The Real Poisoning of America – Glycation
Of the causes of death below from Wikipedia, Ischaemic heart disease @ 7.4 million ranks right at the top. This is the result of glycation, 5 of the following 8 are also caused by non-enzymatic glycation. Hence my proposal, control the glycation and you control all modern diseases.
According to Wikipedia;
It is estimated that of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes because they have aged prematurely. Glycation is responsible for aging and the more of that, that you allow to happen in your body, the quicker your age. That is why keeping glycation to a minimum is what’s going to help you live longer and healthier. Even though aging may not be able to be reversed completely, it can be slowed dramatically by eating the right diet. (Deep down you know that to be true. It’s just so hard to stick to when you have to.)
Leading causes of preventable death worldwide as of the year 2001, according to researchers working with the Disease Control Priorities Network (DCPN) and the World Health Organization (WHO). (The WHO’s 2008 statistics show very similar trends.) Imagine what they are right now, 8 years later and what they will be eight years from now if nothing is done about it. Think it might be time for a cure?
The top 10 causes of preventable death, ones influenced by glycation are in red. Although it may be difficult to stop all glycation in the body, due to its commonality, you can control a major portion of it. Excessive Carbohydrate Consumption, the primary cause of glycation is controllable. Failure to control your consumption leads directly to any of the following disorders in red ;
- Ischaemic heart disease @ 7.4 mil
- Stroke@ 6.7 mil
- COPD @ 3.1 mil
- Lower Respiratory infection @ 3.1mil
- Trachea bronchus, lung email@example.com mil
- HIV/AIDS@1.5 mil
- Diarrheal firstname.lastname@example.org mil
- Diabetes email@example.com mil
- Road firstname.lastname@example.org mil
- Hypertension@1.1 mil
40% of these deaths or 16.7 million are directly linked to ECC, Excessive Carbohydrate Consumption, making them the most preventable causes of death. 16.7 million deaths each and every year amounts to over 45,750 people each and every day. That includes approximately 1830 Americans each and every day. We have full control of this. All it would take is to say no to the sugar and grain industries. This one response would allow over 1830 more Americans to stay alive, every day. The cessation of carb consumption could add an additional 10-20 years to their lives, simply by eliminating the primary cause of inflammation, glucose. The continuation of carb consumption will, by contrast, prove the destructive power of sugar, by eventually killing its hosts.
Glycation is a common everyday experience that you accelerate with a carbohydrate diet. The more carbs you eat, the more glycation you’ll get to deal with. Glycation is controllable by controlling what you put in your mouth to eat. Although not totally responsible for some of these cancers, they would not exist if the glycation didn’t exist. This is the basis of my contention that if you eliminate the reason for the glycation, you eliminate the reason for inflammation, which in turn will eliminate the reason for these diseases, thereby eliminating the disease. It’s really not hard to see, once you take a good look at it; carb consumption is responsible for the inflammation that builds in the blood that is responsible for 90% of all modern diseases. Remove the inflammation by removing the sugar, which means removing the carbs. A simpler solution doesn’t exist and this cure can be yours.
These Are the Smoking Gun Articles Of
Evidence That The FDA Are Ignoring.
They’re Putting Your Health and Life at Risk.
48 of the 11667 studies done on glycation are below. These research studies were chosen from 231 studies that I examined for evidence of what glycation does to the body. By going through only 7% of these studies, I was able to find enough damning evidence to condemn this food 31 times over. By this ratio, I’ll end up finding at the least 850 more studies showing damage that glycation does.
I chose to search glycation because I know that it’s at the root of all modern diseases from cancer to CVDs to arthritis to dementia including Alzheimer disease. The following studies are the proof of what glycation does, and with sugar being the primary instigator of glycation, removal of sugar from the diet will eliminate everything it’s responsible for. These AGEs are responsible for all modern diseases and thus, are the reason for this book. When you eat carbs, you need to know what those carbs do to your body.
Foundation of Glycation
The study that piqued my interest initially was the report on RAGEs,
This report can be found on PubMed at Receptor for advanced glycation end‐products‐mediated inflammation and diabetic vascular complications. It explains how glycation turns your body’s fuel (cholesterol) and proteins (hemoglobin) into AGEs before they can be used for fuel and body repair.
“Exposure of amino residue of proteins to reducing sugars, such as glucose, glucose 6‐phosphate, fructose, ribose and intermediate aldehydes, results in non‐enzymatic glycation, which forms reversible Schiff bases and Amadori compounds. A series of further complex molecular rearrangements then yield irreversible advanced glycation end‐products (AGE). The aldehydes, highly reactive AGE precursors, are produced by both enzymatic and non‐enzymatic pathways. The enzymatic pathways include a route of myeloperoxidase in inflammatory cells, such as activated macrophages, which produces hypochlorite, then reacting with serine to generate glycolaldehyde.” Study Link
I’d be willing to bet that you had no idea that carb consumption is behind Amyotrophic Lateral Sclerosis (ALS). Guess what? it is. Here is your proof that MCT fats are beneficial in combating ALS;
- Metabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model
also known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study, we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for a neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.
What does that say about what the grain industry has told you about milk fat? They’ve condemned milk fats when they’re the healthiest fats you can eat. What the industry doesn’t like is that milk fats keep you from needing drugs, something the industry doesn’t want you to know.
Arthritis is a Result of Glycation From Inflammation
The following report is the evidence of glucose’s involvement in arthritis. By being responsible for glycation, the glucose from broken carbs, again, is directly responsible for arthritis, just like it was in the 4,000 yr old ice mummy recovered from a receding glacier.
“Glycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. “ Study Link
Alzheimer’s and Parkinson’s – a Result of Glycation
The following report shows the effects that AGEs have on the body in the diseases it promotes.
“Vast evidence supports the view that glycation of proteins is one of the main factors contributing to aging and is an important element of etiopathology of age-related diseases, especially type 2 diabetes mellitus, cataract and neurodegenerative diseases. Counteracting glycation can therefore be a means of increasing both the lifespan and health span. In this review, accumulation of glycation products during aging is presented, pathophysiological effects of glycation are discussed and ways of attenuation of the effects of glycation are described, concentrating on prevention of glycation. The effects of glycation and glycation inhibitors on the course of selected age-related diseases, such as Alzheimer’s disease, Parkinson’s disease and cataract are also reviewed.” Study Link
This study looks at the damaging effects of glycation along with the protective effects of certain phytochemicals (anti-oxidant producing agents).
“Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. So the AGE-RAGE axis is a novel therapeutic target for numerous devastating disorders. Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGE-RAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart.”
Glycation, Amyloid Plaque and Neurodegenerative Disorders
This report examines the nature of amyloid plaque and glyoxal (Glyoxal is an inflammatory compound formed when cooking oils and fats are heated to high temperatures). It’s also made in your body when your body breaks down glucose.
“Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant.
In view of its inflammatory function in innate immunity and its ability to detect a class of ligands through a common structural motif, rage is often referred to as a pattern recognition receptor.” Study link
This report examines the relationship of high mobility group box 1 (HMGB1) and the effects it has on the body. HMGB1 is one of the most prevalent RAGE’s, as near as I can tell. It comes up in more studies…
RAGE and Inflammation
“Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation end products) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-κB signaling pathway in a MyD88-dependent manner, resulting in pro-inflammatory cytokine production and pain enhancement in vivo. Biophysical and in vitro results highlight an essential role for the C-terminal tail region of HMGB1 in facilitating interactions with TLR5. These results suggest that HMGB1-modulated TLR5 signaling is responsible for pain hypersensitivity.” Study Link
I see HMGB1 come up in almost all modern diseases. This must be the most popular RAGEs.
COPD, Lung Cancer and RAGE
The proof that carb consumption also contributes to lung cancer is in the following report. The underlying cause is inflammation.
Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterize RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model.
Immunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells. Gene expression array data was used to identify AGER expression during lung development in 38 fetal lung samples. RNA-Seq was used to identify AGER transcripts in lung cells. sRAGE levels were assessed in cells and patient serum by ELISA. BEAS2B-R1 cells were transfected to overexpress RAGE protein with either the Gly82 or Ser82 variant and sRAGE levels identified.
Immunohistochemical assessment of 6 adult lung samples identified high RAGE expression in the alveoli of healthy adults and individuals with COPD. AGER/RAGE expression increased across developmental stages in human fetal lung at both the mRNA (38 samples) and protein levels (20 samples). Extensive AGER splicing was identified. The rs2070600T (Ser82) allele is associated with higher FEV1, FEV1/FVC and lower serum sRAGE levels in UK smokers. Using an airway epithelium model overexpressing the Gly82 or Ser82 variants we found that HMGB1 activation of the RAGE-Ser82 receptor results in lower sRAGE production.
This study provides new information regarding the expression profile and potential role of RAGE in the human lung and shows a functional role of the Gly82Ser variant. These findings advance our understanding of the potential mechanisms underlying COPD particularly for carriers of this AGER polymorphism.” Study Link
I wonder if the ACS, American Cancer Society will take this information and realize what foods are responsible for this report showing how RAGEs have a role in COPD and ultimately lung cancer? Will it provoke a response from the ACS on the consumption of the foods responsible for this RAGE? Will they issue a warning or are they more concerned with an industry that depends on this disorder, the pharmaceutical industry, or maybe an industry that provokes this disorder, the grain industry?
You may ask though, shouldn’t smoking play a larger role in this equation? I submit that if the glycation never existed in the first place, the smoking wouldn’t play as large of a role as it does with the inflammation in the body. It takes the glycation to create the RAGE responsible for lung cancer, yet no one knows of glycation or its effects from the FDA, the USDA or the CDC. Who are they trying to protect? Why isn’t glycation considered a disease?
Skin Cancer and Glycation
In the following study the emergence of the HMGB1 RAGE in head and the skin cancer, neck squamous cell carcinoma;
“Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers.
Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas.
Data Synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity.
Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.” Study Link
Cataracts and Glycation
Although the study above was published in Oct 2016, this kind of evidence has been around for over 20 years. These reports started showing up in 1984;
We have examined the nonenzymatic glycation of human lens crystallin, an extremely long-lived protein, from 16 normal human ocular lenses 0.2-99 yr of age, and from 11 diabetic lenses 52-82-yr-old…the nonenzymatic glycation of nondiabetic lens crystallin may be regarded as a biological clock…The glucitol-lysine (Glc-Lys) content of soluble and insoluble crystallin was determined after reduction with H-borohydride followed by acid hydrolysis, boronic acid affinity chromatography, and high-pressure cation exchange chromatography…Over an age range comparable to that of the control samples, the diabetic crystallin samples contained about twice as much Glc-Lys.
Cardiovascular Disease and RAGE
This study shows glycations implication in cardiovascular disease;
“Advanced glycation end products (AGEs) are heterogeneous group of molecules formed from non-enzymatic reaction of reducing sugars with amino group of proteins, lipids, and nucleic acid. Interaction of AGEs with its cell-bound receptor (RAGE) results in generation of oxygen radicals, nuclear factor kappa-β, pro-inflammatory cytokines and cell adhesion molecules, and is involved in the pathophysiology of cardiovascular diseases (CVD). Circulating soluble forms of RAGE (sRAGE) and endo-secretory RAGE (esRAGE) compete with RAGE for ligand binding and function as a decoy. This paper describes the endogenous and exogenous (high dietary AGEs, cooking food under high dry heat, elevated pH, and long period) sources of AGEs. AGE-RAGE-mediated CVD includes atherosclerosis, coronary artery disease, carotid artery disease, hypertension, peripheral vascular diseases, heart failure, cardiomyopathy, and microangiopathy. The therapeutic intervention with reduction in AGEs and RAGE, and elevation in sRAGE has been reported for the treatment of AGE-RAGE-mediated CVD. Reduction in levels of AGEs can be achieved by reduction in consumption of food containing or creating low amount of AGEs, cooking food at low temperature, moist heat, and shorter duration. AGE formation can be reduced with drugs, vitamins and stoppage of cigarette smoking. Statins, telmisartan, and curcumin have been used for suppression of RAGE. Statins, ACE-inhibitors, Rosiglitazone and vitamin D have been used to increase levels of sRAGE. Finally exogenous administration of sRAGE can be helpful in amelioration of CVD. In conclusion, AGE-RAGE-mediated CVD could be attenuated with reduction in consumption of AGEs, suppression of RAGE and elevation of sRAGE.”
Dangers of Statins
Statins are the most dangerous in the above equation as they unbalance your cholesterol which puts everything in your body out of balance. It’s your cholesterol that regulates a good portion of your hormones. You should already know how much your hormones affect your emotions, energy, intelligence, aging, and basic proper functioning of your body, right down to digesting carbs (insulin). Granted insulin is made in the pancreas, although other more influential hormones are made in your fat which is what statins reduce. Side effects of statins include; Common statin-related side effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins. Side effects of statins include muscle pain, increased risk of diabetes mellitus, and abnormalities in liver enzyme tests. Additionally, they have rare but severe adverse effects, particularly muscle damage. As of 2010, a number of statins are on the market: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Several combination preparations of a statin and another agent, such as ezetimibe/simvastatin, are also available. In 2005 sales were estimated at $18.7 billion in the United States.
Side effects ultimately lead to other drugs down the road. It’s inevitable. This is how the pharmaceutical corporations make as much money as they do. And you gladly give it to them, simply to keep up your addiction and later to fight your CVD or cancer. How much sense this makes to you?
What concerns me more than anything else is the fact the atorvastatin in the best selling pharmaceutical in history, with sales of $12.4 billion in 2008. With all of the side effects listed above, how many patients taking these drugs will not ever have to use any more pharmaceuticals. This is the way they guarantee a return consumer. I know. (I was one of them. I won’t be anymore due to my keto diet.)
The best-selling statin is atorvastatin, which in 2003 became the best-selling pharmaceutical in history. The manufacturer Pfizer reported sales of US$12.4 billion in 2008. Pfizer and Monsanto were under one roof at in 2003. That was the year Pfizer started their divestiture of Monsanto. (Maybe it was the lawsuits that were starting to pile up, that they didn’t appreciate.) I wonder how many lawsuits Pfizer has against itself for its pharmaceutical statins. Below are the contraindications for atorvastatin (Lipitor);
Active liver disease: cholestasis, hepatic encephalopathy, hepatitis, and jaundice
Unexplained elevations in AST or ALT levels
Pregnancy: Atorvastatin may cause fetal harm by affecting serum cholesterol and triglyceride levels, which are essential for fetal development.
Breastfeeding: Small amounts of other statin drugs have been found to pass into breast milk, although atorvastatin has not been studied, specifically.
Markedly elevated CPK levels or if a myopathy is suspected or diagnosed after dosing of atorvastatin has begun. Very rarely, atorvastatin may cause rhabdomyolysis, and it may be very serious leading to acute renal failure due to myoglobinuria. If rhabdomyolysis is suspected or diagnosed, atorvastatin therapy should be discontinued immediately. The likelihood of developing a myopathy is increased by the co-administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, and azole antifungals.
The side effects of Lipitor are even longer and include diarrhea, dyspepsia, myalgia and nausea. Are you on statins? Did you read over your drug disclosure? Were you told that you could cure this without drugs? Were you ever told that this disorder started in your diet of carbs? The earliest report in the PMC I found was dated Jan 1974 and simply stated that weight reduction was important to controlling hyperlipoproteinemia, a fancy word for high amounts of apolipoproteins in the body which indicate levels of cholesterol.
According to a study completed in 1995;
Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.
Another study from 1994 showed the rethinking of the low-fat hi-carb diet that has been pushed for over 40 years (probably at the insistence of Monsanto). Since they owned GD Searle at the time it makes me wonder, was their intent to hook us on more drugs? Even as recent Dec 31, 2016, the dept of research at Kaiser Permanente Southern California, Pasadena came to the conclusion; Statin use rather than cholesterol level was associated with lower mortality risk in patients with pancreatic cancer. Statins appear to improve survival through a lipid-independent mechanism. Apparently, they’re rethinking their strategies. I have a strategy, don’t eat carbs. I go keto and let the fasting take care of the illnesses. If it can work for me it can work for you.
Our medical industry has had research for over 20 years on the benefits of cholesterol and the dangers of lowering it, yet because of our dependence on grains and sugar and Monsanto’s influence in the FDA and USDA, the recommendations from the USDA’s agency for food labeling to food safety to MyPlate, the CCNP and at least 3 other agencies in the USDA alone, the CDC, the ADA, the ACS still recommend that you keep whole grains in your diet, regardless of the studies completed that show their danger. Why? Monsanto is in the crop seed industry owning over 15 crop seed companies, all wanting to sell GMO seed ready to handle Roundup herbicide to farmers contracted by Monsanto waiting to plant their next crop. They’ll spray their crops according to their contract with Monsanto. It then goes on your table.
This article appeared 22 years ago in PubMed in Aug 1994. Even then low cholesterol was being questioned, yet in some corners, it’s still promoted today;
Although hypercholesterolemia is associated with increased liability to death from heart disease, it is as frequently associated with increased overall life expectancy as with decreased life expectancy. These findings are incompatible with labeling hypercholesterolemia an overall health hazard. Moreover, it is questionable if the cardiovascular liability associated with hypercholesterolemia is either causal or reversible. The complex relationships between diet, serum cholesterol, atherosclerosis, and mortality and their interactions with genetic and environmental factors suggest that the effects of simple dietary prescriptions are unlikely to be predictable, let alone beneficial. These cautions are borne out by numerous studies which have shown that multifactorial primary intervention to lower cholesterol levels is as likely to increase death from cardiovascular causes as to decrease it. Importantly, the only significant overall effect of cholesterol-lowering intervention that has ever been shown is increased mortality.
With Monsanto’s influence in the FDA, the USDA, the EPA and who knows what else, who’s to protect our food supply? You have to protect yourself. Monsanto has proven they can’t self-regulate their industry and keep us safe. The best way to start being safe is to not eat their food, which happens to include all grains. If you don’t buy them, that may send the message.
Direct Influence of Glycation in Cancer
More evidence of its influence in cancer is when this HMGB1 RAGE rears its ugly head again, influencing cancer;
“High Mobility Group Box 1 (HMGB1) is a member of the damage-associated molecular patterns (DAMPs), which cause inflammation and trigger innate immunity through Toll-like receptors (TLRs) 2/4 and the receptor for advanced glycation end products (RAGE). We examined the effect of glycyrrhizin, a selective inhibitor of HMGB1, on the induction of cytotoxic T-lymphocytes (CTLs) in mice. B6 mice, either OT-1 spleen cell-transferred or untransferred, were immunized with an s.c. injection of OVA257-264 peptide with topical imiquimod, and glycyrrhizin was mixed with the antigen peptide. Proliferation of OT-1 cells after immunization was enhanced by glycyrrhizin. The effect of glycyrrhizin was confirmed in other adjuvant systems, such as CpG oligonucleotide and monophosphoryl lipid A (MPL), but glycyrrhizin was not effective in Freund’s incomplete adjuvant system. The augmenting effects of glycyrrhizin were also observed in other synthetic HMGB1 inhibitors, i.e., gabexate mesilate, nafamostat, and sivelstat. Thus the effects are common to the HMGB1 inhibitors. Induction of CTLs detected by IFN-γ ELISPOT assay was similarly augmented by glycyrrhizin. In a therapeutic vaccine model, glycyrrhizin inhibited the growth of s.c. transplanted EG.7 tumors. Expression of inflammatory cytokines in the skin inoculation site was downregulated by glycyrrhizin. These results suggest that HMGB1 inhibitors might be useful as a co-adjuvant for peptide vaccination with an innate immunity receptor-related adjuvant. This article is protected by copyright. All rights reserved.” Study Link
Were you ever told that this could happen if you continued your diet of bread, corn, soy and other carbs? (Neither was I.)
This is evidence of glycation’s effect on the kidneys:
“Interaction of advanced glycation end products (AGEs) with its cell-bound receptor (RAGE) results in cell dysfunction through activation of nuclear factor kappa-B, increase in expression and release of inflammatory cytokines, and generation of oxygen radicals. Circulating soluble receptors, soluble receptor (sRAGE), endogenous secretory receptor (esRAGE) and cleaved receptor (cRGAE) act as decoy for RAGE ligands and thus have cytoprotective effects. Low levels of sRAGE and esRAGE have been proposed as biomarkers for many diseases. However sRAGE and esRAGE levels are elevated in diabetes and chronic renal diseases and still tissue injury occurs. It is possible that increases in levels of AGEs are greater than increases in the levels of soluble receptors in these two diseases. Some new parameters have to be used which could be an universal biomarkers for cell dysfunction. It is hypothesized that increases in serum levels of AGEs are greater than the increases in the soluble receptors, and that the levels of AGEs is correlated with soluble receptors and that the ratios of AGEs/sRAGE, AGEs/esRAGE and AGEs/cRAGE are elevated in patients with end-stage renal disease (ESRD) and would serve as an universal risk marker for ESRD. The study subject comprised of 88 patients with ESRD and 20 healthy controls. AGEs, sRAGE and esRAGE were measured using commercially available enzyme linked immune assay kits. cRAGE was calculated by subtracting esRAGE from sRAGE. The data show that the serum levels of AGEs, sRAGE, cRAGE are elevated and that the elevation of AGEs was greater than those of soluble receptors. The ratios of AGEs/sRAGE, AGEs/esRAGE and AGEs/cRAGE were elevated and the elevation was similar in AGEs/sRAGE and AGEs/cRAGE but greater than AGEs/esRAGE. The sensitivity, specificity, accuracy, and positive and negative predictive value of AGEs/sRAGE and AGEs/cRAGE were 86.36 and 84.88 %, 86.36 and 80.95 %, 0.98 and 0.905, 96.2 and 94.8 %, and 61.29 and 56.67 % respectively. There was a positive correlation of sRAGE with esRAGE and cRAGE, and AGEs with esRAGE; and negative correlation between sRAGE and AGEs/sRAGE, esRAGE and AGES/esRAGE, and cRAGE and AGES/cRAGE. In conclusion, AGEs/sRAGE, AGEs/cRAGE and AGEs/esRAGE may serve as universal risk biomarkers for ESRD and that AGEs/sRAGE and AGEs/cRAGE are better risk biomarkers than AGEs/esRAGE.” Study Link
Breast Cancer and RAGE
This is the evidence that breast cancer is influenced by glycation;
The receptor for advanced glycation end-products (RAGE) is a multiligand transmembrane receptor that is overexpressed in various pathological conditions including cancers. However, the expression pattern of RAGE in breast cancer tumors is still not completely clear.
In this study, we investigated the expression levels of RAGE in 25 fresh-frozen breast cancer samples and corresponding noncancerous tissue samples collected from breast cancer patients, by real-time polymerase chain reaction (PCR). Additionally, we performed immunohistochemistry on breast cancer specimens.
The results indicate a high expression of the RAGE-encoding gene in the cancerous tissues. RAGE expression at the mRNA and protein levels was statistically significantly up-regulated in advanced-stage and triple-negative breast tumors and node-positive tissues compared with other tissues (p < 0.001). A significant association between RAGE expression and tumor size was observed (p = 0.029).
Overexpression of RAGE in advanced-stage tumors may be a useful biomarker for diagnosis and the prediction of breast cancer progression.” Study Link
I’m only sorry that I could include studies and reports for all forms of cancer, but with they’re being so many of them, that’s a virtually impossible task.
Evidence of bone density decline from glycation;
“Diabetic patients have a higher fracture risk than expected by their bone mineral density (BMD). Poor bone quality is the most suitable and explainable cause for the elevated fracture risk in this population. Advanced glycation end products (AGEs), which are diverse compounds generated via a non-enzymatic reaction between reducing sugars and amine residues, physically affect the properties of the bone material, one of a component of bone quality, through their accumulation in the bone collagen fibers. On the other hand, these compounds biologically act as agonists for these receptors for AGEs (RAGE) and suppress bone metabolism. The concentrations of AGEs and endogenous secretory RAGE, which acts as a “decoy receptor” that inhibits the AGEs-RAGE signaling axis, are associated with fracture risk in a BMD-independent manner. AGEs are closely associated with the pathogenesis of this unique clinical manifestation through physical and biological mechanisms in patients with diabetes mellitus.” Study link
Evidence of Alzheimer’s disease from glycation;
“Genetic association between RAGE polymorphisms and Alzheimer’s disease and Lewy body dementias in a Japanese cohort: a case-control study.”
Interaction of receptor for advanced glycation end products (RAGE) with amyloid-β increases amplification of oxidative stress and plays pathological roles in Alzheimer’s disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs.
Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls.
Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population.
Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.” Study Link
With the above evidence showing its involvement in brain diseases, how does this information get hidden? Doesn’t anyone of authority examine these reports? More evidence below of cancer-causing agents from glycation leaving me to wonder; is anyone looking out for our benefit?
“Tumor-associated macrophages (TAMs) are key elements in orchestrating host responses inside tumor stroma. This population may undergo a polarized activation process, thus rendering a heterogeneous spectrum of phenotypes, where the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2) represent two extreme phenotypes. In this commentary, based on very recent research findings, we intend to highlight how complex could be the crosstalk among all components of tumor stroma, where the coexistence of non-natural partners may even skew the canonical responses that we can expect.” Study Link
This is where your addiction starts with this evidence of glycation causing agents in baby food. This is indicative of the glucose in the formula. Ask yourself why this is done if glucose is capable of doing this much harm;
“Protein modifications occurring during sterilization of infant formulas can affect protein digestibility and release of bioactive peptides. The effect of glycation and cross-linking on protein breakdown and release of β-casomorphins was evaluated during in vitro gastro-intestinal digestion (GID) of six sterilized model systems of infant formula. Protein degradation during in vitro GID was evaluated by SDS-PAGE and by measuring the nitrogen content of ultrafiltration (3kDa) permeates before and after in vitro GID of model IFs. Glycation strongly hindered protein breakdown, whereas cross-linking resulting from β-elimination reactions had a negligible effect. Only β-casomorphin 7 (β-CM7) was detected (0.187-0.858mgL(-1)) at the end of the intestinal digestion in all untreated IF model systems. The level of β-CM7 in the sterilized model systems prepared without addition of sugars ranged from 0.256 to 0.655mgL(-1). The release of this peptide during GID was hindered by protein glycation.” Study Link
This study explains that it’s the glycative results are what drives inflammation and in type 1 diabetics, this was just released Oct15, 2016. Watch to see if you’ll hear anything about it. If you don’t, it’s probably because Big Pharma has something to say about it;
“The ways in which environmental factors participate in the progression of autoimmune diseases are not known. After initiation, it takes years before hyperglycemia develops in patients at risk for type 1 diabetes (T1D). The receptor for advanced glycation endproducts (RAGE) is a scavenger receptor of the Ig family that binds damage-associated molecular patterns and advanced glycated endproducts and can trigger cell activation. We previously found constitutive intracellular RAGE expression in lymphocytes from patients with T1D. In this article, we show that there is increased RAGE expression in T cells from at-risk euglycemic relatives who progress to T1D compared with healthy control subjects, and in the CD8+ T cells in the at-risk relatives who do versus those who do not progress to T1D. Detectable levels of the RAGE ligand high mobility group box 1 were present in serum from at-risk subjects and patients with T1D. Transcriptome analysis of RAGE+ versus RAGE– T cells from patients with T1D showed differences in signaling pathways associated with increased cell activation and survival. Additional markers for effector memory cells and inflammatory function were elevated in the RAGE+ CD8+ cells of T1D patients and at-risk relatives of patients before disease onset. These studies suggest that expression of RAGE in T cells of subjects progressing to disease predates dysglycemia. These findings imply that RAGE expression enhances the inflammatory function of T cells, and its increased levels observed in T1D patients may account for the chronic autoimmune response when damage-associated molecular patterns are released after cell injury and killing.”
Evidence of the role of AGEs in the process of neurodegenerative diseases;
“Non-enzymatic protein glycosylation is the addition of free carbonyls to the free amino groups of proteins, amino acids, lipoproteins and nucleic acids resulting in the formation of early glycation products. The early glycation products are also known as Maillard reaction which undergoes dehydration, cyclization and rearrangement to form advanced glycation end-products (AGEs). By and large the researchers in the past have also established that glycation and the AGEs are responsible for most type of metabolic disorders, including diabetes mellitus, cancer, neurological disorders and aging. The amassing of AGEs in the tissues of neurodegenerative diseases shows its involvement in diseases. Therefore, it is likely that inhibition of glycation reaction may extend the lifespan of an individual. The hunt for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, especially polyphenols and other natural antioxidants. Extrapolation of results of in vitro studies on the in vivo situation is not straightforward due to differences in the conditions and mechanism of glycation, and bioavailability problems. Nevertheless, existing data allow postulating that enrichment of diet in natural anti-glycating agents may attenuate glycation and, in consequence may halt the aging and neurological problems.” Study Link
The following is evidence of glycations role in cardiovascular disease;
“Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD). To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs) stimulated calcium deposition in vascular smooth muscle cells (VSMCs) through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5) was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA). Apoptotic cells were identified by Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA) for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD (P)H oxidase components including Nox4 and p22(phox), and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22 (phox). Double knockdown of Nox4 and p22 (phox) showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD (P)H oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD.”
Evidence of glycation in mental disorders like schizophrenia;
“Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.” Study Link
Evidence of glycation in renal disease and kidney cancer;
Growth arrest specific 2-like protein 1 (GAS2L1) protein is a member of the GAS2 family of proteins, known to regulate apoptosis and cellular cytoskeleton reorganization in different cells. Recently we identified that Gas2l1 gene expression in podocytes is influenced by advanced glycation end product-bovine serum albumin(AGE-BSA).
The study was performed employing cultured podocytes and diabetic (db/db) mice, a model of type 2 diabetes. Akbuminuria as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion as measured with specific ELISAs. Gene expression was analyzed via semiquantitative and real-time polymerase chain reaction. The protein levels were determined by western blotting and immunostaining.
We found that the Gas2l1α isoform is expressed in podocytes. Treatment with AGE-BSA induced Gas2l1α and Gas2 mRNA levels compared with controls incubated with non-glycated control BSA (Co-BSA). Moreover, application of the recombinant soluble receptor of AGEs (sRAGE), a competitor of cellular RAGE, reversed the AGE-BSA effect. Interestingly, AGE-BSA also increased the protein levels of GAS2L1α in a RAGE-dependent manner, but did not affect the GAS2 expression. Periodic acid-Schiff staining and albuminuria as well as urinary NGAL excretion revealed that db/db mice progressively developed diabetic nephropathy with renal accumulation of Nε-carboxy-methyl-lysine (immunohistochemistry, western blots). Analyses of GAS2L1α and GAS2 proteins in diabetic mice revealed that both were significantly elevated relative to their non-diabetic littermates. In addition, GAS2L1α and GAS2 proteins positively correlated with the accumulation of AGEs in the blood plasma of diabetic mice and the administration of sRAGE in diabetic mice reduced the glomerular expression of both proteins.
We show for the first time that the protein expression of GAS2L1α in vitro and in vivo is regulated by the AGE-RAGE axis. The suppression of AGE ligation with their RAGE in diabetic mice with progressive nephropathy reversed the GAS2L1α expression, thus suggesting a role of GAS2L1α in the development of diabetic disease, which needs to be further elucidated. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.” Study Link
Methylglyoxal is what makes up pyruvic acid which is a foundation for energy expenditure. It comes from glycogen which comes from glucose and can be made into lipids to be used for cholesterol or glucose to be used by your brain when the ketones aren’t enough to power all lobes in the brain. This the link from glucose to disease through its conversion to AGEs, advanced glycation endproducts as explained by this study published Sep 2016;
“Glucose and fructose metabolism originates the highly reactive by-product methylglyoxal (MG), which is a strong precursor of advanced glycation end products (AGE). The MG has been implicated in classical diabetic complications such as retinopathy, nephropathy, and neuropathy, but has also been recently associated with cardiovascular diseases and central nervous system disorders such as cerebrovascular diseases and dementia. Recent studies even suggested its involvement in insulin resistance and beta-cell dysfunction, contributing to the early development of type 2 diabetes and creating a vicious circle between glycation and hyperglycemia. Despite several drugs and natural compounds have been identified in the last years in order to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the endogenous and exogenous sources of MG, also addressing the current controversy about the importance of exogenous MG sources. The mechanisms by which MG changes cell behavior and its involvement in type 2 diabetes development and complications and the pathophysiological implication are also summarized. Particular emphasis will be given to pathophysiological relevance of studies using higher MG doses, which may have produced biased results. Finally, we also overview the current knowledge about detoxification strategies, including modulation of endogenous enzymatic systems and exogenous compounds able to inhibit MG effects on biological systems.” Study Link
Evidence of glycations influence in pancreatic cancer;
Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.” Study Link
In my estimation, this is the worst manifestation of bread in the diet. Amyloid plaque is at the root of most modern diseases, ranging from cancer to heart disease to arthritis to Alzheimer’s disease and Parkinson’s disease;
“The non-enzymatic reaction (glycation) of reducing sugars with proteins has received increased interest in dietary and therapeutic research lately. In the present work, the impact of glycation on structural alterations of camel serum albumin (CSA) by different glucose metabolites was studied. Glycation of CSA was evaluated by specific fluorescence of advanced glycation end-products (AGEs) and determination of available amino groups. Further, conformational changes in CSA during glycation were also studied using 8-analino 1-nephthlene sulfonic acid (ANS) binding assay, circular dichroism (CD) and thermal analysis. Intrinsic fluorescence measurement of CSA showed a 22 nm red shift after methylglyoxal treatment, suggesting glycation induced denaturation of CSA. Rayleigh scattering analysis showed glycation induced turbidity and aggregation in CSA. Furthermore, ANS binding to native and glycated-CSA reflected perturbation in the environment of hydrophobic residues. However, CD spectra did not reveal any significant modifications in the secondary structure of the glycated-CSA. Thioflavin T (ThT) fluorescence of CSA increased after glycation, illustrated cross β-structure and amyloid formation. Transmission electron microscopy (TEM) analysis further reaffirms the formation of aggregate and amyloid. In summary, glucose metabolites induced conformational changes in CSA and produced aggregate and amyloid structures.”
This is more evidence of glycation’s involvement in Alzheimer’s disease. This report was submitted on Aug 24, 2016, have you heard anything about this yet? Who doesn’t want you to know? Who have interests in selling your medication for memory loss? How would you learn this information if you didn’t see it here? Do you know where to look for it? Do you even know to look for it? Am I fishing or can this be a conspiracy?
The blood-brain barrier (BBB) dysfunction represents an early feature of Alzheimer’s disease (AD) that precedes the hallmarks of amyloid beta (amyloid β) plaque deposition and neuronal neurofibrillary tangle (NFT) formation. A damaged BBB correlates directly with neuroinflammation involving microglial activation and reactive astrogliosis, which is associated with increased expression and/or release of high-mobility group box protein 1 (HMGB1) and thrombin. However, the link between the presence of these molecules, BBB damage, and progression to neurodegeneration in AD is still elusive. Therefore, we aimed to profile and validate non-invasive clinical biomarkers of BBB dysfunction and neuroinflammation to assess the progression to neurodegeneration in mild cognitive impairment (MCI) and AD patients.
We determined the serum levels of various proinflammatory damage-associated molecules in aged control subjects and patients with MCI or AD using validated ELISA kits. We then assessed the specific and direct effects of such molecules on BBB integrity in vitro using human primary brain microvascular endothelial cells or a cell line.
We observed a significant increase in serum HMGB1 and soluble receptor for advanced glycation end products (sRAGE) that correlated well with amyloid beta levels in AD patients (vs. control subjects). Interestingly, serum HMGB1 levels were significantly elevated in MCI patients compared to controls or AD patients. In addition, as a marker of BBB damage, soluble thrombomodulin (sTM) antigen, and activity were significantly (and distinctly) increased in MCI and AD patients. Direct in vitro BBB integrity assessment further revealed a significant and concentration-dependent increase in paracellular permeability to dextrans by HMGB1 or α-thrombin, possibly through disruption of zona occludins-1 bands. Pre-treatment with anti-HMGB1 monoclonal antibody blocked HMGB1 effects and leaving BBB integrity intact.
Our current studies indicate that thrombin and HMGB1 are causal proximate proinflammatory mediators of BBB dysfunction, while sTM levels may indicate BBB endothelial damage; HMGB1 and sRAGE might serve as clinical biomarkers for progression and/or therapeutic efficacy along the AD spectrum.” Study Link
More evidence of the damaging effects of glycation was submitted July 15, 2016. Have you heard anything about this report yet?
“The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and immune responses through production of alarmins. Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the “false alarm” hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link, a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article.” Study Link
The author of this report isn’t fully aware of what causes glycation. He still thinks that protein and fat are important as they are what gets glycated, but they’re not the important factor in this equation. It’s the glucose that’s important, as it’s the glucose that does the glycating. If one were to remove the glucose, they’d remove the glycation.
Again no alert about this evidence of the influence of glycation in dementia submitted in Aug 2016 from the Oxford Journal of Gerontology;
Vascular risk factors, including inflammation, may contribute to dementia development. We investigated the associations between peripheral inflammatory biomarkers and cognitive decline in five domains (memory, construction, language, psychomotor speed, and executive function).
Community-dwelling older adults from the Ginkgo Evaluation of Memory Study (n = 1,159, aged 75 or older) free of dementia at baseline were included and followed for up to 7 years. Ten biomarkers were measured at baseline representing different sources of inflammation: vascular inflammation (pentraxin 3 and serum amyloid P), endothelial function (endothelin-1), metabolic function (adiponectin, resistin, and plasminogen activating inhibitor-1), oxidative stress (receptor for advanced glycation end products), and general inflammation (interleukin-6, interleukin-2, and interleukin-10). A combined z-score was created from these biomarkers to represent total inflammation across these sources. We utilized generalized estimating equations that included an interaction term between z-scores and time to assess the effect of inflammation on cognitive decline, adjusting for demographics (such as age, race/ethnicity, and sex), cardiovascular risk factors, and apolipoprotein E ε4 carrier status. A Bonferroni-adjusted significance level of .01 was used. We explored associations between individual biomarkers and cognitive decline without adjustment for multiplicity.
The combined inflammation z-score was significantly associated with memory and psychomotor speed (p < .01). Pentraxin 3, serum amyloid P, endothelin-1, and interleukin-2 were associated with change in at least one cognitive domain (p < .05).
Our results suggest that total inflammation is associated with memory and psychomotor speed. In particular, systemic inflammation, vascular inflammation, and altered endothelial function may play roles in domain-specific cognitive decline of nondemented individuals. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.” Study Link
Are you beginning to wonder why we’ve never been informed of these dangers? Evidence below of glycation in lung cancer was submitted on Aug9, 2016. I’ve not heard anything about this. Doesn’t the ACS care? They’re still recommending carbs in the diet, so they must not;
“Effects of carboxymethyl-lysine (CML) and pentosidine, two advanced glycation end-products (AGEs), upon invasion and migration in A549 and Calu-6 cells, two non-small cell lung cancer (NSCLC) cell lines were examined. CML or pentosidine at 1, 2, 4, 8 or 16 μmol/L were added into cells. Proliferation, invasion, and migration were measured. CML or pentosidine at 4-16 μmol/L promoted invasion and migration in both cell lines and increased the production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 and transforming growth factor-β1. CML or pentosidine at 2-16 μmol/L up-regulated the protein expression of AGE receptor, p47(phox), intercellular adhesion molecule-1 and fibronectin in test NSCLC cells. Matrix metalloproteinase-2 protein expression in A549 and Calu-6 cells was increased by CML or pentosidine at 4-16 μmol/L. These two AGEs at 2-16 μmol/L enhanced nuclear factor κ-B (NF-κ B) p65 protein expression and p38 phosphorylation in A549 cells. However, CML or pentosidine at 4-16 μmol/L up-regulated NF-κB p65 and p-p38 protein expression in Calu-6 cells. These findings suggest that CML and pentosidine, by promoting the invasion, migration and production of associated factors, benefit NSCLC metastasis.” Study Link
This is the evidence of your back problems being caused by glycation. This study shows how the inflammatory responses to glycation causing vertebral disk degeneration;
“Inflammation and cytokines have been recognized to correlate with intervertebral disc (IVD) degeneration (IDD), via mediating the development of clinical signs and symptoms. However, the regulation mechanism remains unclear. We aimed at investigating the regulatory role of interleukin (IL)β and high mobility group box 1 (HMGB1) in the inflammatory response in human IVD cells and then explored the signaling pathways mediating such regulatory effect. Firstly, the promotion of inflammatory cytokines in IVD cells was examined with ELISA method. And then western blot and real-time quantitative PCR were performed to analyze the expression of toll-like receptors (TLRs), receptors for advanced glycation endproducts (RAGE) and NF-κB signaling markers in the IL-1β- or (and) HMGB1-treated IVD cells. Results demonstrated that either IL-1β or HMGB1 promoted the release of the inflammatory cytokines such as prostaglandin E2 (PGE2), TNF-α, IL-6 and IL-8 in human IVD cells. And the expression of matrix metalloproteinases (MMPs) such as MMP-1, -3 and -9 was also additively up-regulated by IL-1β and HMGB1. We also found such additive promotion to the expression of TLR-2, TLR-4 and RAGE, and the NF-κB signaling in intervertebral disc cells. In summary, our study demonstrated that IL-1β and HMGB1 additively promote the release of inflammatory cytokines and the expression of MMPs in human IVD cells. The TLRs and RAGE and the NF-κB signaling were also additively promoted by IL-1β and HMGB1. Our study implied that the additive promotion by IL-1β and HMGB1 to inflammatory cytokines and MMPs might aggravate the progression of IDD.” Study Link
Even unborn babies are not immune to the effects if glycation;
Ovarian cancer is a consequence of glycation;
“S100B is one of the members of the S100 protein family and is involved in the progression of a variety of cancers. Ovarian cancer is driven by cancer stem-like cells (CSLCs) that are involved in tumor genesis, metastasis, chemoresistance and relapse. We then hypothesized that S100B might exert pro-tumor effects by regulating ovarian CSLCs stemness, a key characteristic of CSLCs. First, we observed the high expression of S100B in ovarian cancer specimens when compared to that in normal ovary. The S100B upregulation associated with more advanced tumor stages, poorer differentiation and poorer survival. In addition, elevated S100B expression correlated with increased expression of stem cell markers including CD133, Nanog and Oct4. Then, we found that S100B was preferentially expressed in CD133+ ovarian CSLCs derived from both ovarian cancer cell lines and primary tumors of patients. More importantly, we revealed that S100B knockdown suppressed the in vitro self-renewal and in vivo tumorigenicity of ovarian CSLCs and decreased their expression of stem cell markers. S100B ectopic expression endowed non-CSLCs with stemness, which has been demonstrated with both in vitro and in vivo experiments. Mechanically, we demonstrated that the underlying mechanism of S100B-mediated effects on CSLCs stemness was not dependent on its binding with a receptor for advanced glycation end products (RAGE), but might be through intracellular regulation, through the inhibition of p53 expression and phosphorylation. In conclusion, our results elucidate the importance of S100B in the maintenance of ovarian CSLCs stemness, which might provide a promising therapeutic target for ovarian cancer. Stem Cells 2016.” Study Link
This study looks at the AGEs responsible for inflammatory bowel disease and Rheumatoid arthritis;
Neutrophils and monocytes belong to the first line of immune defense cells and are recruited to sites of inflammation during infection or sterile injury. Both cells contain huge amounts of the heterodimeric protein S100A8/A9 in their cytoplasm. S100A8/A9 belongs to the Ca2+ binding S100 protein family and has recently gained a lot of interest as a critical alarmin modulating the inflammatory response after its release (extracellular S100A8/A9) from neutrophils and monocytes. Extracellular S100A8/A9 interacts with the pattern recognition receptors Toll-like receptor 4 (TLR4) and Receptor for Advanced Glycation Endproducts (RAGE) promoting cell activation and recruitment. Besides its biological function, S100A8/A9 (also known as myeloid-related protein 8/14, MRP8/14) was identified as an interesting biomarker to monitor disease activity in chronic inflammatory disorders including inflammatory bowel disease and rheumatoid arthritis. Furthermore, S100A8/A9 has been tested successfully in pre-clinical imaging studies to localize sites of infection or sterile injury. Finally, recent evidence using small molecule inhibitors for S100A8/A9 also suggests that blocking S100A8/A9 activity exerts beneficial effects on disease activity in animal models of autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease. This review will provide a comprehensive and detailed overview of the structure and biological function of S100A8/A9 and also will give an outlook in terms of diagnostic and therapeutic applications targeting S100A8/A9. Study Link
HMGB1 is a label that’s been assigned to a type of AGE or RAGE. Its importance lies in its ability to create pain in your body. This is one of over 4976 warnings and notices of what glycation does to the body that available for your perusal on the effects of glycation on PubMed;
Neuropathic pain (NPP) is an intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1) mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR), receptor for advanced glycation end products (RAGE), C-X-X motif chemokines receptor 4 (CXCR4), and N-methyl-D-aspartate (NMDA) receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP. Study Link
The following study was completed in July 2010, explaining the health benefits of calorie restriction. This is what was being researched over 120 years ago, as ketonuria was noticed in the urine of fasting patients, giving them ketonemia. This is a condition that best serves to heal the body for multiple reasons and has been shown to heal many diseases, simply from fasting. Since 500BC fasting has been used to cure many diseases with astonishing success. This is what’s known as ketosis today and is what your body goes through as a healing, fat burning type of metabolism. It uses your own fat to provide everything from hormones to glucose, through gluconeogenesis, the perfect glucose for the body as it made from your fat, making it a clean glucose source;
The societal impact of obesity, diabetes, and other metabolic disorders continues to rise despite increasing evidence of their negative long-term consequences on health span, longevity, and aging. Unfortunately, dietary management and exercise frequently fail as remedies, underscoring the need for the development of alternative interventions to successfully treat metabolic disorders and enhance lifespan and health span. Using calorie restriction (CR)—which is well known to improve both health and longevity in controlled studies—as their benchmark, gerontologists are coming closer to identifying dietary and pharmacological therapies that may be applicable to aging humans. This review covers some of the more promising interventions targeted to affect pathways implicated in the aging process as well as variations on classical CR that may be better suited to human adaptation.
Another report submitted Nov, 08 to the Official Journal of the International League Against Epilepsy, basically said the same thing while they were looking for the best way to approach putting the body into ketosis;
The ketogenic diet (KD) is a 90% fat diet that is an effective treatment for intractable epilepsy. Rapid initiation of the KD requires hospital admission because of the complexity of the protocol and frequent mild and moderate adverse events. The purpose of the study was to compare the efficacy of a gradual KD initiation with the standard KD initiation preceded by a 24- to 48-h fast.
Perhaps the most damning report against aging was issued in January of 1984, yet nothing was mentioned about this report; it was one of the first indications of what glycation does to the body and with a major cause of glycation being glucose or sugar, I have to wonder why the FDA didn’t say anything about it then. Why weren’t we, at least, informed about this study? Industry concerns?
Aging and diabetes mellitus are associated with cross-linking and nonenzymatic glycosylation of collagen. Incubation of tendon fibers with reducing sugars results in increased breaking time in urea similar to that seen in aging, and in nonenzymatic glycosylation and browning. Effect of a sugar is proportional to the amount of sugar available in the open chain form. The increase in breaking time correlates with the appearance of chromophores characteristic of crosslinked browning products. Collagen altered by nonenzymatic browning may play a role in some age-like major complications of diabetes. Study Link
This evidence of glycation’s role in atherosclerosis was in this study submitted in May 1988. Was this publicized? Did you hear about this? Did the FDA know?
Adhesion of bovine endothelial cells on fibronectin and collagen before and after nonenzymatic glycation in vitro has been studied. Nonenzymatic glycation of these proteins reduced their ability to bind endothelial cells. Furthermore, nonenzymatically glycated fibronectin failed to bind to normal and nonenzymatically glycated gelatin and to fibrin. So gelatin and fibrin Sepharoses can be used to separate highly glycated fibronectins from fibronectins with a low degree of nonenzymatic glucose substitution. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis did not demonstrate a covalent cross-link between nonenzymatically glycated fibronectins. These results present further evidence for the role of nonenzymatic glycation of proteins in the development of vascular complications in long-term diabetes and of atherosclerosis. Study Link
This shows the damage done by glycation on the blood. I posted this study because I wanted to note what the first sentence states, that this damage, at the time of publication, had been known for 20 years. The date of this study is marked as July 29, 1968. That means that his damage was discovered in 1968, 48 years ago.
The association between elevated levels of glycated hemoglobins and diabetes mellitus has been known for twenty years . Since then the determination of glycated hemoglobins has become a valuable tool for the objective assessment of long-term glycemia in diabetic patients. The marked clinical interest in reliable measurements of glycated hemoglobins has stimulated the development and perfection of the necessary methodology. Limitations of the techniques have led to investigations of the underlying causes. Some of them led to the recognition of processes that were not known to occur in vivo before, such as glycation at sites other than the amino terminus of the beta-chains, modification of hemoglobin by reactants other than glucose or the existence of labile hemoglobin adducts. With ideal methodology, these features would have gone unnoticed. Furthermore, the determination of glycated hemoglobin in large populations of diabetic patients has lead to the discovery of new, clinically silent mutant hemoglobins. Today, the routine determination of glycated hemoglobins in diabetic patients probably represents the broadest screening for mutant hemoglobins. The experience with glycated hemoglobins shows that overcoming difficulties in their determination, and progress in biomedical research, are closely intertwined.
This study shows how proteins exposed to glucose undergoes oxidative stress, the basis of aging;
Studies have shown that glycation in vitro is complicated by the ability of glucose to oxidize, in the presence of trace amounts of a transition metal, generating protein-reactive ketoaldehydes, hydrogen peroxide, and diverse free radicals. Protein exposed to glucose undergoes fragmentational and conformational alterations, and these, as well as thiol oxidation, appear to be caused by hydroxyl radicals. Glycofluorophore formation is dependent upon ketoaldehyde formation. It is suggested that glucose autoxidation contributes to oxidative stress in pathophysiology associated with diabetes and aging via this newly described process of “autoxidative glycosylation”.
The following report from Oct 30, 1981, shows the effects of glycation on cholesterol, LDL particles particularly and how it leads to atherosclerosis ;
Atherosclerosis occurs at an accelerated rate in patients with diabetes mellitus. Since some proteins undergo nonenzymatic glycosylation in diabetic patients and because certain chemical modifications of low-density lipoproteins produced alterations in their interactions with certain cultured cells, a fact that may be relevant to atherogenesis, we investigated the effect of in vitro glycosylation on cell-related properties of low-density lipoproteins. Glycosylation was carried out by incubating LDL (1-10 mg LDL-protein/ml) with glucose (0-100 mM) in 0.5 M phosphate buffer, pH 8.0, at 37 degrees C. The amount of glucose incorporated into LDL after 1-2 wk of incubation was estimated to be in the range of 1-10 mol/mol LDL-protein. Amino acid analysis of glycosylated LDL showed that glucose was covalently bound to lysine residues. In studies with cultured human fibroblasts, glycosylated LDL was internalized and degraded significantly less than control LDL, in proportion to the estimated degree of glycosylation (12% of control for the most extensively glycosylated LDL). Glycosylation of LDL also impaired significantly its ability to stimulate cholesteryl ester synthesis by cultured fibroblasts. Glycosylated LDL did not stimulate cholesteryl ester synthesis in rat peritoneal macrophages. If glycosylation of LDL occurs in diabetic patients, some pathophysiologic consequences related to the increased incidence of atherosclerosis in these patients may result.
In 1981 this was discovered, yet it’s been 35 years since then and yet few people are aware of this. My question is, why? Maybe I should ask the sugar industry.
The following study shows the how the adhesive qualities of glucose creates fibrinogen, which becomes a target for glycation;
Polymerisation and crosslinking of fibrin monomers were studied in 35 healthy volunteers and in 42 poorly controlled diabetic patients. Polymerisation did not show any difference between control subjects (n = 10) and diabetic patients (n = 11) (p greater than 0.1), although fibrinogen was 35% more glycated in the diabetic patients (p less than 0.001). Alpha chain crosslinking in the diabetic patients, however, was impaired as is shown from an increase in intermediate alpha polymers with a concomitant decrease in alpha monomer disappearance. A significant positive correlation was found between the degree of glycation of fibrinogen and the defective alpha chain polymerization (r = 0.86, p less than 0.005). These results were consistent with the results of thrombin and reptilase experiments. The reaction rate with reptilase did not show any difference between the two groups (p greater than 0.1), whereas the reaction rate with thrombin was significantly slower in the diabetic group compared to the control subjects (p less than 0.001). Purified fibrin clots obtained from the diabetic patients were more susceptible to plasmin than clots obtained from control subjects. It is concluded that in poorly controlled diabetic patients polymerization of fibrin monomers is normal, but crosslinking of the alpha chains is impaired, leading to a higher susceptibility of the clots to plasmin degradation.
From Wikipedia on Fibrinogen;
Fibrinogen (factor I) is a glycoprotein in vertebrates that helps in the formation of blood clots. It consists of a linear array of three nodules held together by a very thin thread which is estimated to have a diameter between 8 and 15 Angstrom (Å). The two end nodules are alike but the center one is slightly smaller. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 Å. The length of the dried molecule is 475 ± 25 Å.
Non-enzymatic glycation of low-density lipoprotein (LDL) may contribute to the premature atherogenesis of patients with diabetes mellitus. To assess whether glycation of apolipoprotein B, the predominant protein of LDL, interferes with the ability to immunologically quantify this protein, we prepared and purified glycated LDL by incubating normal plasma samples with high concentrations of glucose. Although both the plasma and the LDL specimens incubated with glucose contained significantly more glycated protein than control specimens, the quantitative interaction of an apolipoprotein B-specific antibody with glycated vs nonglycated LDL was not significantly different. We conclude that apolipoprotein B can be accurately quantified immunologically despite the presence of clinically excessive degrees of LDL glycation.
I included the following study from November 1989 because of its explanation of how glycation is responsible for inflammation;
Quantitative changes of concanavalin A (Con A)-reactive proteins in serum samples obtained from rats with induced inflammation and from patients with inflammatory and autoimmune diseases were examined by use of lectin blots. Treatment of rats with a single dose of fermented yeast to induce inflammation caused an extensive increase in Con A-reactivity. These changes were time-dependent and were similar in both sexes of the animals. When we examined serum samples obtained from patients with various inflammatory disorders for their Con A-reactive proteins as compared with normal donors, we noted that the Con A-reactivity increased in patients with rheumatoid arthritis and systemic lupus erythematosus. Among all the glycoproteins examined by lectin blots with use of Con A, a set of five proteins was selected for detailed analysis by densitometric scanning. These included alpha 2-macroglobulin, P-150, P-95, P-40, and P-35, of Mr 180,000, 150,000, 95,000, 40,000, and 35,000, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Densitometric scanning analysis of the lectin blots revealed that the Con A-reactivity of these proteins increased during inflammation. Because alpha 2-macroglobulin is not an acute-phase protein in humans, an increase in Con A staining of this protein suggested that altered glycation is associated with autoimmune diseases. Thus, a study of changes in Con A-reactive proteins in human sera may facilitate our understanding of the etiology and pathophysiology of autoimmune diseases. Study Link
“Abstract Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data Synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.”
“Diabetes is frequently associated with cardiovascular diseases (coronary heart disease, cerebrovascular disease, peripheral vascular disease), and several risk factors have been proposed. Recent studies have strengthened the importance of chronic hyperglycemia because this modifies a variety of circulating substances including lipoproteins, and the glycosylated ones can be involved in the process of accelerating atherosclerosis. In this review, previous studies indicating the significance of glycosylated lipoproteins in the progression of atherosclerosis were overviewed. We also discussed AGE (advanced glycation end products) which may play an important role of atherogenesis in diabetes.”The most recent study, submitted in October 2016 reveals some of the known damage that glycation is responsible for;
BACKGROUND OF STUDY:
Enhanced protein glycation in diabetes causes irreversible cellular damage through membrane modifications. Erythrocytes are persistently exposed to plasma glycated proteins; however, little is known about its consequences on membrane. The aim of this study was to examine the relationship between plasma protein glycation with erythrocyte membrane modifications in type 2 diabetes patients with and without vascular complications.
We recruited 60 healthy controls, 85 type 2 diabetic mellitus (DM) and 75 type 2 diabetic patients with complications (DMC). Levels of plasma glycation adduct with antioxidants (fructosamine, protein carbonyl, β-amyloids, thiol groups, total antioxidant status), erythrocyte membrane modifications (protein carbonyls, β-amyloids, free amino groups, erythrocyte fragility), antioxidant profile (GSH, catalase, lipid peroxidation) and Glut-1 expression were quantified.
Compared with controls, DM and DMC patients had significantly higher level of glycation adducts, erythrocyte fragility, lipid peroxidation and Glut-1 expression whereas declined levels of plasma and cellular antioxidants. Correlation studies revealed a positive association of membrane modifications with erythrocyte sedimentation rate, fragility, peroxidation whereas a negative association with free amino groups, glutathione, and catalase.
Our data suggest that plasma glycation is associated with oxidative stress, Glut-1 expression and erythrocyte fragility in DM patients. This may further contribute to the progression of vascular complications.
More evidence of the role glucose plays in brain degradation;
Protein glycation is an age-dependent posttranslational modification associated with several neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. By modifying amino-groups, glycation interferes with folding of proteins, increasing their aggregation potential. Here, we studied the effect of pharmacological and genetic manipulation of glycation on huntingtin (HTT), the causative protein in Huntington’s disease (HD). We observed that glycation increased the aggregation of mutant HTT exon 1 fragments associated with HD (HTT72Q and HTT103Q) in yeast and mammalian cell models. We found that glycation impairs HTT clearance thereby promoting its intracellular accumulation and aggregation. Interestingly, under these conditions autophagy increased and the levels of mutant HTT released to the culture medium decreased. Furthermore, increased glycation enhanced HTT toxicity in human cells and neurodegeneration in fruit flies, impairing eclosion and decreasing lifespan. Overall, our study provides evidence that glycation modulates HTT exon-1 aggregation and toxicity, and suggests it may constitute a novel target for therapeutic intervention in HD.
Evidence of the glycative effects in Cataracts was known in the fall of 1974, yet nothing was said that I can remember, but then I was just getting out of Jr College then;
J Clin Invest. 1984 Nov;74(5):1742-9.
Garlick RL, Mazer JS, Chylack LT Jr, Tung WH, Bunn HF.
We have examined the nonenzymatic glycation of human lens crystallin, an extremely long-lived protein, from 16 normal human ocular lenses 0.2-99 yr of age, and from 11 diabetic lenses 52-82-yr-old. The glucitol-lysine (Glc-Lys) content of soluble and insoluble crystallin was determined after reduction with H-borohydride followed by acid hydrolysis, boronic acid affinity chromatography, and high-pressure cation exchange chromatography. Normal lens crystallin, soluble and insoluble, had 0.028 +/- 0.011 nanomoles Glc-Lys per nanomole crystallin monomer. Soluble and insoluble crystallins had equivalent levels of glycation. The content of Glc-Lys in normal lens crystallin increased with age in a linear fashion. Thus, the nonenzymatic glycation of nondiabetic lens crystallin may be regarded as a biological clock. The diabetic lens crystallin samples (n = 11) had a higher content of Glc-Lys (0.070 +/- 0.034 nmol/nmol monomer). Over an age range comparable to that of the control samples, the diabetic crystallin samples contained about twice as much Glc-Lys. The Glc-Lys content of the diabetic lens crystallin samples did not increase with lens age.
This study look at the effects of glycation on your eyes and the cataracts is responsible for. Yes, glycation and a glucose diet will buy you cataracts. My mother had two of them. A good who loved to eat her bread had cataracts in both of her eyes as well. What’s interesting, this person was always complaining of headaches and stomach aches, both manifestations of an ECC diet. Again, here is more evidence of the glycative and addictive effects of a grain diet.
The following report provides evidence of glycation’s role in Leukemia.
Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia.
“Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B cells that are highly dependent on the microenvironment for maintenance and expansion. However, little is known regarding the mechanisms whereby CLL cells create their favorable microenvironment for survival. High-mobility group protein B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted by innate immune cells and passively released by injured or dying cells. We found significantly increased HMGB1 levels in the plasma of CLL patients compared with healthy controls, and HMGB1 concentration is associated with absolute lymphocyte count. We therefore sought to determine potential roles of HMGB1 in modulating the CLL microenvironment. CLL cells passively released HMGB1, and the timing and concentrations of HMGB1 in the medium were associated with differentiation of nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the markers for NLCs, was associated with shorter overall survival of CLL patients. HMGB1-mediated NLC differentiation involved internalization of both receptor for advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9). Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway. In conclusion, this study demonstrates for the first time that CLL cells might modulate their microenvironment by releasing HMGB1.” Free PMC Article
J Clin Invest. 1984 Nov;74(5):1742-9.
After searching these last few disorders I got a yen to search any disorder & glycation, and glycation turned up in everything except halitosis. The following report shows its involvement in stomach ulcers. I originally searched just ulcers and got back 30 studies showing involvement. The first few studies in the list were reports on foot ulcers, so I search stomach ulcers and found 3 studies, the following report was the first;
High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR) 2, TLR4, and receptor for advanced glycation end products (RAGE), leading to tissue injury. Although HMGB1’s ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1’s effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO) activity, and the expression of tumor necrosis factor α (TNFα) mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO) mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses. Free PMC Article
- Nonenzymatic glycation of human lens crystallin. Effect of aging and diabetes mellitus.
Garlick RL, Mazer JS, Chylack LT Jr, Tung WH, Bunn HF.
This study looked at the effects of glycation on your eyes and the cataracts it’s responsible for. Yes, glycation and a glucose diet will buy you cataracts. My mother had two of them. A good friend who loved to eat her bread had cataracts in both of her eyes as well. What’s interesting, this person was always complaining of headaches and stomach aches. Both of those manifestations are from an ECC diet. Again, here is more evidence of the glycative and addictive effects of a grain diet. In all, there were 3,629 studies on the effects of glucose glycating proteins, hemoglobin, and cholesterol dating back to March 1984. Incidentally, that was one month after I was released from the hospital after spending a month in a coma and suffering two strokes while comatose. I could have never come back this far without Dr. Perlmutter’s help. Again, I have to thank you, Dr. Perlmutter.
I found this study done Sep 5, 2014, on autism and environmental factors. The only factor that mirrored the rise in autism was the use of glyphosate herbicides. Note the similarity. For me, this is enough to shut down the use of Roundup and all generic versions. Will the USDA recommend this? Knowing who runs the USDA, I seriously doubt it. Although it has little to do with glycation, it expresses the danger of the herbicide that’s used on virtually all grains today.
Temporal trend in autism compared to temporal trend in U.S. application of glyphosate to genetically-modified corn and soy crops, as estimated from US Department of Agriculture data (see Additional file 1 ).
The author of this last report tries to dance around the issue of the glyphosate herbicide’s relationship to autism, but the evidence is clear.
They’ve had some of this evidence for over 30 years, why hasn’t the public been told about glycation or the AGEs they create? It’s those AGEs that are at the root of all modern diseases. If this was uncovered starting 30+ years ago, why have we just found out about it from the bestselling books from two doctors? Is someone trying to hide something? My guess is yes. This is Monsanto’s path to power and freedom. They’ve politically engineered their freedom to wreak whatever havoc they can on your health by masturbating your taste buds with their glucose laden products, to grant them power by buying into their pharmaceutical cycle in the very near future. By near, I mean, it only takes a couple days before you’re indebted. (That means addicted.) If you want true power and freedom, you can have it in two weeks to two months. That’s how long it takes to break the addiction.
Each and every one of these 11,000+ studies has been vetted and examined by the NIH and PubMed for whom I thank.
You have two choices;
- Continue to masturbate your taste buds and collect these diseases and disorders in return.
- Cut out as much as possible the starchy carbohydrates, (grains) and live free from dependence.
You need to realize that the comfort in comfort food, brings massive discomfort in the future, starting immediately, with a process called glycation. This is the real poisoning of America and we can correct it. It lies within our power, each and every one of us can correct this. I offer a cure, not a therapy or treatment, My cure simply involves removal of all glycating substances from the diet to eliminate this problem of glycation so that it never affects the body The glycating substances = carbs, sugar, glucose, fructose.
The above reports on the effects of glycation appeared in many cases, over 30 years ago in PubMed. I’ve only shown you 47 reports out of 11,750 studies to date detailing the damaging effects of Excessive Carbohydrate Consumption, the primary cause of glycation, why doesn’t the FDA or the USDA say anything about that? The 42nd study, submitted in November 1989 shows how it causes inflammation, and with inflammation a factor in so many diseases, it truly is a wonder that the FDA and USDA never even issued anything so simple as a warning. The FDA’s involvement in this issue is mostly explained by their influence from the one industry, where they get most of their execs from, Monsanto.
From every form of cancer to Alzheimer’s disease to heart disease and cardiovascular disease to arthritis to hypertension to high cholesterol these food sources (sugar and grains) are responsible for each and every one of these disorders. These studies are proof of exactly what sugar does to the body. To cure the glycation factor in these diseases, the best way is to eliminate it as much as possible. To do that you must eliminate its source and to eliminate the source, you have to eliminate the grains and sugar. Thank you, Dr. Davis and Dr. Perlmutter for bringing this to my attention.
In all, there were 3,629 studies in the FDA’s database on the effects of glucose glycating proteins, hemoglobin, and cholesterol dating back to march, 1984. Incidentally, that was one month after I was released from the hospital after spending a month in a coma and suffering two strokes while comatose. I could have never come back this far without Dr. Perlmutter’s help. Again, I have to thank you, Dr. Perlmutter. The above, reports on the effects of glycation, appeared, in many cases over 30 years ago in PubMed. With 11,667 studies to date detailing the damaging effects of Excessive Carbohydrate Consumption, the primary cause of glycation, why doesn’t the FDA say anything? The last study, submitted in November 1989 shows how it causes inflammation and with inflammation a factor in so many diseases, it truly is a wonder that the FDA never even issued anything as simple as a warning. The FDA’s involvement in this issue is largely explained by the influence they receive from the one industry where they get a good portion of their execs from, Monsanto.
With having the evidence for over 30 years, why hasn’t the public been told about glycation or the AGEs they create? It’s those AGEs that are at the root of all modern diseases. If this was uncovered 30+ years ago, why have we just found out about it from the bestselling books from two doctors? They weren’t published in 2010 and 2012 and they had to dig this information out of the archives. Is someone trying to hide something? In whose best interest would it be to hide this information? The grain industry? My guess is yes.
Consider this; due to the pain cycles this food is responsible for, you can blame the opioid crisis on Monsanto and their amplification of glycation as it’s the pain that’s ramped up by the glycation, done to the crop, right before harvest. Whether intentional or not, it multiplies the profits of the pharmaceutical industry. All because you buy into it.
From every form of cancer (with the possible exception of brain cancer, which I suspect is influenced by glycation simply because of the inflammation factor) to Alzheimer’s disease to heart disease and cardiovascular disease to arthritis to hypertension to high cholesterol these food sources (sugar and grains) are responsible for each and every one of these disorders. These studies are proof of exactly what sugar does to the body. To cure the glycation factor in these diseases, the best way is to eliminate it as much as possible. To do that you must eliminate its source and to eliminate the source, you have to eliminate the grains and sugar. Thank you, Dr. Davis and Dr. Perlmutter for bringing this to my attention. It would have been nice if someone could have done it 20 or 30 years ago. For that, I thank the FDA, the USDA, and Monsanto. Don’t allow them to be in your driver’s seat. As long as you remain on your carbohydrate diet, they’re in the driver’s seat for your health. Give up the carbs and put yourself back in the driver’s seat. You are the only one who can change yourself. Enable yourself to do so.
Documentaries worth watching;
- Food, Inc
- Food Matters
- Food Beware (French)
- Genetically Modified Foods
- David vs Monsanto
- Of the Land
- Hungry for Change
- That Sugar Film
- Love Paleo
- Heal Yourself
- Who Wants to Live Forever
- Overfed and Undernourished
- My Big Fat Body
- Facing the Fat
- Just Eat It; A Food Waste Story