Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
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Wednesday, February 12, 2014

Diabetic Hypertension, Browning of the Arteries

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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.

10 comments:

aaron ashmann (halotek) said...

I agree with everything in this post but I have a bit of an off topic question. what about all the data to suggest that hypo caloric high carb diets really dont mess with insuoin much or even increase insulin sensitivity (especially when fructose is kept down) also what do u have to say about low carb diets increasing the stress hornones like cortisol as it seems some people really dont seem to adapt well to the diet

Raj said...

Hi Dr.Art,

This one is OT but I am relating to your previous posts on relationship between inflammation and civilization.

My second elder brother got malaria twice but rest of us mom,dad,eldest brother and I never got sick in spite of excess mosquito bits and living under same roof. Now fast forward he is the only person in the family with full set of hair on his head.

I was reading an article on how Plasmodium falciparum down regulates NF-κB before Invasion. Correlating this to a person with food based inflammation with elevated NF-kB could have waged better battle with this type of infection. Please let me know if there is any truth and is this reason you said inflammation might have helped civilization in few cases. This is fascinating to me now or I have understood it wrongly.

Thanks

Dr. Art Ayers said...

Hi Raj,
I think that you are onto something. You can also add other parts of the immune system into the equation, including the impact of gut flora on Tregs:
http://www.nature.com/icb/journal/v92/n2/abs/icb201373a.html?WT.ec_id=ICB-20
Also, some forms of baldness are sequelae of celiac via anti-tTG attack on hair follicles.

As always, thanks for the thought and comments.

Dr. Art Ayers said...

Halotek,
I am afraid that I don't have much of interest to add, except that low carb diets have a lot of impact on gut flora, because they are usually low soluble fiber. So much of the impact is just unhappy gut flora. Study populations have very diverse gut flora.

Thanks for the questions.

Raj said...
This comment has been removed by the author.
George Henderson said...

Methylglyoxal is a ketone body product, so low-carb doesn't avoid AGE that much. But glycation is reversible at low levels. Thiamine is involved in its reversal, which is why you get neuropathy as a symptom of B1 deficiency before metabolism (pyruvate clearance) is impaired (metabolic B1 use is co-enzymatic, glycation control is non-enzymatic, so triage favours metabolism).
Any excess thiamine after that also keeps the mosquitoes away.

I'm pretty sure that AGEs are beibg used for signalling, there will be an optimum level and we may well die without them. The sugar cross-linking of age that makes old muscle meat tough is probably not damage but an essential patching job that keeps us lasting longer than we otherwise would.

Dr. Art Ayers said...

George,
I enjoyed your comments. It makes sense for the body to play with glycation and just eliminate the problem AGE enzymatically. I think that modern diet and diabetes-based hyperglycemia is outside of evolutionary experience. The transglutaminase issues, e.g..celiac, are similar.

BTW, did you notice that I have mentioned several computational modeling and docking experiments that my group did with metformin binding to carbohydrate binding enzymes and RAGE?

aaron ashmann (halotek) said...

art, I wish i could reconcile all the people that seem to have all types of things go wrong when they keep carbs under 100grams a day. or exhibit issues with too much fat. my other question to ask is do you think omega 6s as in nuts would be an issue if your body fat is very low and one gets at least 200-300mg of dha?

AlmondD'oh said...

Dr ayers. What are your thoughts about using inulin in baked goods? Does high heat break it down to fructose?

Rob said...

Hi Dr. Art,

So would you recommend eating some resistant starch everyday as part of an anti-inflammatory diet?

Going a bit off-topic. I remember you mentioned in one of your post the effects of peppermint on gut flora. However, you mentioned briefly.

Is it possible to elaborate a bit more on the subject? For example, what would be the effect of having peppermint tea everyday on gut flora?

Any feedback will be much appreciated.