly error of listing it as a protein) (erythritol, another simple sugar alcohol is added to make the stevia granular) that is sweet, doesn't raise blood sugar, no insulin spike and no AGE 
  • Glucose - raises blood sugar, spikes insulin and produces AGE 
  • Xylitol - is a sugar alcohol that inhibits dental bacteria, doesn't raise blood sugar, no insulin spike or AGE 
  • Corn Syrup - raises blood sugar, spikes insulin, produces AGE, low sweetness  
  • Sucrose - raises blood sugar, spikes insulin and produces AGE, and liver damage 
  • Honey - is half fructose and half glucose, raises blood sugar, spikes insulin, produces high AGE and may damage liver  
  • Artificial Sweeteners, aspartame, sucralose, saccharin, etc. - don't raise blood sugar or produce AGE, but may have other risks, including hunger 
  • HFCS - is high fructose corn syrup, raises blood sugar and spikes insulin, produces very high AGE and causes liver damage 
  • Fructose - doesn't raise blood sugar or spike insulin, produces very high AGE and causes liver damage,  does not produce satiety and may encourage consumption of other sugars 
  • Agave Nectar - is mostly fructose, doesn't raise blood sugar or spike insulin, produces very high AGE and causes liver damage 
 ...to Least Healthy or Health Risk--

Tuesday, November 24, 2009

Superoxide Causes Insulin Resistance, Type 2 Diabetes

Intracellular Nutrient Excess Produces Mitochondrial Electron Accumulation
 (Article referenced below was brought to may attention by Cristian Stremiz - thanks)

Insulin resistance blocks insulin-based transport of glucose into cells that are already overloaded with nutrients. The spilling-over of excess high energy electrons in the mitrochondrial electron transport chain onto oxygen produces superoxide. Superoxide is the trigger to block the import of still more glucose. Thus, insulin resistance is a cellular defense against sudden death by superoxide and other reactive oxygen species (ROS).

High Energy Electrons of Glucose Are Used to Make ATP

Cells are biochemical machines that turn on genes to produce enzymes to convert the high energy electrons on the carbon and hydrogen atoms of glucose into ATP energy and molecular components of the cell. The high energy electrons are systematically depleted of energy, protons are pumped to produce a proton gradient across the inner mitochondrial membrane, ATP is made using the proton gradient and the low energy electron are passed off to oxygen molecules to make water. That is a quick summary of cytoplasmic glycolysis, the tricarboxylic acid cycle (mitochondrial matrix) and the mitochondrial electron transport chain. The final step of transferring the depleted electrons to oxygen to make water is how oxygen is consumed in respiration. Note that if everything works well, the high energy electrons of glucose, which could suddenly release all of their energy directly interacting with oxygen and start a fire, just produce water. Another bad alternative would be for the high energy electrons to bind to molecular oxygen making superoxide.

Cells Adjust their Glucose Individually to Match ATP Use

If the supply of ATP from the mitochondrial electron transport chain of a cell gets low, this triggers the migration of vesicles with glucose transport proteins to the cytoplasmic membrane. Since the number of transport proteins determines the rate of import of glucose, then more transporters means an increase in glucose and more ATP. Type 2 diabetes and insulin resistance represents the others extreme, i.e. what happens when cells get too much glucose, max out their capacity to make ATP and high energy electrons build up in the electron transport chain.

High Blood Sugar Triggers Insulin Production to Import the Glucose into Cells


Cells can also participate in body-wide metabolism coordinated by hormones, such as insulin. A sudden increase in blood glucose concentration triggers the pancreas islet cells to release insulin into the blood. The insulin binds to insulin receptor proteins on the surface of cells and that signal brings more glucose transport proteins to the cytoplasmic membrane. The cells import additional glucose and their metabolism increases and more ATP is produces. This lowers the blood glucose level. Some cells can continue to accumulate glucose in the form of glycogen or fat droplets, but other cells do not have this storage capacity. If glucose is supplied beyond the capacity of the cell to use it, then the mitochondrial electron transport chain begins to produce superoxide.

Superoxide Is a Reactive Oxygen Species (ROS)

Oxidation stress is the reason that plant antioxidants, vitamin C and N-acetyl-cysteine are recommended to avoid inflammation. One of the major sources of oxidation stress is the production of superoxide. Cells produce an enzymes, superoxide dismutase, to convert superoxide into hydrogen peroxide, and catalase to convert hydrogen peroxide into oxygen and water. Superoxide can also interact with nitric oxide to produce the nitric oxide radical. Unfortunately, superoxide can also produce hydroxyl radicals that can react with unsaturated lipids to produce lipid peroxides. Thus, superoxides can contribute to the production of many ROS, cause oxidation damage and trigger inflammation.

Many Different Processes that Produce Insulin Resistance all Produce Superoxide

The trigger for insulin resistance appears to be mitochondrial superoxide accumulation. A recent article used numerous mouse models of insulin resistance that mimic the typical human risk factors for insulin resistance and type 2 diabetes, e.g. excess nutrition, physical inactivity, pregnancy, polycystic ovarian syndrome, metabolic syndrome, inflammation, oxidative stress, anti-inflammatory corticosteroids, etc. and demonstrated that in each case mitochondrial superoxide accumulated. Moreover, mutant mice with lowered superoxide dismutase were more susceptible to insulin resistance and mutants producing an overabundance of superoxide dismutase were resistant to insulin resistance.

Insulin Resistance Is a Natural Defense Against Energy Excess

Superoxide sensing and insulin resistance protect cells against too much energy input and oxidative stress, but without the ability to reduce blood sugar, hyperglycemia leads to the suite of degenerative reactions that provide the symptoms of type 2 diabetes.

reference
Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, Van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, James DE.Insulin resistance is a cellular antioxidant defense mechanism.Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17787-92. Epub 2009 Sep 30.