What do Salmonella, E coli, and bread have in common?

Say you happen to eat some chicken fingers contaminated with bacteria because the 19-year old kid behind the counter failed to wash his hands after using the toilet, or because the kitchen is poorly managed with unwashed counters and cutting boards, or because the food is undercooked. You get a bout of diarrhea and cramps, along with a desire to banish chicken from your life.

Here's yet another odd wheat phenomenon: About 30% of people who eliminate wheat from their lives experience an acute food poisoning-like effect on re-exposure. You've been wheat-free for, say, 6 months. You've lost 25 lbs from your wheat belly, you've regained energy, joints feel better. You go to an office party where they're serving some really yummy looking bruschetta. Surely a couple won't hurt! Within a hour, you're getting that awful rumbling and unease that precede the explosion.

The majority of people who experience a wheat re-exposure syndrome will have diarrhea and cramps that can last from hours to days, similar to food poisoning. (Why? Why would a common food trigger a food poisoning-like effect? It happens too fast to attribute to inflammation.) Others experience asthma attacks, joint pains that last 48 hours to a week, mental fogginess, emotional distress, even rage (in males).

Wheat re-exposure in the susceptible provides a tidy demonstration of the effects of this peculiar product of genetic research. So if you are wheat-free but entertain an occasional indulgence, don't be surprised if you have to make a beeline to the toilet.

The world of intermediate carbohydrates

There are clear-cut bad carbohydrates: wheat, oats, cornstarch, and sucrose. (Fructose, too, but in a class of bad all its own.)

Wheat: The worst. Not only does wheat flour increase blood sugar higher than nearly all other carbohydrates, it invites celiac disease, neurologic impairment, mental and emotional effects, addictive (i.e., exorphin) effects, asthma, irritable bowel syndrome, acid reflux, sleepiness, sleep disruption, arthritis . . . just to name a few.

Oats: Yeah, yeah, I know: "Lowers cholesterol." But nobody told you that oats, including slow-cooked oatmeal, causes blood sugar to skyrocket.

Cornstarch: Like wheat, cornstarch flagrantly increases blood sugar.It also stimulates appetite. That's why food manufacturers put it in everything from soups to frozen dinners.

Sucrose: Not only does sucrose create a desire for more food, it is also 50% fructose, the peculiar sugar that makes us fat, increases small LDL particles, increases triglycerides, slows the metabolism of other foods, encourages diabetes, and causes more glycation than any other sugar.

But there are a large world of "other" natural carbohydrates that don't fall into the really bad category. This includes starchy beans like black, kidney, and pinto; rices such as white, brown, and wild; potatoes, including white, red, sweet, and yams; and fruits. It includes "alternative" grains like quinoa, spelt, triticale, amaranth, and barley.

For lack of a better term, I call these "intermediate" carbohydrates. They are not as bad as wheat, etc., but nor are they good. They will still increase blood glucose, small LDL, triglycerides, etc., just not as much as the worst carbohydrates.

The difference is relative. Say we compare the one-hour blood glucose effects of 1 cup of wheat flour product vs. one cup of quinoa. Typical blood sugar after wheat product: 180 mg/dl. Typical blood sugar after quinoa: 160 mg/dl--better but still pretty bad.

Some people are so carb-sensitive that they should avoid even these so-called intermediate carbohydrates. Others can have small indulgences, e.g., 1/2 cup, and not generate high blood sugars.

Heroin, Oxycontin, and a whole wheat bagel

For a substantial proportion of people who remove wheat from their diet, there is a distinct and unpleasant withdrawal syndrome. Here are the comments of Heart Scan Blog reader, Scott, from Texas:

Hello Dr. Davis,

I've been experimenting with diet, converging upon a Paleo type diet, but I keep running into problems. I have isolated the problem to cutting out wheat.

Sugar, rice, fruit, corn, potatoes, etc. are relatively ok to add or remove from the diet, but cutting out wheat in particular brings on a moderate headache with heavy fatigue all day long. This resembles the wheat withdrawal symptoms I found on your blog. As I write this, I'm on day 8 of wheat-free. I consume a fair variety of meat and veggies each day with a moderate amount of white rice for carbs. Perhaps a bowl of corn flakes with milk and half a bar of dark chocolate a day. I've learned from experience over the past 5 months or so that none of these foods affect the withdrawal. It's purely wheat.

My question is, what is the range of times for withdrawal symptoms that you've heard from different people? Has there been anyone who never recovered from the wheat withdrawal symptoms even after many months?

It's very tough to get work done like this, and even though my body and head feel much healthier in general, my sinuses have cleared, don't have to take a big nap after I eat, etc., I don't want to go down a path where this is the way things are going to be forever. 



People who have never experienced wheat withdrawal pooh-pooh the effect. But, for about 30% of people, wheat withdrawal is a real, palpable, and sometimes incapacitating experience.

Beyond removing an exceptionally digestible carbohydrate that yields blood sugar rises higher than nearly any other known food (due to the unique amylopectin structure of wheat-derived carbohydrate), wheat withdrawal is a form of opiate withdrawal, somewhat like stopping heroin, Oxycontin, and other opiates. Stop eating whole wheat toast for breakfast, whole grain sandwiches for lunch, or whole grain pasta for dinner, and the flow of exorphins, i.e., exogenous morphine-like compounds, stops. You experience dysphoria (sadness, unhappiness), mental "fog," inability to concentrate, fatigue, and decreased capacity to exercise. It is milder than withdrawal from prescription opiates. Unlike withdrawal from more powerful opiates like heroine, there are, thankfully, no seizures or hallucinations. There are also no deaths.

In my experience, most people get through with wheat withdrawal in about 5 days. An occasional person will struggle for as long as 4 weeks. Thankfully for Scott, I've never seen it last longer than 4 weeks. (Interestingly, people who survive the withdrawal syndrome are often prone to a peculiar re-exposure phenomenon that I will discuss in future, i.e., they get sick upon re-exposure.)

The modern dwarf mutant variant of Triticum aestivum (that our USDA urges us to eat more of) contains greater proportions of gluten proteins compared to wheat pre-1970; glutens are the source of wheat-derived exorphins.

Incidentally, a drug company should be releasing a drug in the next year that will contain naltrexone, an oral opiate blocking drug, for a weight loss indication. They claim it is a blocker of the "mesolimbic reward system." I say it's a blocker of wheat exorphins.

The five most powerful heart disease prevention strategies

You've seen such lists before: 5 steps to prevent heart disease or some such thing. These lists usually say things like "cut your saturated fat," eat a "balanced diet" (whatever the heck that means), exercise, and don't smoke.

I would offer a different list. You already know that smoking is a supremely idiotic habit, so I won't repeat that. Here are the 5 most important strategies I know of that help you prevent heart disease and heart attack:

1) Eliminate wheat from the diet--Provided you don't do something stupid, like allow M&M's, Coca Cola, and corn chips to dominate your diet, elimination of wheat is an enormously effective means to reduce small LDL particles, reduce triglycerides, increase HDL, reduce inflammatory measures like c-reactive protein, lose weight (inflammation-driving visceral fat), reduce blood sugar, and reduce blood pressure. I know of no other single dietary strategy that packs as much punch. This has become even more true over the past 20 years, ever since the dwarf variant of modern wheat has come to dominate.

2) Achieve a desirable 25-hydroxy vitamin D level--Contrary to the inane comments of the Institute of Medicine, vitamin D supplementation increases HDL, reduces small LDL, normalizes insulin and reduces blood sugar, reduces blood pressure, and exerts potent anti-inflammatory effects on c-reactive protein, matrix metalloproteinase, and other inflammmatory mediators. While we also have drugs that mimic some of these effects, vitamin D does so without side-effects.

3) Supplement omega-3 fatty acids from fish oil--Omega-3 fatty acids reduce triglycerides, accelerate postprandial (after-meal) clearance of lipoprotein byproducts like chylomicron remnants, and have a physical stabilizing effect on atherosclerotic plaque.

4) Normalize thyroid function--Start with obtaining sufficient iodine. Iodine is not optional; it is an essential trace mineral to maintain normal thyroid function, protect the thyroid from the hundreds of thyroid disrupters in our environment (e.g., perchlorates from fertilizer residues in produce), as well as other functions such as anti-bacterial effects. Thyroid dysfunction is epidemic; correction of subtle degrees of hypothyroidism reduces LDL, reduces triglycerides, reduces small LDL, facilitates weight loss, reduces blood pressure, normalizes endothelial responses, and reduces oxidized LDL particles.

5) Make exercise fun--Not just exercise for the sake of exercise, but physical activity or exercise for the sake of having a good time. It's the difference between resigning yourself to 30 minutes of torture and boredom on the treadmill versus engaging in an activity you enjoy and look forward to: go dancing, walk with a friend, organize a paintball tournament outdoors, Zumba class, plant a new garden, etc. It's a distinction that spells the difference between finding every excuse not to do it, compared to making time for it because you enjoy it.

Note what is not on the list: cut your fat, eat more "healthy whole grains," take a cholesterol drug, take aspirin. That's the list you'd follow if you feel your hospital needs your $100,000 contribution, otherwise known as coronary bypass surgery.

Topping up your vitamin D tank

Now that my vitamin D replacement experience dates back nearly 5 years, I've been witnessing an unusual phenomenon:

The longer you take vitamin D, the less you need.

Let me explain. You take 10,000 units D3 in gelcap form. 25-hydroxy vitamin D levels, checked every 6 months, have remained consistently between 60 and 70 ng/ml. Three years into your vitamin D experience and 25-hydroxy vitamin D level rises to 98 ng/ml--an apparent need for less vitamin D.

So we cut your intake from 10,000 units per day to 8000 units per day. Another 25-hydroxy vitamin D level 6 months later: 94 ng/ml. We cut dose again to 6000 units, followed by another 25-hydroxy vitamin D level of 66 ng/ml.

This has now happened in approximately 20% of the people who have been taking vitamin D for 3 or more years. I know of no formal analysis of this effect, what I call the "topping up" phenomenon. Reasoned simply, it seems to me that, once your vitamin D "tank" is topped up (i.e., tissue stores have been replenished), it requires less to keep it full.

No one has experienced any adverse consequence of this topping up effect though it has potential for some people to develop toxic levels if 25-hydroxy vitamin D levels are not monitored long-term. In my office, I measure 25-hydroxy vitamin D levels every 6 months.

It means that long-term monitoring of 25-hydroxy vitamin D is crucial to maintain favorable and safe levels.

Thirteen catheterizations later

When I first met her, Janet couldn't stop sobbing. She'd just been through her 10th heart catheterization in two years.

It started with chest pains at age 56, prompting her first heart catheterization that uncovered severe atherosclerotic blockages in all three coronary arteries. Her cardiologist advised a bypass operation.

Six months after the bypass operation, Janet was back with more chest pains, just as bad as before. Another heart catherization showed that two of the three bypass grafts had failed. The third bypass graft contained a severe blockage that required a stent, along with multiple stents in the two now unbypassed arteries.

In the ensuing 18 months, Janet returned for 8 additional catheterizations, each time leaving the hospital with one or more stents.

Janet's doctor was puzzled as to why her disease was progressing so aggressively despite Lipitor and the low-fat diet provided by the hospital dietitian. So he had Janet undergo lipoprotein testing (NMR):

LDL particle number: 3363 nmol/L
Small LDL particle number: 2865 nmol/L
HDL cholesterol: 32 mg/dl
Triglycerides: 344 mg/dl
Fasting blood glucose 118 mg/dl
HbA1c 5.8%

Unfortunately, Janet's doctor didn't understand what these values meant. He pretty much threw his arms up in frustration. That's when I met Janet.

From her lipoprotein panel and other values, it was clear to me that Janet was miserably carbohydrate-sensitive and carbohydrate-indulgent, as demonstrated by the extravagant quantity (2865 nmol/L) and proportion (2865/3363, or 85%) of small LDL, the form of LDL particles created by carbohydrate exposure. Janet struggled with depression over the years and had been using carbohydrate foods as "comfort" foods, often resorting to cookies, pies, cakes, breads, and other wheat-containing foods for emotional solace.

It took a bit of persuasion to convince Janet that it was low-fat, "healthy whole grains," as well as comfort foods, that had led her down this path. I also helped Janet correct her severe vitamin D deficiency, mild thyroid dysfunction, and lack of omega-3 fatty acids.

Since meeting Janet and instituting her new prevention program, she has undergone three additional catheterizations (performed by another cardiologist), all performed for chest pain symptoms that struck during periods of emotional stress. All showed . . . no significant blockage. (Apparently, the repeated "need" for stents triggered a Pavlovian response: chest pain = "need" for yet more stents.)

In short, correction of the causes of coronary atherosclerotic plaque--small LDL, vitamin D deficiency, omega-3 fatty acid deficiency, and thyroid dysfunction--and Janet's disease essentially ground to a halt.

Imagine, instead, that Janet had undergone 1) a heart scan to identify hidden coronary plaque 5-10 years before her first heart procedure, then 2) corrected the causes before they triggered symptoms and posed danger. She might have been spared an extraordinary amount of life crises, hospital procedures, expense (nearly $1 million), and emotional suffering.

High blood pressure vanquished

Heart Scan Blog reader, Eric, related his blood pressure success story to me:

I'm 34 and have been battling chronic hypertension (systolic 150-200, depending on my anxiety levels) even with multiple prescriptions for over a decade now. I've seen four different cardiologists, all stumped as to what is causing my hypertension. First, they suspected coarctation of my aorta [a constriction in the aorta], but an angiogram determined blood pressure readings were the same on both sides of the narrowing.

The second angiogram performed last year to determine if my coarct had worsened determined that it had not, but that my aorta had calcium build up. The cardiologist was stumped because he told me he hasn't seen calcium in a patient so young. Needless to say, this scared me to death, with my wife being pregnant with our first child. I asked if it could be reversed and he didn't know so he sent me to get a Berkeley lab.

The Berkeley came back with LDL 91, HDL 41, Triglycerides 73, CRP 4.1, vit D 26. The doctors weren't very knowledgeable about explaining to me what these meant and how I could correct the low vit D and high CRP. They told me to follow the low-fat diet recommended by Berkeley. Well I've already tried the DASH diet and didn't like how I felt or my energy levels, so I didn't transition.

I was at a loss until I encountered your blog and it was truly a gift. It was a refreshing feeling to meet a knowledgeable Dr. who knew what I was going through and seems to truly care about reversing calcium in the heart (something I never got from my any of my cardiologists). With your blog I have an appointment to get a heart scan here in CO and take that number along with my Berkeley results and join Track Your Plaque.

For the past 2 weeks I've been following your advice by taking a D3+K2 supplement with Omega3 Fish oil and avoiding all grain, wheat, sugar and I'm already down 4lbs to 223.5lbs at 6'5" tall and my blood pressure readings have been 128/54 and 129/60 the past 2 days! With your help I may not have the dark future my father had: dead at 48 with a massive heart attack.

Stay on the look out because I look forward to telling you how I'm one of your top calcium losers!

Eric, Colorado


Conventional medical care fails at so many levels for so many people. While Eric's doctors were busy contemplating the next angiogram, they were neglecting several crucial aspects of his health.

It's really not that tough. But it can mean doing the opposite of what conventional "wisdom" tell us.

DHEA and Lp(a)

DHEA supplementation is among my favorite ways to deal with the often-difficult lipoprotein(a), Lp(a).

DHEA is a testosterone-like adrenal hormone that declines with age, such that a typical 70-year old has blood levels around 10% that of a youthful person. DHEA is responsible for physical vigor, strength, libido, and stamina. It also keeps a lid on Lp(a).

While the effect is modest, DHEA is among the most consistent for obtaining reductions in Lp(a). A typical response would be a drop in Lp(a) from 200 nmol/L to 180 nmol/L, or 50 mg/dl to 42 mg/dl--not big responses, but very consistent responses. While there are plenty of non-responders to, say, testosterone (males), DHEA somehow escapes this inconsistency.

Rarely will DHEA be sufficient as a sole treatment for increased Lp(a), however. It is more helpful as an adjunct, e.g., to high-dose fish oil (now our number one strategy for Lp(a) control in the Track Your Plaque program), or niacin.

Because the "usual" 50 mg dose makes a lot of people bossy and aggressive, I now advise people to start with 10 mg. We then increase gradually over time to higher doses, provided the edginess and bossiness don't creep out.

The data documenting the Lp(a)-reducing effect of DHEA are limited, such as this University of Pennsylvania study, but in my real life experience in over 300 people with Lp(a), I can tell you it works.

And don't be scared by the horror stories of 10+ years ago when DHEA was thought to be a "fountain of youth," prompting some to take megadose DHEA of 1000-3000 mg per day. Like any hormone taken in supraphysiologic doses, weird stuff happens. In the case of DHEA, people become hyperaggressive, women grow mustaches and develop deep voices. DHEA doses used for Lp(a) are physiologic doses within the range ordinarily experienced by youthful humans.

No more cookies

Jeanne enjoyed her Christmas holidays. She especially liked sharing the cookies she made for her grandchildren, sneaking 2 or 3 every day over a couple of weeks. On top of this, she enjoyed the Christmas candy, egg nog, leftover stuffing and cranberry sauce, topped off with a night of nutritional debauchery on New Year's Eve.

Lipid panel in October:

Total cholesterol 146 mg/dl
LDL cholesterol 72 mg/dl
HDL cholesterol 64 mg/dl
Triglycerides 49 mg/dl

Lipid panel in early January:

Total cholesterol 229 mg/dl
LDL cholesterol 141 mg/dl
HDL cholesterol 59 mg/dl
Triglycerides 147 mg/dl


I call the holidays The Annual Wheat and Sugar Frenzy. It's the carbohydrates, especially those from products made of wheat and sucrose, that caused the marked shifts in Jeanne's lipid patterns. Let's take each parameter apart:

--Triglycerides go up due to de novo lipogenesis, liver conversion of carbohydrates into triglycerides. Triglycerides enter the bloodstream as VLDL particles which, in turn, interact with LDL and HDL.

--LDL goes up because carbohydrate exposure increases VLDL, followed by conversion to LDL. The triglyceride-rich LDL created is converted to small LDL particles. Had we measured small LDL changes in Jeanne, we likely would have measured something like an increase (by NMR) from 800 nmol/L to 1600 nmol/L, a carbohydrate effect.

--The increased VLDL also makes HDL triglyceride-rich, cause more rapid degradation of HDL particles. (It also makes them smaller, like LDL.) Given sufficient time (a few more months), HDL would drop into the 40's.

--Total cholesterol changes reflect the composite of the above numbers. (Total cholesterol = LDL cholesterol + HDL cholesterol + Trig/5) (Note that, as HDL drops, so will total cholesterol; that's why this value is worthless and should be ignored.)

So don't be surprised by the above distortions after a period of carbohydrate indulgence. Although your unwitting primary care doc will see such changes as opportunity for Lipitor, it is nothing more than the cascade of effects from a carbohydrate-driven distortion of lipoproteins.

How to become diabetic in 5 easy steps

If you would like to become diabetic in as short a time as possible, or if you have someone you don't like--ex-spouse, nasty neighbor, cranky mother-in-law--whose health you'd like to booby trap, then here's an easy-to-follow 5-step plan to make you or your target diabetic.


1) Cut your fat and eat healthy, whole grains--Yes, reduce satiety-inducing foods and replace the calories with appetite-increasing foods, such as whole grain bread, that skyrocket blood sugar higher than a candy bar.

2) Consume one or more servings of juice or soda per day--The fructose from the sucrose or high-fructose corn syrup will grow visceral fat and cultivate resistance to insulin.

3) Follow the Institute of Medicine's advice on vitamin D--Take no more than 600 units vitamin D per day. This will allow abnormal levels of insulin resistance to persist, driving up blood sugar, grow visceral fat, and allow abnormal inflammatory phenomena to persist.

4) Have a bowl of oatmeal or oat cereal every morning--Because oat products skyrocket blood sugar, the repeated high sugars will damage the pancreatic beta cells ("glucose toxicity"), eventually impairing pancreatic insulin production. (Entice your target even further: "Would you like a little honey with your oatmeal?") To make your diabetes-creating breakfast concoction even more effective, make the oatmeal using bottled water. Many popular bottled waters, like Coca Cola's Dasani or Pepsi's Aquafina, are filtered waters. This means they are devoid of magnesium, a mineral important for regulating insulin responses.

5) Take a diuretic (like hydrochlorothiazide, or HCTZ) or beta blocker (like metoprolol or atenolol) for blood pressure--Likelihood of diabetes increases 30% with these common blood pressure agents.

There you have it! Perhaps we should assemble a convenient do-it-yourself-at-home diabetes kit to help, complete with several servings of whole grain bread, a big bottle of cranberry juice, some 600 unit vitamin D tablets, a container of Irish oatmeal, and some nice bottled water.
Vytorin study explodes--But what's the real story?

Vytorin study explodes--But what's the real story?

The makers of Vytorin, Merck/Schering-Plough Pharmaceuticals, issued a press release about the the Enhance Study yesterday. The news has triggered a media frenzy.

The NY Times reporting of the story:

Drug Has No Benefit in Trial, Makers Say

The 700 participants in the trial all had a condition called "heterozygous hypercholesterolemia," a genetic disorder that permits very high LDL cholesterols. The average LDL at the start was 318 mg/dl.

The Times reported that, while Vytorin cut "LDL levels by 58 percent, compared to a 41 percent reduction with simvastatin alone," but "the average thickness of the carotid artery plaque increased by 0.0111 of a millimeter in patients taking Vytorin, compared to an increase of 0.0058 of a millimeter in those taking only simvastatin." There was no difference in heart attacks or other "events" between the two groups.

(Vytorin is the combination of simvastatin and Zetia.)

In other words, the participants taking Vytorin had 53 ten-thousands of a millimeter more plaque growth than the group taking just simvastatin.

I am always uncomfortable when put in the position of defending a drug or drug company. However, it is patently absurd that this study has generated such attention. I suspect the public and media are waiting for another Vioxx-like debacle, with memories of concealed or suppressed data that suggested heightened heart attack risk that was dismisssed by the drug manufacturer. (That's not to say that the company hasn't been trying to delay or modify the outcome of the study, which they apparently have, much to the objections of the FDA.)

However, at this point, there is no reason to believe that this question possesses any parallels to the Vioxx fiasco.

If we accept the data as reported, however, we might say it calls the entire "Lipid Hypothesis" into question: If LDL cholesterol is significantly reduced but is not correlated with reduction in plaque, is LDL the means by which atherosclerotic plaque progresses? This trial does not answer that question, but does serve to raise some doubt.

Another issue: Heterozygous hypercholesterolemia, and thereby LDL cholesterol, may not be the overwhelming driver of plaque growth in this population. It is probably the number of small LDL particles, a factor which is not revealed by LDL cholesterol. For this reason, heterozygous hypercholesterolemia by itself is insufficient to cause heart disease. Some other factor(s) needs to be present. I would propose that it is the size of the LDL particle: When small, heart disease develops; when large, heart disease is less likely to develop. This issue was not addressed by this study. Readers of The Heart Scan Blog know that conventional LDL cholesterol, the number used in this study, is a virtually worthless number for truly gauging plaque behavior because of its flagrant inaccuracy.

So, there are substantial uncertainties, contrary to the absolute certainty expressed by people like Dr. Steve Nissen (who, by the way, has no expertise in lipoprotein disorders). It is premature to reach any firm conclusions from this study. The only conclusions that I personally come to are 1) Is this yet another reason to question the entire Lipid Hypothesis as it stands? and 2) What would the results have been had LDL particle number and LDL particle size been examined, not just LDL?

I would not automatically conclude that Zetia causes carotid plaque. This is absurd. And I am definitely not one to come to the rescue of a drug or drug manufacturer. I am simply after understanding and truth.

As an interesting aside, Dr. Howard Hodis of the University of Southern California and an expert in carotid scanning for heart disease prevention research, made a comment relevant to us in the Track Your Plaque program:

"Clearly, progression of atherosclerosis is the only way you get events,” Dr. Hodis said. “If you don’t treat progression, then you get events."

Comments (28) -

  • Anonymous

    1/16/2008 1:01:00 AM |

    What am I missing here? Has it not been proven that Statin + Niacin combo is like 90% affective in stopping plaque progression in its tracks? Why does that not say that LDL reduction AND particle size reduction,(Niacin for LP(a),works best? Its not just LDL, I developed heart disease with a 90-100 LDL before my Dr discovered  high LP (a). Treated with 10mg statin,1500 Niacin, diet,I am at a30/30 count. OVER&OUT

  • Peter

    1/16/2008 11:20:00 AM |

    Let's just summarise. First there was Keys with his total cholesterol. This turned out to be garbage. Then there was LDL vs HDL. But LDL is calculated and, as we know from this site, tells us nothing about anything. Then we have LDL particle size. Small dense is bad, big fluffy is good, noting that big fluffy contains lots of cholesterol per particle and can increase your calculated, or even absolute, LDL. Two factors, most studies use calculated LDL. The bin is there, file promptly.

    The second is that something controls your LDL particle size. How, on a practical basis, does Dr Davis control LDL size and density? No wheat and no sugar. Does wheat and sugar elimination alter anything in the body? Wheat contains both an insulin mimetic and two insulin potentiators, plus starches and sugars both increase blood insulin levels per se. Perhaps there is a message here. It's been known for decades that insulin drives the proliferation of the arterial media we call arteriosclerosis.

    If insulin also controls LDL particle size (I have no information on this, but I'm willing to bet it does) then Yudkin and Stout are correct, Keys is wrong and the cholesterol hypothesis, what remains of it, describes the effects of insulin on blood lipids. While insulin and glucose do the damage to the arteries.

    Just a cholesterol skeptic view.

    Peter

    Statins are anti-inflammatory, antioxidant, anti-proliferative and probably anti other things too. Unfortunately they drop cholesterol levels (in humans anyway). Zetia, like torcetrapib and clofibrate, does the cholesterol dropping thing without the anti everything else that statins bring along. No wonder they killed so many people in the clinical trials. Clofibrate. Torcetrapib.

    If a drug company develops a drug which converts small dense LDL to light fluffy LDL without affecting insulin sensitivity or glucose, I predict it will go the way of clofibrate and torcetrapib. There's the bin.

  • Dr. Davis

    1/16/2008 1:06:00 PM |

    I especially find it interesting that, among the so-called pleiotropic, or non-lipid, effects of statin drugs is a modest rise in 25-OH-vitamin D3 levels.

  • Anonymous

    1/16/2008 3:25:00 PM |

    I think this just once again shows that statins DO reduce heart disease but NOT because of the reduction in LDL. I'm always amazed at the Dr. who say you don't need to be on a statin your LDL is fine. Statins have been proven to reduce death rates in cardiovascular disease by 30 to 40% and yes with niacin by 90%!!!!!!!! Anybody worried about heart disease should be taking them. And save me the "side effects" alarm of statins that is so over blown. The fact is we invented a drug to reduce LDL, it does that but thats not why it reduces heart attacks and we're still not sure why they do. We accidently created a great class of drugs.

  • kdhartt

    1/16/2008 3:31:00 PM |

    I remember in Taubes reading that small LDL are the result of particles being formed in a high-triglyceride environment--if so there is a more direct link to diet than through insulin.

    About the merits of statins, can't we at least say that through reducing the number of all LDL particles and hence the number of small particles arteries are protected?

    Keith

  • Jenny

    1/16/2008 4:29:00 PM |

    The drug company slanted this study so that they'd get a wonderful result, that they didn't and the lengths that they went to hide or misrepresent the data that came out of the study has to make you suspicious of what ELSE they have learned.

    Did you catch that they also suppressed other study results showing liver damage from Zetia?

    Also, did you catch the BMJ story today about the calcium supplementation trial that lowered LDL raised HDL and increased cardiac and stroke events in older women?

    While that too isn't a death blow to the LDL hypothesis, it certainly doesn't bolster it.

  • Bad_CRC

    1/16/2008 6:03:00 PM |

    Peter,

    Good post; you have an impressive grasp of the literature on this!  I have a question for you, though:  Besides the epidemiology (which I know you don't buy), aren't there still tons of animal studies linking atherosclerosis to dietary saturated fat?  In fact, to promote atherogenesis in lab animals so they can study it, don't they feed them a diet rich in palmitic, stearic, myristic and lauric acids from animal and tropical plant fats, which works predictably?

  • Dr. Davis

    1/16/2008 6:24:00 PM |

    Drug companies are actually scrutinized fairly closely, though plenty of shenanigans still go on.

    What scares me even more is what may have been going on BEFORE the intensified scrutiny began a few years ago.

    Nowadays, the return on investment for treatment of chronic diseases like cholesterol, osteoporosis, and hypertension are so substantial that it is causing them to see a blur between right and wrong.

  • Dr. Davis

    1/16/2008 6:41:00 PM |

    Yes. I believe that the evidence for that effect of statin drugs is quite confident.

    When I question the Lipid Hypothesis, what I really mean is that I question the wisdom of the simple "high cholesterol means more atherosclerosis" philosophy, a belief that is clearly oversimplified, though it contains a germ of truth.

  • Peter

    1/16/2008 8:12:00 PM |

    For anonymous,

    Of course statins reduce cardiac mortality and obviously it's nothing to do with LDL cholesterol lowering. But before you pop one on the off chance (they are available OTC in the UK) go very carefully through this paper.

    You need the full text, the abstract tells you nothing, so here's a summary:

    There were 2913 patients in the placebo group. A total of 306 died during their 3 years of not taking a statin. That is 10.5% died. In the treatment group there were 2891 patients and 298 died, that's 10.3%. Bear in mind that these were high risk cardiovascular patients, the sort for whom statin therapy is supposed to be effective in saving lives.

    There was undoubtedly a significant improvement in cardiac mortality WITHOUT improvement in overall mortality. To sum up the PROSPER trial, you can have the cause of death changed from heart attack to cancer, but not the date on the death certificate. You choose. Perhaps you're too young to be in the PROSPER trial, but live long enough and you won't be!

    PS if you EVER see a statin trial without the overall mortality figures, just assume there was no benefit or worse. If there is even a miniscule benefit it will be broadcast far and wide.

    Keith,

    Thanks for the pointer. Obviously high triglycerides are a classic marker of hyperinsulinaemia and insulin resistance. I'll follow that one when I get that far in to Taubes' book. Seems it's looking good for Yudkin.

    bad_crc,

    Yes, there are thousands of papers like that. They usually use D12451 or something like it. High fat alright, 45% calories from lard. As the rest is? A bit of corn starch, a mass of maltodextrin and an even bigger mass of sucrose!!!!! But of course it's the lard that kills....

    Whereas using a real high fat diet you get this paper. I would suggest the 60% of calories from fat us a little low for a rodent. Choosing for themselves they can go to around 80%, get plump but don't develop insulin resistance.

    Peter

  • Jenny

    1/16/2008 10:11:00 PM |

    My understanding is that studies show that statins are effective in reducing heart attacks ONLY in people who have already HAD heart attacks. Not in the general population.

    This would confirm the growing suspicion that statins work by limiting the inflammation associated with heart disease. Not through their effect on lipids.

    To get back to Zetia/Vytorin, what Dr. Nissen pointed to, which IS in my mind worth noting, was that while the variation in individual endpoints did not rise to statistical significance every single endpoint measured went in the wrong direction. That argues against random effects in my mind.

    Beyond that, we know that in most people heart disease develops over a longer period than that spanned by this study, which only lasted 2 years. If all these parameters measured were trending negatively at 2 years, what happens at 5? Or 10? This is one of those drugs that once they put on on it, you take them forever. So the 5 or 10 year result could be devastating if this turns out to be a significant finding.

    My suggestion would be continue testing this drug in small studies involving people who are very well informed of the risks, but end the writing of the current 1 million prescriptions a month. That's a LOT of guinea pigs, and if there turned out to be an accelerating pace of problems with it, a lot of people could die unnecessarily.

  • Dr. Davis

    1/16/2008 10:20:00 PM |

    Statins reduce the number of LDL particles, which is very poorly represented by the conventional (Friedwald)calculated LDL cholesterol.

    More importantly, when someone with heterozygous hypercholesterolemia (as in this Vytorin study) has a high number of SMALL LDL particles, then statin drugs, in my view, do provide benefit. But a superior effect would be to specifically reduce the number of small LDL particles, best accomplished with such strategies as elimination of wheat, weight loss via low carbohydrate diet, fish oil, vitamin D, and niacin.

    This raises the question of how well the two groups in this study were matched for the number of small LDL particles. To my knowledge, this was not measured.

    Let me also remind everybody that the measure obtained and used for comparison was carotid IMT, not carotid plaque.

  • wccaguy

    1/16/2008 10:39:00 PM |

    I'm certain I'm not alone in feeling bewildered that such a dominant theory of the disease could turn out to have been so wrong for so long at such great cost in lives and treasure.

    Just as a question of historical interest, how far back in the history of science do we have to look to find this kind of reversal of understanding of what the facts are with such broad and great consequence?

  • Dr. Davis

    1/16/2008 11:45:00 PM |

    Hi, WC--

    I'm not sure, but it's not the first time.  

    Is the earth still flat?

  • wccaguy

    1/17/2008 12:49:00 AM |

    Hi Dr. D.

    I was thinking of Galileo also and his remarkable discovery that the earth orbits the sun.

    But then I thought "surely we don't have to go that far back do we to get to such a broad and consequential paradigm shift?"

    Maybe we do.

  • Richard A.

    1/17/2008 3:52:00 AM |

    Could zetia be interfering with the absorption  of simvastatin?

  • Peter

    1/17/2008 5:52:00 AM |

    Hi wccaguy,

    You may enjoy this discussion article from PLoS. The authors intend it to be provocative, put it does pose the question "on which day did medicine stop making mistakes?"

    Peter

  • Anonymous

    1/17/2008 11:23:00 AM |

    In response to Jenny, not all studies on reducing heart attack death havwe been done on people who already had a heart attack. The reduction of 30 to 40% is whether you've had one or not.

  • kdhartt

    1/17/2008 1:18:00 PM |

    Our saturated fat question keeps coming up, but the current common wisdom is that saturated fats are "neutral" in the sense that they raise both LDL and HDL. But do we know what they do to the number of small particles? Of course, if LDL is raised by making particles fluffy then saturated fats are clearly protective.

    Keith

  • Dr. Davis

    1/17/2008 1:34:00 PM |

    Hi, Richard-
    No, there was indeed a substantial further drop in LDL with Vytorin over simvastatin.

  • Dr. Davis

    1/17/2008 1:41:00 PM |

    There is a very modest shift from small to large LDL.

  • Jenny

    1/17/2008 1:47:00 PM |

    Zetia dropped my very high, inherited LDL to normal, BUT I afer a couple months on Zetia my post-menopausal body stopped making estrogen--my gynecologist remarked on it.  

    I also started having a problem with persistent visual afterimages which the ophthalmologist said might also be from having too little cholesterol.

    Both problems went away when I stopped the Zetia. I have very high LDL but I also have the "longevity" cholesterol gene which makes for big fluffy LDL as well as very low Apo(b). My doctors--including the cardiologist I saw--are ignorant about the implications of both findings and just obsess about the high LDL.

    Since naturally produced estrogen seems to be protective for heart disease, I wonder if some people with inherited high LDL are like me have the large fluffy LDL molecules which give a deceptively high LDL value on tests. For them lowering it with Zetia drops LDL TOO low, so that the body doesn't have the cholesterol it needs for important functions, like making the naturally produced female hormones that may be protective against heart disease.

  • Dr. Davis

    1/17/2008 1:52:00 PM |

    Hi, Jenny-
    Keep in mind that conventional LDL is a flagrantly inaccurate number. In my experience, LDL of 150 when accurately measured (we use the NMR LDL particle number as the "gold standard"), the true number is between 80 and 270 mg/dl.

    In my view, conventional LDL is a silly number. It is also the basis of a $23 billion (annual revenue) industry.

  • Anonymous

    1/24/2008 4:06:00 AM |

    In Dec 05 I had a heart scan score of 145.  I went from 10 mg of Lipitor to 80mg of Vytorin and 1000 Niacin, 1 fish oil.  At that time my particle number was 1325 and small particle # 977.  A year later it went to 1503/1277.

    In Nov 07 my heart scan went to 291. I then went to 2000 mg of Niacin and 150 COQ10,4 fish oil, 500 mg C, Vitamin D.

    My new liposcience profile taken Dec 27 07 shows small particle down to 249 and particle number down to 279.

    I dont know why my plaque increased so much but the new lipo profile is impressive in reduction.

    Is there anything here that seems weird or is it just the plaque grew fast and is likely now under control with the much improved scores?  All other factors on the profile were great and my Vitamin D is very good and CRP excellent too.  My homosistine was 15.7 is the only thing a bit high.

    Thanks!!

  • Dr. Davis

    1/24/2008 12:53:00 PM |

    Sorry, but I do not assess entire programs on this blog.

    I would invite you to participate in the conversations in the Track Your Plaque Forum for detailed discussions like this. There is also a free report on "10 steps to take if your heart scan score increases" on the www.trackyourplaque.com website.

  • buy jeans

    11/2/2010 7:37:41 PM |

    I would not automatically conclude that Zetia causes carotid plaque. This is absurd. And I am definitely not one to come to the rescue of a drug or drug manufacturer. I am simply after understanding and truth.

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