Why do the Japanese have less heart disease?

24. April 2011 William Davis (49)
We should look to the Japanese to teach us a few lessons about preventing heart disease. A Japanese male has only 65% of the risk of an American male (despite 40% of Japanese men being smokers), while a Japanese woman has 80% less risk than an American woman. While the U.S. is near the top of the list of nations with highest cardiovascular risk, Japan is the lowest.

What are they doing right?

There is no one explanation, but several. Genetics probably does not play a substantial role, by the way, as demonstrated by observations of Japanese people who emigrate to Western cultures. People of Japanese heritage living in Hawaii, for instance, develop the same cardiovascular risk as non-Japanese living in Hawaii. They also develop obesity and diabetes.

Among the factors that likely contribute to reduced risk in Japanese people:

--A style of eating that does not include a lot of sweet foods. No breakfast cereal or donuts for breakfast, for instance, but miso soup with tofu, fish, green onions, and daikon (as takuan, or pickled radish).
--Seaweed--It's probably a combination of the green phytonutrients and iodine. Typical daily iodine intake is in the neighborhood of 5000 mcg per day from nori, kombu, wakame, and other seaweed forms. (The average American obtains 125 mcg per day of iodine from diet.)
--Seafood--Fish in many forms not seen in the U.S. are popular.
--Green tea--Consumption of green tea has been confidently linked to reduced cardiovascular risk, probably via visceral fat-reducing, anti-oxidative, and anti-inflammatory effects. Although tea in Japan is often the less flavonoid-rich oolong tea, softer benefits from this form are likely.
--Soy--Tofu, miso, and soy sauce are staples. It's not clear to me whether soy is intrinsically beneficial or whether it is beneficial because it serves to replace unhealthy alternatives. (Genetic modification may change this effect.)
--Reduced exposure to cooked animal products (except seafood). This is not a saturated fat issue, but probably an advanced glycation end-product/lipoxidation issue that result from cooking.
--The lack of a "eat more healthy whole grain" mentality, the advice that has plunged the entire U.S. into the depths of a diabetes and obesity crisis (along with high-fructose corn syrup and sugar). Noodles like udon and ramen do have a place in their diet, as do some dessert foods. But the overall wheat exposure is less--no bagels, sandwiches, and breakfast cereals.
--Less overweight and obesity--The above eating style leads to less weight gain.

Japanese foods have a unique taste, consistency, and mouth-feel that go well with saltiness, thus the downside of their diet: salt consumption. On a broad scale, high salt consumption has been associated with hypertension and gastric cancer. But the tradeoff has, on the whole, been a favorable one.


One study trying to find some answers:

Dietary patterns and cardiovascular disease mortality in Japan: a prospective cohort study.

Shimazu T, Kuriyama S, Hozawa A et al.
Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Japan.


We prospectively assessed the association between dietary patterns among the Japanese and CVD mortality. Dietary information was collected from 40 547 Japanese men and women aged 40-79 years without a history of diabetes, stroke, myocardial infarction or cancer at the baseline in 1994.
During 7 years of follow-up, 801 participants died of CVD.

Factor analysis (principal component) based on a validated food frequency questionnaire identified three dietary patterns: (i) a Japanese dietary pattern highly correlated with soybean products, fish, seaweeds, vegetables, fruits and green tea, (ii) an 'animal food' dietary pattern and (iii) a high-dairy, high-fruit-and-vegetable, low-alcohol (DFA) dietary pattern. The Japanese dietary pattern was related to high sodium intake and high prevalence of hypertension. After adjustment for potential confounders, the Japanese dietary pattern score was associated with a lower risk of CVD mortality (hazard ratio of the highest quartile vs the lowest, 0.73; 95% confidence interval: 0.59-0.90; P for trend = 0.003). The 'animal food' dietary pattern was associated with an increased risk of CVD, but the DFA dietary pattern was not.

The Japanese dietary pattern was associated with a decreased risk of CVD mortality, despite its relation to sodium intake and hypertension.

Niacin: What forms are safe?

20. April 2011 William Davis (52)
Niacin, or vitamin B3, remains a confusing issue for many people. It shouldn't be.

It doesn't help that most physicians and many pharmacists also do not understand the basic issues surrounding niacin. The only reason why there is any level of prevailing knowledge about niacin is that Kos Pharmaceuticals managed to "pharmaceuticalize" a niacin preparation, prescription Niaspan, that provided the revenue to fund professional "education."

Niacin can be helpful to increase HDL, reduce small LDL particles and shift them towards the more benign large particles, reduce triglycerides, and reduce lipoprotein(a).

So here's a brief description of the various forms that you will find niacin:

Immediate-release niacin--Also called crystalline niacin or just niacin. This is the original niacin that releases within minutes of ingestion. Because it releases rapidly, it triggers the most intense "hot flush." While this form of niacin works wonderfully well, is the safest, and is dirt cheap, the majority of people are simply unable to tolerate the intense flush. It also works best taken twice a day, generating two intolerable flushes per day.

Slow-release niacin--These preparations were popular in the 1980s, since the slow 12 to 24 hour pattern of release minimized the annoying hot flush. But, with prolonged use, it also became apparent that an unnaceptable frequency of liver toxicity developed. Unfortunately, this means that any niacin preparation that trickles niacin out over an extended period, including many of the slow-release preparations now sold in health food stores and pharmacies, have potential for liver toxicity. These preparations should be avoided.

6-hour release niacin--Releasing niacin more slowly than immediate-release niacin but more rapidly than slow-release niacin, 6-hour release (or what the Niaspan people call "extended-release" niacin) is nearly as effective as immediate-release niacin with approximately the same low potential for liver toxicity. It is far less liver toxic than slow-release niacin. 6-hour release niacin therefore offers the best balance between effectiveness and safety. Preparations that show this pattern of release include Niaspan ($180 per month), the poorly-named Sloniacin (about $8 per month), and Enduracin (about $7 per month) for 1000 mg per day. (Some Track Your Plaque Members have also determined that several other over-the-counter preparations have been demonstrated to share a similar pattern of release.)

Then there are the scam products that have no useful effect at all:

Flush-free or no-flush niacin--Inositol hexaniacinate, or 6 niacin molecules bound to the sugar, inositol, has no effect in humans, at least not with the dozen or so preparations that I've seen used. Nor are there any data to document the effectiveness of flush-free niacin. It's also more expensive.

Nicotinamide--This niacin derivative likewise has no effect on the usual targets for niacin treatment.

While I used to prescribe Niaspan, the ridiculous pricing and aggressive marketing really turned me off. I now advise my patients and our online followers to use only Sloniacin or Enduracin, unless you can tolerate immediate-release niacin.

Introduction to the New Track Your Plaque book, version 2.0

18. April 2011 William Davis (0)

Out with the old,
in with the new  



“I believe that you are suffering from what is called a fatty degeneration of the heart.”

Dr. Tertius Lydgate to Mr. Casaubon on making a diagnosis with the new medical device, the stethoscope.

George Elliot
Middlemarch, 1871





Old notions in medicine have a peculiar way of lingering.

In 1882, Dr. Robert Koch discovered the tubercle bacillus in tissues of people with “consumption.” By connecting a bacterium with the disease, he usurped the long held notion that tuberculosis was a degenerative disease caused by lack of fresh air. But, for decades after Dr. Koch’s revelation, the “bad air” belief persisted. Surgical collapse of the lung, a painful and barbaric treatment for tuberculosis, persisted well into the 1960s, years after effective antibiotics were discovered in 1947.

The medical community of the 19th century viewed mental illness as the hereditary end-product of ancestral nervousness, alcoholism, prostitution and criminal behavior, a bias that remained widespread well into the mid-20th century. Nazi physicians invoked the theory of heritable “mental degeneration” to justify wholesale extermination of schizophrenics. Electro-convulsive therapy (ECT, or “electroshock therapy”) was widely applied to treat schizophrenia, depression, homosexuality, and criminal behavior for over 30 years, gradually abandoned (at least in its original form) after years of abusive application to subdue patients, demonized in the 1975 movie, “One Flew Over the Cuckoo’s Nest,” depicting the author’s real-life experience with ECT.

Long after a theory or practice has been discredited, it can persist, refusing to die. The new and improved may not be adopted into mainstream practice for years, even decades.

Back to the 21st century: What if you realized that, by quirks of human nature and the uneven adoption of health information, your doctor practiced medicine appropriate for 1985? 1975?

While digital information nowadays is transmitted at the speed of light, disseminating as fast as it takes the next juicy tidbit to be “virally” reproduced via social networking websites, it’s the human factor that still operates with the inertia of human behavior. Habits and attitudes slow the adoption of new information in time measured not in seconds, but in years or decades.

A century ago, 20 years were required for the new technology of blood pressure measurement to be adopted after its introduction in the U.S. in 1910, since physicians were long comfortable with the practice of “pulse palpation” (feeling the pulse). (The arcane language of pulse palpation persists to this day, terms like “pulsus parvus et tardus,” the slow rising pulse of a stiff aortic valve; and the "water-hammer" pulse of a leaking aortic valve.)

The discovery of new, health-changing information today in the 21st century disseminates through the ranks of modern healthcare providers at much the same pace as measuring blood pressure did in the early 20th century.

It’s also tempting to paint American medicine as a fiefdom intent on maintaining exclusive rein over health information. Look back over the hierarchical relationship of medicine over nursing in the past century: When blood pressure measurement was adopted on a broad scale in the 1930s, it was practiced only by physicians, since nurses were deemed incapable. (Modern-day nurses should surely have a hearty laugh over this.) Stethoscopes, around even longer than blood pressure cuffs, weren’t permitted to fall into the hands of nurses until the 1960s, since the medical community feared that nurses might command too much control over patient care. Even after nurses were permitted to have their own stethoscopes, great pains were taken to be certain the nurses’ version was readily distinguishable from the “real” tool wielded by physicians; nurses’ stethoscopes were therefore labeled “nurse-o-scopes,” or “assistoscopes,” and were required to be smaller and flimsier.

Old and ineffective doesn’t always give way to new and better at once; it is slowed by habit as well as an unwillingness to relinquish control.

Somehow technology marches on. But it does so unevenly, sweeping some along in its first wave, others in its wake, some never at all.

Just as effective antibiotics to cure tuberculosis were available for 20 years while surgeons continued to remove patients’ lungs, so better solutions to heart disease are already available but not yet employed by your neighborhood physician. The primary care physician may have heard about some of the newest means to prevent heart disease, but is too overwhelmed with the day-to-day of sore throats, diarrhea, and rashes. Cardiologists, intent on inserting the next best stent or defibrillator, have little but passing interest in strategies that might halt or reverse the heart disease that can be “managed,” no matter how imperfectly, with procedural solutions like angioplasty and bypass surgery. We should bear these flawed human tendencies in mind as we explore the world of heart disease prevention.

We need look no farther than the front page of the newspaper to find evidence of the failure of present-day heart disease detection and management. Over the past several years, headlines have carried the likes of Tim Russert, Bill Clinton, Larry King, Dick Cheney, David Letterman, Tommy Lasorda, Ed Bradley, Mike Ditka, Walter Cronkite, Alberto Salazar, all heart disease sufferers. Some, like talk show host David Letterman, survived their brush with heart catastrophe and underwent successful bypass surgery. Others, like marathoners Fixx and Salazar, raised none of the conventional red flags for heart disease. All received standard, “modern” medical care . . . all the way up to their heart attack, bypass surgery, or untimely death.

Like the sphygnomanometer (blood pressure) cuffs of 1910, Track Your Plaque represents an example of the new. But, unlike the simple practice of taking blood pressure in the early 20th century, Track Your Plaque represents an entirely new way to look at coronary heart disease: a new way to measure it, a new way to identify its causes, and a new way to seize control over it, often to the point of achieving reversal of the process. It also puts control over much of this process into your hands and away from hospitals, cardiologists, and heart procedures. 

I could speak of revealing “secrets,” but that’s not true. In Track Your Plaque, I simply convey information about heart disease that you were likely unaware existed, strategies that doctors fail to discuss. I assemble them into a “package” that, together, create an enormously empowering unique approach to prevent heart disease and heart attack.

Track Your Plaque also challenges the high-tech status quo, practices that occupy exalted places in the enormous cardiovascular healthcare machine that has dominated American healthcare for the past 40 years. I propose that high-tech hospital procedures should join the practice of ECT for homosexuality and insanity¾and become yet another relic of the past.

What are "normal" triglycerides?

12. April 2011 William Davis (67)
Among the most neglected yet enormously helpful values on any standard cholesterol panel is the triglyceride value.

Triglycerides traverse the bloodstream by hitching a ride on water (serum)-soluble lipoproteins, or lipid-carrying proteins. We measure triglycerides as an indirect index of triglyceride-containing lipoproteins.

Triglycerides are a basic currency of energy. While the average American ingests around 300 mg of cholesterol per day, he or she also ingests 60,000-120,000 mg (60-120 grams) of triglycerides, i.e., 200 to 400 times greater amounts, from fat intake. Zero triglycerides in the diet or in the bloodstream is not an option.

But what represents too much triglycerides in the bloodstream? There are several observations to help us make this determination:

1) When fasting triglycerides are 133 mg/dl or greater, 80% of people will show show at least some degree of small LDL particles.

2) When fasting triglycerides are 60 mg/dl or less, most (though not all, since genetic factors enter into the picture) people will show little to no small LDL particles.

3) When fasting triglycerides are 200 mg/dl or greater, small LDL particles will dominate and large LDL particles will be in the minority or be gone entirely.

4) When triglycerides are 88 mg/dl or greater after eating, then risk for heart attack is doubled. Non-fasting triglycerides in the 400+ mg/dl range are associated with 17-fold greater risk for heart attack.



From Austin et al 1990. "Phenotype A" means that large LDL particles dominate; "phenotype B" means that small LDL particles dominate.

Note that conventional "wisdom" (i.e., NCEP ATP-3 guidelines) is that triglycerides of up to 150 mg/dl are okay, a level that virtually guarantees expression of small LDL particles and increased cardiovascular risk.

Based on observations like these, in the Track Your Plaque program we aim for fasting triglycerides of no higher than 60 mg/dl and postprandial (after-meal) triglycerides of no more than 90 mg/dl.

Curiously, while fat intake (i.e., triglyceride intake) plays a role in determining postprandial triglyceride blood levels, it's carbohydrate intake that plays a much larger role. That will be an issue for another day.

1985: The Year of Whole Grains

9. April 2011 William Davis (30)
In 1985, the National Cholesterol Education Panel delivered its Adult Treatment Panel guidelines to Americans, advice to cut cholesterol intake, reduce saturated fat, and increase "healthy whole grains" to reduce the incidence of heart attack and other cardiovascular events.

Per capita wheat consumption increased accordingly. Wheat consumption today is 26 lbs per year greater than in 1970 and now totals 133 lbs per person per year. (Because infants and children are lumped together with adults, average adult consumption is likely greater than 200 lbs per year, or the equivalent of approximately 300 loaves of bread per year.) Another twist: The mid- and late-1980s also marks the widespread adoption of the genetically-altered dwarf variants of wheat to replace standard-height wheat.

In 1985, the Centers for Disease Control also began to track multiple health conditions, including diabetes. Here is the curve for diabetes:


Note that, from 1958 until 1985, the curve was climbing slowly. After 1985, the curve shifted sharply upward. (Not shown is the data point for 2010, an even steeper upward ascent.) Now diabetes is skyrocketing, projected to afflict 1 in 3 adults in the coming decades.

You think there's a relationship?

Have some more

7. April 2011 William Davis (37)
Wheat, via exorphin effects, is an appetite stimulant. Eat a whole wheat bagel or bran muffin, you want another. You also want more of other foods. You also want something to eat every two hours due to widely-swinging insulin-glucose responses: blood sugar high followed by a sharp downturn that triggers a powerful impulse to eat (thus the cravings for a snack at 9 and 11 a.m. after a 7 a.m. breakfast).

If wheat is a stimulant of appetite, then removing it should yield reduced appetite and reduced calorie intake. That is precisely what happens.

When wheat products are removed from the diet--without calorie restriction, without counting fat or carbohydrate grams, no exercise program, no cleansing regimen, no skipping meals . . . nothing--calorie intake drops 350 to 400 calories per day. This calorie figure remains curiously consistent across multiple studies in which wheat was eliminated.

400 calories per day results in 21 lbs lost over 6 months, based just on calories. (3500 calories per pound lost.) That is what happens in wheat elimination diets: 21-26 lbs lost over 6 months.

Wheat is the processed food industry's nicotine, a means of ensuring repeat food purchases. It's also low-cost (subsidized by the U.S. government), high-yield, an ingredient that even has its very own withdrawal syndrome should you miss a "hit."

When MIGHT statins be helpful?

7. April 2011 William Davis (17)
I spend a lot of my day bashing statin drugs and helping people get rid of them.

But are there instances in which statin drugs do indeed provide real advantage? If someone follows the diet I've articulated in these posts and in the Track Your Plaque program, supplements omega-3 fatty acids and vitamin D, normalizes thyroid measures, and identifies and corrects hidden genetic sources of cardiovascular risk (e.g., Lp(a)), then are there any people who obtain incremental benefit from use of a statin drug?

I believe there are some groups of people who do indeed do better with statin drugs. These include:

Apoprotein E4 homozygotes

Apoprotein E2 homozygotes

Familial combined hyperlipidemia (apoprotein B overproduction and/or defective degradation)

Cholesteryl ester transfer protein homozygotes (though occasionally manageable strictly with diet)

Familial heterozygous hypercholesterolemia, familial homozygous hypercholesterolemia

Other rare variants, e.g., apo B and C variants

The vast majority of people now taking statin drugs do NOT have the above genetic diagnoses. The majority either have increased LDL from the absurd "cut your fat, eat more healthy whole grains" diet that introduces grotesque distortions into metabolism (like skyrocketing apo B/VLDL and small LDL particles) or have misleading calculated LDL cholesterol values (since conventional LDL is calculated, not measured).

As time passes, we are witnessing more and more people slow, stop, or reverse coronary plaque using no statin drugs.

Like antibiotics and other drugs, there may be an appropriate time and situation in which they are helpful, but not for every sneeze, runny nose, or chill. Same with statin drugs: There may be an occasional person who, for genetically-determined reasons, is unable to, for example, clear postprandial (after-eating) lipoproteins from the bloodstream and thereby develops coronary atherosclerotic plaque and heart attack at age 40. But these people are the exception.

Advanced topics in nutrition

5. April 2011 William Davis (0)
Nutrition in the modern world has become an increasingly problematic topic. From genetic modification to commercialized methods of mass production, we are having to navigate all manner of complex issues in food choices, particularly if ideal health, including maximal control over coronary plaque, is among our goals.

We will therefore be releasing a series of discussions on the Track Your Plaque website in the coming months, a series I call "Track Your Plaque Advanced Topics in Nutrition." These will be, as the series title suggests, discussions for anyone interested in more than the "eat a balanced diet" nonsense that issues from "official" sources. Among the topics to be covered:

1)Advanced Glycation End-products--both endogenous and exogenous, including peripheral issues like lipoxidation and acrylamides.

2)Dietary influences on LDL oxidation--including the concept of "glycoxidation." Protection from oxidative phenomena is not just about taking antioxidants.

3) Foods you MUST eat--We've talked a lot about foods that you shouldn't eat. How about foods you should eat?

The New Track Your Plaque Guide now available

4. April 2011 William Davis (5)
The New Track Your Plaque Guide is now available!

The Track Your Plaque program has evolved over its 8 year history. While the original Track Your Plaque book reflected the program details that got the program started back in 2003-2004, plenty has changed.

This new version of the book, what I call the program Guide, represents version 2.0 of Track Your Plaque and includes:

--Updated lipoprotein treatment strategies--including new and expanded treatment choices for small LDL and lipoprotein(a).

--An entire chapter on vitamin D and its crucial role in cardiovascular health and plaque control.

--A new and expanded diet--All the reasons why the New Track Your Plaque Diet can achieve spectacular improvement in lipids/lipoproteins, reversal of insulin resistance/pre-diabetes/diabetes, weight loss, reduction in blood pressure, etc. are discussed in considerable detail. The diet is crafted to achieve maximum control over both metabolic responses and coronary plaque.

--An entire chapter on the role of omega-3 fatty acids is included.

--A detailed discussion on the role of iodine and thyroid health--One of the newest additions to the Track Your Plaque menu of strategies is to achieve and maintain ideal thyroid health. This tips the scales in your favor for improved control over lipids/lipoproteins, weight, blood sugar, and coronary plaque.


The new guide, as well as our new Member kits that include the new Track Your Plaque Recipe Book, At-Home Lab Test kits, and nutritional supplements, are all available in the Track Your Plaque Marketplace.

Don't wet yourself

3. April 2011 William Davis (13)
While there is more to wheat's adverse effects on human health than celiac disease, studying celiac disease provides important insights into why and how wheat--the gluten component of wheat, in this case--is so destructive to human health.

Modern wheat, in particular, is capable of causing "celiac disease" without intestinal symptoms---no cramping or diarrhea--but instead shows itself as brain injury (ataxia, dementia), peripheral nervous system damage (peripheral neuropathy), joint and muscle inflammation (rheumatoid arthritis, polymyalgia rheumatica and others), and gastrointestinal cancers.

One neurological manifestation of wheat's effect on the human brain is a condition called cerebellar ataxia. This is a condition that can affect adults (average age 48 years) and children and consists of incoordination, falls, and incontinence.

Because brain tissue has limited capacity for healing and regeneration, symptoms of cerebellar ataxia usually improve slowly and modestly with meticulous elimination of wheat and other gluten sources.

Such observations are relevant even to people without celiac disease. Celiac disease sufferers are more susceptible to such extra-intestinal phenomena, but it can also happen in people without positive celiac antibodies.



Some references:

Neurological symptoms in patients with biopsy proven celiac disease

A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 +/- 15 years, mean disease duration 8 +/- 11 years) were recruited through advertisements. All participants adhered to a gluten-free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment.



Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics

Two hundred and twenty-four patients with various causes of ataxia from North Trent (59 familial and/or positive testing for spinocerebellar ataxias 1, 2, 3, 6 and 7, and Friedreich's ataxia, 132 sporadic idiopathic and 33 clinically probable cerebellar variant of multiple system atrophy MSA-C) and 44 patients with sporadic idiopathic ataxia from The Institute of Neurology, London, were screened for the presence of antigliadin antibodies. A total of 1200 volunteers were screened as normal controls. The prevalence of antigliadin antibodies in the familial group was eight out of 59 (14%), 54 out of 132 (41%) in the sporadic idiopathic group, five out of 33 (15%) in the MSA-C group and 149 out of 1200 (12%) in the normal controls. The prevalence in the sporadic idiopathic group from London was 14 out of 44 (32%). The difference in prevalence between the idiopathic sporadic groups and the other groups was highly significant (P < 0.0001 and P < 0.003, respectively). The clinical characteristics of 68 patients with gluten ataxia were as follows: the mean age at onset of the ataxia was 48 years (range 14-81 years) with a mean duration of the ataxia of 9.7 years (range 1-40 years). Ocular signs were observed in 84% and dysarthria in 66%. Upper limb ataxia was evident in 75%, lower limb ataxia in 90% and gait ataxia in 100% of patients. Gastrointestinal symptoms were present in only 13%. MRI revealed atrophy of the cerebellum in 79% and white matter hyperintensities in 19%. Forty-five percent of patients had neurophysiological evidence of a sensorimotor axonal neuropathy. Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia.
The Anti-AGEing Diet

The Anti-AGEing Diet

22. October 2010 William Davis (36)
Advanced Glycation End-products, AGEs, are a diverse collection of compounds that have been associated with endothelial dysfunction, cataracts, kidney disease, and atherosclerosis in both animal models and human studies. Not all involve glycation nor glucose, but the catch-all name has stuck.

There are a number of actively-held theories of aging, such as the idea that aging is the result of accumulated products of oxidative injury; a genetically pre-programmed script of declining hormones and other phenomena; genetic "mis-reading" that results in disordered gene expression, debris, and uncontrolled cell proliferation (e.g., cancer); among others.

One of the fascinating theories of aging is, cutely, the AGEing theory of aging, i.e., the accumulation of AGE debris in various tissues. Such AGEs have been recovered in lenses from the eyes, atherosclerotic plaque in arteries, kidney and liver tissue, even brain tissue of people with Alzheimer's dementia. AGEs perform no known useful physiologic function: They are relatively inert once formed (especially polymeric AGEs), they do not participate in communication, they make no contribution of significance. They simply gum up the works--debris. (AGEs are to health as the USDA food pyramid is to dietary advice: material for the junkyard.)

There are two general ways to develop AGEs:

1) Endogenous--High blood glucose (any blood sugar above 100 mg/dl) will permit glycation of the various proteins of the body. The higher the blood glucose, the more glycation will proceed. Glycation also occurs at low velocity at blood glucose levels below 100 mg/dl, though this would therefore represent the "normal," expected rate of glycation. Endogenous glycation explains why people with diabetes appear to age and develop all the phenomena of aging faster than non-diabetics (kidney disease, eye diseases, atherosclerosis, dementia, etc.). Hemoglobin A1c, HbA1c, is a readily-obtainable blood test that can show how enthusiastically you have been glycating proteins (hemoglobin, in this case) over the last 2 to 3 months.

A low-carbohydrate diet is the nutritional path that limits endogenous glycation leading to AGE formation. Restricting the most obnoxious carbohydrates, the ones that increase blood sugar the most, such as wheat, cornstarch, rice starch, potato starch, tapioca starch, and sucrose, will limit endogenous AGE formation.

2) Exogenous--AGEs (here especially is where the "AGE" label is misleading, since many other reactions besides glycation lead to such compounds) are formed with cooking at high temperatures, especially meats and animal products. Therefore, a rare steak will have far less than a well-done steak. A thoroughly baked piece of salmon will have greater AGE content than sashimi.

The forms of cooking that increase AGE content the most: roasting,deep-frying, and barbecuing. Temperatures of 350 degrees Fahrenheit and greater increase AGE formation.

Therefore, cooking foods at lower temperature (e.g., baking, sauteeing, or boiling), eating meats rare whenever possible (not chicken or pork, of course), eating raw foods whenever possible (e.g., nuts) are all strategies that limit exogenous AGE exposure. And minimize or avoid butter use, if we are to believe the data that suggest that it contains the highest exogenous AGE content of any known food.

If we connect the dots and limit exposure to both endogenous and exogenous AGEs, we will therefore not trigger this collection of debris that is likely associated with disease and aging. So following a low-AGE diet may also be an anti-aging strategy.

The New Track Your Plaque Diet, soon to be released on the Track Your Plaque website, has incorporated strategies to limit both endogenous as well as exogenous AGEs.
Tags :

Comments (36) -

  • August

    10/22/2010 4:04:38 PM |

    I could see this might be a problem if gut health was compromised; exogenous AGEs would then have a pathway to get into our tissues.  Assuming someone is on a low carbohydrate paleolithic style diet, what evidence is there that the exogenous AGEs do anything other than merely pass through the digestive system?

  • Tyler

    10/22/2010 5:02:07 PM |

    Hi August, I echo the same question. Is there any research on exogenous AGE's absorbing in to our bodies?

  • Davide

    10/22/2010 5:21:48 PM |

    Dr. Davis,

    Are palm oils/hydrogenated oils a significant source of AGE's like butter?

  • Anonymous

    10/22/2010 5:55:23 PM |

    What about clarified butter (ghee)?

  • Martin Levac

    10/22/2010 6:36:40 PM |

    Dr. Davis, now you're delving into the unknown with your suggestion of an anti-AGE diet. You don't know. You're suggesting we eat that diet but you haven't any data to support such a suggestion. Don't do like they did with saturated fat. Think of the alternative we adopted then that brought us here. Think of the alternative we will adopt now that will bring us who knows where.

    If the advice of the day is to avoid AGEs in food, what kind of food will we eat then? Since meat contains a boatload of AGEs, that's out but what will replace it, soy? See how your advice is already turning on itself?

    Stick to what works on the TYP program as a good doctor should and leave the speculation to the speculators.

  • Anonymous

    10/22/2010 7:11:25 PM |

    Martin, there have been numerous studies connecting the association of AGEs with various health issues. There is nothing novel or or new about this.

    Avoiding AGEs doesn't mean you can't eat meat. All you have to do is eat good fresh meat and don't over cook it until it is well done or overbrowned. If you like your meat chared and well done, then you may have to make a sacrifice.

    Yes even properly prepared meat has some AGEs in it. But no one food or diet is perfect. You just do the best you can and try to avoid the big mistakes. Just my opinion for what it is worth.

  • Anonymous

    10/22/2010 7:49:52 PM |

    Doc - with regards to exogenous AGEs, it sounds like this could be the new cholesterol-is-bad-for-you theory. My apologies if I have overlooked something in your post, but I don't see any logical argument leading to the conclusion that exogenous AGEs affect your health. Your previous post on butter also makes you sound like an alarmist. Of course, if you have a diet coming up, this is understandable.

    Frown

  • Anonymous

    10/22/2010 8:02:14 PM |

    what do stomach acid and bile do to ingested ages?? ...and the rest of the digestive process? sss

  • Joel

    10/22/2010 9:46:44 PM |

    One of the primary AGE components of milk products is pyrraline:

    Glycation in food and metabolic transit of dietary
    AGEs

    Here are some quotes from this study:

    "Given the data for pyrraline excretion, it
    can be concluded that dietary pyrraline is nearly completely
    released and resorbed during digestion, followed by rapid
    elimination via the kidneys, thus leading to nearly complete
    recovery of dietary pyrraline in the urine. This indicates that,
    in contrast with Amadori products, of which only up to 5%
    are recovered in the urine [24,25], pyrraline obviously is not
    metabolized within the body."

    "Above all, however,
    it has to be realized that the term ‘AGE’ comprises a large
    number of individual amino acid derivatives, of which only a
    minority have been identified and quantified either in foods
    or in vivo."

  • Joel

    10/22/2010 9:56:29 PM |

    Now that everyone is speculating in the last two posts, is it possible that some AGEs are much more harmful than others? (As the previous study indicates?)

    Are we distinguishing the types of AGEs when we measure them? (Or are we lumping them all together like what was done with cholesterol?)

    Are food derived AGEs eaten as part of a meal less harmful then analogues produced in a lab and fed in isolation? (Like most AGE studies I've read?)

    Again, if butter is as bad as these measurements indicate, why hasn't it been identified epidemiologically as such a bad food? Those with the highest butter consumption tend to be the healthiest (although I suppose because it displaces margarine).

    I can understand why all AGEs might be harmful to someone with compromised kidneys, but I agree with Martin Levac that we're really delving into the unknown.

    "Martin, there have been numerous studies connecting the association of AGEs with various health issues. There is nothing novel or or new about this."

    Please give us a study. This sort of broad statement is hard to counter argue otherwise!

  • Nancy

    10/22/2010 10:35:39 PM |

    I'm not really convinced AGEs you eat are a problem. But if you're enamored of low temperature cooking, looking into Sous Vide cooking. It yields delicious results by cooking at much lower temperatures than normal.

  • Ned Kock

    10/23/2010 12:26:20 AM |

    Speaking of endogenous AGEs, caused by high blood glucose levels, here is an interesting factoid - blood glucose levels in birds are very high yet their HbA1c levels are low:

    http://healthcorrelator.blogspot.com/2010/10/blood-glucose-levels-in-birds-are-high.html

    There are a few possible reasons for this. One of the most interesting mechanisms is vitamin C synthesis. Not only is vitamin C a powerful antioxidant, but it also has the ability to reversibly bind to proteins at the sites where glycation would occur.

  • Michael Barker

    10/23/2010 2:30:23 PM |

    All humans cook food and have done so for thousands of years. This is natural for us. If you've ever cooked meat on a camp fire, you know that the some of the meat becomes very crisp. Paleo people didn't have temperature gauges so I'm very sure there were plenty of exogenous AGE's. In fact, I would suggest, since these pieces of foods tend to taste very good to humans that they are an important piece of our nutrition not the opposite.

  • Geoffrey Levens

    10/24/2010 1:17:10 AM |

    "High blood glucose (any blood sugar above 100 mg/dl) will permit glycation"

    I would love to know some research that backs this claim. I have seen it numerous times but have not been able to find any research that specifically deals with it.  Also, just guessing, but I would bet that damage occurs at considerably lower blood sugar levels for those eating a conventional, nutrient sparse diet as compared to those replete w/ vitamins, minerals, phyto-nutrients etc who eat a diet containing very large amounts of "real food" particularly non-starchy vegetables

  • Jonathan

    10/24/2010 1:19:54 PM |

    Has anyone ever taken an A1C of a grain-feed cow?  Maybe that high AGE butter was from a diabetic cow!

  • Lori Miller

    10/24/2010 2:48:42 PM |

    I don't know if AGEs are harmful either, but a pressure cooker is great for low-temperature cooking. It's also much faster and keeps in the juices better than oven roasting.

  • Lori Miller

    10/24/2010 4:32:39 PM |

    Re: sausage (from the last post), the list of ingredients from the chorizo I eat is pork, water, salt, paprika, spices and garlic powder. "No nitrates, MSG, preservatives, sugar or soy," reads the label. I don't understand why this is worse than any other meat.

  • Anonymous

    10/25/2010 1:09:48 AM |

    Sausage could be a problem because,

    1)The meat is ground up so more of the surface area was exposed to oxygen. More of the meat is oxidized.

    2)Sausage unlike unground cuts of meat must be cooked through because of bacterial contamination. The more you cook meat the more you get AGEs.

    3)Some sausages as with hot dogs are pre cooked. Then you cook them again. This should also increase AGEs.

  • Dr. William Davis

    10/25/2010 2:42:03 AM |

    There are indeed studies that 1) measure serum levels of AGEs in humans after consumption of exogenous sources, and 2) relate AGE levels to biologic effect, e.g., endothelial response.

    There is no question that the exogenous AGE conversation requires more exploration. I've followed this conversation for some years, but I believe it is gathering real momentum and looks and feels like a genuinely meaningful issue.

    We need more info, no doubt. The notion of endogenous AGEs already fits quite nicely into our observations of the benefits of a low-carb diet. But  exogenous AGEs have potential for taking us one step farther in crafting an ideal diet. Recall that the "Paleo" approach is one reconstructed to mimic ancient behaviors, not necessarily one to achieve a new set of modern goals, such as reversal of coronary disease or osteoporosis.

  • Peter

    10/25/2010 11:25:03 AM |

    It's clear that in the US we eat lots of carbs and get lots of heart disease and diabetes.  But there are lots of traditional cultures that eat even higher percentages of carbs (cassava, beans, rice and others) but that don't get those diseases.  How does the AGE theory explain that?

  • LeenaS

    10/25/2010 12:58:51 PM |

    Dear Dr Davis,

    I know your opinion against butter, but disagree, based on a lifelong experience, as a skin chronic healed by milkfats and (land)animal fats.

    For the first 40 years of my life I was never free of allergic reactions and imflammated skin symptoms. Raw food helped not, vegetables and salads helped not, and the official healthy lifestyle helped not either. 10 years ago, when the stsart of Zonish lowcarb (much like your style) finally helped me incredibly much... Yet my skin has healed fully only after I switched to very, very buttery and egg-yolky diet close to Jan Kwasniewski.

    I live far up North, but have no symptoms of vitamin D deficiency, in spite of not eating the pills and not having much sun for the better part of the year. Furthermore, I cannot eat fish, and do no longer supplement with fish oil either, due to problems induced by it. Yet my skin has never been as good as now, fully without irritation or other symptoms. And unlike my frends and colleagues, I no longer seem to catch seasonal colds, either.

    So far the only thing I can blame for the last few years of well-being is increased use of milkfat and non-muscle parts of animals (fat, marrow, liver and skin collagen). Of these the milkfats make up a major part of the daily calories, often more than 50 E%.

    I'm interested to hear your thought on possible causes, which make this butter strategy work the best of all that we've ever tried; both for myself and for others in our family Smile

    With regards,
    LeenaS

  • Steve Cooksey

    10/25/2010 2:50:34 PM |

    I am a Type 2 Diabetic with normal blood sugar who takes -0- drugs and -0- insulin.

    I experienced tremendous benefits from going low carb primal. I won't detail them here but I have not been sick in 20 mos.

    This summer I performed a one week dairy fast (I'd been off milk for almost a year) and then added back butter.

    Butter was very inflammatory. I no longer eat it. Clarified butter or Ghee and Cheese are not inflammatory and I eat it occasionally.

    So for me, I agree with butter.

  • Lori Miller

    10/25/2010 9:47:14 PM |

    Anonymous, thanks for the info on sausage. I buy raw sausage and I'm careful to avoid over-cooking any meat, mostly because it gets like shoe leather.

    Another question: is cream high in AGEs? Does the churning action required for butter contribute to oxidation or AGEs?

  • Anonymous

    10/25/2010 11:43:50 PM |

    What's the consensus on carnosine ? I've read some articles claiming it helps with AGE factors.

  • Martin Levac

    10/26/2010 8:47:46 AM |

    Dr. Davis, it's fine to have data on a diet that contains AGEs, but where's the data on a diet that avoids AGEs? Where is the justification for adopting such a diet? Avoiding something leads to adopting something else. What will that be? You can't predict. Nobody can predict. This is the danger of advising to avoid something just like that was the danger of advising to avoid saturated fat and pretty much all animal fat altogether in one big swoop.

    If we can't eat fat, we must eat sugar. There's no other alternative. If we can't eat meat, we must eat some other form of protein. What will that be, soy, wheat, any other grain, legumes? If we can't eat meat, we must eat some other form of those essential nutrients like B12 and EFAs. But where can we get such a high quality source of those nutrients but in animal flesh? The quick answer is nowhere.

    When you advise to avoid AGEs without giving us a safety threshold, the safe course is to avoid all AGEs, not just a little bit. When you give a safety threshold, it doesn't matter because the substance has been declared bad entirely anyway so the safe course is the same.

    We can see this with animal fat and pretty much any kind of fat. Fat is bad, so any fat is bad, so less fat is good or better, but no fat is best. That's how it works in spite of having some form of safety threshold we can abide by like say 10g of saturated fat per day maximum. Why is that? The safety threshold is declared as a maximum with no minimum.

    So tell us Dr. Davis, what is the maximum and the minimum amount of AGEs you advise we eat? But more relevant to the discussion, how can we find out exactly how much AGEs is in the food we eat every day so that we can make an informed decision on exactly how much AGEs we eat every day? Is there a tool that will allow me to find that out? The point is that even if you give us a precise number on how much AGEs we can and cannot eat, we can't even control how much AGEs we eat. Accordingly, the best course of action is to avoid all AGEs and not just a little bit just to be safe because the contention is that lots of AGEs is worse than none.

    With endogenous AGEs production due to high blood glucose and other simple sugars like fructose, the problem is much simpler. That's because this AGEs aspect of sugars is merely the last installment of How Sugars Kill Us Slowly. We already know that sugars kill us slowly and we already know just how much of it will do it and how long it will take and etc. But until you find out exactly how much exogenous AGEs we must avoid and exactly how much we can get away with and how to measure the AGEs in the food we eat, this problem will remain unresolved and unresolvable.

    In other words, the best course of action with exogenous AGEs is to just ignore them outright. After all, we've been ignoring them outright for the past couple million years without so much trouble.

  • Fred Hahn

    10/26/2010 4:52:57 PM |

    Bill,

    Butter is high in AGEs? Wow - why? What about Ghee?

    Do you know what the AGEs are in smoked meats like smoked trout?

    Does the canning process increases ages as in canned wild caught salmon?

  • Dr. William Davis

    10/27/2010 1:47:27 AM |

    Hi, Fred-

    I believe that smoked fish tend to be moderately high in exogenous AGEs.

    One of the difficulties with quantification of AGEs in foods is we have limited data on the AGE content of various foods. It's not like grams fats or carbohydrates listed in plain sight on the label.

    I find the AGE conversation a fascinating new potential insight into helping us decide how to best manage food choices, as well as food preparation.

    As with all new ideas, it will cause upheaval in preconceived notions.

  • Poisonguy

    10/27/2010 7:34:44 AM |

    Given some of the previous blog posts, the largest preconceived notion might be yours toward butter. So, it's no big deal if you aren't up to the challenge of defending what you posted. That's okay. Trying to be coy about it, not so much.

  • Anna

    10/28/2010 7:28:18 PM |

    Count me as a skeptic on this one.

  • Anonymous

    10/29/2010 3:54:56 PM |

    Very good review on AGEs. Dr. Davis is 100% right to be concerned.

    http://biomedgerontology.oxfordjournals.org/content/65A/9/963.full#ref-109

  • blogblog

    10/30/2010 12:31:18 PM |

    People are confusing exogeneous AGEs which are generally harmless compared to the dangerous endogenous AGEs.

    Endogenous AGEs are created by proteins in our bodies reacting with reducing sugars.  Practically the only sources of dietary reducing sugars are fructose (table sugar, HFCS) and  cooked starches. The obvious solution is to eat far more meat and butter and drastically reduce carbohydrates.

    Humans have been eating cooked food for 1.8 million years and are very well adapted to them. The novel foods in the human diet are large quantities of plant proteins, starches and sugars.

    I'm surprised you think kale and spinach are so wonderful. Renowned toxicologist Dr Bruce Ames says that there are considerable amounts of natural toxins and carcinogens present in all food plants.
    http://www.fortfreedom.org/n16.htm

    Any potential benefits from eating kale is likely to be due to hormesis.

    In fact there is absolutely nil direct scientific evidence that eating fruit and vegetable has any health benefits whatseover. The benefits of vegetables have only been found in a few poorly designed population studies. Any observed 'benefits' of eating vegetables are probably just due to confounding variables - people who eat vegetables smoke less, drink less alcohol, are more active and eat less sugar and junk foods.

  • Apra -- The Shaman

    10/30/2010 4:35:41 PM |

    Gary Taubes is skeptical of the claims about exogenous AGES

    http://www.healthcentral.com/diabetes/c/36758/17729/gary-taubes

  • blogblog

    10/31/2010 8:12:44 AM |

    Hi Apra,

    In 'The Diet Delusion' Gary Taubes says that the natural diet of humans is almost purely carnivore with a few berries. Taubes studied physics at Harvard and aerospace engineering at Stanford before becoming a journalist. Because he was properly trained in using rigorous scientific methods he can readily see the flaws in nutrition research.

  • Ed

    11/16/2010 3:06:38 AM |

    I've read the sole paper that lists butter as a high-AGE food: "Advanced Glycoxidation End Products in Commonly Consumed Foods" (2004, Journal of the American Dietetic Association, via Google Scholar cache).

    The data is in Table 1, which refers to "foods prepared by standard cooking methods" (these include frying), but the table says nothing specific about how the butter was processed. I am willing to bet that the butter in question had been treated at high temperature (maybe used in frying).

    Consider these values:

    Milk, cow, whole .... 0.05 kU/mL
    Butter .............. 265 kU/g

    Expecting high AGEs in uncooked butter -- over 5000 times the level in milk! -- would make little sense.

    Would you consider revising your post in light of this?

  • Mary McNeill

    8/5/2012 4:10:37 PM |

    The data table lists butter as 100 gm serving, or over 3 ounces (23,000 - 26,000).  In the serving size database, the amount of AGEs normalize a bit, at 1100 - 1300.  I wish they had done organic vs commercial butters, but maybe next time we can see that data.  No surprise on pan fried bacon at 91,577 for 3 ounces and 11,905 for the serving size (2 slices is the norm).   As with all foods, moderation.  And thank you for your blog - it is very informative!

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