AGEing gracefully

5. May 2010 William Davis (32)
Advanced Glycation End-products, or AGEs, have the potential to change our entire conversation about diet.

AGEs come from two principal sources:

1) Endogenous--Glucose-protein interactions that arise from high blood glucose levels

2) Exogenous--From diet

The first is sensitive to glucose levels: the higher the glucose level, the greater the AGE formation. The second depends on the quantity of AGE in the food consumed.

A compelling body of evidence points towards AGEs as an agent of aging, as well as kidney dysfunction, dementia, and atherosclerosis. Some of the observations made include:

--If AGEs are infused into an experimental animal, it develops atherosclerosis, kidney disease, and other "diseases of senescence" within weeks to months.

--In endothelial cells (cells lining arteries), AGE induces expression of adhesion molecules and inflammatory signals. In fibroblasts, AGE provokes collagen production. In smooth muscle cells, AGE triggers migration and proliferation. In monocytes and macrophages, AGEs induce chemotaxis and release of inflammation mediators. In short, AGEs have been implicated in just about every step leading to atherosclerosis.

--In humans, greater quantities of AGEs are present in diabetics, pre-diabetics and people with insulin resistance. We all know that these people develop atherosclerosis, kidney disease, cataracts, and other conditions at an accelerated rate.

--Foods containing greater quantities of AGEs cause endothelial dysfunction, i.e., artery constriction via blockade of nitric oxide and other mechanisms.

Short of taking agents that block AGE activity, how can you minimize the absorption or production of AGEs? There are two general strategies:

1) Keep blood glucose low--The Whitehall study demonstrated increased cardiovascular mortality with a postprandial (actually 2-hour post- 50-gram glucose challenge) blood sugar of 83 mg/dl. Lower blood glucose, less glycation. Less carbohydrates in the diet, the lower the blood sugar, the less the glycation. Studies like Whitehall demonstrate that glycation begins with glucose values within the normal range. Thus, aging occurs even with normal glucose levels. It occurs faster with higher glucose levels.

2) Choose and prepare foods with lower AGE content. Food content of AGEs is a major determinant of blood AGE levels. Fats and meats are the primary dietary source of AGEs, particularly if cooked at high temperature (broiling, frying). While this does not mean that meats and fats need to be avoided, it can mean that limiting serving size of meats and fats, while being selective in how they are prepared, are important. This can mean cutting your meats in thinner slices or smaller pieces to permit faster cooking, eating rare when possible (not poultry, of course), avoiding cooking with sauces that contain sugar (which enhances AGE formation). Is this an argument in favor of sashimi?

Minimizing exposure to AGEs, endogenous or exogenous, has the potential to slow the aging process, or at least to lessen the likelihood of many of the phenomena of aging.

More on this to come.
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Comments (32) -

  • yoyo

    5/5/2010 11:17:44 AM |

    I'm more worried about endogenous AGEs; exogenous the evidence seems a bit more mixed.

    Are food advanced glycation end products toxic in biological systems?

    Chuyen NV, Arai H, Nakanishi T, Utsunomiya N.

    Japan Women's University, Department of Food and Nutrition, 2-8-1 Mejiro-dai, Bunkyo-ku, Tokyo 8681, Japan. nvc@fc.jwu.ac.jp
    Abstract

    Model food advanced glycation end products (AGEs) were prepared as glycated casein (GC) and glycated soy protein (GS) by the reaction of casein or soy protein with glucose at 50 degrees C, relative humidity 75% for seven days in a powder state. These browned proteins were used as materials for animal experiments. A mixture of 20% glycated proteins (GC:GS = 1:1) diet was fed to streptozotocin (STZ)-diabetic rats for 11 weeks. The results showed that: (1) fructoselysine was observed in the hepatic portal veins, arteries, and femoral veins of rats fed with glycated proteins after 2 h of feeding; (2) blood sugar of glycated protein-fed rats was lower than that of diabetic rats fed with intact protein, while HbA1C in blood and glucose in urine of both groups were similar; (3) lipid peroxidation status in serum, liver, and kidney of both groups was similar; (4) superoxide dismutase (SOD) and glutathione-S-transferase (GST) enzymatic activity in serum and liver of both groups were also similar; (5) there were no differences in degree of cataract formation and concentration of glucose, fructose, sorbitol, and lipid peroxide in the lenses of both groups. From the above results, it can be estimated that food AGEs are not toxic in biological systems, and reactive oxygen species increase in diabetic rats is not caused by glycated proteins but by other pathways.

    PMID: 16037268 [PubMed - indexed for MEDLINE]

    Unfortunately, starches have much lower AGE content. Any preparation of meat has large amounts, though still variable. This might be why high-carb diets work well for traditional societies where obesity is not common.

  • Joel

    5/5/2010 11:49:11 AM |

    Less carbs, less meats, less fats--sounds like you're just promoting calorie restriction since that doesn't leave much that you can eat in significant quantities.

  • Denny Barnes

    5/5/2010 12:16:33 PM |

    Looking forward to your future writings on AGEs. I hope you will talk about the role of fructose which can form ten times as many AGEs as glucose. Not all carbs are created equal. As a fellow T2 diabetic, I think we focus too much on blood glucose and miss the stealth carb -- frutose.  It is by far the most insidious.

    Forgive me for saying it, but I feel that the ghost of your vegetarian past still haunts your writing.  Yes, barbecued, fried and broiled meats can have way too much AGEs, especially if cooked with sweet sauces, but animal protein cooked with water has 1/10 as many AGEs. I am a happy carnivore who loves stewed meats and chicken and steamed fish.

  • Martin Levac

    5/5/2010 12:49:37 PM |

    Then there's ketosis which stimulates something called chaperone-mediated autophagy (CMA). This process is basically the recycling of junk protein. AGEs would constitute such junk. So it's not only a question of low blood glucose but of ketosis as well. Incidentally, if one eats only meat or very little carbs, then he will be in ketosis most of the time. In that sense, it doesn't matter how much AGEs come from this diet since the same diet would provide the recyclers as well. Here's the post by Eades on the subject:

    http://www.proteinpower.com/drmike/ketones-and-ketosis/ketosis-cleans-our-cells/

  • Ned Kock

    5/5/2010 1:20:12 PM |

    Supporting your point regarding endogenous AGEing, there is also reliable evidence that blood glucose control before age 55 may increase your chances of living beyond 90:

    http://healthcorrelator.blogspot.com/2010/04/blood-glucose-control-before-age-55-may.html

    However, I am yet to see reliable evidence that significant damage can be caused by ingested AGEs through cooked meat and fat (e.g., resulting from Maillard reactions).

    I don't doubt that injecting AGEs into model animals, particularly rodents, will lead to problems. But human digestion in a healthy person (e.g., no leaky gut) is another story. Moreover, cooked meat is denatured and thus rendered more easily digestible.

  • Jen

    5/5/2010 3:42:07 PM |

    Thanks for the post Dr. Davis!

    I would love to get info on what happens to the body as you are lowering your blood sugar via diet.  I have been using a monitor and feel my best at around 85 but at times crave sugar pretty bad and have energy spikes and dips.  I exercise too, so curious how this factors in?

  • Apra -- The Shaman

    5/5/2010 3:42:07 PM |

    I agree with Yoyo.  It seems to me this could be another red herring, like the dietary cholesterol nonsense.  Until they can tease apart whether the issue is due to dietary AGEs of the stuff produced from hyperglycemia then I don't necessarily see any reason to jump on an anti-meat bandwagon.

    Still, if you're truly concerned, invest in some Sous Vide equipment and cook your meat at low temperatures and don't finish it with a nice sear.

  • Stephan

    5/5/2010 6:36:09 PM |

    I just read the Whitehall study, it really didn't show that CHD mortality increases from 83 mg/dL.  That's based on their mathematical extrapolation, which didn't fit the actual data very well at the lower range of blood glucose.  According to the data itself, CHD risk didn't begin increasing until 5.7 mmol/L, or 102 mg/dL.  

    That makes sense because 83 mg/dL is totally normal fasting glucose.

  • Adolfo David

    5/5/2010 9:55:08 PM |

    Sad to say: Dr Michael Holick recommends at the end of his new book VITAMIN D SOLUTION essentially one brand of vitamin D supplements: Nature Made! :S

  • Anonymous

    5/6/2010 1:02:37 AM |

    2 things might help AGE's.
    I read that Carnosine which is a combo of 2 amino acids helps prevent glycation and many anti-aging experts recommend this supplement.
    Metformin reduces glucose production in the liver, reduces glucose absorption in the intestines and increases tissue sensitivity to actual glucose in the blood.
    Also may decrease cancer risk
    I have started these supplements in hopes of combating AGE's

  • Lori Miller

    5/6/2010 1:29:00 AM |

    Another way to cook meat quickly is by using a pressure cooker. The 1.5-pound roast I'm having for dinner was done in 20 minutes--15 probably would have been fine. The package called for roasting it for four hours in the oven.

  • Anonymous

    5/6/2010 2:05:20 AM |

    A fasting glucose of 80-109 mg/dl was optimal for CVD and overall mortality in this paper.

    http://circ.ahajournals.org/cgi/content/full/101/17/2047

  • pmpctek

    5/6/2010 2:51:51 AM |

    I've heard that Benfotiamine (200mg twice/day) is a potent AGE inhibitor.  I haven't been able to find much study on humans that backs up that claim though.

  • Anonymous

    5/6/2010 4:19:34 AM |

    Forgive my extreme ingnorance in this area, but how do meat and fats contain AGEs?

    A grilled steak? An egg fried in coconut oil? Where is the source of glucose here?

  • Fran

    5/6/2010 4:29:09 AM |

    "Fats and meats are the primary dietary source of AGEs..." I'm sorry, but this makes no sense to me... that fats and meats will increase blood sugar levels. My understanding to this point is that carbs are the cause, while good saturated fats and protein stabilize blood sugar levels.

  • Dr. John Mitchell

    5/6/2010 4:31:51 AM |

    I'd like to see references for many of your statements.

  • Bruce

    5/6/2010 4:34:46 AM |

    May I offer a little anecdotal evidence? After hearing a researcher from Australia's Baker Heart Institute describe how a low exogenous AGE diet appeared to reverse the complications of Type II Diabetes - although not Diabetic, I was intrigued enough to devise my own low-AGE regime.

    During the subsequent 5 months, with no attempt to restrict calories, I have lost nearly 15 kg, have had my total Cholesterol drop from 5.9 to 4.6, blood pressure drop from 128/88 to 110/62. Part of my strategy has been to avoid all sugars, including most fructose sources, in the interest of limiting endogenous AGE formation.

    BTW, I am 60 years (suddenly) young.

  • Michael Barker

    5/6/2010 2:57:54 PM |

    Humans have been cooking meats, at least, 100,000 years before the invention of agriculture. The fact that it is so ubiquitous suggests that we are quite adapted to this even without thinner slices or smaller portions.

  • Anonymous

    5/6/2010 3:26:07 PM |

    Marinating meat with acid (vinegar) before grilling greatly reduces the maillard reaction and the formation of AGEs in meat.

  • Peter

    5/6/2010 4:48:23 PM |

    As we learn more about food, we learn more about the downsides: fish have mercury, meat has AGE's, carbs increase insulin sensitivity, etc. If you ask an expert what to eat, each one gives you a different answer.  How can we tell truth from belief?

  • CB Predator

    5/7/2010 10:50:32 AM |

    I wanted to thank you for this great read!! I definitely enjoying every little bit of it I have you bookmarked to check out new stuff you post

  • foodnearsnellville

    5/7/2010 4:54:40 PM |

    At what point is research like this going to limit the use of sugary glazes and marinades in meats and restaurant foods?

  • Anne

    5/8/2010 12:05:57 PM |

    Could adding spices and herbs reduce the bad effects of cooked meat. The study is small and funded by McCormick. Simple Addition to Meat Helps

  • Marianne

    5/8/2010 9:22:51 PM |

    Just discovered this blog so forgive me if this has already been covered.  What about Neu5Gc?  Some recommend all mammal products be avoided as they all contain this substance and it sets up an inflammatory process in the body as humans do not have Neu5Gc and recognize it as foreign.  I  have recently been poking around at eating better (not that my past was bad!) and I have never been so confused in my entire life!!! Everyone has their own opinion and most of it is contradictory. High carb, low carb, no meat, more meat, more fish, all whole grains.  It's like a crap shoot.

  • yoyo

    5/9/2010 10:57:30 AM |

    I don't have access to the original study, but the best one i could find has the food levels of AGEs reproduced with some comments at this gentleman's blog: http://inhumanexperiment.blogspot.com/2009/09/age-content-of-foods.html

    meat, even with low heat low pH preparations, seems to be high. eggs and legumes are low for their protein content.

  • Dr. William Davis

    5/9/2010 12:25:34 PM |

    Yoyo, Joel--

    Much of the work on the AGE content of food, its absorption, and its consequences have been generated by Dr. Helen Vlassara's group in New York. The Japanese group Yoyo cites has, indeed, found some conflicting observations.

    I do not think that we can construct an "AGE-free" diet nor lifestyle, nor are the data on AGE-blockers sufficiently solid to justify taking them, in my view.

    However, this is such a fascinating line of research that I think it's worth being aware of and discussing.

  • Dr. William Davis

    5/9/2010 12:33:50 PM |

    Bruce--

    Fascinating experience!

    How did you handle the AGE in meats issue?

  • Dr. William Davis

    5/9/2010 12:36:17 PM |

    Marianne--

    Sorry, no insights into Neu5Gc.

    As I mentioned in the post, this is not a "no meat" comment. It is simply discussing the fascinating observations made by Helen Vlassara's group that, when taken as a whole, fit like a perfect puzzle piece into the question of why people with high blood sugars, e.g., diabetics and pre-diabetics, develop all the undesirable health effects they do.

  • Bruce

    5/9/2010 11:50:47 PM |

    May I add a few more comments?

    Regarding meat, I have been eating normal and even generous portions - but I purchased a steamer and slow cooker to keep the cooking temps as low as possible. There is a limit in how far you can lower exogenous AGEs unless you adopt an extreme Raw regime.

    Then, your body will still produce its baseline of indogenous AGEs. I eat virtually zero sugar except for a minimal amount of fruit - usually 2 servings or 3 per day at most.

    We're really talking about a low Maillard Reaction Products diet, then I think. AGEs are many in type and the chemistry is complex. But there is good and growing evidence that the overall mix of MRPs are toxic. One study I read stated that lowering the exogenous AGE load by 40% reduces the circulating AGEs  by 60% and at this level, the body's own ability to scavenge out these compounds recovers.

    This suggests to me that we can tolerate MRPs up to a certain level, but the western diet is increasingly loading with these compounds. I wonder if this provides a (at least) partial explanation of the obestity epidemic.

    Food has been plentiful and cheap for at least 3 generations now, yet obesity is 'exploding' at the same time that the food industry is in an 'arms race' to heighten the marketability of their products.

  • Kevin

    5/10/2010 3:38:54 PM |

    I wonder how calorie restriction affects AGEs.  Is this possibly how CR influences longevity?  

    kevin

  • Santiago

    5/10/2010 11:34:41 PM |

    Hi Dr Davis
    I've hear from some diabetics how honey doesn't seem to affect them that bad.
    I looked arround and found some studies showing that honey after eaten for a while lowers blood sugar levels improiving liver function.
    Was wondering if you have an opinion related to honey

  • Anonymous

    8/30/2010 3:50:39 PM |

    So don't eat meat or carbs.  Good advice.

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Cureality | Real People Seeking Real Cures

Vitamin D toxicity

6. February 2008 William Davis (26)
It is the craziest thing.

The notion of vitamin D being easily and readily toxic has grabbed hold of many people, including my colleagues who were taught that vitamin D was toxic in medical school based on the skimpiest (and often misinterpreted) observations in a handful of unusual cases.

In my practice and in the Track Your Plaque program, we routinely use doses of 2000-10,000 units per day, occasionally more. We are guided by blood levels of 25(OH) vitamin D3. I have personally never witnessed vitamin D toxicity.

Here's an interesting graph from Dr. Reinhold Vieth. Those of you familiar with the vitamin D argument know that Dr. Vieth is among the few genuine gurus in the vitamin D world.



















From Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842-856. (Full text is available without charge.)

In the graph, the X's represent toxicity; circles fall within the non-toxic range. (Toxicity is generally defined as a level sufficient to raise blood calcium levels, "hypercalcemia.") Note that the 25(OH) vitamin D3 levels are given in nmol/L; to convert to ng/ml units that are customary in the U.S., divide the nmol/L value by a factor of 2.5.

You will notice that toxicity is virtually unheard of until the dose exceeds 10,000 units per day. Beyond 10,000 units per day, the curve heads upward sharply and toxicity does become a possibility, though not an absolute (since there are circles above 10,000 units).

You may also notice that the curve is relatively flat from vitamin D doses between 200 units and 10,000 units (log scale on x axis; arithmetic scale on y), the range of most common doses for vitamin D supplementation.

Another perspective on vitamin D blood levels is to examine the blood levels of people who are young and obtain plentiful sun exposure. Lifeguards, for instance, have blood levels of 84 ng/ml (210 nmol/L) without ill-effect. (Sun exposure cannot generate vitamin D toxicity, because of a feedback safety mechanism in skin.) While this may not represent an ideal level since they represent an extreme, it does provide reassurance that such levels are non-toxic. I also point out these levels occur in the youthful since most people lose 75% or more of vitamin D activating capacity in the skin by their 70s. Most of us over 40 are kidding ourselves if we think that a suntan provides sufficient vitamin D.

Keep in mind that it is not necessarily the dose of vitamin D that is toxic, but the blood level it generates. I take 10,000 units of vitamin D as a gelcap per day to maintain my blood level between 50-60 ng/ml (125-150 nmol/L). This strategy helps me keep my HDL in the 70-80 mg/dl range, my blood sugar around 90 mg/dl, my blood pressure <120/80, and I no longer experience colds nor winter "blues."


Copyright 2008 William Davis, MD

Turning plaque into profit

3. February 2008 William Davis (7)
For reasons unknown to me, I received a solicitation to invest in a company called Prescient Medical, with a slogan that caught my eye:


Detect and treat heart attacks before they occur.


The glossy brochure details their technology development strategy:

Predict(TM) Optical Catheter System--A catheter introduced into the coronary artery during a catheterization procedure to determine whether a specific plaque or vessel area is "vulnerable," i.e., prone to rupture in future.

Protect(TM) Luminal Shield--A stent-like metal device deployed into the coronary artery at the region of vulnerable plaque to prevent future plaque rupture.

The company anticipates FDA approval for their systems by 2009 and sales to begin by 2010. They predict sales of $7 billion.

Let's stop and think about this for a moment. It seems to me that, rather than pursuing the market of another stent for a "severe blockage," this company is going after the untapped procedural market of vulnerable plaque. In other words, their technology (an optical sensor technology that emits and analyzes light wavelengths to map specific plaque characteristics) identifies plaque that may rupture in months or years, followed by implantation of stent(s) that presumably prevent plaque rupture.

Thus, conceivably, many 20%, 30%, 40% etc. "blockages", atherosclerotic plaques that do not block flow and thereby pose no need for a conventional stent, will end up with this new type of stent. One patient could therefore receive multiple "Luminal Shields" in a single procedure.

When would these devices be employed? One pathway I could conceive of that my colleagues will be sure to exploit is 1) identify plaque by CT angiography, then 2) bring patient to the catheterization laboratory and perform this procedure for whatever hot, vulnerable plaques are identified. In other words, symptoms are no longer necessary. Reduced blood flow is no longer necessary. An abnormal stress test is no longer necessary. All that is required is that you have plaque. If the plaque is then determined to be vulnerable, then it is stented.

What bothers me about all this is the emerging effort to exploit this untapped market--a big one--of early heart disease as identified by coronary atherosclerotic plaque. As heart scans have demonstrated, there is an enormous amount of hidden heart disease in this world. This company has discovered a way to turn plaque into a profit opportunity, much as the statin drug industry found a way to "turn cholesterol into money."

The conventional stent market has plateaued and now has been, to some degree, battered by the drug-coated stent argument. Prescient has found a new and significant market for procedures and stents.

Is this really necessary? Why does plaque have to become a procedural disease? Doesn't it make more sense that, if vulnerable plaque is identified, that clinical trials are then designed to develop treatment strategies that modify vulnerable characteristics? Shockingly, this has not been done to any significant extent. Instead, the easiest path to a profit opportunity is to implant a "Luminal Shield."

You and I are able to inactivate, disempower, and essentially shut down plaque, while others are working furiously to convert it into a procedural profit opportunity. I personally find this so distasteful that I would sooner endorse a high-dose statin strategy than this approach.

You can view a video of my colleague, Dr. Martin Leon, on the Prescient Medical website, (or click here to go directly to the video), talking about how this technology will "change the treatment paradigm of the interventionalist from reactive to proactive." Scary stuff. Dr. Leon has made millions of dollars (probably more like tens of millions of dollars) from his support of technology companies for the interventional coronary device market.

My hope is that word of the sorts of techniques we use in the Track Your Plaque program disseminate before this sort of luminal coating idiocy gets off the ground.

(In actuality, a different version of this approach has been available for years using intravascular ultrasound (IVUS), another procedure that involves threading a catheter down each coronary artery during a catheterization procedure. IVUS can also cross-sectionally map a plaque's anatomy and identify "vulnerable" features, like a thin cap overlying a collection of semi-liquid fat ("lipid pool"). There has been some discussion of using this approach to identify vulnerable plaque followed by stent implantation, but it has never gotten off the ground and has certainly not found validation in any clinical study. By the way, any stent prevents plaque rupture, since by their very nature, the plaque contents are compressed, modified, and excluded to the exterior of the stent. Plaque rupture within a stent is very rare in its few millimeters of length. It may therefore not require some new technology to prevent plaque rupture.)

Statin mono-failure

1. February 2008 William Davis (6)
Evan's first heart scan score in November, 2006 yielded a high score for a 56-year old male: 542.

So he put up little fuss when his doctor prescribed simvastatin at a high dose.

Evan's LDL cholesterol before simvastatin: 158 mg/dl

Evan's LDL cholesterol on simvastatin: 72 mg/dl.

By conventional standards, Evan has had an excellent response. The rest of his lipid (cholesterol) panel was unrevealing: HDL 62 mg/dl, triglycerides 78 mg/dl. Evan doesn't smoke, has a normal blood pressure, and he is not diabetic. That should do it, right?

So his doctor thought. So Evan asked if another heart scan was in order. In December, 2007, after one year of simvastatin, his second heart scan score: 705--a 30% increase over one year.

Recall that, with no effort at prevention whatsoever, the natural progression of heart scan scores is a 30% per year increase. Did simvastatin do nothing?

This is quite typical of people who do nothing more than take a statin drug. While some people do slow plaque growth (we say "decelerate") modestly on a statin drug, Evan's experience is not unusual: plaque continues to grow despite high-dose statin drug and an apparently favorable cholesterol panel.

In fact, I can count the number of people who reduced their heart scan scores taking a statin drug alone on one finger.

Statins do not represent a cure for heart disease. They cannot be used as sole therapy to reduce risk for heart attack. In fact, given sufficient time, the majority of people who do nothing more than follow this standard line of treatment (along with the equally lame low-fat diet, etc.) will have done nothing more than postpone their heart attack. Elimination of risk? Nope.

This is among the reasons we developed the Track Your Plaque approach. While not foolproof, I know of no better approach to seize control over plaque growth.

Additional conversations on clinical studies which, as with Evan's experience, demonstrated how statin drugs fail to slow plaque growth can be found in previous Heart Scan Blog posts:

Don't be satisfied with "deceleration"

Study review: Yet another Lipitor study



Copyright 2008 William Davis, MD

Triglyceride traps

31. January 2008 William Davis (17)
Triglycerides are a potent trigger for coronary plaque growth.

Triglycerides in and of themselves probably do not cause plaque growth. Instead, triglycerides contribute to the formation of abnormal lipoproteins in the blood that, in turn, trigger coronary plaque, like VLDL, intermediate-density lipoprotein (IDL), and small LDL. Excess triglycerides also modify HDL structure and cause you to lose HDL in the urine.

I see plenty of people who begin with triglycerides of 200 mg/dl, 300, 700, even over 1000 mg/dl. It doesn't take long before you learn what works, what doesn't to reduce triglycerides. This is especially true in the Track Your Plaque approach, in which our target for triglycerides is 60 mg/dl or less.

Here's a list of things to consider if you are trying to gain control of your triglycerides:

--Fish oil--A mainstay of treatment. The omega-3 fatty acids from fish oil are the number one most potent treatment for high triglycerides.

--Reduction of high-glycemic index foods--Most notably wheat. Everybody knows that we shouldn't eat Snickers bars or bags of licorice. But many people eat plenty of wheat-containing breads, pastas, pretzels, crackers, breakfast cereals, etc., all in the name of increasing whole grains and fiber. In reality, they are causing triglycerides to skyrocket, dropping HDL, forming small LDL, increaaing blood sugar and blood pressure, and increasing obesity.

--Eliminating fructose and high-fructose corn syrup--This ubiquitous sweetener is now consumed in enormous quantities by the average American, nearly 80 lbs per year per person. You'll find it in soft drinks, ketchup, beer, breads, breakfast cereals, and many other processed foods. You'll find none in green peppers, cucumbers, and raw nuts. Fructose causes large rises in triglycerides, as well as diabetic patterns. Don't let "fat-free" claims fool you. Take a look at the ingredients in Kraft Fat-Free Caesar Italian salad dressing, for instance:

Kraft Fat-Free Caesar Italian

Ingredients:
Water, Vinegar, High Fructose Corn Syrup, Corn Syrup, Salt, Parmesan Cheese, Part-Skim Milk, Cheese Culture, Salt, Enzymes, Contains less than 2% of Garlic, Whey, Onion Juice, Autolyzed Yeast Extract, Phosphoric Acid, Worcestershire Sauce, Vinegar, Molasses, Corn Syrup, Water, Salt, Caramel Color, Dried Garlic, Sugar ,Spices, Tamarind, Natural Flavors, Hydrolyzed Soy Protein, Xanthan Gum, Potassium Sorbate and Calcium Disodium EDTA as Preservatives, Dried Garlic, Buttermilk, Spice, Dried Parsley, Caramel Color, Sodium Phosphate, Oleoresin Paprika.



--Alcohol--While a couple of drinks a day raises HDL, exerts anti-inflammatory effects, and reduces blood pressure, more than this begins to raise triglycerides. Although I've come across no formal studies on this question, my gut sense is that beer, in particular, raises triglycerides more than wine or other alcoholic beverages. Could it be the wheat source of beer? Or its high-fructose corn syrup? I don't know, but beer is the least desirable form of alcohol of the choices we have.


Following these simple steps, it is unusual in my experience that you cannot achieve a triglyceride level <60 mg/dl. Rarely do we need to add fibrate drugs or other prescription agents to reduce triglycerides.



Copyright 2008 William Davis, MD

High-dose fish oil for Lp(a)

30. January 2008 William Davis (16)
Lipoprotein(a), or Lp(a), is a problem area in coronary plaque reversal.

While our current Track Your Plaque record holder for largest percentage reduction in heart scan score has Lp(a), it remains among the more troublesome lipoprotein patterns.

One unique treatment for Lp(a) is high-dose omega-3 fatty acids from fish oil. While the data are relatively meager, there is one solid study from Lp(a) expert, Dr. Santica Marcovina of the University of Washington, called "The Lugalawa Study."

In this unique set of observations, 1300 members of a Bantu tribe living in Tanzania were studied. What made this population unusual is the fact that two groups of Bantus lived under different circumstances. One group lived on Nyasa Lake (3rd largest lake in Africa and reputed to have the greatest number of species of fish of any lake in the world) and ate large quantities of freshwater fish providing up to 500 mg of omega-3s, EPA and DHA, per day. Another Bantu group lived away from the lake as farmers, eating a pure vegetarian diet without fish.

Nyasa Lake












This situation among genetically similar stock provided a unique learning opportunity, a chance to assess whether different diets influenced Lp(a) levels.

The results: The fish-eating Bantus had an average Lp(a) level of 14.0 mg/dl. The farming, non-fish eating Bantus had an average Lp(a) of 27.0--a 48% difference. Curiously, a comparison of the apo(a) component of Lp(a) between the groups also showed that the fisherman expressed fewer dangerous small apo(a) forms, despite equal potential to express both.

The Lugalawa Study opens the question of whether similar results can be obtained not by moving to Tanzania and fishing Nyasa Lake, but by mimicking their experience by supplementing high doses of omega-3 fatty acids.

It's an intriguing question. In the Track Your Plaque program, we have no specific experience with this strategy, but it is certainly worth exploring further.

Watch for two upcoming Special Reports on the Track Your Plaque website in which we will be detailing 1)unique strategies for Lp(a) reduction, and 2) the usefulness of high-dose fish oil for coronary plaque reversal.

Interesting enough for a Virtual Clinical Trial?


Image courtesy Wikipedia.


Copyright 2008 William Davis, MD

The many faces of LDL

29. January 2008 William Davis (0)
Pam has an LDL cholesterol of 144 mg/dl.

To most people, this means that she has a mildly elevated LDL value. Many people would respond by cutting the saturated fat in their diet. Most physicians would concur and talk about prescribing a statin drug.

Let me tell you what an LDL cholesterol of 144 mg/dl means to me:

1) It could mean an LDL of all large particles (which is good) or an LDL of all small particles (which is very bad). Or, perhaps it's some combination of big and small. I can't tell which just by knowing that LDL is 144.

Small LDL responds to a diet reduced in processed carbohydrates and wheat flour; large LDL does not. Small LDL responds in an exagerrated way to niacin; large LDL does not. It makes a difference.

2) It could mean that, hidden within LDL, is lipoprotein(a), or Lp(a). Recall that Lp(a) is a high-risk genetic pattern that can provide the false appearance of high LDL cholesterol. If Pam were prescribed a statin drug, it would have little effect and little benefit. (See Red flags for Lipoprotein(a).)

Knowing that Pam has Lp(a) can point us in an entirely different direction than just LDL cholesterol. It might mean high-dose fish oil, a more serious approach to niacin, hormonal treatments like DHEA or testosterone. It might mean more attention to warning your children about the possibility that they, too, might share this genetic trait.

3) It could mean both small LDL and Lp(a) are present simultaneously, an especially dangerous combined pattern that is among the highest risks for heart disease known.

4) Because Pam's LDL of 144 mg/dl was not measured, but calculated, it means that it is subject to tremendous inaccuracy.

In my office, calculated LDL cholesterols can be inaccurate by 50 or 100 mg/dl--commonly. So Pam's LDL of 144 mg/dl could really be 70 mg/dl, or it could be 244 mg/dl. Once again, it's a big difference.


Just like The Three Faces of Eve, the 1957 film in which Joanne Woodward played the three wildly different sides of Eve's personality--the daytime Eve White, the fun-loving and daring Eve Black, and Jane--so can LDL assume several different faces, all with different personalities, different implications.

Accepting LDL cholesterol as LDL cholesterol is a fool's game. It is only a starting point, nothing more. Accepting a statin drug based on LDL is, likewise, a trap fraught with uncertainty, the potential for limited or ineffective results, the price being your heart and health.

Drive-by angioplasty

26. January 2008 William Davis (7)
Don had an angioplasty 6 months ago. When asked about the symptoms that prompted him to go to the hospital, he explained:

"I remember feeling really tired for about a week before I went. I'd read that fatigue can sometimes be a sign of heart disease. But then I had some trouble breathing. You know, like not being able to get a deep breath."

"My wife and I were planning on going on vacation. So I wanted to be certain something wasn't going on in my heart. That's when my wife insisted that she take me to the hospital.

"I kind of remember going there and arriving in the emergency room, but then I don't remember anything. Next thing I know, I'm waking up in a hospital bed. My wife and kids were there, looking all concerned. They said that I just got two stents and that the doctor just barely saved my life."

Happy story, happy ending? Not quite.

I reviewed the angiograms made during Don's hospital stay. They did, indeed, show some plaque, but not anywhere close to the amount necessary to account for symptoms like fatigue or breathlessness. For symptoms like this to occur without physical exertion, say, at your desk or relaxing at home, a critical >90% blockage would be required.

The worst "blockage" Don had was 50% at most. The leap was made to connect his relatively vague symptoms with these "blockages," leading to the implantation of two stents.

This is not as uncommon as you think. Yes, the practice of cardiology can be a life of acute procedures, urgent situations, and crises. Unfortunately, some people with questionable need for these procedures also get swept up in the wave. Sometimes it's due simply to the doctor's need to do "something," nervous family waiting in the wings. Sometiems it's intellectual laziness: putting in two stents seems to satisfy many patients' needs to have something "fixed," even when symptoms like fatigue could be due to anemia, sleep deprivation, a thyroid disorder, or any other myriad conditions that require a diagnostic effort (otherwise known as thinking). And sometimes it's simply done with financial motives, since angiplasty and related procedures pay well.

I call this "drive-by angioplasty," the impulsive, poorly considered coronary procedure that really should never have happened. How often does this happen? What percentage of heart procedures fall into this category? There are no clear-cut estimates. There are crude attempts by independent agencies that have put the number of unnecessary heart catheterizations up to 20% of the total number performed. The proportion of angioplasty procedures, stents, etc. that are not necessary is a tougher number to pinpoint, given the uncertainties surrounding the indications for these procedures, physician judgment that factors into the decision-making process, and the fact that many decisions are made on a qualitative basis, not precise quantification.

In real life, I would put the proportion of flagrant drive-by procedures at no more than 10%. However, that is 10% of an enormous number. The annual cardiovascular healthcare bill is $400 billion. 10% of that is $40 billion--an unimaginable sum. It also adds up to tens of thousands of people per year needlessly subjected to procedures. Consider that 10,000 heart procedures were performed today alone.

Should we push for legislation to control how and when heart procedures are performed? I don't think so. Despite my criticisms of the status quo in heart care, I still favor the freedom and rapid development of a free-market approach. However, you as a healthcare consumer need to be armed with information. You don't go to the car dealer unarmed with information on prices and comparative performance of the car you want. You should do the same with health. Information is your weapon, your defense against becoming the victim of the next drive-by heart procedure.

"Heart Healthy" and other lies

23. January 2008 William Davis (7)
"Bankers believe liquidation has run its course and advise purchases."

New York Times headline, Oct 30, 1929, at the start of the Great Depression.






"I did not have sexual relations with that woman, Ms Lewinsky."

Former President Bill Clinton at a Washington Press Conference, 1998.






"The third quarter is going to be great."

Enron CEO, Ken Lay, just before the company reported a $638 million third-quarter loss, triggering the company's collapse.




Should we add the following to the list?


Heart Healthy Bisquick





















Heart Healthy snacks according to the National Heart, Lung, and Blood Institute:

Animal crackers, devil's food cookies, fig and other fruit bars, ginger snaps, graham crackers, vanilla or lemon wafers

Angel food cake or other lowfat cakes

Low fat frozen yogurt, ice milk, fruit ices, sorbet, sherbet

Pudding (make it with fat free or 1% milk), gelatin desserts

Popcorn without butter or oil; pretzels, baked tortilla chips






67% digestible carbohydrates/sugars from corn syrup, sugar, raisins, and honey. Oh, yes . . . and it contains plant sterols.





"Heartzels are a healthy snack alternative for anyone wanting to control fat intake and add fiber to their diet," said Tracy LaRosiliere, a Frito-Lay vice president of marketing. "What better time for Frito-Lay to launch its first heart-healthy snack than during American Heart Month and just in time for Valentine's Day."

The relationship with the American Heart Association and the launch of Rold Gold Heartzels Pretzels is the latest move by Frito-Lay to continue its commitment to offering a wide variety of low-fat and better-for-you snacks nationally, which like the company's assortment of regular chips can be enjoyed as part of a healthy diet and lifestyle.

Calcium chaos

23. January 2008 William Davis (30)

Imagine that I'm planning to build a wall of bricks. I start by throwing cement at a pile of bricks, hoping that it forms a nice, orderly brick wall.

Fat chance, you say.

I believe that is what appears to be emerging as the situation with calcium supplementation.

A recent study from New Zealand reported an experience with 1,471 postmenopausal women, mean age of 74 years, who were randomized to treatment with either calcium supplements or placebo. Calcium was supplied as calcium citrate (Citrical) to provide 1000 mg of (elemental) calcium per day (400 mg morning, 600 mg evening).

(Bolland MJ, Barber PA, Doughty RN et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. Brit Med J BMJ, doi:10.1136/bmj.39440.525752.BE; published 15 January 2008)

Over 5 years, women taking calcium had twice the risk of having a heart attack compared with women taking the placebo; women taking calcium had a 47 percent higher risk of having any one of three "events" (heart attack, stroke or sudden death) than women in the placebo group.

The findings of this study run counter to what we've been telling people all these years: Calcium supplementation, usually taken to halt deteriorating bone health and osteoporosis, modestly reduces blood pressure, reduces LDL and raises HDL cholesterol. At first blush, we might thereby presume that it also reduces cardiovascular events.

This study suggests that calcium supplementation does not result in reduction of cardiovascular events, perhaps even increases risk.

Certainly, this new finding will serve to confuse the public even more than it is already, particularly when it comes to strategies that modify risk for heart attack. However, this may make more sense once we stop and think for a moment.

Calcium supplementation inarguably slows, occasionally halts, calcium resorption from bone (through suppression of parathyroid hormone). Calcium also accumulates as part of atherosclerotic plaque in coronary and other arteries.

How does oral calcium know where to go--bones, not arteries or kidneys, in addition to serving all its other crucial functions?

Keep in mind that, in many roles, calcium is passive, something that responds to control exerted by some other factor. Vitamin D is that factor. Vitamin D controls the absorption of calcium in the intestinal tract (calcium aborption quadruples when vitamin D is restored to normal), it controls whether calcium is deposited in bone or extracted from arteries. It is the master control over the fate of calcium. Calcium just goes along for the ride.

Bone and arterial health do indeed intersect via calcium, but not through calcium supplementation. Instead, the control exerted by vitamin D (and vitamin K2, another conversation) connects the seemingly unrelated processes.

At what calcium dose threshold do the benefits stop and the adverse effects begin? That remains unanswered, particularly in light of this new study. However, this study calls into serious question the wisdom of supplementing calcium at a dose of 1000 mg, particularly when taken without normalization of vitamin D.

Calcium is therefore emerging as an important player in artery health. But just taking calcium makes no more sense than our brick wall and cement analogy. You might regard vitamin D as the mason that skillfully lays down both brick and cement in a neat, orderly way.

Another big Track Your Plaque success story

22. January 2008 William Davis (2)
Lorenzo is an 81-year old retired manufacturing engineer whose intial heart scan score in late 2006 was an alarming 1102.

Recall that, despite feeling well and having a normal stress test, Lorenzo was facing a heart attack and death risk that was as high as 25% per year without preventive action.

Lorenzo was moderately interested in the Track Your Plaque concepts. While not exactly the most highly motivated, he did see the rationale in our approach. But he came to us mostly because his primary care doctor told him to.

Nonetheless, one year later, he underwent another heart scan. His score: 588--a 46.6% drop in score, nearly cutting his plaque in half. While Lorenzo didn't set any new records in terms of percentage drop in score, he has reduced his score in real numbers more than anybody else before: a 514 point drop in score.

Lorenzo joins the ranks of our current record holders, Amy, with a 63% drop in heart scan score, and Neal with a 51% drop in score. Both of these Track Your Plaque record holders, while achieving larger percentage reductions in score, achieved less when viewed on an absolute number basis.

Now, breaking records is not necessary to succeed in the Track Your Plaque program or at heart disease reversal. Even 1% reversal is still a big success, certainly more than is achieved in conventional practice.

No special commitment was necessary in Lorenzo's case. All he required was a little of the right kind of information. I can tell what he didn't do: Lorenzo did not follow a low-fat American Heart Association diet, he did not take high-dose statin drug, he did not deprive himself of food, he did not exercise to extremes. He just applied some simple strategies from the Track Your Plaque program.

I play these sorts of games just to make a point and to show just what is possible. While the world of hospital procedures and emergency management of coronary disease marches on, we are quietly reversing the disease. Sometimes, we achieve results that even surprise ourselves.

Lorenzo's full story will be detailed in the February 2008 Track Your Plaque newsletter. If you are not yet a subscriber, you can sign up (without cost)here.


Copyright 2008 William Davis, MD