Another interview with Livin' La Vida Low Carb's Jimmy Moore

I recently provided another interview for Livin' La Vida Low Carb's Jimmy Moore.

You may remember Jimmy as the irrepressible host of the Livin' La Vida Low Carb Show who lost around 200 lbs, dropping from 410 to 230 lbs on a low-carbohydrate diet.

In this hour-long interview, we discussed some of the dietary strategies that we use in the Track Your Plaque program.

Jimmy's website is definitely worth exploring. It's loaded with great interviews, including with Good Calories, Bad Calories author, Gary Taubes.

"Millions of needless deaths"

"Millions of needless deaths" is the title of an editorial by Life Extension Magazine's Bill Faloon.

". . . If vitamin D’s only benefit was to reduce coronary heart attack rates by 142%, the net savings (after deducting the cost of the vitamin D) if every American supplemented properly would be around $84 billion each year. That’s enough to put a major dent in the health care cost crisis that is forecast to bankrupt Medicare and many private insurance plans."

Although I don't agree with all the over-the-top commentary that issues from Mr. Faloon or Life Extension (although I sit on their Medical Advisory Board), I agree with virtually all of the issues he raises with vitamin D.

Despite the enormously compelling observations of vitamin D potential effects in populations, the medical community's reluctance comes from the lack of treatment data. In other words, what we lack are long-term data on vitamin D supplementation vs. placebo on rate of heart attack, vitamin D vs. placebo on risk of colon cancer, etc.

The data that exists connecting vitamin D levels with cardiovascular risk originate from three population observations:

1) The NHANES data in 16,000 participants showed 20% increased risk of cardiovascular events in those with vitamin D levels <20>20 ng/ml after factoring in all standard risk factors.

Another NHANES analysis showed the high prevalence of vitamin D deficiency in those with cardiovascular disease.

2) A German study of 2500 participants that showed showed the lowest quartile of vitamin D levels (<13.3>28.4 ng/ml.

3) The Health Professionals' Follow-Up Study of 18,000 males showed a 2.4-fold increase in cardiovascular events in those with vitamin D levels <15>30 ng/ml.

While we lack treatment data (vitamin D vs. placebo) in a large population, we do have data that Suzie Rockway, Mary Kwasny (both from Rush University, Chicago) and I generated on the effect of vitamin D as a part of a broader treatment program on coronary calcium scores:

Effect of a Combined Therapeutic Approach of Intensive Lipid Management, Omega-3 Fatty Acid Supplementation, and Increased Serum 25 (OH) Vitamin D on Coronary Calcium Scores in Asymptomatic Adults.
Davis W, Rockway S, Kwasny M. Amer J Ther 2008 (Dec 15).

The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3 supplementation on atherosclerotic plaque was assessed through serial computed tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol reduction with statin therapy has not been shown to reduce or slow progression of serial CCS in several recent studies, casting doubt on the usefulness of this approach for tracking atherosclerotic progression. In an open-label study, 45 male and female subjects with CCS of >/= 50 without symptoms of heart disease were treated with statin therapy, niacin, and omega-3 fatty acid supplementation to achieve low-density lipoprotein cholesterol and triglycerides /=60 mg/dL; and vitamin D3 supplementation to achieve serum levels of >/=50 ng/mL 25(OH) vitamin D, in addition to diet advice. Lipid profiles of subjects were significantly changed as follows: total cholesterol -24%, low-density lipoprotein -41%; triglycerides -42%, high-density lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18 months, 20 subjects experienced decrease in CCS with mean change of -14.5% (range 0% to -64%); 22 subjects experienced no change or slow annual rate of CCS increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS progression exceeding 29% (44%-71%). Despite wide variation in response, substantial reduction of CCS was achieved in 44% of subjects and slowed plaque growth in 49% of the subjects applying a broad treatment program.


I also summed up the data as of early 2008 in a Life Extension article:

Vitamin D's Crucial Role in Cardiovascular Protection


I do agree with Mr. Faloon: It's time to take the vitamin D issue very seriously. Personally, I think it is foolhardy to not correct vitamin D deficiency, even in the absence of long-term treatment data.

Should we subject people living in tropical climates with vitamin D blood levels of 90 ng/ml to long-term observation? Though that has not yet been done, it has been done--in effect--through observations on the prevalence of diabetes, heart disease, and various cancers by latitude: the farther away from the equator, the greater the prevalence of these diseases.

That's more than good enough for me.

Thiazide diuretics: Treatment of choice for high blood pressure?

Thiazide diuretics are a popular first-line treatment for hypertension among the primary care set.

This practice became especially well-established with the 2002 publication of the ALLHAT Study (Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic:The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)).

ALLHAT showed that an inexpensive diuretic like chlorthalidone (a weak diuretic in the thiazide class, similar to hydrochlorothiazide) as first-line treatment for hypertension achieved equivalent reductions in cardiovascular events (cardiovasular death and heart attack) as non-thiazide antihypertensives, lisinopril (an ACE inhibitor) and amlodipine (a calcium channel blocker, better known as Norvasc).

After 7 years of treatment, there was 14% death or heart attack among all three groups--no difference.

This was interpreted to mean that inexpensive thiazide diuretics like chlorthalidone offer as much benefit as other blood pressure medications at reduced cost.

On the surface, that's great. Anything that detracts from the ubiquitous pharmaceutical industry propaganda of bigger, better, more expensive drugs to replace old, inexpensive, generic drugs is fine by me.

But you knew there'd be more to this issue! If we accept that thiazides are equivalent to other single-drug treatments for high blood pressure, what do we do with the following issues:

--Thiazides deplete body potassium-This effect can be profound. In fact, built into the ALLHAT mortality rate is an expected death rate from potassium depletion. When potassium in the body and blood go low, the heart becomes electrically unstable and dangerous rhythms develop.

--Thiazides deplete magnesium--Similar in implication to the potassium loss, magnesium loss also creates electrical instability in the heart, not to mention exaggeration of insulin resistance, rise in triglycerides, reduction in HDL.

--Thiazides reduce HDL cholesterol

--Thiazides increase triglycerides

--Thiazides increase small LDL particles--You know, the number one cause for heart disease in the U.S.

--Thiazides increase uric acid--Uric acid is increasingly looking like a coronary risk factor: The higher the uric acid blood level, the greater the risk for heart attack. Thiazides have long been known to increase uric acid, occasionally sufficient to trigger attacks of gout (uric acid crystals that precipitate in joints, like rock candy). (Fully detailed Special Report on uric acid coming this week on the Track Your Plaque website.)

What about the advice we commonly give people to hydrate themselves generously? Yet we give them diuretics? Which is it: More hydration or less hydration? You can't have both.

Do thiazides exert an apparent cardiovascular risk reduction in a society due to its flagrant sodium obsession?

Thus, there are a number of inconsistencies in the thinking surrounding thiazides. In my experience, I have seen more harm done than good using these agents. While I cannot fully reconcile the reported benefit seen in ALLHAT with what I see in real life, all too often I see people having to take another drug to make up for a side-effect of a thiazide diuretic (e.g., high-dose prescription potassium to replace lost potassium, allopurinol to reduce uric acid, etc.). I have seen many people get hospitalized, even suffer near-fatal or fatal events from extremely low potassium or magnesium levels.

My personal view: ALLHAT or no, avoid thiazide diuretics like the plague. Sure, it might save money on a population basis, but I suspect that the ALLHAT data are deeply misleading.

What's better than a thiazide, calcium blocker, or ACE inhibitor? How about vitamin D restoration, thyroid normalization, wheat elimination?

"High-dose" Vitamin D

I stumbled on one of the growing number of local media stories on the power of vitamin D.

In one story, a purported "expert" was talking about the benefits of "high-dose" vitamin D, meaning up to 1000, even 2000 units per day.

I regard this as high-dose---for an infant.

Judging by my experiences, now numbering well over 1000 patients over three years time, I'd regard this dose range not as "high dose," nor moderate dose, perhaps not even low dose. I'd regard it as barely adequate.

Though needs vary widely, the majority of men require 6000 units per day, women 5000 units per day. Only then do most men and women achieve what I'd define as desirable: 60-70 ng/ml 25-hydroxy vitamin D blood level.

I base this target level by extrapolating from several simple observations:

--In epidemiologic studies, a blood level of 52 ng/ml seems to be an eerily consistent value: >52 ng/ml and cancer of the colon, breast, and prostate become far less common; <52 ng/ml and cancers are far more likely. I don't know about you, but I'd like to have a little larger margin of safety than just achieving 52.1 ng/ml.

--Young people (not older people >40 years old, who have lost most of the capacity to activate vitamin D in the skin) who obtain several days to weeks of tropical sun typically have 25-hydroxy vitamin D blood levels of 80-100 ng/ml without adverse effect.

More recently, having achieved this target blood level in many people, I can tell you confidently that achieving this blood level of vitamin D achieves:

--Virtual elimination of "winter blues" and seasonal affective disorder in the great majority
--Dramatic increases in HDL cholesterol (though full effect can require a year to develop)
--Reduction in triglycerides
--Modest reduction in blood pressure
--Dramatic reduction in c-reactive protein (far greater than achieved with Crestor, JUPITER trial or no)
--Increased bone density (improved osteoporosis/osteopenia)
--Halting or reversal of aortic valve disease

(I don't see enough cancer in my cardiology practice to gauge whether or not there has been an impact on cancer incidence.)

My colleagues who have bothered to participate in the vitamin D conversation have issued warnings about not going "overboard" with vitamin D, generally meaning a level of >30 ng/ml.

I know of no rational basis for these cautions. If hypercalcemia (increased blood calcium) is the concern, then calcium levels can be monitored. I can reassure them that calcium levels virtually never go up in people (without rare diseases like sarcoid or hyperparathyroidism). Then why any hesitation in recreating blood levels that are enjoyed by tropical inhabitants exposed to plentiful sun that achieve these extraordinary health effects?

For the present, I have applied the target level of 60-70 ng/ml without apparent ill-effect. In fact, I have witnessed nothing but hugely positive effects.

Vitamin D Home Test

The ever-resourceful Dr. John Cannell of the Vitamin D Council has announced the availability of an at-home, self-ordered vitamin D test kit for $65. The Vitamin D Council newsletter is reprinted below.

(However, please note that, as wonderful as the advice Dr. Cannell provides, I don't agree on several small points, such as the lack of need for vitamin D if you use a tanning bed or obtain "sufficient" sun; I have seen many people with dark tans, virtually all over 40 years old, who are still severely deficient. I attribute this to the lost capacity for vitamin D activation as we age.)

I have not used this service. Should anyone choose to try it, please let us know how it goes.



The Vitamin D Newsletter
December 28, 2008

The Vitamin D Council is happy to announce that we have partnered with ZRT Laboratory to provide an inexpensive, $65.00, in-home, accurate, vitamin D [25(OH)D] test. The usual cost for this test is between $100.00 and $200.00.

If you read this newsletter, you know about our interest in accurate vitamin D testing. In the next few weeks, you may read about the Vitamin D Council's quest for accurate vitamin D blood tests in the national media. Before we partnered with ZRT, we verified, repeatedly, that ZRT provides accurate and reliable vitamin D tests and that their method corresponds very well to the gold standard of vitamin D blood tests, the DiaSorin RIA.

Our ZRT service is not just inexpensive, it means no more worrying about your doctor ordering the right test or interpreting it correctly. You buy the test kit on the internet or by phone, a few days later the kit comes in the mail, you or a nurse friend do a finger stick, collect a few drops of blood, and send the blotter paper back to ZRT in the postage paid envelope provided with the kit. A week later you get results back in the mail and know accurate 25-hydroxy-vitamin D levels of you and your family.

For every test you order, ZRT will donate $10.00 to the Vitamin D Council. Please read the new page hyperlinked below on our website as it both explains the procedure and how to order the test.

http://www.vitamindcouncil.org/health/deficiency/am-i-vitamin-d-deficient.shtml

Executive summary: keep your family's 25-hydroxy-vitamin D blood test above 50 ng/ml, year around. Most adults need at least 5,000 IU per day, especially this time of year. Most children need at least 1,000 IU per day per every 25 pounds of body weight. Bio Tech Pharmacal provides high quality and inexpensive vitamin D. Currently Bio Tech Pharmacal is providing vitamin D for numerous scientific studies. To see their prices and for ordering, click the hyperlink below.

http://www.bio-tech-pharm.com/catalog.aspx?cat_id=2

As a gift to our readers for the New Year, Thorne publications have provided a free download to a basic paper about vitamin D. I wrote it earlier this year for educated lay people as well as health care practitioners. Please read this paper carefully, your family's well-being, even lives, may depend on you understanding it.

http://www.thorne.com/altmedrev/.fulltext/13/1/6.pdf

Seasons Greetings
John Cannell, MD
vitamindcouncil.org

Where do Track Your Plaque membership revenues go?

People pay about $90 per year to become Members on the Track Your Plaque website. This provide access to our in-depth Special Reports, guides, webinars, and our proprietary software data tracking tools. Members can also participate in online discussions, such as those in the Track Your Plaque Forum and chats.

Why is there a charge for membership in the program and where does the money go?

Money raised from membership fees goes towards:

1) The costs of doing business, e.g., server fees, software purchases, legal fees. Hosting webinars, for instance, costs us about $99 per month for the GoToWebinar software service.

2) Software development--Our most recent round of software data tracking tools, for instance, cost us nearly $30,000. That may not be a lot from big business standards, but it is onerous enough that obtaining membership dues really helps.

3) Graphics development--A website without graphics would be awfully dull, regardless of the quality of the textual content. Some of the newest tools on the Track Your Plaque website require photography and graphics work, which can add up very quickly.


Where membership fees do NOT go:

1) In our pockets--In fact, except for the various contractors who are paid for their services (e.g., software developers), NOBODY on the Track Your Plaque staff are paid: not me, nor any of the behind-the-scenes staff. Some of the staff overlap with my office staff, but they are paid purely out of the office revenues, not out of Track Your Plaque membership dues.

2) Towards overhead costs beyond those listed above--For example, membership fees do not pay for office lease, utilities, phones, etc.


We rely on membership fees because we have chosen to remain as free of commercial bias as possible. We host no advertising, we have no behind-the-scenes corporate or institutional agendas, we show no favoritism to any business or commercial operation. We believe this permits editorial freedom that few other health websites can enjoy. (In fact, I know of no other that is so free of commercial bias, outside of small blogs or narrow-interest websites.)

If you want to see what damage commercial bias can create, just go to a health website like WebMD. I challenge you to find information that is not flagrantly biased by commercial influence, namely that of the drug industry. (According to the WebMD SEC filings, in fact, the great majority--approximately 80%--of their $331 million revenues (2007) were derived directly or indirectly from the drug industry.) This commercial bias reaches into all of WebMD's related businesses, including MedicineNet.com, RxList.com, Medscape.com, and several others.

Preventing heart disease is not a money maker, sad to say. It is, from the perspective of conventional heart care, a big money loser. Undergo a heart catheterization, hospitalization, stent or bypass for anywhere from $14,000 to well over $100,000---or pay $90 for in-depth health information that dramatically reduces the potential need for the hospital and its procedures, minimizes need for prescription medication (statins alone, of course, are a $27 billion annual revenue phenomenon), and achieves all this by maximizing nutrition, self-purchased nutritional supplements, and inexpensive heart scans. Nobody is going to make a bundle off of this approach.

So that is why we charge a membership fee. I often get a laugh from some of the comments of people on this blog or even in my office who believe that we are rolling in money from the website from membership dues. The opposite is true: We don't pay ourselves. Virtually every penny is reinvested back into the website to better serve the Members.

Getting your dose of fish oil right

Confusion often stems from the simplest of calculations: dose of fish oil.

Actually, you and I don't take fish oil for fish oil. We take fish oil for its content of omega-3 fatty acids, the dominant ones being EPA and DHA. The contents of fish oil outside of its EPA + DHA content likely exert little or no benefit (beyond that of other dietary oils).

To determine what you are currently taking, simply examine the back of your fish oil bottle and look for the EPA + DHA composition. This should be clearly and prominently labeled. If not, don't buy that brand again. Add up the EPA + DHA content per capsule, then multiply by the number of capsules you take per day. That yields your daily EPA + DHA intake.

The only other substantial source of omega-3 fatty acids is fish. Other food sources, such as non-fish meats, eggs, etc., contribute little or none. Processed foods that bear health claims of "contains heart healthy omega-3" often contain linolenic acid or flaxseed oil, which contributes very little to total EPA + DHA, or contain relatively trivial quantities of DHA. What are you doing eating processed foods, anyway?

What should the total daily dose of EPA + DHA dose be? That depends on what your goals are.

If your goal is to modestly reduce the risk of dying from heart attack, then just eating fish a couple of times per month will begin to exert an effect, or just taking a dose of 300 mg EPA + DHA per day from a low-potency capsule will do it. However, that's an awfully unambitious goal.

Our starting omega-3 dose in the Track Your Plaque program has, over the years, increased and now stands at 1800 mg EPA + DHA per day. However, the dose for 1) full reduction of triglycerides and/or triglyceride-containing abnormal lipoproteins, 2) reduction of Lp(a), and 3) the ideal dose for coronary and carotid plaque control are substantially higher.

But once you know your desired daily target of total EPA + DHA, you can easily determine the quantity of capsules to take by doing the above arithemetic, totaling the EPA + DHA per capsule. For example, if you have been instructed to take 6000 mg per day EPA + DHA, and your capsule contains 750 mg EPA + DHA, then you will need to take 8 capsules per day (6000/750).

Flat tummy . . . or, Why your dietitian is fat

When I go to the hospital, I am continually amazed at some of the hospital staff: 5 ft 4 inch nurses weighing over 200 lbs, etc.

But what I find particularly bothersome are some (not all) hospital dietitans--presumably experts at the day-to-day of healthy eating--who waddle through the halls, easily 40, 50, or more pounds overweight. It is, to say the least, credibility-challenging for an obese dietitian to be providing nutritional advice to men or women recovering after bypass or stent while clearly not in command of nutritional health herself.

What's behind this perverse situation? How can a person charged to dispense "healthy" nutritional information clearly display such clear-cut evidence of poor nutrition?

How would you view a success coach dressed in rags? Or a reading coach who can barely read a sentence?

Easy: She follows her own advice.

Hospital dietitians are essentially forced to adhere to nutritional guidelines of "official" organizations, such as the American Heart Association and the USDA. There is some reason behind this. Imagine a rogue dietitian decides to advocate some crazy diet that yields dangerous effects, e.g., high-potassium diets in people with kidney disease. There is a role for oversite on the information any hospital staff member dispenses.

The problem, of course, doesn't lie with the dietitian, but with the organizations drafting the guidelines. For years, the mantra of hospital diets was "low-fat." More recently, this dated message has begun--only begun--to falter, but now replaced with the "healthy, whole grain" mantra. And that is the advice the hapless dietitian follows herself, unwittingly indulging in foods that make us fat.

Sadly, the "healthy, whole grain" message also contributes to heart disease via drop in HDL, increased triglycerides, a huge surge in small LDL, rise in blood sugar, increased resistance to insulin, tummy fat, and diabetes. Yes, the diet provided to survivors of heart attack increases risk.

The "healthy, whole grain" message also enjoys apparent "validation" through the enormous proliferation of commercial products cleverly disguised as healthy: Cheerios, Raisin Bran, whole grain bread, whole wheat pasta, etc. The "healthy, whole grain" message, while a health disaster, is undoubtedly a commercial success.

I'll bet that our fat dietitian friend enjoys a breakfast of healthy, whole grains in skim milk, followed by a lunch of low-fat chicken breast on two slices of whole grain bread, and ends her day with a healthy meal of whole wheat pasta. She then ascribes her continually climbing weight and size 16 figure to slow metabolism, lack of exercise, or the once-a-week piece of chocolate.

Wheat has no role in the Track Your Plaque program for coronary plaque control and reversal. In fact, my personal view is that wheat has no role in the human diet whatsoever.

More on this concept can be found at:

What's worse than sugar?

The Wheat-Deficiency Syndrome


Nutritional approaches: Large vs. Small LDL

Are you wheat-free?

Statin drug revolt

I sense a growing revolt against the intrusion of statin drugs into our lives.

No doubt, the statin drug industry is, at least from an economic perspective, a huge success: $27 billion annual revenues at last accounting. The latest big plug for more and more statins was the JUPITER trial that showed reduced cardiovascular events on Crestor in people with "normal" LDL cholesterol levels and increased c-reactive protein.

It seems that not one day passes that doesn't include some news story about the "benefits" of statin drugs: reduction in heart attack, stroke, colon cancer, osteoporosis, heart failure, etc.

Ironically, the overwhelming economic success of the statin drug industry also seems to be encouraging a grassroots revolt.





More and more people are coming to the office, more people commenting on the web over how they want to avoid statin drugs, stop a drug they are already taking, or at least reduce the dose of an ongoing drug.

My day-to-day experience with coronary plaque control and reversal is that, while statin drugs are helpful tools, they are not necessary tools for full benefit of a prevention program. "Need" for statin drugs can differ by the patterns measured, though not the usual patterns suggested by the drug industry. For instance, using C-reactive protein, a la JUPITER, as justification for statin prescription is, in my view, totally absurd and makes no sense whatsoever, since inflammatory responses can be effective reduced with plenty of other strategies besides statin drugs. Conventional LDL, likewise, is a fictitious number that often bear little or no resemblance to the true and genuine measured value (apoprotein B or LDL particle number).

So here are a number of strategies that can help reduce or eliminate the "need" for a statin drug:

--Elimination of wheat and cornstarch--This is no namby-pamby dietary strategy, as low-fat diets were. This is a powerful, enormously effective strategy, particularly if LDL is in the small category. Small LDL drops like a stone when these foods are eliminated. This means no breads, pasta, breakfast cereals, pretzels, crackers, chips, tacos, wraps, etc.
--Non-wheat fibers--Especially raw nuts, ground flaxseed, and oat bran.
--Vitamin D restoration
--Fish oil
--Weight loss
--Niacin

There are additional strategies that focus on specific subsets of LDL cholesterol (e.g., Lp(a) masquerading as LDL). But the above list can reduce LDL cholesterol substantially, reducing the apparent "need" for a statin drug.

You will notice that there are few money makers in the above list, compared to the billions of dollars reaped by the statin drug industry. There is therefore little incentive to allow a pretty sales rep to go to your doctor and pitch the use of over-the-counter vitamin D or make changes in diet.

Statin drugs in my view need to be shoved back into their more limited role as drugs to be used on occasion when necessary (e.g., heterozygous familial hypercholesterolemia with LDL cholesterol values of 250 mg/dl in a person with measurable coronary plaque). These should never have achieved the "celebrity" status they enjoy, complete with gushing endorsements by TV personalities, daily news stories, and back-to-back TV commercials.

Join the revolt!

Lovaza Rip-off

Lovaza is GlaxoSmithKline's prescription fish oil, an ethyl ester modification to allow higher concentration of omega-3 fatty acids, EPA + DHA, per capsule. Each capsule contains 840 mg EPA + DHA.

It is FDA-approved for treatment of high triglycerides (>500 mg/dl). In their marketing, they claim "Unlike LOVAZA, dietary supplements are not FDA approved to treat any disease." They also highlight the "patented five-step" purification process that eliminates any concerns over mercury or pesticide residues.

What does Lovaza cost? In Milwaukee, it costs about $70 per capsule per month (PCPM). Most people are taking four capsules per day: $280 per month, or $3360 per year to obtain 3360 mg of EPA + DHA per day. (Funny coincidence with the numbers.)

Did you catch that? $3360 per year, just for one person to take Lovaza.

What if I instead went to Costco and bought their high-potency fish oil. This is also an ethyl ester form. It costs $14.99 for 180 capsules, or $2.50 PCPM; each capsule contains 684 mg EPA + DHA. I would therefore have to take five capsules per day to obtain the same 3360 mg EPA + DHA per day. This would cost me 5 x $2.50 = $12.50 per month, or $150 per year.

$3360 per year vs. $150 per year to obtain the same dose of omega-3 fatty acids, or a 22.4-fold difference.

Lovaza is FDA-approved for treatment of high triglycerides. But I am seeing more and more people take it for other reasons at this four-capsule-per-day dose. Regardless, this "drug" is adding $3360 per year costs to our healthcare. A school teacher, for instance, recently commented to me that she didn't care about the costs, since her insurance (in Milwaukee county, teachers have unbelievably generous healthcare coverage) covers Lovaza. I've heard this from others: insurance covers it, so they don't care how much it costs.

Guess who eventually has to pay the $3360 per year per person costs? Yup, you and me. We all bitch and moan about the costs of healthcare and health insurance, but many of us are more than willing to shift the costs to our friends and neighbors to save a few bucks. You think Lipitor makes a bundle of money for Pfizer at about $120 per month? Lovaza is making a bundle of money for GlaxoSmithKline, and all because people are cheap and willing to selfishly shift costs to other people.

Keep in mind that $3360 per year is just for fish oil. It's not for surgery, it's not for hospital care, it's just for stinking fish oil.
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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