You might consider Heart Disease, Stroke, Cancer, Diabetes and Dementia as the leading causes of death and disability that accompany aging, but underlying all of these is a slow, subtle aging mechanism called Glycation. Glycation is the accidental bonding of sugars to proteins and fats to form Advanced Glycation End-products (or AGEs – a very appropriate acronym) which then accumulate in all the body’s tissues, slowly disabling their normal function. In time, all these popular diseases are directly fostered by the accumulation of AGEs in our various tissues and organs. The science of all this has been growing for the last 25 years, but doctors and health authorities have been slow adopters of the knowledge; drug companies and the food industry have resisted purposefully against revising the published ‘truths’ and acting against this powerful aging mechanism underlying all these diseases. The science is also quite complex, not easily grasped by the casual reader, but I want to try to explain it in street terms so we can begin taking strategic action against this killer.

Glycation – a primary mechanism of aging

Glycation is the accidental chemical bonding of a sugar molecule to a molecule of protein or fat. It happens outside the body in cooking (‘browning’ of anything, for example grilling meats, veggies or toast) and it happens inside the body in nearly every tissue because we use glucose (blood sugar) as a primary fuel for producing energy. All animals have developed mechanisms for sequestering AGEs and ushering them out of the body, but they don’t get them all. Some AGEs escape and are incorporated into our tissues, and accumulate over time.  Our immune system progressively sees these as foreign enemies to be destroyed, and they become the primary cause of rising inflammation with age.

Blood Sugar level – the key parameter

The rate at which AGEs are formed is dependent on blood glucose levels; higher glucose yields higher AGE formation rates. Metabolism of glucose also creates residual chemicals called aldehydes (alcohol metabolism likewise produces aldehydes) and these are also agents of glycation. Glycation from dietary sugars such as glucose, fructose and galactose are the first of several steps to forming AGEs, with fructose and galactose being about 10 times more active than glucose. This is why High-Fructose Corn Syrup (HFCS) is perhaps the worst sweetener we can use. All the mechanisms forming AGEs are higher in diabetics, as are the rates of progression of the diseases associated with aging – it all happens faster in diabetics. One of the sources I have researched stated that many of the artificial sweeteners in use today also, even though non-caloric, are glycating agents (for instance: Aspartame is metabolized into formaldehyde in the liver and taken up several organs). The take home on this is that the higher our blood sugar, the faster we age, and the faster we acquire the diseases that are going to disable us and kill us.

Disease-specific damage: How glycation makes us sick

Heart disease: AGEs damage LDL cholesterol, glycating the apoB belt circling the molecule, making it more easily oxidized, smaller and more invasive to the inner lining (endothelium) of arteries and vessels. The endothelial cells respond directly by loosening their cohesiveness to one another making the layer more permeable to damaged LDL, starting the plaque-building process.

Endothelial cells have receptors for AGEs (called RAGE, as do most cells), which, when AGEs land on,  signal the cell to up-regulate NFkB ( a nuclear gene switch that turns on inflammation signaling) and start an inflammatory cascade (basically tells our immune system to send macrophages and other immune cells to kill and eat the damaged cholesterol, but when they do so, they become foam cells and become part of the artery-inflaming, plaque-building process). Such sensitized cells also build more RAGE structures, becoming increasingly sensitive to AGEs, and more inflamed. AGE-modified LDL also invades the smooth muscle cells of arteries, stiffening their walls and raising blood pressure. At the same time, glycated HDL loses much of its ability to collect cholesterol from the plaque and eliminate it through the liver.

Now, with our youth drinking sodas at an early age, we see the process of arterial damage starting before adolescence. The point is that AGEs alarm our immune system, putting it in a state of hyper-alertness, causing chronic inflammation of many of the body’s tissues and organs.

Cancer: The nursery for cancer is inflamed tissues that are oxygen-deprived. Stiffening of the vascular system reduces oxygen supply to cells, inflammation from the immune system damages cells, and if not killed they may be damaged in ways that turn on genes that promote cancer. One would hope that the hyper immune system would recognize this change and kill the renegade cells, but cancer cells seem to be able to highjack functions of the immune system to help them grow and thrive.   Glycation, oxidative stress and inflammation are mutual promoters; increasing any one increases the others, creating an escalating cycle of damage.

Dementia: AGEs that cross the blood-brain barrier are involved in damage of the brain’s blood vessels and in the miss-folding of ameloid-beta, leading to stroke, dementia and Alzheimer’s.

Connective tissue: AGEs bond to collagen, stiffening and destroying the elasticity of skin, tendons, ligaments and the fascia surrounding every element of our body. All our cells are imbedded in what is called the extracellular matrix which allows the movement of fluids, nutrients, waste products and signalling chemicals in and around all cells. AGEs slowly destroy these functions and invite the immune system to generally inflame our bodies. AGEs accumulate in our skin, caused by diet and excessive sun exposure, creating wrinkles, sags and loss of elasticity. Smoking floods the bloodstream with AGEs created on the hot end of pipes, cigars and cigarettes – there are few faster ways to look older than we actually are than smoking; and of course our insides are doing the same.

Strategies for minimizing glycation – slowing aging of every part of our body:

Keep blood sugar low: This is the key parameter to control. How do we do this? Consider the following:

• Eliminate sugar entirely, and all sugar substitutes, with the exception of Stevia Extract and small amounts of raw honey – the key is to train your brain not to need sweets. No agave or HFCS; remember, fructose glycates tissues 10 times faster than glucose. This means eating virtually no manufactured food items.
• Eliminate/minimize grains and things made from grains, including things made with wheat, corn and flours in general; they all turn to sugar rapidly and spike blood sugar. The FDA food pyramid is deadly wrong; every culture in history that has turned largely to grains for staples has had high levels of the major degenerative diseases of aging mentioned above.
• Eat no more than three times/day, with 5-6 hours between meals. This lets insulin levels fall to zero between meals, promoting insulin sensitivity for all the body’s cells. Eating more frequently (a favorite weight loss strategy) is the primary cause of insulin resistance and metabolic syndrome in the long term. Learn to drink water between meals, not soft drinks and juices.
• Eat real, unadulterated foods; grass fed livestock, free range fowl and eggs, wild caught seafood and tons of vegetables – green, colored, mostly non-starch fibrous types. These foods will not excessively elevate blood sugar. Add some root vegetables, legumes and nuts for flavor and variety. Dairy (milk) should be avoided by many, depending on cultural development. Butter is OK for most, and the cultured milk items like cheese, yogurt (plain, full-fat, goat milk yogurt is my favorite), and kefir (https://chriskresser.com/kefir-the-not-quite-paleo-superfood – for more info) can be good for most.
• Eat modestly – rarely feast to the level of discomfort.  Using supplemental Betaine HCl and digestive enzymes with meals can make digestion a breeze and heartburn non-existent. Get off all acid blockers (Nexium etc.), they make absorption of proteins and minerals impossible. Finish dinner 3-4 hours before bed, and go to bed on an empty stomach.

What supplement can be used to hold down blood sugar/glycation?

• Berberine and Bitter Melon extracts are helpful for undoing insulin resistance, thereby lowering blood sugar; 500 mg each, taken before meals.
• Pyridoxamine (vitamin B6 or its metabolite Pyridoxyl-5-phosphate) blocks the glycation process; 100mg with meals.
• Garcinia Cambogia, cinnamon extract, chromium picolinate, gymnema sylvestre; all featured as weight loss agents, improve insulin sensitivity of our cells and lower blood sugar.
• Alpha-Lipoic Acid – a powerful master antioxidant soluble in water and fat, protects all body tissues and crosses the blood-brain barrier protect the brain, and acts as an insulin mimic to move sugar out of the blood into muscle cells; 600 to 900 mg/day.
• Carnosine is a glycation blocker, most suggestions are for at least 1000 mg/day, best divided with each meal
• Magnesium – the mineral is required for insulin sensitivity in all cells; lacking in fast food diets, supplement up to 1000mg/ day, divided with meals.

What else holds down blood sugar?

• Daily movement and exercise is critical to preserving insulin sensitivity of muscle cells, which absorb the bulk of dietary sources of glucose and other sugars. Muscles store dietary sugar as glycogen; the more muscle we carry, the more dietary carbs are stored as glycogen instead of fat. Muscle glycogen holds more water in the muscle cells, making them look fuller and making them considerably stronger and less prone to damage.
• The older we get the more we need strength training to hang onto our muscle structure, or in many cases to actually grow stronger with age; mobility depends on muscle – independent living depends on mobility!

Bottom Line: Adopt these dietary and exercise strategies and your aging rate will plummet. You will live a far more active life with less disability and likely attend most of your friends funerals before they attend yours.

Good Living – Frank

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