Sugar Toxicity: A Silent Epidemic

A View from the Trenches of Daily Primary Integrative Medical Praxis

by David A. Edwards, MD, HMD; Jean Malik, MD, APH; Edna Espig, CNA, CHA; Renoir Morillo, BSN, CHA; Erika Bryant, EECP Tech; and Jesusa

Ludahl

Sugar is the generalized name for sweet, short-chained soluble carbohydrates. Carbohydrates are composed of carbon, hydrogen and oxygen (basically carbon + water). The term sugar refers loosely to a number of different types of carbohydrates, including monosaccharides (glucose, fructose), disaccharides (sucrose, lactose), oligosaccharides and polysaccharides (common components of glyco-proteins and glyco-lipids). The most biologically important and well known monosaccharide is glucose. Glucose is the main source of energy fueling aerobic metabolism… a fundamental necessity of living mammalian cells. The most common disaccharide is sucrose (glucose + fructose) or common table sugar. Bio-polymers (oligo and polysaccharides) of sugar are common structural forms of carbohydrates in nature. Plants produce sugar and sugar bio-polymers through the process of photosynthesis. These bio-polymers are converted into structural polysaccharides, such as cellulose and pectin found in plant cell walls. They also may serve as a form of energy storage, such as starch or inulin. In addition, DNA and RNA are polymers of the monosaccharides deoxyribose and ribose respectively and constitute the basis of genetic blueprint and memory for almost all forms of life. The importance of sugar in its various functional and structural forms for life cannot be overstated. However, like Oxygen, which is both essential for most life forms and also extremely toxic to life (physiologic function versus toxic free-radical damage), sugar also has a dark side for living tissue.

Studies in animals and humans have suggested that chronic consumption of added sugar contributes to metabolic and cardiovascular dysfunction. There is also growing evidence that added fructose is more damaging than refined glucose in terms of cardiovascular risk [1

]

Cardiac performance has been shown to be impaired by switching from a low carbohydrate diet including fiber to a high carbohydrate diet.[2] Switching from saturated fatty acids to carbohydrates with high glycemic index values shows a statistically significant increase in the risk of myocardial infarction.[3] Other studies have shown the risk of developing coronary heart disease is decreased by adopting a diet high in polyunsaturated fatty acids and low in sugar, but a low fat, high carbohydrate diet showed no reduction.[4] This suggests that consuming a diet with high glycemic load (“high glycemic” = causes a rapid rise in blood sugar) is strongly associated with the development of coronary artery disease.[4] The consumption of added sugars has been positively associated with multiple measures known to increase cardiovascular disease risk in adolescents as well as adults.[5] Multiple studies suggest the impact of refined carbohydrates or high glycemic load carbohydrates is more significant than the impact of saturated fatty acids on cardiovascular disease.[6-26] In addition, a connection between Alzheimer’s disease and fructose has been suggested, but remains the subject of debate.[27,28] Finally, the possible addictive effects of refined sugar simply adds to the scientific concern regarding the toxic effects of sugar in the development of cardiovascular disease.[29]

Glycocalyx

One of the lesser-known structural/functional physiologic aspects of sugar is the glycocalyx

. The glycocalyx is a polysaccharide sugar polymer coating that surrounds all cell membranes

.[30-32] This “

suga

r” coating consists of several carbohydrate moieties of structural membrane

glyco

lipids and

glyco

proteins which serve as a backbone for support and cell to cell communication. Pischinger’s Matrix Theory of rapid cell to cell communication is centered on the functional aspects of the glycocalyx. (Pischinger A. Matrix and Matrix Regulation Basis for a Holistic Theory in Medicine [English Edition]. Haug International, Brussels. 1991). This carbohydrate (“sugar”) portion of plasma membranes contributes to cell-cell recognition, communication and intracellular adhesion.[30] The slime on the outside of a fish is a common example of a glycocalyx.

It is essentially a functional

“

bio-film

.” The term glycocalyx was initially applied to the polysaccharide matrix coating epithelial cells, but its functions have been discovered to go well beyond that. The glycocalyx plays a major role in regulation of endothelial vascular tissue, including the modulation of red cell volume in capillaries.[33] It is located on the apical surface of vascular endothelial cells which line the lumen of all blood vessels and may be up to 11um thick [34,35] It is present throughout a diverse range of micro-vascular beds (capillaries) and macro-vessels (arteries and veins). The glycocalyx also consists of a wide range of enzymes (eNOS, ACE, SOD3, etc.) and proteins (growth factors, chemokines, antithrombin, etc.) that regulate and protect the endothelium. They serve to reinforce the glycocalyx barrier against vascular and other diseases. Another function of the glycocalyx within the vascular endothelium is to shield the vascular walls from direct exposure to blood flow while serving as a vascular permeability barrier.[36] Its protective functions are universal throughout the vascular system. In micro-vascular tissue the glycocalyx inhibits coagulation and leukocyte adhesion. It also affects the filtration of interstitial fluid from capillaries into the interstitial space. [37] Research has shown that the

glycocalyx is composed of a negatively charged network

of proteoglycans, glycoproteins and glycolipids.[36]

The glycocalyx plays a crucial role in cardiovascular system health. Initial

dysfunction of the glycocalyx can be caused by hyperglycemia

or oxidized LDL cholesterol. In the micro-vessels, dysfunction of the glycocalyx leads to internal fluid imbalance and potentially edema. In arterial vascular tissue glycocalyx disruption causes inflammation and atherothrombosis. [37] Fluid shear stress is also a potential problem if the glycocalyx is disrupted for any reason. This type of frictional stress is caused by the movement of viscous fluid (i.e. blood) along the lumen boundary damaging the delicate glycocalyx.

Minimal ischemic damage to the glycocalyx increases capillary hematocrit

. Endothelial (glycocalyx) dysfunction can be tested by a variety of methods.

Of all the current tests employed in a research setting, flow mediated dilatation (post-occlusive reactive hyperemia or PORH) is the most widely used non-invasive test for assessing endothelial dysfunction

. This technique measures endothelial function by inducing reactive hyperemia via temporary arterial occlusion and measuring the resultant relative increase in blood vessel (capillary) diameter via ultrasound or plethysmography.

A reduction of small arteriole/capillary compliance is a marker for endothelial (glycocalyx) dysfunction

that is associated with both functional and structural changes in the micro-circulation

and is predictive of subsequent morbid events.[37] These changes can be distinguished from large artery (Macro-circulation) stiffness and obstruction by the use of

pulse volume recording (PVR)

.

Endothelium

The

endothelium

is a thin layer of squamous endothelial cells that line the inner surface of blood and lymphatic vessels, forming an interface between circulating blood or lymph fluid in the lumen and the vessel wall. Endothelial cells in direct contact with blood are called vascular endothelial cells, whereas those in direct contact with lymph fluid are known as lymphatic endothelial cells.

Endothelium is

mesodermal in embryonic origin.

Vascular endothelial cells line the entire circulatory system, from the heart (“endocardium”) to the smallest capillaries. These cells have unique functions in vascular biology. Both blood and lymphatic capillaries are composed of a single layer of cells called a monolayer. All endothelial cells are coated with glycocalyx bio-polymers. Endothelial dysfunction is a hallmark for vascular disease, and is often regarded as a key early event in the development of cardio-vascular disease. Impaired endothelial function has been related to hypertension and vascular thrombosis and is seen in patients with coronary artery disease, diabetes mellitus and hypercholesterolemia. Endothelial dysfunction is a systemic pathological state of the inner lining of blood vessels and can be broadly defined as an imbalance between vaso-dilating and vaso-constricting forces acting on endothelial cells. Endothelial dysfunction has been shown to be of prognostic significance in independently predicting vascular events including stroke and myocardial infarction. Endothelial dysfunction can result from and contribute to several disease processes (hypertension, diabetes) and can also result from environmental factors such as smoking and exposure to air pollution. Thus, endothelial dysfunction is a major pathophysiological mechanism of vascular disease. Endothelial dysfunction is synonymous with glycocalyx dysfunction.

Macro- vs. Microcirculation

There are actually two “functionally interrelated” blood circulatory or vascular systems found in the human body: the

Macro-circulation

and the

Micro-circulation

. The

Macro-circulation

consists of the larger “conduit” arteries that conduct blood to the major organs. Included among these arteries are the aorta (chest and abdomen), carotid (neck), femoral (legs), coronary (heart) arteries and others. These are the blood vessels commonly treated with surgery and angioplasty (balloon therapy/stenting). The

treatment of these large conduit “macro” vessels is commonly the focus of cardiologists, vascular surgeons, the news media, internet web sites and television shows. These treatments are routinely used and “sold” by scientific (more properly called statistical) “evidenced-based” medical practitioners. These

Macro-vessels

are the arteries said to be

chronically

“plugged up” (arterial plaque buildup) from the common “statistical” risk factors promoted by “evidence-based” scientific medicine: cholesterol, “bad” genes, high blood pressure, smoking, etc.

Please note that no one that speaks from scientific authority has

ever said that cholesterol or smoking actually “cause

s”

plaque

. No, that’s not what has been said, but commonly that is what is

. What is being “said” is

these factors are statistically

associated with plaque

,

but science still does NOT know what actually causes arterial plaque

to form.

Arterial plaque occurs in localized, “specific” sites within

Macro–vessels

, but, oddly enough, the statistical risk factors, which occur throughout the entire vascular system, theoretically should affect

all Macro-arteries in the same way

. Despite this, one commonly sees plaque blocking 90% of one coronary heart artery and no evidence of any blockage in the heart artery right next to the blocked one in the same patient. Isn’t just as much cholesterol passing through each artery? Why the difference in presence and/or size of plaque? No one, and certainly no one in “evidence-based” scientific medicine, knows. They simply “know”

statistical risk factors that are associated (statistically) with the presence of plaque

. Scientific “evidence-based” statistical treatment and/or prevention consists of advising life style changes (weight reduction, exercise, stress control, etc.), and/or prescribing pharmaceutical drugs (statin drugs, ACE inhibitors, ARB blockers, beta-blockers, aspirin, Plavix^TM, etc.), angioplasty and/or surgery. The typical advice in mild to moderate plaque buildup is to reduce or lower weight, lower cholesterol, lower blood pressure, reduce inflammation, and increase blood thinning… all things that have been “statistically” (“evidence-based”) demonstrated to reduce the risk and severity of

Macro–vascular

disease. Interestingly, these statistically based approaches are

effective in all patients, simply a “statistically significant” number of patients. Therefore, many patients following the correct “evidence-based” scientific diet and life style and using appropriate “evidence-based” medications or surgery will continue to demonstrate advancing plaque buildup over time. Advanced or high grade plaque buildup (80-90-100%) is mechanically (surgery, angioplasty) repaired as if it is simply defective plumbing, but this mechanical therapy does

correct the actual

That’s about it, “scientifically speaking,” for Macro-Circulation treatment from a scientific, “evidence-based” prospective.

Micro-circulation

is turning out to be radically “different.”

Micro–circulation

is also referred to in scientific medical literature as the “

capillary circulation

,” “

terminal circulation

” or “

end-circulation.

” These are the tiny blood vessels (capillaries and capillary networks) that actually supply oxygen and nutrients and remove carbon dioxide and other metabolic waste from the vital organs (i.e. heart, brain, kidney, liver, etc.). Incredibly, it now appears from a scientific perspective that

Micro-circulatory disease is primarily related to the biological toxicity of Sugar,

not fat as in Macro-circulatory theory.[38-48 ] The “joke” of Mother Nature on modern medical science is that substances that are absolutely “essential” to life (oxygen, sugar) also turn out to be extremely toxic to life. Nature has placed a hidden “tax” on aerobic-based (Oxygen-Carbohydrate-Sugar) metabolic energy efficiency. Thus, metabolically utilizing (“burning”) oxygen and sugar for efficient production of energy comes at a potentially high metabolic price… free radical toxicity and protein glycation or glucotoxicity. By way of analogy, oxygen toxicity can be thought of in simple terms as being similar to “

rusting

” of molecules in the tissue or organ that these molecules make up (Free-Radical pathology). Sugar Toxicity is being discovered to act by causing “

glycation

,” or “

caramelization

” of essential structural and functional proteins, including the glycocalyx or endothelium. This process can be thought of in simple terms as causing protein “

wrinklin

g.” Another simple analogy would be that of melting caramel over an apple and the caramel-sugar “coating” then hardens or stiffens, thus slowly, but progressively “caramelizing” the Micro-circulatory endoskeleton of the affected vital organ (i.e. heart, brain, kidney, etc.). When this process involves living tissue it occurs with subtle, but devastating physiological consequences over time. The “non-enzymatic” (meaning in the absence of the enzyme Insulin) attaching of a sugar to a protein is currently thought to destroy (glycate or caramelize) proteins.

Protein Glycation is currently generally assumed to be non-reversible

. This assumption is actually no longer scientifically correct.[48-57]

The most widely scientifically

recognized

clinical condition involving abnormal tissue glycation leading to clinical Micro-circulatory disease is diabetes. This is the biochemical, structural and regulatory basis of the commonly encountered condition of diabetic gangrene. Once a “black toe or foot” develops in diabetes there is no bypass vascular operation, angioplasty or drug that will help. There is only amputation of the dead tissue and usually problems with wound healing due to the subclinical Micro-vascular disease in the remaining “viable” tissue.

Diabetes is a condition that exists in the annals of “evidence-based” scientific medicine by definition, and is, “by definition,” irreversible.

Diabetes is defined as a blood sugar that goes “too high…” that exceeds the statistically derived “normal” height or peak of blood sugar seen in an “average” population. The definition includes establishing the “normal” and “abnormal” blood sugar levels during fasting, after eating and/or during a laboratory glucose tolerance test. This definition of diabetes is focused on how

high

the blood sugar goes. It turns out that glycation from gluco-toxicity also occurs from glucose (Sugar) being in

prolonged

contact with tissue. Thus, the newly described “

metabolic syndrome” (also called dys-metabolic syndrome, syndrome X or insulin resistance

), which also exists

by definition (and is “by definition” reversible

), involves the inability of potentially toxic sugar to exit or, in more technically correct scientific terminology, be “disposed of” from the blood into the cellular metabolism as quickly as possible. Thus, Diabetes,

by definition

, is about

how high

blood sugar goes and Metabolic Syndrome,

by definition

, is also about

how long sugar

remains in the blood (impaired glucose disposal).[58-64]

The pathological effect of Micro-Circulatory protein glycation is a stiffening of the capillaries throughout the affected organ… actually a

caramelization

of the Micro-vascular skeleton within the organ involved. This process involves both abnormal biochemistry (protein glycation) and structural circulatory regulation changes (increased Micro-vascular resistance). The gradual glycation of protein molecules (“endothelium”) lining the small capillary Micro-circulation stiffens those Micro vessels so they cannot pulsate with the heartbeat. In addition, glycation of the proteins on the red blood cell stiffens their external membranes making it more difficult for the stiffened red cells to pass through the caramelized capillary beds one at a time. The resultant structural problem is the inability of the Micro-circulation to pulsate open with the kinetic (pumping) force of the heartbeat, coupled with the red blood cells’ inability to bend, twist and deform to slip through these stiffened capillaries one at a time. A capillary that is pulsed open during cardiac systole is 10 microns in diameter. During diastole the capillary reduces to 5 microns in diameter. A red blood cell is 8 microns in diameter. Thus, the caramelized capillary cannot dilate effectively and the older caramelized red cell has reduced flexibility. This situation results in small capillary “infarcts or strokes” in the affected Micro-circulatory vessel directly involving the affected organ or tissue (i.e. brain, heart, kidney, etc.).

Over time (years to decades) the collective effects of this process appears clinically. Interestingly, the clinical syndrome that appears depends on which organ(s) is (are) affected. Micro-circulatory disease somewhat mimics

Macro-circulatory

disease in that it may “skip” around, affecting different organs or areas of the body differently. Thus, if

Micro-circulatory

glycation occurs in the heart there will be a development

of a major clinical “heart attack” (myocardial infarction), but small areas of tissue damage (i.e. slight elevation of enzymes without ECG changes) or, more importantly, the gradual development of

Diastolic Heart Failure

. [65-82] This process does

involve the active process of the heart contracting, but its inability to

effectively (diastole) after contraction due to

Micro-vascular

stiffening of capillaries within the involved heart muscle. Thus, the heart fails to fill effectively and clinical congestive heart failure or CHF (fluid back up into the lungs, legs, etc.) develops. CHF is the now the most common and least curable form or heart disease affecting the American population, with a large proportion being diastolic heart failure. Similarly, if capillary glycation involves primarily the kidney high blood pressure will develop. Interestingly, diastolic dysfunction, diastolic heart failure high blood pressure and sugar toxicity (“metabolic syndrome”) are now “epidemic” among Americans, old and young.[83,84] If capillary glycation occurs mainly in the brain, a condition called

Leukoaraiosis

or coalescing tiny (lacunar) strokes leading to scaring of the gray matter in the brain occurs, and memory loss/cognitive dysfunction and/or small strokes (lacunar infarcts) will develop.[79-80]

Leukoaraiosis

is still being taught in scientific medical schools as “a result of aging” and is of “no medical consequence.” This outdated thinking has been clearly and scientifically dis-proven. The presence of leukoaraiosis on an MRI or CT brain scan should be taken as direct clinical evidence of abnormal Micro-vascular glycation (endothelial dysfunction).[85-128] The connection between heart disease, hypertension and Alzheimer’s syndrome, suggesting a common underlying mechanism (Micro-vascular disease) is now being formally recognized.[129-134]

Figure 1 [86] depicts a diagrammatic representation of this gradual process of capillary cross sectional attrition over time from normal capillary flow through a tissue or organ in the upper diagram to an intermediate reduction in the middle and then finally a significant loss of the illustrated Micro-vascular capillary bed on the bottom. The organ or tissue most affected is where the clinical “syndrome picture” will manifest (heart, kidney, brain, etc.) Figure 2[86] is a photomicrograph of a section of brain clearly demonstrating the loss of the Micro-circulatory capillary bed in a histologic section of brain from a patient with dementia.

Interestingly, in addition to the toxic

Micro-circulatory

effects of glucose and subsequent endothelial glycation now being described in

Alzheimer’s like senile dementia

, scientific evidence also shows that the accumulation of abnormal proteins (Beta or β-amyloid and Tau protein) in Alzheimer’s disease also causes reduced Micro-circulation (vaso-constriction) in the brain. Beta (β)-amyloid protein also reduces endothelium-dependent brain vaso-dilation. As if to add insult to injury, any temporary lack of oxygen in the brain can also lead to increased production of β-amyloid protein. Thus, it is apparent that

Micro–circulatory

compromise plays a very large role in the development of memory loss, cognitive dysfunction and dementia syndromes

, regardless of the actual “official name” of the clinical syndrome. In addition to and as further proof of this situation, the microscopic changes in brain tissue that are thought to be “specific” for Alzheimer’s disease (β-amyloid, Tau protein, neurofibrillary tangles) have also been described in patients with heart vascular disease and no evidence of dementia

.

The increase in body fat that is part of “metabolic syndrome” also contributes to the “bad” situation. Centralized body fat is actually a functioning endocrine organ. Body fat secretes certain pro-inflammatory cytokine hormones (Tumor Necrosis Factor alpha [TNF-α] and Inter-Leukin-6 [IL-6], etc.). Thus, increased body fat leads to increased inflammation (a statistical risk factor for Macro-circulation disease). Inflammation can be measured using the blood test

C-reactive protein or CRP

. Thus, many previously recognized “independent risk factors” can now be connected through the understanding of the biologically toxic properties of sugar related to malfunction of cellular insulin receptors.

Insulin Resistance/Metabolic Syndrome

The underlying metabolic basis of gluco-toxicity is the inability of the enzyme Insulin to activate

Insulin receptors

on cell surfaces (“membranes”) that allow the sugar to move quickly from the blood into the cellular metabolism where it can be used for energy production (and the production of Free Radicals!). Thus insulin acts as a “key” that must fit into an

insulin receptor

or “lock” and open that lock so that potentially toxic sugar can be transported (“disposed of”) quickly and efficiently from the blood into the cellular metabolism. When sugar is not disposed of quickly several “bad” things begin to happen: 1) glycated Micro-vessels and cellular red corpuscles “stiffen” and lose their ability to pulsate with the heart; 2) the un-disposed of sugar is immediately shunted into centralized body fat production. One of the clinical markers used to

define metabolic syndrome

is centralized body fat (a large waist line); 3) additional pathological events related to poor glucose disposal include excess sorbitol production leading to nerve damage (diabetic neuropathy) and cataracts. The “

defining components

” of metabolic syndrome that have been “suggested” or adopted by various scientific groups and societies are high blood pressure, high cholesterol, high triglycerides, high fasting Insulin levels and/or high fasting blood sugar. Interestingly, all the different criteria put forth by various scientific medical groups (The WHO, American College of Cardiology, American Association of Clinical Endocrinology, etc.)

do not

include any evidence of direct tissue sugar-protein glycation as criteria for diagnosis. Usually, the presence of three or more of these statistical risk factors “qualifies” as a diagnosis of “metabolic syndrome.” In reality, by the time any individual actually “qualifies” for the formal diagnosis of metabolic syndrome they are already manifesting significant and late stage clinical evidence of severe Micro-vascular glycation (i.e. high blood pressure, obesity, heart disease, dementia, etc.).

The main

biochemistry involved in the pathology of gluco-toxicity

is known as the

Maillard reaction

. This common chemical reaction has been known for over 100 years. The main scientific focus of this reaction usually involves food spoilage and industrial applications. Other than in diabetes mellitus (“sugar diabetes”), there was really little medical scientific interest in the Maillard reaction in medical science or practice.[135] However, with the recent and gradually increasing scientific realization that the cholesterol (“fat” toxicity) theory of cardio-vascular disease is, at best, incomplete, or more likely simply wrong, more scientific interest and resources have been re-evaluating the patho-physiological effects of the Maillard (sugar toxicity) reaction.[136-141] There is also overwhelming scientific evidence rapidly accumulating that in vivo pathological Maillard reactions accumulate both from internal dys-metabolism of sugar and

ingesting Advanced Glycosylation

End-products (AGE) created by excessive heating of food that are toxic in living tissue

[142] In addition to the Maillard reaction, the

Amadori rearrangement and Schiff base reactions

are also part of the complex biochemistry of sugar toxicity.[135]

One major problem faced by clinicians interested in prevention and early intervention of the manifestations of abnormal tissue glycation is that there is no single test in “evidenced-based” medicine that can “diagnose” metabolic syndrome. Abnormal glycation diseases can be diagnosed using several clinical and laboratory findings, but

NOT

by a single laboratory test. A simple blood test called the

Hemoglobin A1C or Glyco-hemoglobin (Hbg

A1C)

test easily and cheaply provides critical clinical information about the ongoing degree of glycation in the body due to inadequate glucose disposal from blood.[143-146] The “trick” in using this scientific (evidence-based) test as a “new and emerging risk factor for clinical vascular disease” (as it is now being discovered and described in scientific medical journals) is to understand that the laboratory statistical “norms” are not related to individual optimal values. A value for

Hbg A1C above 4.6 should be considered “abnormal”

(meaning evidence of accelerated cellular membrane glycation). In most commercial laboratories Diabetes is said to be present,

by definition

, if the value is 6.4 or higher. This is why most diabetics demonstrate severe vascular disease before scientific medicine diagnoses it. Membrane receptor resistance to the hormone Insulin is not acknowledged until late in the process (advanced tissue glycation) or a “high” Hbg A1C. Objectively testing using

PORH

for disturbed Micro-circulatory function and /or

Pulse Volume Recordings or PVR

(Micro-vascular disease of the vasa vasorum in Macro-vessels) can also demonstrate the effects of abnormal vascular glycation (loss of Micro-vascular compliance.

As an aside regarding laboratory measurement of Insulin or any other “hormone level,” the clinical reality is that no hormone actually works in the blood (or urine, or saliva)… hormones do their metabolic work by activating a hormone receptor (i.e. the “key in lock” analogy) located on a specific cell or nuclear membrane. The hormone receptor is usually located on the cell membrane (i.e. insulin receptor) or the nuclear membrane (i.e. thyroid receptor). Thus, in many individuals (“

NOT

statistical”) cases the “blood level” (and urine or saliva, for that matter) of a given hormone (i.e. thyroid, insulin, vitamin D, etc.) may be “statistically” normal or even “optimal” and yet the clinical symptoms of the particular hormone “deficiency” may clearly be present. This is a very common clinical phenomenon seen with insulin resistance syndrome. Blood simply acts as a transport medium to get the hormone from where it was made to where it will have its metabolic effect. As stated earlier, the insulin receptor is located on the cell membrane… and some cells have many more insulin receptors than others. This is the functional basis of IPT (Insulin Potentiation Therapy) cancer chemotherapy… to use insulin to activate the insulin receptors on cancer cells. Cancer cells revert to a more primitive cellular metabolism referred to as

anaerobic or “without Oxygen” glycolysis

(fermentation). Thus, cancer cells have significantly more insulin receptors on their cell surface than non-cancer cells. Giving Insulin to cause a drop in blood sugar, and at the low point of the blood sugar very small (15 to 20% of standard, recommended) doses of chemotherapy drugs to allow the cancer cell to preferentially take in the drugs as they are in their insulin activated sugar “feeding frenzy,” creates a physiologic “Trojan Horse” approach that significantly minimizes side-effects and yet maximizes therapeutic benefit of chemotherapy to actually target the problem cancer cells, thus sparing drug toxicity to normal cells and tissue. The clinical results in cancer can be quite amazing when appropriately employing IPT therapy.

Returning to the discussion of

Micro-vascular

glycation related stiffening or lack of pulsatile ability of vascular tissue, pulsation of the Micro-circulation turns out to be critical for all major organ health. This is the simple reason that scientific medicine has not yet developed an effective implantable artificial heart.

Pulsatile flow

is something that is required in normal physiology. Any experimental animal that is put on a heart bypass pump that uses

non-pulsatile or laminar

flow dies within days of progressive, multiple organ (kidney, heart, brain) failure due to progressive Micro-vascular dysfunction… called scientifically

increased peripheral vascular resistance

.[147] Our best technological engineers can make pumps smaller than a dime that can operate in climates as alien as the Martian surface, but they have not yet mastered the essential, life-sustaining properties of biologically imperative pulsatile flow. The main physiologic cause of pathological Micro-vascular stiffness is gluco-toxicity.[139] Clinical counterparts of this “laboratory” phenomenon of increased organ

Micro–circulatory

stiffness are commonly encountered, but just as commonly, the causal underlying mechanism (

Micro-vascular

stiffening due to glycocalyx/endothelial caramelization) is usually

NOT

clinically recognized and thus crude, non-curative symptomatic drug or surgical therapy follows. One commonly missed clinical example of this phenomenon may be

heart and peripheral arterial vascular stunning and hibernation

.[148-149] Integrative Medicine employing

Chelation Therapy

has demonstrated clinical effectiveness in reversing stunning and hibernation, in both entire organs (heart

Micro–circulation

) and extremities (leg

Macro

–

circulation/Vasa Vasorum

).[148-149] The actual cause of the phenomenon of stunning and hibernation is “unknown” in evidence-based medicine, but gluco-toxicity of the

Micro–circulation

in the corresponding capillary bed of the heart muscle or the Vasa Vasorum (or

Micro

–

circulatio

n) of the

Macro

-Vessel arterial wall may be involved.

Another clinical “symptom pattern” manifestation of insulin resistance is

polycystic ovary syndrome (PCOS

). The currently accepted treatment for PCOS is either using synthetic hormone birth control pharmaceuticals (BCP) or the off-label use of the anti-diabetic drug

Metformin

.[150-151] Interestingly, birth control helps PCOS symptomatically, although it is known to cause weight gain, high blood sugar and, more importantly, increase vascular resistance.[152] It appears that while improving the clinical picture BCP’s seem to be making the manifestations of endothelial dysfunction worse. The clinical and laboratory effects of Metformin in PCOS were found to be clinically superior to BCP’s.[153] It is also possible that other chronic degenerative diseases may be related to underlying Micro-vascular pathology. For example, osteoarthr

itis

, which is really osteoarthr

osis,

since no true inflammation (“

itis

”) is involved, may be related to reduced Micro-circulation to the associated joint and cartilage tissue. This could explain why the simple clinical methods of heat, massage and/or injecting

Ozone (prolozone therapy

) into the affected joint and/or peri-articular tissue results in reduction and elimination of pain by increasing Micro-circulation.

Chronic unexplained pelvic pain

in both sexes may be related to regional Micro-vascular disease. Localized “

trigger points

” in muscles may also be due to localized Micro-circulatory disturbance. Much like the phenomenon of localized compromise of Micro-circulation in the brain (dementia), heart (diastolic heart failure) and/or kidney (hypertension) lead to different clinical patterns resulting from the same underlying pathology, perhaps other degenerative conditions will be found to be related to reduced Micro-circulation to an affected organ or anatomic/physiologic area.

in dealing with sugar toxicity.

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The entire text and notes of “Sugar Toxicity: A Silent Epidemic” are available on TownsendLetter.com.

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