Watch your intake of advanced glycation end products

[RightSide]

This past week, my dietitian informed me about an issue I hadn't heard about before--the damaging effects on the body caused by excessive intake of "advanced glycation end products (AGEs)" in the diet.

Advanced glycation end products (AGEs) are compounds formed when sugars combine chemically with fats or proteins as part of the cooking process.  Some of these compounds, called glycotoxins, can cause oxidative stress, those nasty "free radicals" you've heard so much about. And oxidative stress is suspected to contribute to several nasty problems, including cardiovascular disease and even the narrowing of an AV fistula, possibly leading to failure of the access.

In a healthy person, AGEs are eventually eliminated through the kidneys.  But in us ESRD patients with greatly impaired renal clearance, AGEs can build up in the body to high levels.  It therefore seems prudent to restrict our intake of AGEs when possible.

Boiling, steaming, and microwaving seem to produce fewer AGEs than broiling, roasting or toasting. And frying, particularly where carbohydrates are present (as with French fries or fried onions) seems to be worst of all.

Of course, it's best if you ask your own dietitians about this issue.  There's also lots of stuff about it on the Internet.  Happy googling!

[natnnnat]

I got curious and did some quick searches.  First in google I found this, which says kind of what RightSide said
(goddamit, I just baked a delicious batch of cookies and ate many, only to read that they're packed full of sugar melded to fat.  Sigh)

from http://clinical.diabetesjournals.org/content/21/4/186.full
Peppa, M, Uribarri, J, Vlassara, H, 2003, Glucose, Advanced Glycation End Products, and Diabetes Complications: What Is New and What Works, Clinical Diabetes, vol. 21  no. 4  186-187

[...excerpt...]
In addition to those endogenously formed, AGEs can also be introduced in the body from exogenous sources. Tobacco smoke, for example, is a well-known exogenous source of AGEs. The combustion of various pre-AGEs in tobacco during smoking gives rise to reactive and toxic AGEs. Serum AGEs or LDL-linked AGEs are significantly elevated in cigarette smokers. Diabetic smokers, as a result, are reported to exhibit greater AGE deposition in their arteries and ocular lenses.

More importantly, recent studies have provided evidence that diet is a significant exogenous source of highly reactive AGEs. Food processing, heating in particular, has a significant accelerating effect in the generation of glyco- and lipoxidation products. Heat helps create tasteful flavors that humans have learned to enjoy. In recent decades, food manufacturers have been using this knowledge to boost the flavor of natural foods by incorporating synthetic AGEs into foods. Consequently, the AGEs content of the Western diet has increased vastly in the past 50 years, as has the quantity of food consumed.

A significant proportion (∼10%) of ingested AGEs is absorbed with food. There is apparently a direct correlation between circulating AGE levels and those consumed. Studies in animals have demonstrated an important relationship between high dietary AGE intake and development or progression of diabetes-related tissue damage, e.g., vascular and renal. In all instances, this was prevented by dietary AGE restriction.

A similarly significant contribution to the human body AGE pool by diet was demonstrated recently. More importantly, its effective reduction by a restriction of dietary AGEs was associated with a significant suppression of circulating levels of vascular disease markers (e.g., adhesion molecules) as well as of inflammatory mediators.

This new evidence suggests that modulation of food-AGE content could become an important ingredient of the therapeutic armamentarium in the management of diabetic patients. Until effective and safe drugs become available, physicians and dieticians can, for instance, advise increased reliance on fresh foods, cooked by brief applications of heat, in the presence of ample water or humidity. A diet designed to be low in AGEs is apparently not lacking in taste, while not requiring compromises in important nutrients. Such a regimen can decrease AGE intake by more than 50%; this in turn was shown to reduce circulating AGEs by ∼30% within a month without a change in A1C. On the contrary, short-term euglycemia or temporary normalization of A1C are not sufficient means for reducing serum AGEs; instead this requires extended periods of time, e.g., months or years.
[...end excerpt...]

[natnnnat]

Next I went and looked in CINAHL, a major medical academic journal database.
(CINAHL Plus with Full Text provides indexing for 3,024 journals from the fields of nursing and allied health, with indexing back to 1937") 
I found these.   
Note:  this is the results from an hour's searching, in one database, there may be other articles out there which contradict these.  I didn't come across anything suggesting that AGE products aren't potentially problematic for diabetes / renal patients, only ones like these, exploring in what ways they may cause problems.  But I am not medically trained, perhaps I missed the wording of those articles, as they're using medical mumbo jumbo which as a lay person, I don't read easily.

Hartog, J. W. L., A. J. Smit, et al. (2004). "Advanced glycation end products in kidney transplant patients: a putative role in the development of chronic renal transplant dysfunction." American Journal of Kidney Diseases 43(6): 966-975.
   Chronic renal transplant dysfunction is one of the leading causes of graft failure in kidney transplantation. A complex interplay of both alloantigen-related and alloantigen-unrelated risk factors is believed to underlie its development. We propose that advanced glycation end products (AGEs) are involved in the development of chronic renal transplant dysfunction. AGE formation is associated with different alloantigen-unrelated risk factors for chronic renal transplant dysfunction, such as recipient age, diabetes, proteinuria, hypertension, and hyperlipidemia. In vitro studies have shown that AGEs induce the expression of various mediators associated with chronic renal transplant dysfunction. Furthermore, AGE-induced renal damage has been found in multiple experimental studies. This renal damage shows similarity to the damage found in chronic renal transplant dysfunction. Together, several lines of evidence support a role of AGEs in the development of chronic renal transplant dysfunction and suggest that preventive therapy with AGE inhibitors may be helpful in preserving renal function in transplant recipients. Copyright © 2004 National Kidney Foundation, Inc.

Kalousová, M., M. Hodková, et al. (2006). "Soluble receptor for advanced glycation end products in patients with decreased renal function." American Journal of Kidney Diseases 47(3): 406-411.
   BACKGROUND: Advanced glycation end products (AGEs) accumulate in patients with decreased renal function and exert various toxic effects through the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) is a naturally occurring inhibitor of AGE-RAGE action. The aim of the study is to describe the relationship of sRAGE to renal function and dialysis modalities. METHODS: The studied group consisted of 81 patients: 25 patients with various degrees of decreased renal function, 20 long-term hemodialysis (HD) patients, 15 peritoneal dialysis (PD) patients, and 21 healthy age-matched subjects. sRAGE was assessed immunochemically (enzyme-linked immunosorbent assay), and routine biochemical parameters were measured by means of certified methods. RESULTS: sRAGE level correlates positively with serum creatinine concentration (r = 0.50; P < 0.05), and its relationship to creatinine clearance is hyperbolic. sRAGE levels are elevated significantly, mainly in patients with end-stage renal disease (3,119.0 +/- 968.4 pg/mL in HD patients and 3,652.7 +/- 1,677.7 pg/mL in PD patients versus 1,405.1 +/- 426.1 pg/mL in controls; both P < 0.001 versus controls). In PD patients, sRAGE is detectable in spent dialysate (median, 75.8 pg/mL), correlates with its serum levels (r = 0.67; P < 0.05), and is related to protein losses in dialysate. In HD patients, sRAGE levels increase by 50% (P < 0.001) from 0 to 15 minutes during both HD and hemodiafiltration, and then decrease until the end of the session. CONCLUSION: Serum sRAGE levels increase in patients with decreased renal function, mainly patients with end-stage renal disease. It remains to be elucidated whether the increase is caused just by decreased renal function or whether sRAGE is upregulated to protect against toxic effects of AGEs. Copyright © 2006 National Kidney Foundation, Inc.

McLennan, S. V., D. J. Kelly, et al. (2007). "Advanced glycation end products decrease mesangial cell MMP-7: a role in matrix accumulation in diabetic nephropathy?" Kidney International 72(4): 481-488.
   Increased extracellular matrix material is a pathological hallmark of diabetic nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins such as fibronectin also accumulate in the kidney of diabetics. The effect of diabetes on degradative pathways, in particular those involving non-collagenous proteins, are relatively unexplored. In this study, we determined the expression of the major matrix metalloproteinase (MMP) responsible for degrading the non-collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these MMPs by advanced glycation end products (AGE), a key factor in the diabetic milieu, was explored. Exposure of mesangial cells to AGEs led to a significant reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing anti-transforming growth factor-beta (TGF-beta) antibody. In streptozotocin-induced diabetic rats, the diminution in MMP-7 expression and excessive fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2 diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent counterparts. Our findings suggest that diminished expression of the glycoprotein-degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the diabetic kidney in response to AGEs and/or TGF-beta.

Noordzij, M., J. Lefrandt, et al. (2008). "Advanced glycation end products in renal failure: an overview." Journal of Renal Care 34(4): 207-212.
   The article aims to present an overview of the existing knowledge on advanced glycation end products (AGE). They are moieties that bind to proteins, but also lipids and nuclear acids. AGE are formed during glycation and oxidative stress. Accumulation of AGE occurs especially in diabetes and chronic renal failure and plays a major pathogenetic role. The deleterious effects of AGE result from cross-linking of proteins and activation of the receptor for advanced glycation end products. AGE accumulation can be noninvasively assessed by the skin autofluorescence reader. In diabetics, the skin autofluorescence predicts cardiac mortality and the occurrence of macro- and microvascular complications. In patients on haemodialysis, skin autofluorescence is highly elevated and predicts mortality. After renal transplantation AGE accumulation is lower than during haemodialysis, but still remains elevated and is a strong risk factor for chronic renal transplant dysfunction. Some of the potential methods to intervene with AGE accumulation are discussed in this article.

Semba, R. D., J. C. Fink, et al. (2010). "Serum carboxymethyl-lysine, a dominant advanced glycation end product, is associated with chronic kidney disease: the Baltimore longitudinal study of aging." Journal of Renal Nutrition 20(2): 74-81.
   OBJECTIVE: Advanced glycation end products (AGEs) are modifiable risk factors for renal disease that were primarily studied in persons with diabetes or endstage renal disease. Our objective was to characterize the relationship between AGEs and renal function in community-dwelling adults. DESIGN: The presence of serum L-carboxymethyl-lysine (CML), a dominant AGE, was compared with renal function in a cross-sectional analysis. SETTING: This study was part of the Baltimore Longitudinal Study of Aging in Baltimore, Maryland. PATIENTS OR OTHER PARTICIPANTS: Participants included community-dwelling men and women, aged 26 to 93 years, seen during a regular follow-up visit to the Baltimore Longitudinal Study of Aging between 2002 and 2007. MAIN OUTCOME MEASURES: The main outcome measures included chronic kidney disease (CKD) at stage >/=3 of the National Kidney Foundation classification (estimated glomerular filtration rate [eGFR] of<60 mL/minute/1.73 m(2)) and eGFR. RESULTS: Of 750 adults, 121 (16.1%) had CKD. Serum CML was associated with CKD (odds ratio expressed per one standard deviation, 1.37; 95% confidence interval, 1.11 to 1.67; P=.003) in a multivariate logistic regression model adjusting for age, race, smoking, and chronic diseases. Serum CML was associated with eGFR (mL/minute/1.73 m(2)) (beta=-2.21, standard error=0.57, P=.0001) in a multivariate linear regression model, adjusting for age, race, smoking, and chronic diseases. After excluding patients with diabetes, serum CML was associated with CKD (odds ratio per one standard deviation, 1.38; 95% confidence interval, 1.12 to 1.70; P=.003) and eGFR (beta=-2.09, standard error=0.59, P=.0005), adjusting for the same covariates. CONCLUSION: Serum CML, a dominant AGE, is independently associated with CKD and eGFR.
Copyright © 2010 by Elsevier Inc.

Thomas, M. C., J. M. Forbes, et al. (2005). "Advanced glycation end products and diabetic nephropathy." American Journal of Therapeutics 12(6): 562-572.
   Chronic hyperglycemia and oxidative stress in diabetes results in the formation and accumulation advanced glycation end products (AGEs). AGEs have a wide range of chemical, cellular, and tissue effects that contribute to the development of microvascular complications. In particular, AGEs appear to have a key role in the diabetic nephropathy. Their importance as downstream mediators of tissue injury in diabetic kidney disease is demonstrated by animal studies using inhibitors of advanced glycation to retard the development of nephropathy without directly influencing glycemic control. AGE modification of proteins may produce in changes charge, solubility, and conformation leading to molecular dysfunction as well as disrupting interactions with other proteins. AGEs also interact with specific receptors and binding proteins to influence the renal expression of growth factors and cytokines, implicated in the progression of diabetic renal disease. The effects of AGEs appears to be synergistic with other pathogenic pathways in diabetes including oxidative stress, hypertension, and activation of the renin-angiotensin system. Each of these pathways may be activated by AGEs, and each may promote the formation of AGEs in the vicious cycle associated with progressive renal damage. It is likely that therapies that inhibit the formation of AGEs or remove established AGE modifications will form an important component part of future therapy in patients with diabetes, acting in concert with conventional approaches to prevent diabetic renal injury.

Thornalley, P. J. (2006). "Advanced glycation end products in renal failure... Proceedings of the 4th International Congress on Uremia Research and Toxicity, September 14-17, 2006, Izmir, Turkey." Journal of Renal Nutrition 16(3): 178-184.
   Cellular and extracellular proteins suffer significant damage in vivo by glycation. Physiological proteolysis of proteins damaged by glycation forms glycation free adducts that are released into plasma for urinary excretion. Inefficient elimination of these free adducts in uremia leads to their accumulation. In mild renal insufficiency, plasma glycation free adducts accumulated as renal clearance declined. In patients with end-stage renal disease, plasma glycation free adducts were increased up to 18-fold on peritoneal dialysis and up to 40-fold on hemodialysis. Glycation free adduct concentrations in peritoneal dialysate increased with dialysate dwell time, achieving concentrations in the dialysate higher than in plasma--suggesting that glycation adduct formation may occur in the peritoneal cavity and active transport into the peritoneal cavity may occur. In hemodialysis, plasma glycation free adducts equilibrated rapidly across the dialysis membrane, with both plasma and dialysate concentrations decreasing during a dialysis session. Therefore, protein glycation free adducts normally excreted efficiently in urine show profound mishandling and accumulation in chronic renal failure. Their accumulation may impair vascular cell function and contribute to morbidity and mortality in renal disease. Copyright © 2006 by the National Kidney Foundation, Inc.

[paul.karen]

Well thats all over my head.

All i understood was no French fries & smoking is bad.

[natnnnat]

Sorry, it really is a load of gobbledigook that post I made above, isn't it.  I feel like I've got one big eye and one small weepy eye, after reading it. 
They all seem to be saying that these AGEs may contribute to diabetes, and maybe also to CDK, and maybe also to chronic renal transplant dysfunction.  I get the impression that in healthy kidneys, AGEs are removed from the system, but when kidneys are unhealthy, AGEs build up, and maybe contribute to actually stuffing the kidneys in some kind of cyclic effect.  Does that sound right to anyone else who can read this stuff?  Where's that kidney doctor with the blog?  If I was to pull the guts out of that lot I’d boil it down to these quotes:

…a role of AGEs in the development of chronic renal transplant dysfunction (Hartog et al 2004)

After renal transplantation AGE accumulation...remains elevated and is a strong risk factor for chronic renal transplant dysfunction. (Noordzij et al 2008)

Serum CML, a dominant AGE, is independently associated with CKD and eGFR. (Semba et al 2010)

AGEs also interact with specific receptors and binding proteins to influence the renal expression of growth factors and cytokines, implicated in the progression of diabetic renal disease. (Thomas et al 2005)

Therefore, protein glycation free adducts normally excreted efficiently in urine show profound mishandling and accumulation in chronic renal failure. Their accumulation may impair vascular cell function and contribute to morbidity and mortality in renal disease.  (Thornalley et al, 2006)



Gregory's comment wasn't very helpful, and wont be reported here.

[Zach]

As Grandma always said, "Moderation is the key to a long life."

[okarol]

As Grandma always said, "Moderation is the key to a long life."

Gotta love grandmas!

[Zach]

I guess it's back to Steak Tartare and raw oysters!
 

[natnnnat]

and obviously its more healthy to eat my cookie dough raw in future. 

[Rerun]

Well crap!  Why eat!   

[MooseMom]

So, now only do we have to restrict what we eat but also HOW we prepare it.  That's just bloody brilliant.  I agree with Rerun...sometimes I think it is just easier not to eat at all.  Perhaps if I just cut in half what I eat during the course of the day, then I cut in half all of the potassium/phosphorus/other fatal crap.  Seems simple!

[MooseMom]

Boiling, steaming, and microwaving seem to produce fewer AGEs than broiling, roasting or toasting. And frying, particularly where carbohydrates are present (as with French fries or fried onions) seems to be worst of all.

Of course, it's best if you ask your own dietitians about this issue.  There's also lots of stuff about it on the Internet.  Happy googling!

Why should we have to ask dieticians about this?  Shouldn't they already know and tell us about it?  Who among us has EVER had a dietician mention this issue?  Yours, RightSide, must be particularly well informed because this is the first time I've heard about this...that you should "wet" cook your food instead of dry/heat cook it.  So as of tomorrow, should we all just start eating fewer foods that are cooked with dry heat?

I still can't get used to the idea that food is the enemy...

[natnnnat]

Moosemom, not only do I wonder why this wasn't already old news if its important, I also dread the kind of "home made" searching for info that creates a collection of patched together "I reckons".   Which I am now doing, and thinking aloud by dumping here.

I went to the supermarket yesterday afternoon with this on my mind and got stranded and lost.  I couldnt see anything that would both work with the heat/bake/fry thing, and also seem to be renal friendly, except salad, and I feel that I don't have time for salad.  Not that I have to worry about renal friendly, but I had it on my mind.  I was stranded in the meat section for so long I didn't know who i was, made an impulse buy and ran away.  Gregory was happy with the impulse buy:  steak.  He loves steak and almost never gets its because I don't have time for homey cooking stuff and steak requires side dishes prepared separately    Apparently, I read today on websites with poor credentials, cooking steak rare or medium rare is "alright".

I wonder if crockpot cooking is cool enough to work?  That's a low heat.  Ever since I first discovered crock pot cooking by reading VictoriaG mention hers on IHD (I said to myself, why have I never heard of a crockpot?... looked it up online, and rushed out that day to buy a big one) my life changed, I could stay at work all day and come home to a fragrant house and have a meal on the table in seconds.  Thanks VictoriaG.

More quick and nasty googling uncovers stuff which isn't authoritative, but is interesting.

1.  a cooking website says crock pots are good:
    * Studies have shown that the low, constant heat crockpots cook by may help prevent disease! Some compounds called "advanced glycation end products" are formed when sugars, fats, and proteins are heated at high temperatures, as when food is grilled, broiled, or microwaved.
    * These AGE's irritate cells and may be a factor in the formation of heart disease, cancer, and diabetes. Since slow cookers only heat between 200 and 300 degrees, fewer of these compounds form in crockpot cooked meals, so slow-cooked meals are healthier.
http://busycooks.about.com/od/slowcookerrecipes/a/crockpot102.htm -

2.  .... secondly, a person named Catherine M. Haug, who uses wikipedia as a reference,  thinks crock pots are good.  There is other interesting info on this page about AGE products, but no information about who the author is or why she should know. Regarding crock pots, she says:
Instead, look for cooking methods that bathe the food in moisture:  stewing, steaming and slow-roasting in a low temperature oven, dutch oven, or crock pot.  If you want a cake, try a steamed "pudding," which is cooked slowly by surrounding it with steam. 
The important thing is to cook at temperatures below which the Maillard reaction (glycation) cannot occur; that is no hotter than the boiling point of water (212deg F, or 100deg C).  This is why cooking in a moist environment is so good.  As long as water is present, the heat cannot rise above the boiling point of water.
http://web.mac.com/catherinehaug/iWeb/Health-Disease/Glycation.html


3.   This is from a sports coach (sigh)
There are a few steps you can take to keep yourself safe from a toxic load of these compounds.
    * Keep blood sugar low with a Real Foods [TM] diet – This will reduce sugar supplies available for glycation.
    * Eat vegetables and fruits raw, boiled, or steamed – When eating raw, there is no formation of these compounds because there is no cooking, while boiling and steaming introduce water to the cooking process.
    * Avoid processed carbohydrates and browned foods – Food manufacturers take steps to increase caramelization and browning in their foods, directly increasing the levels of AGEs in the foods.
    * Cook meats low and slow – Higher temperatures produce more AGEs than lower temperature, longer cooking times. Rare and medium-rare meats will have fewer AGEs than fully cooked meats, like barbeque or well-done steak.
http://www.fitnessspotlight.com/2008/12/01/what-are-advanced-glycation-end-products/

I also found this: 
Meanwhile, food manufacturers have deliberately added AGEs to foods to enhance their appearance and flavor; for example,  donuts, barbecued meats, cake, and dark colored soda pop.   http://web.mac.com/catherinehaug/iWeb/Health-Disease/Glycation.html
...remembering Gregory's serious addiction to coke followed by diet coke. Hmmm.

I tried to find stuff from government webpages, or university web pages, or organisation type web pages,  (e.g. diabetes organisations) but came up with donut.  I bet that stuff is out there but I want breakfast (raw muesli with apple.  At least I do that right...)

[natnnnat]

I am sorry to so flog the horse here, and to keep making long posts too, but I’ve found another interesting “I reckon”, this one is about drinking tea to counteract some of the trouble.
this time written by the editor of “Life enhancement” magazine: Will Block is a journalist, and Life Enhancement is a company which produces nutritional supplements.
http://www.life-enhancement.com/article_template.asp?id=1943

He says:  One way to slow AGEing involves the use of certain supplements that have been shown—in laboratory experiments, animal studies, or human clinical trials—to inhibit the formation of AGEs. Notable in this regard are: benfotiamine, a fat-soluble form of thiamine (vitamin B1); the amino acid histidine; the dipeptide carnosine, which consists of linked histidine and beta-alanine; alpha-lipoic acid, a saturated fatty acid renowned for its potent and versatile antioxidant actions; and rutin, a flavonoid found in many plants, notably buckwheat, black tea, and apple skins.
end quote.

Tea!!! (winds up the tea propaganda machine…..rrrrrrr.r….rrrr .. if only you drank tea!!!!)
A quick google using “Advanced Glycation End products tea” produces results which only seem to mention green tea (pulls face). 

I'll stop googling and posting all this way-too-much-information now.  With apologies. This AGE thing got me going for some reason.  [Bowing out quietly][famous last words]

[MooseMom]

No, no, no, natnnnat, keep posting about this!  You are the academic and I am the lazy sod, so you just keep on!  We all know that a lot of stuff found on the internet is garbage and/or propaganda, but from multiple sources, we can cobble together the basics of a plan.  I have a crockpot and enjoy making stews and roasts, so this is a great option.  I have a microwave and a vegetable steamer, so I have the basic tools; I bet I'm not the only one on IHD who has this stuff, either.

We already know that everyone, whether renally challenged or not, should stay away from processed foods, and I bet if we could just keep to that one rule, we'd be way ahead of the game.  And if, as a general rule, we use steam vegetables instead of roasting them, and if we eat our fruit raw, then those are simple steps that address a complicated issue.

I drink a lot of home brewed tea, both black and green, so that's good, I guess.

[RightSide]

My dietitian has now started me on benfotiamine (150 mg/daily, after dialysis on dialysis days).  This is to try to reduce the level of Advanced Glycation End Products (AGEs) in my body.

http://en.wikipedia.org/wiki/Benfotiamine

The list of my meds is getting longer and longer every month.

It's a good thing that my fluid restrictions aren't too severe, because I must be taking between 50 and 100 pills and capsules every day with that water.  These days, every single mouthful of water or bouillon that I consume has at least one pill in it!   

[MooseMom]

My dietitian has now started me on benfotiamine (150 mg/daily, after dialysis on dialysis days).  This is to try to reduce the level of Advanced Glycation End Products (AGEs) in my body.

What kind of test do they do to determine the level of AGEs in your body?  I've never seen this on any lab request form.

[Zach]

I'm becoming more skeptical of what one finds on Wikipedia.
More often than before, some of the items posted there are public relations and promotion.

[calypso]

Interesting:

AGEs are the subject of ongoing research. Glycation inhibitors include benfotiamine, pyridoxamine, alpha-lipoic acid,[28] taurine,[29] aminoguanidine,[30], aspirin [31], carnosine[32], resveratrol[33], and Alagebrium.

from: http://en.wikipedia.org/wiki/Advanced_glycation_endproducts

[tyefly]

very interesting.....  I have never heard of this ......   thx for all the info......  more things to think about.....

[RichardMEL]

Everything will be much better if you only eat in a sauna.....