However, neither the magnitude nor the persistent nature of this increased prooxidant state are completely understood. A significant correlation has been found between ingested and circulating AGEs in humans in recent years. Based on animal studies, the injurious impact of diet-derived AGEs to vascular and kidney tissues is estimated to rival or even exceed that caused by high blood sugar and high blood fat levels. Consistent with this view, dietary AGE restriction has been associated with suppression of several immune defects, insulin resistance, and diabetic complications, whether genetically or diet induced, despite persistent diabetes.

This is an interesting observation because there are also many studies showing that the diet contribution to AGEs is minimal.

This research goes on:

These findings are in support of clinical evidence from subjects with diabetes or vascular or kidney disease. Most recently, evidence from animal studies points to AGE restriction as an effective means for extending median life span, similar to that previously shown by marked caloric restriction.

It’s believed that excessive AGE consumption, in the current dietary/social structure, represents an independent factor for inappropriate oxidant stress responses, which may promote the premature expression of complex diseases associated with adult life, such as diabetes and cardiovascular disease.

There is a growing body of evidence that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, and are thus involved in the pathogenesis of various diseases such as diabetic vascular complications and neurodegenerative diseases. Therefore, inhibition of AGE formation may be a promising target for therapeutic intervention in AGE-related disorders.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds that form continuously in the body. Their rate of internal formation is markedly increased in diabetes mellitus, a condition in which AGEs play a major pathological role. It is also known, however, that AGEs form during the cooking of foods, primarily as the result of the application of heat. There’s evidence of a direct association between dietary AGE intake and markers of systemic inflammation such as C-reactive protein. Together with previous evidence from diabetics and renal failure patients, these data suggest that dietary AGEs may play an important role in the causation of chronic diseases associated with underlying inflammation.

Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. There is a focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), the receptor for advanced glycation end products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity.

In another viewpoint: dividing methylglyoxal in selected foods into 220 mg/d (averaged from the 2 approximations) and then applying FDA reference serving values yields the intake amounts and calculated number of servings of each that would have to be consumed within a 24-h period to equal daily internal production of methylglyoxal. For example, 1129 servings/d of carbonated soft drink or 1800 servings/d of toast would need to be consumed to equal amounts produced by natural physiological processes. Such exaggerated quantities are clearly beyond the capacity of even the heartiest appetites. From this perspective, it is clear that food sources of methylglyoxal are inconsequential in comparison with internal production.

That sparks the debate over the contribution of food to glycated end products.

However, many low carb diet programs advocate a dramatic cut in carbs too rapidly and this can cause problems, such as dizziness etc. This is because your body is used to using glucose for fuel and you are taking that source of fuel away and that is why people experience adverse reactions in the early days.

Make sure that you make the switch from your body using glucose for fuel, to fat, over a gradual period of time and this can take up to six months to complete the process. In this way you will not experience any adverse side effects and remember that most Americans consume as much as 300 grams of carbs per day, so cut back gradually, say a few grams per day and if you experience any side effects, then slow down even more.

Take breakfast for example; there is no need to avoid the piece of buttered toast with your bacon and eggs and a spoonful of sugar in your coffee – that amounts to around 20 grams of sugar. Now go for lunch and take a tuna sandwich with mayo and you have consumed another 30 grams of carbs, assuming that you are using regular sliced bread. At dinner, say you have a steak with salad and a medium baked potato, then you have added another 30 or so grams of sugar and your total daily intake of sugar is 80 grams and just to be conservative, let’s add another 20 grams for good measure and now we have hit 100.

If you are consuming a 2000 calorie a day diet, your total intake of carbs should not exceed 500 grams and with carbs yielding around 4 calories per gram, you sugar grams are 125 and you have eaten 100. Now I am assuming that you have controlled the portions of each meal to total 2000 calories for the day, but you can see that it is hardly a problematic diet to follow and you are still eating your favorite foods. Would it be better to eat less sugar? Sure, but I am trying to show you that it does not have to be that hard!

However, neither the magnitude nor the persistent nature of this increased prooxidant state are completely understood. A significant correlation has been found between ingested and circulating AGEs in humans in recent years. Based on animal studies, the injurious impact of diet-derived AGEs to vascular and kidney tissues is estimated to rival or even exceed that caused by high blood sugar and high blood fat levels. Consistent with this view, dietary AGE restriction has been associated with suppression of several immune defects, insulin resistance, and diabetic complications, whether genetically or diet induced, despite persistent diabetes.

This is an interesting observation because there are also many studies showing that the diet contribution to AGEs is minimal.

This research goes on:

These findings are in support of clinical evidence from subjects with diabetes or vascular or kidney disease. Most recently, evidence from animal studies points to AGE restriction as an effective means for extending median life span, similar to that previously shown by marked caloric restriction.

We conclude that excessive AGE consumption, in the current dietary/social structure, represents an independent factor for inappropriate oxidant stress responses, which may promote the premature expression of complex diseases associated with adult life, such as diabetes and cardiovascular disease.

There is a growing body of evidence that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, and are thus involved in the pathogenesis of various diseases such as diabetic vascular complications and neurodegenerative diseases. Therefore, inhibition of AGE formation may be a promising target for therapeutic intervention in AGE-related disorders.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds that form continuously in the body. Their rate of endogenous formation is markedly increased in diabetes mellitus, a condition in which AGEs play a major pathological role. It is also known, however, that AGEs form during the cooking of foods, primarily as the result of the application of heat. This review focuses on the generation of AGEs during the cooking of food, the gastrointestinal absorption of these compounds, and their biological effects in vitro and in vivo. We also present preliminary evidence of a direct association between dietary AGE intake and markers of systemic inflammation such as C-reactive protein in a large group of healthy subjects. Together with previous evidence from diabetics and renal failure patients, these data suggest that dietary AGEs may play an important role in the causation of chronic diseases associated with underlying inflammation.

Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. This review will focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), The receptor for advanced glycation end products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity.

Dividing methylglyoxal in selected foods into 220 mg/d (averaged from the 2 approximations) and then applying FDA reference serving values yields the intake amounts and calculated number of servings of each that would have to be consumed within a 24-h period to equal daily internal production of methylglyoxal. For example, 1129 servings/d of carbonated soft drink or 1800 servings/d of toast would need to be consumed to equal amounts produced by natural physiological processes. Such exaggerated quantities are clearly beyond the capacity of even the heartiest appetites. From this perspective, it is clear that food sources of methylglyoxal are inconsequential in comparison with internal production.

That sparks the debate over the contribution of food to glycated end products.

The authors propose that any hypothetical potential therapeutic agent should be an anti-inflammatory agent, which is also an antioxidant that chelates metal ions, in addition to possessing antiglycating activity with the ability to scavenge dicarbonyls, such as methylglyoxal, and suppress advanced glycation end product formation and reactivity. It should be noted that the processes that the hypothetical therapeutic should suppress or inhibit also describe the principal factors that promote the accumulation of altered proteins and which accompany (or cause) animal and human aging.

However, it can be argued that long-lived tissues of long-lived animal species might also contain suitable protective agents that help to suppress the formation of altered proteins, especially when an animal is young. A particular example is the dipeptide carnosine (β-alanyl-L-histidine).

It has been proposed that carnosine can inhibit generation of many of the protein alterations accompanying aging, especially those associated with AD  and diabetes and its complications.

Carnosine is an antioxidant and antiglycating agent that inhibits sugar-mediated protein crosslinking and also chelates a number of metal ions (including copper and zinc). Carnosine reacts with methylglyoxal and it has been described as a glyoxalase mimetic. The dipeptide can react with a number of deleterious aldehydic products of lipid peroxidation and thereby suppress their toxicity. Carnosine can also react with glycated proteins and inhibit advanced glycation end product formation. There is also some evidence from animal studies that carnosine can inhibit some of the deleterious effects of a high fructose diet.

Carnosine has been described as an anti-aging peptide.

In conclusion, it is suggested that carnosine, an almost nontoxic natural product, satisfies the criteria proposed by Maher and Schubert, that lead compounds should possess for eventual development of drugs to combat AD and T2D. There is evidence of carnosine’s efficacy from animal models. Unfortunately, as noted in general by Maher and Schubert, the fact that carnosine and many of its related structures are not patentable may be an impediment to their immediate exploration by the commercial sector. Perhaps charities and the public sector might be encouraged to explore carnosine’s therapeutic potential to help keep at bay these two conditions that threaten to overwhelm future medical provision.

Let’s take a closer look at the techniques of the medical epidemiologist. Clearly, modern nutritional epidemiology is contributing to the mass of confusion in the public mind about diet and health.

Dr. Alvin Feinstein, Yale University statistician, states that it’s extremely important to understand that all sciences aren’t at the same stage of development. Epidemiology, in his estimate, is distinctly a junior science. The essence of epidemiology is, wherever possible, to simplify. Epidemiologists, by necessity, study very large groups of free-living individuals and, in that process, face a multitude of variables, many of them unknown.

 Epidemiologists must not, but often do, convert that which in reality, is mere association into a demonstration of causation. For example, a report appears in a prominent medical journal. It’s followed immediately by wide publicity in newspapers, television, and other media. This report claims that yet another aspect of daily life has been “indicted” as a “menace” to health. But, the uncovering of the “menace” can inevitably be traced back to a statistical analysis of epidemiologic data.

The scientific “tactics” that produce the evidence are almost always difficult to understand and evaluate. The “tactics” include such statistics as relative risk vs. rate. The evidence is not supported through experiments. In experiments, healthy people are randomly assigned to two different groups so that relationships can be studied.

Rather than experiments, epidemiologists fall back upon modern computers, exploring enormous amounts of information via the epidemiologists’ stock-in-trade technique: “data dredging.” Each of the multiple “causative agents”: diet, smoking, drinking, pollutants, driving without seat belts, to which large groups of free-living individuals are exposed, is “number-crunched.” The “arm-chair” epidemiologists do this to determine whether a relationship exists between any of the agents and a particular disease.

Unfortunately, whenever a “statistically significant” result emerges through the endless number-crunching process, such as eggs being a risk factor for heart disease, the result of the “number-crunching” process is proposed as a cause-effect relationship rather than what it actually is: an association, a correlation, nothing more.

This “statistically significant” result from an epidemiological study does not imply causation; at best, it suggests candidates for future experimental study. In the absence of an experiment, it’s impossible to determine cause-effect.

Lewis Thomas has suggested that epidemiologic studies of noninfectious diseases have produced their own adverse side effects: an “epidemic of apprehension.” This epidemic grows with each new alarm about a new menace in daily life. When epidemiologists talk about cause-effect, as they do, with no experimental back-up for their conclusions, their epidemiology slides into religion; their methodologies, into sacraments.

The epidemiologists have learned that they can manipulate statistics so as to create something from nothing. There is no criticism or rebuke. They can generate large volumes of grant money to sustain endless studies: perks from funding by the food industry, and the pharmaceutical industry, and the national government continue to flow. Their coffers fill to overflowing.

 What’s more, they continue to get away with obscuring the facts. No matter what they study, there’s no significant difference between rates of heart disease death, even among groups pursuing different lifestyles. What we hear about is not rates but risks.

 Classic modern epidemiological studies substitute conjecture for facts, in this case the facts attendant upon real, hard experimental research. These arm-chair medical theorists have been studying disease processes for the last fifty years, a half century in which mere association has been passed-off as cause. Because of all this, society has lost its sense of reality: Risk factors aren’t demonstrative of cause and effect. Their arm-chair studies, which have never demonstrated any real causes and effects have, nonetheless, cost millions of the public’s dollars and have gotten us, in return, nothing but a bogus statistical technique, Relative Risk Analysis.

 Relative Risk Analysis is a grotesque technique used by epidemiologists to deceive gullible physicians and an even-more gullible public.

 It should be pointed out to all health-seekers that Relative Risk Analysis is the basis of all the studies performed by Dr. Willet and his Harvard colleagues. They have their own agenda, and it is to teach the world that fat and cholesterol cause heart disease. Their so-called studies, none of which involves any experiment, always lead to the conclusion that diet and lifestyle represent significant “causal” risk factors. Their studies appear in all the major media and provide the basis for all the current doomsday reports about the hazards of daily living. They’re the reason why everyone is so confused.

The urgency with which the medical Establishment has seized the Glycemic Index theory as an armament in its war on disease is an outgrowth of the epidemiological studies that I’ve pilloried in previous blog posts. Indeed, the aforementioned Dr. Walter Willet is one of the leading medical advocates of the idea that the Glycemic Index influences disease risk. The main epidemiological studies are those from his Nurses Health Study and the Health Professionals Follow-Up Study, authored by Dr. Willet.

 Dr. Willet has observed that dietary glucose is involved in body changes other than those produced by its effect on the rate of release of insulin and glucose and their associated peak values, or “spikes.” He recognizes that the amount of carbohydrate consumed, and the subsequent quantity of glucose released by the digestive tract, is also important in any discussion of carbohydrate metabolism. His explanation of these changes is premised, however, upon the Glycemic Index and a new but related concept of his own development: Glycemic Load, which is measured by multiplying the Glycemic Index of a food by the quantity of carbohydrate consumed. The limitation to his analysis is that the Glycemic Index is without meaning and, it is, in fact, the amount of carbohydrate that is the sole determinant of carbohydrate and fuel metabolism.

 Dr. Willet has ignored the conclusions released by many of his colleagues who participated in developing the 2002 position statement for the American Diabetes Association:

 The ADA technical review and position statement reviewed the role of the GI in medical nutrition therapy for diabetes. The reports acknowledge that differing food sources of carbohydrates have different glycemic responses when the food is studied independently, in 50-g portions, and compared with either 50 g of either glucose or bread. However, after reviewing the evidence, it was concluded that the total amount of available carbohydrate in meals or snacks is more important than the source (starch or sugar) or type (low or high GI, and although low-GI foods may reduce post-prandial hyperglycemia, there was not sufficient evidence to recommend use of low-GI diets as a primary strategy in food/meal planning. 

As he philosophizes from his computer and his armchair, Glycemic Load is implicated in the cause of disease. But whatever else might be at work here, it isn’t a matter of causation but of association. With his usual flair, Dr. Willet “suggests” (note the favorite weasel word of the epidemiologists, here: “suggests”). When they have no experimental facts to support their arguments, they “suggest.” And, here, he has no facts, so he “suggests.” It’s important to note that the good doctor’s mere “suggestion” went out into the world as a fact (a scientific fact, not a statistical “notion”).

 Although there should be an experimental trial that investigates whether his belief is true, he acknowledges that no such experiment has been conducted and that his brand of “analysis” is, at most, a “best available alternative.” But as we’ve seen, association is, at best, speculative because relative risk analysis is, as discussed earlier, merely a multiplication of percents by percents. Repeated often enough, very small proportions are magnified to gigantic proportions. No, his contribution offers only more damn confusion and public befuddlement.

 Let’s look at the specifics that Dr. Willet has collected from his test subjects’ diets to see just how sound his speculations turn out to be. Subjects filled out something called a food-frequency questionnaire. Men, in one study, were excluded if 70 of 131 total food items were left blank, so if one had just 61 out of 131 items, he would have qualified as a subject. Equally questionable as to credibility, is the fact that the subjects also calculated their own daily calorie intake. Reports from subjects who said they consumed less than 800 and more than 4,200 calories a day were excluded. Careful analysis — over the last decade of so-called “self-reports” of food intake in dietary tests — shows, individually, that the average person underestimates, or under reports, his food intake by 20-50%. The accuracy of all such self-reporting is, hence, inevitably suspect, at best.

 To estimate their Glycemic Load, the subjects had, in effect, to guess the amount of food they’d consumed, relative to a so-called “standard portion.” They also had to estimate the number of servings of a particular food that they’d eaten over a one-year period. The investigators, then, took it upon themselves to relate this to the amount of food consumed per day. The Glycemic Index of the food was then estimated from a standard table. We’ve already learned, of course, that Glycemic Index values vary greatly, and that the Glycemic Index of a food is specific to consuming only that single food, and not a mixture of foods. Humans don’t eat single foods, they eat mixed meals, another fundamental reason why the Glycemic Index has no real-life applicability.

 In the final analysis of the data collection process, we see, then, that three very imprecise numbers have been conjured-up: 1) the Glycemic Index itself, 2) the portion of the food consumed, and 3) the number of times the food was consumed during the preceding year. Can you remember what you ate even last Saturday; how much, and how many pats of butter did you spread on your bread? Did you eat the whole piece of fruit or throw some of it away? I could go on, but you get the point. Asking people what they ate during the preceding year is far from exact science.

By deriving a larger amount of our daily fuel needs from fat and meat, thereby decreasing our reliance on the use of carbohydrates and their end product glucose, we can avoid the increased production of substances that poison our proteins. Less carbohydrate means less flow through the pathway of glycolysis with its potential to produce more MG.

It’s clear that MG strongly influences aging and its related disorders. The ability to replenish NAD is important because it’s involved in the manufacture of stress-proteins, in the stimulation of the cellular compounds that degrade dysfunctional mitochondria, and in the turning-on process of the production of new, healthy mitochondria.

Resveratrol, a nutritional supplement made from grapes, exerts anti-aging effects, promotes increased mitochondrial activity, and seems to suppress glycolysis, all of which decrease the potential for MG synthesis. Another nutritional supplement, acetyl-L-carnitine drives fat into the mitochondria where it can be burned as fuel. There is considerable evidence that increasing the mitochondrial use of fat as fuel serves to decrease the formation of glycated and altered proteins.

Remember, the biochemical pathways for burning carbohydrates as fuel or burning fat as fuel are completely different. In fact, just as a reminder, glucose is quickly turned into fat and when that process is in operation the newly formed chemical (MCoA) will shut down the uptake of fat into the mitochondria.

Increasing the number of active mitochondria has an anti-aging benefit suggesting the importance of increasing physical activity. Lowering the potential for MG formation is additionally helpful because it creates an environment for the active elimination of damaged mitochondria while stimulating the production of new, healthy ones.

Is the ‘Healthy’ Diet Really Healthy?

It’s apparent from the above that the healthy diet recommendations made by all the experts are far from healthy and are, in fact, dangerous and destructive. The scientific literature is overwhelmingly supportive of the claims I’m making. The literature is voluminous yet all recommendations are at odds with the publications. I’ve argued that researchers and other experts are simply not reading the literature and just regurgitate what they hear from various organizations and committees.

My books outline for you the most effective approach for following a carbohydrate-restricted diet. The most popular and most often used low-carbohydrate diet is that developed by Dr. Robert Atkins. I’ll show why that approach has serious flaws and it is not an approach that you’ll want to follow.

But, while these drugs are initially effective in most patients, they do not slow the underlying degeneration in the area of the brain most affected, the substantia nigra (SN) The focus is now toward environmental factors as potential PD initiators or contributors. As the search progresses, a single toxic cause remains elusive but a role for environmental factors seems almost certain.

Whatever the exact degree of contribution from environmental toxins, currently the cumulative evidence suggests PD is a multi-factorial oxidative disease. The main causal, oxidative contributors indicted to date are: (1) measurable amplification of an internally produced oxidative load that impair mitochondrial energy transformations; (2) innate vulnerability of the brain’s substantia nigra region to oxidative challenge; and (3) initiation or promotion by toxic exposure(s) that further deplete antioxidants.

These factors combine to initiate a downhill course for the neurons of the SN and elsewhere in the brain, the end result of which appears to be a slow-acting yet long term progressing, inflammatory process. This eventually results in the micro-anatomic degeneration and clinical symptoms of Parkinson’s disease.

Mitochondrial Energetics Generate Internally Produced Oxidative Burden

All the body’s cells, like oxygen utilizing cells anywhere, generate life energy and simultaneously generate oxygen free radicals (oxyradicals). The resultant oxidative burden is an obligatory, unavoidable by product of oxygen-based (aerobic) respiration. Very early in the progression of life, the adoption of oxygen to drive energetics produced a higher energy yield from food molecules, but with a “downside.” This downside was the production of oxyradicals, so highly reactive they have the potential to destroy the living system.

Antioxidant defenses developed, which curb the toxic threat from oxyradicals and help keep them integrated with the myriad pathways of healthy metabolism. The major cellular “hot spots,” where the bulk of oxyradicals are produced and antioxidant defenses are normally most challenged, are the semi-independent organelles called mitochondria.

Present in all human cells, the mitochondria are the cells’ energy powerhouses since they generate the vast bulk of the ATP that drives life processes. The mitochondria have their own DNA and manage the oxidative phosphorylation process (“oxphos”). In this process carbon-carbon double bonds are split to create pairs of energized electrons, whose electronic energy is then converted into the chemical bond energy of ATP.

As the mitochondria utilize 90 percent or more of the cells’ available oxygen to make ATP, they also generate 90 percent or more of the oxyradicals that make up the internally produced oxidative burden. The mitochondrial electron transfer complexes “pulls” electrons through a series of five steps. The complexes sequentially extract the electrons’ energy, converting it to ATP; at the end the electrons are combined with hydrogen and oxygen to make water.

However, during the transfers single electrons escape enzymatic control; these combine with oxygen to create oxygen free radicals, at a rate of around two percent of all oxygen consumed. To protect against destruction by this flux of oxyradicals, the mitochondria have sophisticated antioxidant defenses; but inevitably a few oxyradicals slip through to attack biomolecules.

Flawed Energetics Characterizes Parkinson’s Disease

Parkinson’s disease subjects have been found to have abnormalities that impair their mitochondrial energy generation and almost surely increase their oxidative burden. Oxidative stress exists when the oxidative burden on a living system is so great that effective antioxidant defenses cannot be maintained.

 Intensified oxidative burden —arising from increased endogenous production of oxyradicals and/or from excessive exposure to oxidative agents — threatens to shift the finely balanced oxidation-reduction state away from reduction and towards oxidation. If sufficiently sustained, oxidative stress can impose lasting oxidative imbalance on the living system, hastening its demise.

Given the confirmed presence of mitochondrial energetic abnormalities in the substantia nigra and elsewhere in the afflicted brain,  nutrients that safely boost mitochondrial function deserve further exploration for clinical benefit in PD. CoenzymeQ10 (ubiquinone; CoQ10) is an electron acceptor and antioxidant that is a key component of mitochondrial electron transfer. Acetyl-L-carnitine is another mitochondrial energy carrier, activating transport into the mitochondria of fatty acids to be used for energy. This nutrient has energizing, protective, and trophic effects. In animal experiments it partially protected the SN against MPP+ attack, enhanced dopaminergic transmission, and boosted intrinsic growth factor production.

Previous studies have reported that KIOM-79 shows a strong inhibitory effect on AGE formation and inhibited a proinflammatory state in a murine macrophage cell line. In the present study, we investigated the effect of KIOM-79 on AGE accumulation and vascular inflammation in the aorta of Zucker diabetic fatty (ZDF) rats, a commonly used model of type 2 diabetes.

Cardiovascular disease is one of the most common complications of diabetes. Chronic hyperglycemia accelerates the formation of advanced glycation end products (AGEs) and accumulation of AGEs in various tissues. AGE accumulation is an important feature in the development of diabetic macrovascular complications, such as atherosclerosis and cardiac dysfunction, and AGEs are believed to play a crucial role in the pathogenesis of diabetic vascular inflammation.

 AGE inhibitors, such as LR-90 and aminoguanidine (AG), have anti-inflammatory properties and help protect against diabetic vascular damage. The inhibition of AGE formation, blockade of the AGE-RAGE interaction, and suppression of RAGE expression or its downstream pathways suggest novel therapeutic strategies for the treatment of the vascular complications of diabetes.

Traditional herbal medicines have been used for the treatment of diabetes or diabetic complications in Korea and Asian countries. The development of KIOM-79, which is a mixture of the 80% ethanol extract of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae rhizome, and Euphorbiae radix, was based on the basic known function of each herb used in traditional Korean medicine for a variety of medical purposes, including diabetes and diabetic complications.

 In our previous studies, KIOM-79 has shown a stronger inhibitory effect on AGE formation than individual herbal medicines in vitro. KIOM-79 has also reduced accumulation of AGEs in the kidney and delayed the development of diabetic nephropathy in animal models for type 1 and 2 diabetes.

Taken together, we concluded that KIOM-79 inhibits AGE accumulation and reduces RAGE expression in the diabetic aorta. Decreased AGE/RAGE interaction decreases NF-κB activation, subsequently decreasing the expression of multiple inflammatory factors, including MCP-1, VEGF, VCAM-1, and iNOS. The present study shows that KIOM-79 may help in the prevention and delay of diabetes-induced vascular inflammation.