A glycation rock and a hard place

Advanced Glycation End-products, or AGEs, the stuff of aging that mucks up brains, kidneys, and arteries, develop via two different routes: endogenous (from within the body) and exogenous (from outside the body).

Endogenous AGEs develop via glycation. Glycation of proteins in the body occurs when there are glucose excursions above normal. For instance, a blood glucose of 150 mg/dl after your bowl of stone-ground oatmeal causes glycation of proteins left and right, from the proteins in the lens of your eyes (cataracts), to the proteins in your kidneys (proteinuria and kidney dysfunction), to skin cells (wrinkles), to cartilage (brittle cartilage followed by arthritis), to LDL particles, especially small LDL particles (atherosclerosis).

At what blood sugar level does glycation occur? It occurs even at "normal" glucose levels below 100 mg/dl (with measurable long-term cardiovascular effects as low as 83 mg/dl). In other words, some level of glycation proceeds even at blood glucose levels regarded as normal.

There's nothing we can do about the low-level of glycation that occurs at low blood sugar levels of, say, 90 mg/dl or less. However, we can indeed do a lot to not allow glycation to proceed more rapidly, as it inevitably will at blood sugar levels higher than 90 mg/dl.

How do you keep blood sugars below 90 mg/dl to prevent excessive glycation? Avoid or minimize the foods that cause such rises in blood sugar: carbohydrates.

What food increases blood sugar higher than nearly all other known foods? Wheat.

Comments (15) -

  • soiltosustenance

    1/12/2011 3:19:52 PM |

    I have been doing some experiments with Blood Glucose control over the past 2 months and have made a huge difference by cutting out grains completely.  Between the reduction in carbs and the addition of some moderate strength training, I have been able to eliminate BG spikes above 150 (now normal highs are in the 120s) and the duration is shorter as well.

  • Anonymous

    1/12/2011 5:01:24 PM |

    Dr Davis I as a neurosurgeon scientist completely agree with you about carbs wheat and glycation but from the literature of diabetics I am far more concerned with lipid peroxidation from PUFA's.  Espcially the omega 6 and 9's which are known to cause six times the "glycation" that glucose does.  I believe a meta analysis was done for Circulation recently and it caused a firestorm in the AHA ACA because of sponsorship issues.  I am more concerned with the guidelines we physcians need to advocate than guidelines that are subject to market forces more than scientific ones.

    Dr. K

  • Anonymous

    1/12/2011 10:05:44 PM |

    Dr. K,

    I tried to find that meta analysis in Circulation and couldn't find it. Could you please provide the reference. Thanks

  • Anonymous

    1/12/2011 11:15:11 PM |

    I have to say I've found giving up wheat, even cutting down substantially, to be damn difficult because it's so widespread and simple habit. I aim for more lean meats and things like rice for carbs, but so dearly love my breakfast cereal and pizza!

    Does anyone have thoughts on aminoguanidine relative to the glycation issue. I took it for some months a few years ago until it got a bit too pricey.

  • revelo

    1/13/2011 12:37:42 AM |

    If wheat and omega-9 fatty acids are so unhealthy, why do the southern europeans live so long? Wheat and olive oil are a huge part of the traditional Mediterranean diet.

  • Anonymous

    1/13/2011 3:55:31 AM |

    Meta-analysis Reveals “Heart Healthy Omega-6 Fat” Increases Risk of Heart Disease
    Bottom Line: The research upon which the American Heart Association based their "eat-your-omega-6-fat" advisory, is fatally flawed, according to the results of a meta-analysis study, which showed that a steady diet of omega-6 polyunsaturated fatty acids increases the risk of heart disease and death, especially for women [1]. British J Nutr. Dec 2010.

           [Here's a link to the full post http://www.scribd.com/doc/44601571 ]
    DR. K

  • Anonymous

    1/13/2011 3:57:10 AM |


  • Might-o'chondri-AL

    1/13/2011 5:01:36 AM |

    Advanced glycation of peroxidized poly-unsaturated fat rate has definitely been claimed to be significantly higher than rate of glucose advanced glycation.

    Dr. Davis' tactic of glucose control does seem easier for patients to see how they can make changes that matter. They are then more open to following his complete program.

    A recent autopsy analysis (2010) of ruptured plaque said there was always iron in there; and yet no iron in the intact plaque. Iron cleaved from the blood is a suspected activator of omega-6 lipid peroxidation at the epithelium. When the fibrin polymerizes it seems iron gets trapped.

    People's genetics make me wonder if some mega-dose multi-vitamin takers are over doing the iron; vitamin C even boosts it's uptake. Old "southern Europeans" probably never took complex vitamin pills until recently. Wheat germ has soluble iron and those old timers ate white flour products if they could.

  • D.M.

    1/13/2011 9:00:32 AM |

    @Anonymous neurosurgeon scientist.
    Isn't omega 9 MUFA rather than PUFA?
    Also there's no reason why a LCHF diet couldn't also minimise PUFA, in preference to SFA/MUFA.

  • Dr. William Davis

    1/13/2011 1:04:46 PM |

    While this post was about endogenous glycation, there is indeed a parallel path of exogenous "glycation," poorly named because many of the so-called exogenous "advanced glycation end-products" do not involve glycation.

    I agree with Dr. K that many of the exogenous factors leading to heart disease, aging, and other phenomena are those that lead to LDL oxidation. Oxidized polyunsaturates, AGEs, and oxidized cholesterol are underappreciated phenomena.

    A topic for future.

  • Anonymous

    1/13/2011 10:08:11 PM |

    Although I had given up oats and other grains because of their adverse effect on blood glucose,I had not been able to give up toast(sprouted wheat). I finally found a great solution--organic frozen green beans. They are easy to cook and go well with eggs. I have been wheat-free for about a month.I feel good and I don't get hungry as often.

  • Alberto

    1/13/2011 11:26:13 PM |

    As revelo, I am curious as how is it that italians eat tons of pasta (they use hard grains) and seem to be healthy.

  • allison

    1/14/2011 5:16:48 AM |

    Peter at Hyperlipid has written about this fasting glucose paradox in carb-restricted individuals.  

    I have been Paleo (<60 grams of carbs) for two years.  I eat no sugar, fructose or grains of any kind.  Yet my fasting glucose is 90 with all other diabetic indicators normal.  Apparently, high normal fasting glucose is common among LCHF diets.  

    I haven't researched this, but since a LCHF diet produces large, fluffy oxidation-resistant LDL, I wonder whether there is a beneficial effect downstream from glycation? Otherwise both a low fat, high carb diet and a LCHF diet would produce the same bad result.  That doesn't quite add up.

  • allison

    2/3/2011 5:28:43 AM |

    Glycation refers only to the initial step of one glucose molecule attaching to a protein without the mediation of an enzyme.  If blood glucose levels are low enough--as would be the case with a HFLC diet--the glucose and protein will disengage and no damage will be done.  If blood glucose remains elevated, the cascade to advance glycation end products will continue to protein cross-linking and all the downstream deleterious effects.  The unavoidable glycation referenced by Dr. Davis is harmless, as long as you avoid refined carbohydrates.  No conundrum there.

  • Kirk

    9/12/2012 6:58:44 PM |

    Couldn't you also keep your blood sugar low through a lot of exercise (if you're so inclined)?  60g of complex carbs going into a sedentary person with 50% bodyfat is going to have a different effect than the same 60g going into a sub-3 hour marathon runner.

The Framingham Crap Shoot

The Framingham Crap Shoot

The Framingham risk score is a risk-assessment tool that has become the basis for heart disease prediction used by practicing physicians.

The Framingham system determines that:

· 35% of the adult population in the U.S., or 70 million, is deemed “low-risk.” Low-risk is defined as the absence of standard risk factors for heart disease; low-risk persons have no more than a 1-in-20 chance (5%) of dying from heart disease in the next 10 years. Physicians are advised by the American Heart Association (AHA) and its experts that no specific effort at risk reduction is necessary.

· 25%, or approximately 50 million, U.S. adults are deemed “high-risk,” based on the presence of 2 or more risk factors. High-risk persons experience a 20%-30% likelihood of heart attack in the next 10 years. People at high-risk are candidates for preventive efforts according to the guidelines set by the Adult Treatment Panel-III (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; ATP-III) for cholesterol-reducing statin drug treatment and for “lifestyle-modifying” advice.

· The remaining 40% of the adult population, or 80 million people, are judged “intermediate-risk,” with the likelihood of heart attack between 5-20% over the next 10 years. This group should receive preventive advice and might be considered for statin drug treatment.

Let’s do some arithmetic. By the above scheme, the low-risk population will experience 3,500,000 heart attacks over the next decade, or 350,000 heart attacks per year.

The intermediate-risk population (without preventive treatment) will experience 8,000,000 heart attacks over the 10-year time period, or 800,000 per year.

The high-risk population, the group most likely to receive standard advice on diet, exercise, and be prescribed statin cholesterol drugs, will have their risk reduced by 35% by preventive efforts over the 10-year period. This means that heart attacks over 10 years will be reduced from 12,500,000 to 8,125,000 by standard prevention efforts, or reduced to 812,500 heart attacks per year.

These numbers are no secret. They are well known facts that have simply come to be accepted by the medical community. In other words, the standard approach to heart attack prediction makes the fact that two million people will succumb to cardiovascular events in the next year no mystery. This exercise in prediction is coldly accurate when applied to a large population.

The problem is that this approach cannot reliably distinguish which individuals will have a heart attack from those who will not.

From 100 people chosen at random, for instance, the numbers game played above will not confidently identify who among those 100 will have a heart attack, who will not, who will develop anginal chest pains and end up with stents or bypass surgery, or who will die. We just know that some of them will. Some people at high risk will have a heart attack, some people at intermediate risk will have a heart attack, some people at low risk will have a heart attack.

For any specific individual (like you or me), it’s a crap shoot.

That's why precise individual measurement of cardiovascular risk is required for real risk assessment, not applying broad statistical observations and forcing them to conform to the unique life of a specific individual, particularly risk calculators with as few risk parameters as the Framingham risk score.

Comments (2) -

  • katherine

    11/24/2008 3:31:00 PM |

    just came across this...thoughts?


  • John

    11/29/2008 3:33:00 AM |

    Good article. One of the most common mistakes made by health conscious individuals is the idea that if study X says A is bad or good then one should adjust one's lifestyle accordingly.

    If only it were that simple. A statistical analysis of a group is applicable to that group, not necessarily the specific individuals within that group; let alone those outside the studied group. We cannot determine individual risk on the basis of such studies yet time and again these studies are mentioned as "evidence" that we must accept. Sadly, too many health promoters, who should know better, tend to make the same logical error.

    Very pleased to see that this error is highlighted here.