Diabetic Hypertension, Browning of the Arteries

...View all 190 posts...

I decorated a flan with a drizzle of honey, and my torch produced a toasted spiral.  That was just fructose plus proteins, with a little heat, to produce advanced glycation end products (AGE) that are brown.  If you prefer, you can do the same reaction with egg whites and sugar in meringues, or by grilling brined pork chops basted with honey and anchovy paste.  Fructose is 10X better than other sugars at producing glycation, AGE and browning.

AGE and Arteries

Why do we care about the Maillard reaction and advanced glycation end products (AGEs)?  Of course, understanding the biochemistry of cooking is inherently satisfying and it helps to explain why Dr. House used vinegar to stop meatballs from browning too fast in his cooking class, but it also explains what’s cooking in atherosclerosis, cardiovascular disease.  It turns out that AGEs are highly inflammatory and inflammation of arteries leads to plaque formation.  [LDL is less important, because it only aggravates the primary event, inflammation, and that is why fish oil is more helpful for cardiovascular disease than statins.]  So increasing blood sugar is a problem, because it increases the rate of the Maillard reaction in binding blood sugar to the amino acids of proteins, such as hemoglobin to produce HgA1C, and causing vessel inflammation.  AGE in small capillaries also kills the capillaries and causes a rise in blood pressure by making harder for the heart to force blood from arteries to veins.  AGE causes hypertension and that is why salt consumption is not as important.   High blood sugar also increases the level of another powerful glycation agent, methylglyoxal, the active antibacterial agent in Manuka honey.  Honey is effective as a wound dressing, because it AGEs microbes to death!

The Trouble with AGE-ing is Inflammation

Cells detect the presence of AGEs with a surface Receptor for AGE (RAGE).  Binding of AGE to RAGE turns on the inflammation transcription factor, NFkB, with the release of inflammatory cytokines and the symptoms of inflammation.  One of my students did some computational protein modeling of the RAGE, because I was interested to see if RAGE would also bind Metformin.  Sure enough, our hunch was confirmed, indicating that Metformin might also reduce some forms of inflammation and be a treatment for diabetic high blood pressure.

Fructose vs. Inulin; AGE vs. Soluble Fiber

Fructose and the storage polymer of fructose, inulin, are similar to glucose and the storage polymer of glucose, starch.  The polysaccharides, inulin and starch can be converted to the sugars, fructose or glucose by industrial heating or enzymes.  Thus, agave inulin is converted into nectar, and corn starch is converted into syrup.  The polysaccharides are not sweet, but the sugars are.  The polysaccharides don't form AGEs with amino acids (unless they are broken up by high heat into sugars first) and fructose is 10X more chemically aggressive in forming AGEs than glucose.  Agave nectar (fructose) is a better browner than honey or high fructose corn syrup (corn syrup treated with a commercial enzyme to convert some of the glucose into sweeter fructose.)  Both inulin and some forms of starch (resistant starch), reach the colon and are digested by gut flora, i.e. they are soluble (fermentable) fiber.  The gut flora convert the resistant starch into short chain fatty acids that are anti-inflammatory.  Typical starch, e.g. corn starch or wheat flour, is digested by gut enzymes and goes directly into the blood as glucose, it is high glycemic and never reaches the gut flora.

AGE in Food

Should we fear browned foods as inflammatory.  I don't think that AGE in foods is any more of a hazard than all of the toxic phytochemicals that are touted as plant antioxidants.  I think that the gut and liver provide protection.  I brown the sugar on my flans and sear my steaks, even as I relish eating my veggies.  The body can detox these natural products in the gut better than it can handle the AGE made by high blood sugars.

Take Home Messages:

• Sugars in baked goods or blood, react with amino acids or proteins to make inflammatory AGEs.
• Blood sugar tests only measure glucose and ignore fructose, which is even more unhealthy.  So, foods laced with fructose can be low glycemic, but very unhealthy.
• The major AGE in blood is HgA1C.
• Diabetics have more stable, lower blood sugar on low carb diets, e.g. my Anti-Inflammatory Diet.  The liver produces needed blood sugar from protein.
• Diabetic use of fructose or agave nectar or honey encourages AGE, inflammation and diseases of diabetes.
• Starch (not RS) is the only polysaccharide digested by gut enzymes and is high glycemic.
• AGE is inflammatory leading to artery plaque and hypertension.
• AGE as browned foods are probably tolerated by the body.

Erectile Dysfunction Diet

Inflammation Leads to Hypertension, Nitric Oxide Inadequacy and Impotence

Drugs for erectile dysfunction (ED), e.g. sidenafil (Viagra), compensate for inadequate nitric oxide (NO) production from arginine by inhibiting the enzyme, phosphodiesterase (PDE5), that hydrolyzes the cyclic GMP that mediates the NO-triggered process of vascular dilation.

Inflammation Is the Core of ED

Drug treatment to compensate for inadequate NO production is a multibillion dollar industry that avoids curing the underlying cause of the ED.  All of the physiological predispositions to ED result in or derive from chronic inflammation.  The major cause of ED, hypertension, frequently as a result of kidney disease, diabetes or metabolic syndrome, can be treated with diet and exercise.  Of course the typically recommended diet is essentially the Anti-Inflammatory Diet, compromised by the unenlightened persistence in the counterproductive use of grain starches, high fructose corn syrup, omega-6 polyunsaturated fatty acids and low saturated fat.

Decreasing Testosterone Results from Declining Health -- not Age

Recent studies also indicate that testosterone levels do not normally decline with age, but rather with declining health.  Healthy men have higher testosterone levels.  I would suggest that reduction in serum testosterone could be used as a measure of chronic inflammation in men.  This also suggests that many of the symptoms associated with aging in men actually reflect increasing chronic inflammation and reduced testosterone.

ED Diets Are Just the Anti-Inflammatory Diet Plus Veggies

A chronic high starch/sugar/HFCS diet with omega-6 oils in place of saturated fats, leads to chronic inflammation, high triglycerides, risk of metabolic syndrome and obesity.  Of course, diabetics have an even lower tolerance for this type of diet.  This diet, which is rather typical in many modern cultures, also provides a high risk of damage to endothelial cells lining the circulatory system and to ED.  The opposite of the inflammatory diet is the low carb, high omega-3 fish oil, no vegetable oil, meat/fish/dairy, Anti-Inflammatory Diet.  This is supplemented with exercise and high vitamin D.  Foods labeled as beneficial to ED also include specific herbs, spices and leafy vegetables, because these contain organic chemicals that inhibit components of the inflammation system or are anti-oxidants.
 
ED and Biofilms

I would suspect that men with ED suffer from chronic dietary inflammation and one of the consequences of this type of diet is the accumulation of pathogenic biofilms.  Hypertension, which is a contributor to ED and a consequence of chronic inflammation, is also associated with periodontal biofilms and kidney disease (aggravated by renal biofilms.)  I suspect that endothelial cells of capillaries are compromised by biofilm-derived endotoxins that ultimately contribute to apoptosis, decrease in capillary beds and elevation of blood pressure.  All of these assaults on endothelial cells undermine penile vasculature and contribute to ED.

Viagra Can Lead to Rosacea

Men taking Viagra or other PDE5 inhibitors typically have compromised vascular systems that are the basis for ED.  Increasing the response to NO in men with ED produces an increased risk of rosacea.  Withdrawal from PDE5 inhibitors stops the rosacea, which returns if the PDE5 inhibitor use is reinitiated.  Thus, the flush that is the goal of Viagra therapy, leaves some redfaced.

ref:
Ioannides, D. et al. (2009) Phosphodiesterase-5 inhibitors and rosacea: report of 10 cases. Br. J. Dermatol. 160: 719-20.