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יום שבת, 1 במרץ 2014

Slow down your aging - Reduce AGEs (Advanced Glycation End Products)

Hiya folks,

How old do you think this guy is? What if I tell you that he’s 27? No way you are saying.



Now how about this woman? How old is she? Is it possible that she’s 72 years old?



Yes you are right the man is clearly 72 years old and the woman is 27 years old. Aging is something that we recognize immediately. Aging is a progressive process that till today we are un-able to stop. Even the health Guros – you look at them through the botox and you know their age. 

Humans don’t need testing for blood pressure in order to gauge quite accurately the age of a person. Actually till today – there’s no test that can provide us with the "biological" age of a person.  We just take a look and we know, it’s the hair color, it’s the wrinkles, it’s the spots on the skin, it’s the color that gets darker brownish, it’s the dowager’s hump that’s develops and sometimes it’s the clogged brain (dementia) that we witness.

But biological aging can be slowed, and actually scientists are starting to explore in the last years the possibilities. Can we slow the formation of wrinkles? Can we delay the onset of Cataracts?  Can we delay the onset of diabetes? Of heart disease?

The answer is that probably yes – and today we are going to explore one of the major age promoting agents – AGEs - Advanced Glycated End products, and we are going to learn how to slow their formation.

What are AGEs?

Advanced glycation end products (AGEs) are a group of compounds that are formed when sugar interacts with proteins. AGEs are useless debris that results in tissue decay as they accumulate. They provide no useful function, they can’t be burned for energy, and they provide no lubricating or communicating functions. AGEs are harmful compounds that are being accumulated by our body and are thought to be one factor in aging and some age- related chronic diseases.  The more we accumulate AGEs, the more we age.

The pathological effects of AGEs are related to their ability to promote oxidative stress and inflammation by binding with cell surface receptors or cross-linking with body proteins, altering their structure and function [1].

Accumulated AGEs are associated with the amount of wrinkles, the general health of the skin, the amount of plaque that fills the arteries leading to arteriosclerosis, the loss of brain cells leading to dementia. AGEs are highly associated with diabetes and other chronic diseases.

They tend to clutter together and sit there in the body as debris, they are resistant to the immune system and the body just can’t get rid of them.


What is the damage that AGEs cause?

AGEs are forming everywhere in the body,  they are the result of proteins being bonded (glycated) with glucose and since we have lots of tissue made of protein and since glucose is flooding our body then this catholic marriage between proteins and glucose occur randomly all the time. But luckily many tissues are being replaced by the body so the AGEs can’t accumulate on those tissues. However there are some tissues that are never replaced in the retina of the eye, in the brain and in some other strategic locations – there the damage is accumulated. If your retina gets AGEs then that's for life!!

So let's go over the damage that these AGEs are causing:

Cardio Vascular diseases

AGEs cause arterial stiffening – healthy arteries can expand and accommodate blood ejected from the heart. This way the arteries kind of smooth the blood stokes into the rest of the body. Arterial stiffness causes the heart to pump harder in order to make them expand – a huge toll on the heart. [2]



AGEs cause atherosclerosis endothelial dysfunction – The endothelium is a thin layer on the artery wall just at the interface between the blood stream and the rest of the artery tissue. When functioning properly it controls the volume of electrolytes and other substances that pass from the blood into the tissues. AGEs  form on this endothelium tissue and cause inflammation there. They also cause generation of reactive oxygen species that bind with low-density lipoproteins (LDL). While cholesterol may not be a problem for your body (yes, yes!) the oxidation of the "bad cholesterol" (small LDL particles) is forming a plaque and eventually blocking the vessels.


As I explained in my blog post about sex - NO (Nitric Oxide) expands the arteries thus counteracting some of the mechanisms for atherosclerosis. AGEs interfere with this activity promoting atherosclerosis and… yes – they are causing erectile dysfunction to.

Semba et al. studied a group of 559 women aged 65 and older for 4.5 years and found that the highest risk for dying of cardiovascular disease were for women with the highest CML – one of the more known AGE compounds. [3]


Muscle Weakness

Muscle weakness is a problem of one third of women and half of men older than 60 in the us. In a study on women over 65 it was found that women with higher concentration of CML had less grip strength than women with lower CML [4]




Kidney failure

AGEs are scarring the kidney's tiny blood vessels that filter urine from the blood (Glomerulosclerosis). It cloggs the blood vessles inside the kidney which eventually end in kidney failure [5].




Alzheimer’s disease

AGEs are throught to be involved in Alzheimer's disease by inducing oxidative stress, inflammation and cell death. Researchers were studying a collections of brain samples from deceased patients who had suffered from Alzheimer's vs. a control group and found evidence for oxidative stress in the hippocampus part of the brain of Alzheimer's patients[6]. 




Eyes diseases

The retina of the eyes is the tissue on which light falls after it goes through the lens. This retina is exposed to lifetime of potentially damaging environmental and physiological factors that make the component cells exquisitely sensitive to age-related processes.  It can cause age-related macular degeneration (AMD) which is the leading cause of irreversible blindness in the western world [7]




It is suggested that advanced glycation plays also a pivotal role in cataract formation – the second leading cause of blindness. Since the lens proteins are long-lived, they too are highly susceptible to damange induced by AGEs. Researches took samples from 44 cataractous eye lenses and 6 non cataractours eye lenses, and found out that AGEs formed in higher degree in cataractous lenses than in noncataractous lenses. [8]




Skin

There is ample evidence that AGEs play an important role in skin aging for example collagen is a major protein in the skin. AGEs impair its function leading to stiffness and decreased flexibility [9]


AGEs and Diabetes

All the above effects of AGEs are illnesses of the elderly, the more we age, the more AGEs we accumulated. It's a progressive thing and the only thing we can do is to try to slow down this process and there are studies that correlate human age with the accumulation of AGEs (10).

Diabetes is this terrible disease that accelerates aging. In diabetes the average level of glucose in the blood is higher than normal people throughout the day which provides more opportunity for this infamous glycation process leading to the accumulation of AGEs. So researchers are studying diabetes because they have this opportunity to see all the above diseases in younger people. And indeed diabetic people suffer from the above, their condition lead eventually to coronary heart disease, to kidney failure, skin aging, cataract, Alzhimer's, etc.

So let's put here some wrinkles to remind you of where you are going to if you continue down the path of diabetis...


What is causing AGEs accumulation?

There are 3 sources in general:
·         Endogenous – AGEs are created internally by a process called glycation on which proteins are bound to carbs.
·         Exogenous –AGEs is input to the body through food that we ingest.
·         Smoking – AGEs are input to the body through the smoke that we inhale.

Endogenous AGEs

Endogenous AGEs are formed inside the body. As explained above they are the result of a process by which proteins are bound to glucose. When we eat , the level of glucose in the body goes up. The glucose is randomly bound to proteins to form AGEs. The higher the blood glucose – the higher the number of AGEs that are formed.

To combat the formation of these AGEs – we should keep the blood glucose level down. Every second that passes the number of AGEs created is linearily proportional to the glucose level at that second. This is why we care about average glucose levels rather than fasting glucose level.

If you eat foods with high glycemic values such as breads then your glucose level shoots up. If you eat the whole wheat ‘healthy’ breads then your blood glucose levels stays high for a long time since the glucose is released slowly to the blood over a long period of time.

If you eat 3 meals per day and you don’t eat nothing between meals then you can see that typically your blood level goes up at the time of the meal, reaches the maximum about one hour later and after two hours it’s back to normal.  This is the point where your psych leads you to the coffee corner to get your dose of coffee with sugar and if you are proud of not adding sugar then you add milk and this milk contains lots of glucose. And perhaps you taste a little cookie – you don’t really let your glucose level go down down to the required zone between 70 and 85, you always keep it above  100 and you are promoting AGE formation every second of your life… well except for when you are sleeping.

Yea - yumm, yumm, yummy eh? And I also watch closely at my work place after these people taking serials with the 3 clock's coffee...




Measuring Endonenous AGEs formation

There are many types of proteins binding to glucose. The most famous of them is called HB1AC. An HB1AC level below 5 is considered excellent, until 6.5 is regarded as normal, beyond 6.5 is already full blown diabetes. This HB1AC is linearily associated with your average blood glucose level in the past 60-120 days !!! The following table shows the linear relation.


I found the table in (11) and it says that actually there's a simple linear relation between your HB1AC and your average blood glucose level (eAG): eAGE(mg/dl) = 28.7*HbA1c - 46.7.
Now think about it – while the AGEs are the accumulated glycation over time, the HB1AC is the velocity… Remember what you learned in physics? S = v*t or AGEs goes like HB1AC * time. If you want to get older faster, then drive your life with a high HB1AC. I am currently measuring my glucose before and after every meal on top of fasting glucose that I measure in the morning. I want to find out which of my meals is increasing the velocity of my aging. Yes, people just don’t get it – they continue snacking between meals, they enjoy good tasty fiberless, processed food and they drive fast to their DEATH. I don’t, I try my best to live slowly. Yes, measuring my blood glucose costs me money (~0.5$ per test) but I am learning valuable information about my body as I am striving for  health excellence.




I am proposing here a hypothesis. Indeed it has to be proven yes I know but let me say it. If HB1AC is the velocity as explained above and we take HB1AC=4.5% as the optimal HB1AC and 120  years is the time we are expected to live if all goes well then the road ahead of us from the day we are born is 4.5%*120 years = 540 years%. As simple as that. Now you can look at the table below and see your life expectancy as a function of your HB1AC measure provided that Endogenous AGEs are the only life shortening effect. Yes Indeed you could be dying from cancer before you reach you AGEs induced life expectancy but if you don’t then you are expected *on average* to live as much as written in this table.
 

Exogenous AGEs


AGEs can be input to the body through the food we eat.  A 2010 study contains tables of foods and their AGEs.  You might want to take a look – it’s interesting. (12)

I averaged the amount of AGEs per serving according to different categories and the following table summarize that.



The highest amount of AGEs per serving can be found in meat products, that is poultry with 4,790 Kilo units per serving, Beef with 4,445 Kilo units per serving and Pork with 3,658 Kilo units per serving.  See the brown thing forming on the chicken? That's a high concentration of AGEs... And... no, if you remove the skin you will are going to meet lots of AGEs in meat.




Fish, cheese, fats and lamb follow with about 1000-1500 Kilo units per serving.

The least amount of AGEs can be found in fruits, eggs, breads, vegetables, milk, fruit juice and vegetable juice – up to 150 Kilo units of AGEs per serving.



But inside the groups there’s lots of variance because the amount of AGEs is a function of how you cook, at which temperature and for how long. If we take the poultry group for example and focus on a serving of chicken breast then broiling dry gets the highest amount of AGEs – 7922. The higher the heat, and the less liquids involved – the higher the AGEs intake. Actually any time you see sear marks on steak, a crispy coating on fried chicken, or a golden crust on bread, you’re looking at AGEs (13).

Deep frying is also a bad option, Grilling too.

Eating the chicken breast raw is the best option (692) followed by steaming, then poaching and boiling.
Sometimes once you fry your food it doesn’t really matter much if you do it for 7 minutes (3,726 KU/serving of chicken breast) or for 13 minutes (4,444 KU/serving of chicken breast). But cooking Paste for 12 minutes double the AGEs than cooking the same pasta for 8 minutes.

The temperature of cooking matters a lot. Cooking chicken breast for one hour yields 1011 KU/serving AGE while broiling it for 15 minutes yield 5,245 KU/serving.


The amount of processing also affects the AGE levels. For example popcorn has 40 KU/serving while perzels have 537 KU/serving !!! This is because of the different processing that these two products are undergoing.




A few studies about intestinal absorption of different AGEs have been conducted. However, the complete extent of absorption of each individual AGE is not well known. The most studied dietary AGEs are CML, pyrraline and pentosidine. Several studies have shown different rates of absorption of each of them. However, their metabolic pathways have not been elucidated. More studies on this area are needed to understand the impact of dietary AGEs on health and aging (14)

If indeed there is a significance absorption rate of exogenous AGEs then it negates the claims made by  those promoting diets based on intake of fat and proteins from meat (Paleo and such).

Practical Advice

So after introducing you to AGEs and going through all the pathologic consequences as well as the why and how's... let's give you a practical advice - how and what you should eat to reduce AGEs :)

  1. Most people start to care about their health when they are old and when the damage has already accumulated. Start Today, oh no no... start YESTERDAY!
  2. Get yourself familiar with the table of glycemic indexes – avoid those with high glycemic values.
  3. Notice that whole wheat bread has the same glycemic value as white bread – eat wheat very rarely or better yet - don't eat wheat at all.
  4. Don’t eat white rice, pasta, instant oat meal, fruit juices, raisings, bagels, white potatoes and junk processed foods,
  5.  Don’t add sugar or fructose to your foods.
  6. Reduce your intake of grains and starches - rice, pasta, etc.
  7. Go test your Hb1Ac– if it’s above 5 then you should do something about it.
  8. Measure your glucose level before eating and 1 hour after eating - study how you respond to different meals. 
  9. Avoid meat & cheese because of their exogenous AGEs.
  10. If you insist on consuming meat then eat it raw or steamed or poached or boiled.
  11. Reduce your intake of Soy and Tofu products because of their exogenous AGEs content.
  12. Avoid fish except for raw salmon, or perhaps canned tuna (Exogenous AGEs again)
  13.  Make greens & beans the center piece of your diet.
  14. Never eat foods that were cooked for a long time. Prefer your food cooked Al-Dante.
  15. Always cook with moistures (e.g. water): steaming, braising and blanching
  16. Avoid deep frying, roasting, broiling and grilling.
  17. Reduce your intake of nuts/seed to about an once a day (Exogenous AGEs again)

AAviel.


Sources

  1. Albert S Eblez, et. al "Nonenzymatic Glucosylation and Glucose-dependent Cross-linking of Protein". (PDF)
  2. Claudia Luevano-Contreas et al "Dietary Advanced Glycation End Products and Again, Nutrients 2010, 2, 1247-1265; doi:10.3390/nu2121247 (PDF)
  3. Semba, R.D.; Ferrucci, L.; Sun, K.; Beck, J.; Dalal, M.; Varadhan, R.; Walston, J.; Guralnik, J.M.; Fried, L.P. "Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women" (LINK)
  4. Dala M et. al "Elevated serum advanced dlycation end products and poor grip strength in older community-dwelling women", J Geronotol A Biol Sci Med Sci 2009 Jan; 64(1): 132-7. (LINK)
  5. Jurgen M. Bohlender et. al "Advanced glycation end products and the kidney" (PDF).
  6. F.F. Cruz-Sanchez et. al "Oxidative stress in Alzheimer's disease hippocampus: A topographical study (PDF)
  7. Glenn JV et. al "The role of advanced glycation end products in the retinal ageing and disease", Biochim Biophys Acta 2009 Oct; 1790(10), 1109-16. 
  8. Frank S, et. al "Increased levels of advanced glycation end products in human cataractous lenses" (Link)
  9. Paraskevi Gkogkolou et. al "Advanced glycation end products" (LINK)
  10. Daniel G. Dyer et. al "Accumulation of Maillard Reaction Products in Skin Collagen in Diabetes and Aging" 6-1-1993 University of South Carolina Scholar Commons (LINK)
  11. HbA1c and Estimated Average Glucose (eAG) (LINK)
  12. Jaime Uribarri, MD, et. al "Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet" (LINK)
  13. Alisa Bowman "Grill, Interrupted" April 8, 2008 Women's Health (LINK)
  14. Claudia Luevano-Contrearas et. al "Dietary Advanced Glycation End Products and Aging" (LINK)










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