Kitchen sink approach for Lp(a)


Lipoprotein(a), Lp(a), can be a tough nut to crack.

Having struggled and wrestled with this genetic pattern for the last 12 years or so in hundreds of patients, I have gained great respect for this difficult to control pattern.

I regard lipoprotein(a) as the number one most aggressive cause for heart disease and coronary plaque known. It can account for heart attacks in men in their 40s, women in their 50s. It can cause heart disease and heart attacks in even the ultra-fit like marathon runners. It accounts for both excessive coronary risk and misleading cholesterol values in slender, healthy-appearing people.

Niacin is the number one treatment choice for Lp(a), followed by testosterone for men, estrogens (preferably human, not horse or other non-human mammal) for women. I then often resort to DHEA, along with adjunctive nutritional agents like raw almonds, ground flaxseed, and others.

Our most recent addition to the Lp(a) treatment list is high-dose fish oil, which appears to exert a significant effect in about 40% of people with Lp(a).

Even with this multi-agent approach, not everybody gains control over Lp(a).

That makes me wonder if someone has Lp(a) at a substantial level of, say, 200 nmol/L or 70 mg/dl (values can differ tremendously, depending on the method of measurement), should we throw everything but the kitchen sink at Lp(a) from the start? Right now, by adding an agent one at a time, it often takes two years to gain control over Lp(a) (if we are going to get it at all).

While many people might find this unpalatable and overwhelming from the starting gate of their program, I do believe it may be a strategy we should consider adopting for full and more immediate plaque control in the Track Your Plaque program. Something to chew on.

Clearly, we need better answers for Lp(a). A "kitchen sink," full-frontal assault might be a way to gain faster control, though not necessarily a superior approach with regards to efficacy and potency.

There are a number of unique, potentially effective therapies for Lp(a) that are worth examining. Given the difficulty of performing clinical trials with non-drug agents (largely a lack of financial support, since nobody gets a financial return with non-patent-protectable agents), I am anxious to put these potential treatments to a test in the Track Your Plaque program Virtual Clinical Trail (VCT). The VCT gives us a quick and relatively easy method to test various potential treatments, with feedback generated in months, rather than years.

Any suggestions on promising agents to test? Of course, they must be widely available nutritional agents, not drugs.

Making Dr. Friedewald an honest man

Colleen started with the usual discrepancy between conventional calculated LDL cholesterol of 121 mg/dl and the far more accurate LDL particle number (NMR) of 1927 nmol/L.

Those of you following this conversation or our many conversations on the Track Your Plaque Forum know that a useful and highly reliable rule-of-thumb for converting NMR LDL particle number to LDL is to drop the last digit: 1927 nmol/L becomes 192 mg/dl. (This is, admitttedly, arrived at empirically, not by design. However, it has held up through thousands of NMR analyses and plays out reasonably when you compare distributions of Friedewald LDL and LDL particle number on a population basis.)

In other words, by this simple manipulation, Colleen's Friedewald calculated LDL is off by 58%. This is very common, a phenomenon I witness several times every day.

By LDL particle size, 75% of all Colleen's LDL particle were abnormally small (small LDL particle number 1440 nmol/L). This is a moderately severe small LDL tendency.

So we took all the steps for reduction of small LDL/LDL, including elimination of wheat and cornstarch, exercise, weight loss (which happens inevitably when wheat and cornstarch are eliminated), fish oil, vitamin D, etc.

Another NMR lipoprotein panel showed an LDL particle number of 882 nmol/L and a Friedewald calculated LDL of 87 mg/dl. Using our rule-of-thumb, LDL by particle number is virtually the same as the calculated LDL. This time, small LDL numbered only 237 nmol/L, or 26.8% of the total, a marked reduction.

Isn't that interesting? As small LDL is corrected, the crude Friedwald calculated LDL approximates the more accurate LDL particle number.

It assumes that accuracy of the Friedewald calculation may be more likely to occur as LDL size approaches normal. However, when LDL size is abnormally small--a condition shared by at least 70% of people with coronary heart disease--then the Friedewald LDL becomes increasingly inaccurate.

The opposite can also happen: When all or nearly all LDL particles are large, Friedewald calculated LDL can markedly overestimate LDL particle number. Yesterday, for instance, a patient had a Friedewald calculated LDL of 183 mg/dl, but an NMR particle number of 1110 nmol/L--drop the zero . . . LDL 110 mg/dl. This woman was advised to take a statin drug by her primary care physician, based on the Friedewald LDL. Instead, she proved to have a far lower LDL. She would not have benefitted from taking a statin drug.

As I've warned many times before: Beware the Friedewald calculated LDL.

Some basic vitamin D issues

The last post on vitamin D raised a number of basic questions among readers. So let me discuss some of these questions one by one. All of them raise important issues surrounding the practical aspects of managing vitamin D in your health.

Anne said:

I think it is important to stress that vitamin D supplementation needs to be continued long term.

I have met too many people who have been prescribed 50,000 IU of D2 for 8-12 weeks and then told to stop because their 23(OH)D went over 30ng/ml. I know one person who's doctor stopped and started the D2 3 times.


Thanks for pointing that out, Anne. Excellent point. I also see doctors do this with statin drugs: start it, check a LDL level which is lower, then think that you're done and stop the drug. What the heck are they thinking?

If vitamin D is not being produced by sun exposure and not obtainable through diet, continued supplementation is necessary, essentially for life.


Twinb asked:

How often you think Vit. D levels should be tested after the initial test is done, especially if the levels are drastically low?

We have used every 6 months in the office. Ideally, levels are in mid-summer and mid- to-late winter in order to gauge the extremes of your seasonal fluctuations. While most adults over 40 fail to fluctuate more than 10 ng/ml in the Wisconsin climate (and this summer, after an initial rainy season early, has been flawlessly bright and sunny, in the high-70s and 80s every single day for months), an occasional person fluctuates more widely. The only way to judge is to check a blood level.


Rich said:

Vitamin D dosage effects appear to be quite idiosyncratic.

Yes, indeed it is. Despite using crude rules-of-thumb, like taking 1000 units of vitamin D per 10 ng/ml desired (a rule I learned from Dr. John Cannell, which he offered fully aware of its inaccuracy), many people will surprise you and have levels that make no sense. Testing is crucial to know your vitamin D level.


Richard asked: Where do we get enough vitamin D wihout worring about laboratory tests?

Well, the entire point of the post was that you absolutely, positively cannot just take vitamin D blindly at any dose and hope that your level is ideal, no more than you can blindly take a dose of thyroid and know you have achieved normal thyroid levels. In my view, vitamin D blood levels are an absolute.


Another simple issue: Don't be afraid of vitamin D. It is, in all practicality, no more dangerous than getting a dark tan. (But, as many of you realize, getting a tan is no assurance of raising vitamin D if you are over 40 years old.)

Wouldn't it be great if someone developed a do-it-yourself-at-home skin test for vitamin D? I know of no effort to develop this, but it would be a huge advantage for all of us.

“How much vitamin D should I take?”

It’s probably the number one most common question I get today:

“How much vitamin D should I take?”

Like asking for investing advice, there are no shortage of people willing to provide answers, most of them plain wrong.

The media are quick to offer advice like “Take the recommended daily allowance of 400 units per day,” or “Some experts say that intake of vitamin D should be higher, as high as 2000 units per day.” Or “Be sure to get your 15 minutes of midday sun.”

Utter nonsense.

The Food and Nutrition Board of the Institute of Medicine has been struggling with this question, also. They have an impossible job: Draft broad pronouncements on requirements for various nutrients by recommending Recommended Daily Allowances (RDA) for all Americans. The Food and Nutrition Board has tried to factor in individual variation by breaking vitamin D requirements down by age and sex, but what amounts to a one-size-fits-nearly-all approach.

Much of the uncertainty over dosing stems from the fact that vitamin D should not be called a “vitamin.” Vitamins are nutrients obtained from foods. But, outside of oily fish, you'll find very little naturally-occurring vitamin D in food. (Even in fish, there is generally no more than 400 units per 4 oz. serving.) Sure, there’s 20 units in an egg yolk and you can activate the vitamin D in a shiitake mushroom by exposing it to ultraviolet radiation. Dairy products like milk (usually) contain vitamin D because the USDA mandates it. But food sources hardly help at all unless you’re an infant or small child.

It all makes sense when vitamin D is viewed as a hormone, a steroid hormone, not a vitamin. Vitamin-no, steroid hormone-D exerts potent effects in tiny quantities with hormone-like action in cells, including activation of nuclear receptors.

It is the only hormone that is meant to be activated by sun exposure of the skin, not obtained through diet. But the ability to activate D is lost by the majority of us by age 40 and even a dark tan is no assurance that sufficient skin prohormone D activation has taken place.

As with any other hormone, such as thyroid, parathyroid, or growth hormones, dose needs to be individualized.

Imagine you developed a severely low thyroid condition that resulted in 30 lbs of weight gain, lose your hair, legs swell, and heart disease explodes. Would you accept that you should take the same dose of thyroid hormone as every other man or woman your age, regardless of your body size, proportion of body fat, metabolism, genetics, race, dietary habits, and other factors that influence thyroid hormone levels? Of course you wouldn’t.

Then why would anyone insist that vitamin D be applied in a one-size-fits-all fashion? (There’s another world in which a one-size-fits-all approach to hormone replacement has been widely applied, that of female estrogen replacement. In conventional practice, there’s no effort to identify need, estrogen-progesterone interactions, nor assess the adequacy of dose, not to mention the perverse non-human preparation used.)

With thyroid hormone, ideal replacement dose of hormone ranges widely from one person to another. Some people require 25 mcg per day of T4; others require 800% greater doses. Many require T3, but not everybody.

Likewise, vitamin D requirements can range widely. I have used anywhere from 1000 units per day, all the way up to 16,000 units per day before desirable blood levels were achieved.

Vitamin D dose needs to be individualized. Factors that influence vitamin D need include body size and percent body fat (both of which increase need substantially); sex (males require, on average, 1000 units per day more than females); age (older need more); skin color (darker-skinned races require more, fairer-skinned races less); and other factors that remain ill-defined.

But these are “rules” often broken. My office experience with vitamin D now numbers nearly 1000 patients. The average female dose is 4000-5000 units per day, average male dose 6000 units per day to achieve a blood level of 60-70 ng/ml, though there are frequent exceptions. I’ve had 98 lb women who require 12,000 units, 300 lb men who require 1000 units, 21-year olds who require 10,000 units. (Of course, this is a Wisconsin experience. However, regional differences in dosing needs diminish as we age, since less and less vitamin D activation occurs.)

Let me reiterate: Steroid hormone-vitamin D dose needs to be individualized.

There’s only one way to individualize your need for vitamin D and thereby determine your dose: Measure a blood level.

Nobody can gauge your vitamin D need by looking at you, by your skin color, size, or other simple measurement like weight or body fat. A vitamin D blood level needs to be measured specifically-period.

Unfortunately, many people balk at this, claiming either that it’s too much bother or that their doctor refused to measure it.

I would rank normalizing steroid hormone-vitamin D as among the most important things you can do for your health. It should never be too much bother. And if your doctor refuses to at least discuss why he/she won’t measure it, then it’s time for a new doctor.

If you’re worried about adding to rising healthcare costs by adding yet another blood test, think of the money saved by sparing you from a future of cancer, heart disease, osteoporosis, diabetes, etc. The cost of a vitamin D blood test is relatively trivial (around $40-50, a fraction of the cost of a one month supply of a drug for diabetes.)

So how much vitamin D should you take? Enough to raise your blood level of 25-hydroxy vitamin D to normal. (We aim for a normal level of 60-70 ng/ml.)

You probably don't take enough fish oil

The results of the recent Heart Scan Blog survey in response to the question: MY DAILY DOSE OF EPA + DHA FROM FISH OIL IS revealed:


Zero--I don't take any
17 (7%) of respondents

Less than 1000 mg per day
24 (10%) of respondents

1000-2000 mg per day
91 (38%) of respondents

2000-3000 mg per day
44 (18%) of respondents

3000-4000 mg per day
40 (16%) of respondents

More than 4000 mg per day
20 (8%) of respondents



Based on the above results, I would say that only a minority of respondents are taking an ideal dose of omega-3 fatty acids. Nearly all of us should consider taking more.

Benefits of omega-3 fatty acids (EPA + DHA) from fish oil begin around a dose of 840 mg per day, according to the GISSI Prevenzione Trial of 1999, an 11,000-participant trial. This dose also corresponds to a quantity of omega-3s that have been shown to raise EPA + DHA blood levels and thereby reduce the notoriously high AA:EPA ratio of Americans.

But what dose is sufficient? What dose is ideal?

Well, the answer to a great degree depends on what you are taking the fish oil for. If being taken to reduce triglycerides and triglyceride-containing lipoproteins, like VLDL and the after-eating (postprandial) IDL, then a higher dose will be necessary. (Triglyceride reduction for the genetically-determined very high triglyceride level of familial hypertriglyceridemia is the FDA-approved indication for prescription Lovaza.)

If you are taking fish oil for treatment of ADHD, depression, or bipolar illness, very high doses are often necessary.

But how about maximal reduction of cardiovascular risk and for control or reversal of atherosclerotic plaque?

This conversation is still evolving. But we can learn some important lessons from three populations of the world that are vigorous consumers of fish:

--The Inuits (aka Eskimos) of Greenland and northern Canada
--The Japanese
--The Bantus of Tanzania who live along Nyasa Lake

All three indigenous populations have several-fold greater intakes of fish and omega-3 fatty acids, have higher blood levels of omega-3 fatty acids, and have enjoyed reduced cardiovascular events, reduced atherosclerotic plaque, or improvement in various surrogates of cardiovascular risk (e.g., Lp(a)).

The most recent addition to this conversation is the ERA JUMP Study, discussed in a previous Heart Scan Blog post. In ERA JUMP, despite being heavy smokers and having other markers for greater risk for heart disease, Japanese men living in Japan had markedly less carotid and coronary plaque, as compared to Caucasian men living in PIttsburgh or Hawaiian men of Japanese descent. The difference appeared to be attributable to serum levels of omega-3 fatty acids.

I believe that the trend is here is to increase the amount of omega-3 fatty acids that most of us take. In the Track Your Plaque program, we have been advocating a rock-bottom starting dose of EPA + DHA of 1200 mg per day. However, I believe that this is due for a change.

We will be increasing the minimum dose for plaque regression and control. Please attend our Webinar this evening for a full, in-depth discussion of the rationale behind this important change.

As always, let me remind you that I am not selling, nor ever have sold, fish oil supplements. If I advocate a specific dose, a higher dose, I do so based on my interpretation of the data and experience with patients, not because I am interested in selling brand X of fish oil.

Vitamin D and HDL

Despite the paucity of scientific documentation of this phenomenon, I am continuing to witness extraordinary increases in HDL cholesterol levels with vitamin D supplementation.

I've touched on the interaction of vitamin D supplementation with HDL in The Heart Scan Blog previously:

Vitamin D: Treatment for metabolic syndrome?

HDL for Dummies


At first, I thought it was attributable to other factors. In real life, most people don't modify one factor at a time. They reduce
processed carbohydrates/eliminate wheat and cornstarch, lose weight, add or increase omega-3 fatty acids from fish oil, begin niacin, increase exercise and physical activity. All these efforts also impact on HDL.

Among the many things I do, I consult on complex lipid (cholesterol) disorders (complex hyperlipidemias) in my office. A substantial number of these people carry a diagnosis of hypoalphalipoproteinemia, a mouthful that simply means these people are unable to manufacture much apoprotein A1, the principal protein of HDL cholesterol particles. As a result, people with hypoalphalipoproteinemia have HDL cholesterol levels in the neighborhood of 20-30 mg/dl--very low. They are also at high risk for heart disease and stroke.

Encourage these people to exercise, attain ideal weight, eliminate wheat and cornstarch: HDL increases 5 mg/dl or so.

Add niacin, HDL increases another 5-10 mg/dl.

Perhaps we're now sitting somewhere around an HDL of 35-40 mg/dl--better, but hardly great.

Add vitamin D to achieve our target serum level . . . HDL jumps to 50, 60, 70, even 90 mg/dl.

The first few times this occurred, I thought it was an error or fluke. But now that I've witnessed this effect many dozens of time, I am convinced that it is real. Just today, I saw a 40-year old man whose starting HDL was 25 mg/dl increase to 87 mg/dl.

Responses like this are supposed to be impossible. Before vitamin D, I had never witnessed increases of this magnitude.

Not all therapies for raising HDL raise the important large (also known as HDL2b) fraction. With lipoprotein analyses, it appears that is principally the large fraction of HDL that rises with vitamin D supplementation.

Why? How?

That I can't tell you. But for those of you struggling with low HDL cholesterols despite your best efforts, vitamin D can make a world of difference.

An interesting corollary: If super-high HDL cholesterols are associated with extreme longevity, as they are with centenarians, does raising HDL to extraordinary levels with vitamin D lead to longer, healthier life, all the way up to age 110 years?

Again, no answers, but an interesting thought. And one I'd bet on. (And I'm not selling vitamin D.)

Weight loss and blood pressure

Here's another thought with regards to time issues with weight loss: reductions in blood pressure (BP).

The previous post talked about how triglycerides initially go up, sometimes way up, when weight drops, only to be followed months later by substantial drops. HDL initially drops in response to the triglyceride fluctuations, only to be followed by a rise.

Blood pressure also shows a curious pattern that is largely dependent on age.

Say someone in their 20s or 30s, for instance, loses 30 lbs (through elimination of wheat and cornstarch, say). BP usually drops within a few weeks, perhaps a month or two at most.

How about someone in their 70s? Say a substantial amount of weight is lost, say 50 lbs over 6 months. BP does indeed drop, but it may require 6 months or longer after weight plateaus for the full effects of BP-reduction to be fully expressed. But it will eventually drop.

Why the age-dependent difference?

It relates to the capacity of arteries to remain flexible and distensible. Over the years, cross-linking of collagen (a structural protein), glycation (glucose molecules attaching to proteins), loss of endothelial responsiveness to generate artery-dilating substances like nitric oxide, and arterial atherosclerotic plaque all all up to making older arteries less able to "relax" and BP to drop.

But given time and the proper effort, BP will eventually drop. Awareness of this time effect can help most people decide better when medications are necessary or if weight loss alone is sufficient to reach BP goals.

"I lost 30 lbs and my triglycerides went . . . up?"

Brad needed to lose weight.

At 6 ft tall, he began the program at 291 lbs, easily 80 lbs overweight. He wore virtually all of it in his belly.

He had laboratory numbers to match: HDL 33 mg/dl, triglycerides 225 mg/dl, LDL (calculated) 144 mg/dl, blood sugar 122 mg/dl (fasting--clearly "pre-diabetic"), c-reactive protein 3.0 mg/dl. Among his lipoprotein abnormalities: small LDL representing 80% of all LDL (no surprise).

Readers of The Heart Scan Blog know that these are the patterns of the carbohydrate-indulgent. I asked Brad to eliminate all wheat flour products, all foods made with cornstarch, and follow a diet rich in healthy oils, raw nuts, vegetables, and lean meats.

Brad returned for a discussion about follow-up basic lipids (cholesterol) values four months later--31 lbs lighter, most of it clearly lost from his abdomen. He claimed he felt more energetic and clear-headed than he had in years.

His lipid panel: HDL 34 mg/dl, LDL 122 mg/dl, triglycerides 295 mg/dl. Brad's smile dissolved. "How could that happen? You said losing weight would make my HDL go up and my triglycerides go down!"

Yes, I had said that. But I was oversimplifying.

The truth is that, when there is weight loss, especially profound weight loss like Brad experienced eliminating wheat and cornstarch products, there is mobilization of fat stores. Fat is stored energy. Energy is stored as . . . triglycerides.

So when there is substantial weight loss, there is a flood of triglycerides in the blood, and triglyceride levels in the midst of weight loss can commonly jump up, not uncommonly to the 200-300+ mg/dl range. When triglycerides go up, there is also a drop in HDL (triglycerides interact with HDL particles, modify their structure and make them more readily destroyed, thereby dropping blood levels). Occasionally, substantial weight loss like Brad experienced will drop HDL really low, as low as the 20's.

Once weight stabilizes, this effect can last up to 2 months before correcting. Only then will triglycerides drop and HDL rise. The rise in HDL occurs even more slowly, requiring several more months to plateau.

In other words, weight loss like Brad's causes triglycerides to increase and HDL to decrease, to be followed later by a drop in triglycerides and a rise in HDL.

I know of no way to block this phenomenon. And perhaps we shouldn't, since this is how fat stores are mobilized and "burned off." Fish oil does blunt the triglyceride rise (perhaps through activation of lipoprotein lipase, an enzyme responsible for clearance of triglycerides), but doesn't eliminate it.

I call these changes "transitional" changes in lipids.

Patience pays. A few more months from now, Brad's numbers will be much happier, as will Brad.

Divorce court for the doctor-patient relationship?

The doctor-patient relationship has gone sour.

This probably comes as no surprise to most of you, particularly if you've been following conversations here in The Heart Scan Blog:

Who is your doctor? discussing the emergence of the physician-as-hospital-employee phenomenon that causes your doctor to become the de facto portal (seller?) of hospital services to you, a model fraught with conflicts of interest.

Exploitation of trust, my observation that the enormous gap in heart disease prevention between the woefully ignorant (by necessity) level of sophistication of the primary care physician and the procedure-obsessed cardiologist leads to an exploitation of humans-for-heart-procedures because of the failure to institute genuine preventive efforts.

Bait and switch , a description of how a minor test or symptom can reap a bonanza of medical testing; a $20 "screening" test yields $10's of thousands in hospital procedures. If it were entirely due to the imprecision of medical testing and detection of disease, that might be forgivable. But it often is not: It has become utterly distorted by the profit model.



Lest you think that I am a kook ranting off in some backwoods corner (Milwaukee), here are the comments of New York Times' Health Editor Tara Parker-Pope in a series called Doctor and Patient, Now at Odds:

Lately I've been hearing a lot from patients who are frustrated, angry, and distrustful of doctors. Their feelings speak to a growing disconnect between doctors and patients and worries that drug companies, insurance rules, and hospital cost-cutting are influencing the care and advice that doctors provide.

Research shows that even among patients who like their personal physicians, there is a simmering distrust of the medical system and the doctors who work inside it.


(There's also a series of candid video interviews with people who echo these sentiments.)

There are a number of reasons for this increasing "disconnect," some of them articulated by Ms. Parker-Pope, others detailed in my blog posts.

The solutions, however, will not be found by advancing technology: the newest robotic surgery, a better defibrillator, a new statin drug, the next best chemotherapeutic agent. It will not be found by adding a new wing to the hospital. It will not be found by the reorganization of healthcare delivery achieved by converting primary care and specialty practice into an arm of hospital care. It will not be improved by employing "hospitalists." It will not emerge from legislation controlling insurance company practices. It certainly will not come from increasing marketing dollars spent by drug companies (who make $4 for every $1 spent on direct-to-consumer marketing).

The solutions will come from shifting the idea of care from a paternalistic, "I'm the doctor and I'll tell you what to do" approach, to the doctor-as-advocate-and-supporter of the patient. The physician should act as someone with a particular sort of expertise that can advise a patient.

But a caveat: The patient MUST be informed.

Proper information will not originate with the doctor. It will originate with internet-based information portals and tools that help you understand the issues, often with far greater depth than your doctor could ever provide. The physician needs to accept this role, one of advocate, adviser, but not of being in charge, not of viewing the patient as profit-center, not as an opponent in a power struggle.

Sadly, the last few years in online information portals has been dominated by the drug company-dominated websites like WebMD, nothing more than a deliverer of the conventional wisdom with nothing whatsoever aimed towards empowering patients in a self-directed healthcare model.

Some people call the emerging new empowered and information-armed patient Medicine 2.0. Unfortunately, Medicine 2.0 will first benefit the intellectual upper crust of Americans, the web-savvy and motivated to engage in health issues. But, give it 10 years, and we will witness the effects on an unprecedented broad scale. Part of the Information Age is acceleration of information dissemination. Imagine your children, facile with a computer mouse, posting comments on FaceBook, doing homework with Google and Wikipedia, now turning their attentions to health.

It will be a startling change.

In the meantime, be wary. Be empowered. Think increasingly about self-direction in your health.


In a comment to the Bait and switch post, Jennytoo offered an insightful response:

You are getting to the essence of the problem, and it's not just cardiology that is rife with what is, at bottom, malpractice.

There is little incentive for the profession as a whole to know anything about or promote prevention, and many incentives from hospitals, drug and insurance companies to stick with the status quo or to change it in their corporate favor. The formulaic, conventional statements purporting to be guidelines for prevention that are put out by various interest groups and in such publications as hospital-sponsored newsletters ("eat a 'balanced diet', avoid stress, etc.") are useless sops to the concept of prevention.

It is, and I fear is going to remain, up to motivated individuals, both physicians and patients, to reshape the system, and it's going to be a long frustrating struggle.

It's my personal conviction that if just 4 things were promoted to the public, and people actually practiced them, we could change the health profiles of the majority of people in this country for the better within two years or less. They are:

(1) education on and promotion of a true low-carbohydrate, whole foods, diet,
(2) measurement and supplementation of Vitamin D3,
(3) supplementation with DHA/EPA (found in Fish Oils), and
(4) measurement and supplementation of intracellular magnesium.

I am not a health professional, and others may want to add to this list, but I don't think any strong case can be made against any of the items. The wonderful and hopeful thing is that each of us can implement them ON OUR OWN, and thereby take charge of our own well-being. (The Life Extension Foundation is one organization which provides access to lab tests you can request on your own.)

If you have a physician who is willing and capable of being your partner, you are richly blessed, and that is the ideal we all should hope for. But in the more likely event that you do not have such a physician, and if your physician demonstrates little potential for becoming one, think about firing the one you have and finding another.

Sometimes we are forced by circumstances, particularly urgent ones, to deal with physicians who are not ideal, but the main impetus for change will come from us, the patients, and the expectations we communicate to our individual doctors. In the meantime, we can be self-reliant in our own prevention practices.


Wow. A woman after my own heart.

How much fish oil is enough?


This post just furthers this line of thinking out loud: How much fish oil is "enough"?

Observations over the last 30 years followed this path: If a little bit of omega-3 fatty acids from fish are beneficial in reducing cardiovascular events, and a moderate intake is even better, is even more better? When have we reached a plateau? When do adverse effects outweigh the benefits?

Some insight can be gained through studies that examined blood levels of omega-3s. Let's take a look at some data from 2002, a comparison of men dying from heart disease vs. controls in the Physicians' Health Study, Blood Levels of Long-Chain n–3 Fatty Acids and the Risk of Sudden Death.

This is a table that shows the blood levels of various fatty acids Group with sudden death vs Control Group:




Several observations jump out:

--The total omega-3 blood content differed significantly, 4.82 vs 5.24% ("Total long-chain n-3 polyunsaturated")
--Total omega-6 content did not differ
--Arachidonic acid (AA) content did not differ
--Linolenic acid content did not differ (i.e., plant sourced omega-3)

The fact that neither omega-6 nor arachidonic acid content differed counters the argument that Simopoulos has made that the omega-6 to omega-3 ratio (intake, not blood levels) is what counts. It also argues against the EPA to AA ratio (and similar manipulations) that some have argued is important. In this study, only the omega-3 level itself made a difference; no ratio was necessary to distinguish sudden death victims vs controls.

Further, quartiles of omega-3 blood levels showed graded reductions of risk:




An omega-3 blood level of 6.87% conferred greatest risk reduction. Depending on the model of statistical analysis, risk reductions of up to 81-90% were observed. Wow.

Taken at face value, this study would argue that:

--An omega-3 fatty acid blood level of 6.87% (or greater?) is ideal
--The omega-3 fatty acid blood level stands alone as a predictor without resorting to any further manipulation of numbers, such as relating EPA and/or DHA to AA levels.

Of course, this is just one study, though an important one. It is also not a study based on any intervention, just an observational effort. But it does add to our understanding.


We will develop these issues further in our upcoming Track Your Plaque Webinar on Wednesday, August 20th, 2008.
Does high cholesterol cause heart disease?

Does high cholesterol cause heart disease?

How often does someone develop coronary heart disease from high cholesterol alone?

Believe drug industry propaganda and you'd think that everyone does. Physicians have bought into this concept also, driving the $27 billion annual sales in statin cholesterol drugs.

In my experience, I can count the number of people who develop coronary disease from high cholesterol alone on one hand. It happens--but rarely.

That's not to say that cholesterol is not an issue. That rant populates many of the kook websites and conversations on the internet that argue that high cholesterol is a surrogate for some other health issue, or that it is part of a medical conspiracy.

The problem with conventional measurement of cholesterol is that it ignores the particle size issue: whether particles are large or small. Small LDL are flagrant causes of coronary atherosclerotic plaque. Large LDL is a rather meager cause. Simple cholesterol measurement also ignores the presence of other factors that lead to heart disease, like lipoprotein(a) and vitamin D deficiency.

Conventional total and LDL cholesterol do not distinguish between large and small particles, nor reveal the presence of other hidden patterns. An LDL cholesterol of 150 mg/dl, for instance, may contain 100% large LDL--a relatively good situation that by itself is unlikely to cause heart disease, or it might contain 100% small LDL--a very bad situation that is likely to cause heart disease. Just knowing that LDL is 150 mg/dl tells you almost nothing. In 2008, most people have some mixture of the two, particularly with the proliferation of "healthy whole grains" in the American diet, foods that trigger formation of small LDL.

The imprecision and uncertainty of conventional total and LDL cholesterol has provided ammunition for some to discount the entire cholesterol concept. And they are right to a degree: cholesterol by itself is indeed a lousy predictor of heart disease. But small LDL is a very reliable predictor of potential for heart disease. Dismissing the entire concept because the standard measurement stinks is not right, either.

It is therefore an unfortunate oversimplification to say that high cholesterol causes heart disease or that it doesn't. It can--but not always, depending on size and other factors. In my view, it is therefore irreponsible to treat total or LDL cholesterol without knowledge of particle size. I've seen this play out many times: Someone with an LDL cholesterol of 150 mg/dl but all large still gets prescribed a statin drug by his/her doctor. Or someone with an LDL of 100 mg/dl--generally "favorable" by most standards--is not treated but it is all small and the person is truly at high risk. (Also, knowledge that all LDL particles are small does not mean that statins are the preferred agent. In my view, they are not.)

Comments (15) -

  • Anonymous

    10/3/2008 4:41:00 AM |

    I've had no success lowering my very high LDL(350), can't tolerate statins..supposedly have combination of large and small LDL, 20-40% blockages per cardiac cath.My HDL (80), Trig.(70)are good, but still concerned since already show athrosclerosis. I'm 55, 100 lbs., and have had high LDL since a teen. Any suggestions? Thanks!

  • Anonymous

    10/3/2008 5:25:00 PM |

    Isn't inflammation the root cause of atherosclerosis ? Isn't cholesterol's role in heart disease only that it happens to be used as the material, with which the body repairs the lesions caused by inflammation ?

  • Steve

    10/3/2008 6:16:00 PM |

    excellent post. 1. if statins not preferred way to go for small LDL, what is- Niacin and elimination of grains? 2. How is it possible that a VAP test showed large Pattern A(by small margin)and two years later NMR shows nearly 100% small dense Pattern B?  Is one test better than the other? 3. Do genetics overwhelmingly determine pattern size?  I have eliminated all grains,sugars, starchy veggies to see if i can get my LDL to be large and fluffy.  Thank you.

  • Anne

    10/4/2008 5:17:00 PM |

    I am an example of someone with "normal" cholesterol and CAD. I was only 54 years old when my LAD blocked. I went on to bypass as I reblocked after each stent.

    In the past few years I have been looking into many of the other factors may have contributed to my  health problems and trying to optimize my health. Yes, coromary heart disease is so much more than elevated cholesterol.

  • Stan (Heretic)

    10/4/2008 5:37:00 PM |

    No it doesn't!

  • Peter

    10/5/2008 2:41:00 PM |

    Hi Dr Davis,

    Excellent post. The value of total cholesterol is irrelevant. While there is a VERY slightly higher cholesterol level in heart attack patients, the overlap with the normal population is such as to make total cholesterol level meaningless. Once it's meaningless and you can then look back to the initial work of Ancel Keys, who appears to have been the primary architect of the lipid hypothesis, and you can see it is based on this now clearly meaningless measurement.

    The very slight increase in TC in cardiac patients is explicable by the fact that glycation of the apoA particle inhibits its attachment to the LDL receptor. I would expect this to produce a slight rise in TC. You then have to pose the question as to which does most damage: persisting apoA containing particles due to glycation of their surface protein, or glycation of all of the body proteins by the same hyperglycaemia that affected the apo A protein. Using HbA1c as a marker of hyperglycaemia there is a reasonable correlation with CVD even within "normal" HbA1c levels in the EPIC study. Whole grains = hyperglycaemia. Hyperglycaemia = apoptosis of vascular endothelium. What more do you need for vascular damage?

    So, as the lipid hypothesis is based on TC and should have been stillborn or drowned at birth, where does particle size come in? We have the situation of good (HDL) cholesterol and bad (LDL) cholesterol to explain why TC is useless. Then we get good LDL (large fluffy) and bad LDL (small dense) to explain why total LDL (by calculation) is utterly useless too. We even now have good and bad HDL. Never mind good (small) VLDL and bad (large) VLDL to explain why some triglycerides are better/worse than others.

    Ultimately small dense LDL, large VLDL and HDL3 are strong markers of the metabolic syndrome. Hyperinsulinaemia and insulin resistance are the cornerstones of metabolic syndrome according to Reaven, who largely popularised the concept. The lipid changes are easily viewed as a consequence, not a cause, of metabolic syndrome. It is undoubtedly believable that sdLDL is stickier/more oxidisable than other lipoproteins, but that becomes unimportant if it's not there in the first place, ie no metabolic syndrome. This would, simply, explain why reducing wheat products works to reduce sdLDL, unless they are replaced by equally insulinogenic "wheat free" comparable junk foods based on non wheat sugar sources. If it turned out that purple spotted LDL, induced by eating blackberries, was stickier than sdLDL we would no doubt have a drive to eliminate blackberries or (more likely) develop a drug to remove the purple spots.

    Following your blog gives me the distinct impression that one day you really could become a cholesterol skeptic. Stranger things have happened.

    Peter

  • JayCee Botha

    10/6/2008 9:37:00 PM |

    Anonymous and Steve - I stronly believe in a propper low carb (note that I say LOW carb, and not NO Carb) way of eating. I would really like to suggest some awesome reading material. It is from dr. James E Carslon who wrote the book "Genocide. How your doctors dietary ignorance will kill you!!!". In the book he explains amongst other things the actual benefits of dietary cholesterol and how a low-carb way of eating will increase the ldl-particle sizes and bring down the triglycerides and dangerous VLDL.

    From a recent personal answer I got from him, he explained to me the benefits of adding dietary cholesterol from a biochemical point of view. I hope this helps in understanding that a correct dietary change can help.

    Here is what he said :

    OK, so what are the benefits of adding cholesterol to the diet? It's not only fascinating, it'll blow your mind. When we eat cholesterol containing foods, the cholesterol in the food we consume actually binds to an enzyme called HMG CoA reductase and inhibits its function. This enzyme is what's known as the rate limiting enzyme in cholesterol biosynthesis. This means that once this enzyme does what it's supposed to do, cholesterol will be made no matter what. By inhibiting the enzyme's function, choilesterol cannot be made. So eating cholesterol actually inhibts its own production.
    But wait, it gets even better.

    The cholesterol in the foods we eat is what's referred to as fat soluble, or lipophilic (or fat loving). Since cholesterol is lipophilic, it diffuses through not only the outer cell membrane, but the cell's=2 0nucleus membrane and attaches the the DNA. Guess where it attaches to on the DNA? It attaches to the sites on DNA WHERE HMG Co A IS MADE!!!!! That's right, so not only does the cholesterol in the food we eat attache and inhibit the function of the enzyme already present to make cholesterol; the cholesterol in the foods we eat also prevents the production of the enzymes needed to make itself. In biochemical speak, this is known as negative biofeedback.

    Eat more cholesterol, make less cholesterol. By the way, the only thing I've seen in eighteen years considerably raise the good cholesterol known as the HDL, is the consumption of more cholesterol. So EAT MORE CHOLESTEROL IT"S GOOD FOR YOU!

  • moblogs

    10/7/2008 12:11:00 PM |

    Inflammation is essentially the cause of heart disease isn't it?
    I'm not medically trained, but I assume small particle LDL is a signifier of crammed, broken up large particles - perhaps a long time accumulation of what was once sent to the skin hoping to be converted to D by UVB but didn't(there is a study that says British gardeners have lower cholesterol in the Summer which seems very interesting).
    The fact that statins work (albeit with alarming side effects), and that according to a Spanish study, that atorvastatin raises vitamin D some degree shows the problem isn't really cholesterol. That is erroneous cholesterol readings are the 'symptom' of either vitamin D deficiency or associated things that domino on to the ability for the heart to succomb to heart disease. As a rule I still think the general cholesterol hypothesis is a farce, not just because of the way the products are marketed but because it's only looking at one station on the tube system. 'High cholesterol causing heart disease' might be better termed as 'low vitamin D causes heart disease' because that's perhaps the root, or at least one root.

  • Steve L.

    11/14/2008 5:43:00 AM |

    Dr. Davis,

    First let me say a big thank you for your blog.  I follow your's, Jimmy Moore's and the Drs. Eades' blogs closely.  As a result of reading your book and blot, I just had my first heart scan at age 50, and was vert happy to hear zero calcium score.

    I do low carb nutrition (~50g/day), so my triglycerides were very low (28).  I've read that all LDL will be large with triglycerides that low (below 70).  Can you confirm that?  Would I be wasting my money on blood work to determine particle size?  HDL is 62, LDL 136.

    Steve L.

  • Wenchypoo

    4/9/2009 1:14:00 PM |

    Simple cholesterol measurement also ignores the presence of other factors that lead to heart disease, like lipoprotein(a) and vitamin D deficiency.

    Conventional total and LDL cholesterol do not distinguish between large and small particles, nor reveal the presence of other hidden patterns. An LDL cholesterol of 150 mg/dl, for instance, may contain 100% large LDL--a relatively good situation that by itself is unlikely to cause heart disease, or it might contain 100% small LDL--a very bad situation that is likely to cause heart disease. Just knowing that LDL is 150 mg/dl tells you almost nothing. In 2008, most people have some mixture of the two, particularly with the proliferation of "healthy whole grains" in the American diet, foods that trigger formation of small LDL.


    I'm looking for heart disease info that isn't related to cholesterol OR grain intake, because my cat has it--cats are obligate carnivores, and therefore do not take in grains unless fed commercially-prepared foods.  Mine do not--I make their food from scratch, using a UC Davis vet-designed diet recipe.  Cholesterol levels aren't a concern either, although I now know to have the SIZE of cells examined, as well as vitamin D levels checked.  As for anti-inflammatories, fish oil is part of the diet recipe.

    I'm going back to the vet for more blood work (now that I have more clues).

  • TedHutchinson

    10/1/2010 8:48:09 AM |

    Statins Do Not Decrease Small, Dense Low-Density Lipoprotein
    Free full text at link.
    In an observational study, we examined the effect of statins on low-density-lipoprotein (LDL) subfractions.
    Using density-gradient ultracentrifugation, we measured small, dense LDL density in 612 patients (mean age, 61.7 ± 12.6 yr), some with and some without coronary artery disease, who were placed in a statin-treated group (n=172) or a control group (n=440) and subdivided on the basis of coronary artery disease status.
    Total cholesterol, LDL cholesterol, apolipoprotein B, and the LDL cholesterol/apolipoprotein B ratio were significantly lower in the statin group. However, the proportion of small, dense LDL was higher in the statin group (42.9% ± 9.5% vs 41.3% ± 8.5%; P=0.046) and the proportion of large, buoyant LDL was lower (23.6% ± 7.5% vs 25.4% ± 7.9%; P=0.011). In the statin group, persons without coronary artery disease had higher proportions of small, dense LDL, and persons with coronary artery disease tended to have higher proportions of small, dense LDL.
    Our study suggests that statin therapy—whether or not recipients have coronary artery disease—does not decrease the proportion of small, dense LDL among total LDL particles, but in fact increases it, while predictably reducing total LDL cholesterol, absolute amounts of small, dense LDL, and absolute amounts of large, buoyant LDL. If and when our observation proves to be reproducible in subsequent large-scale studies, it should provide new insights into small, dense LDL and its actual role in atherogenesis or the progression of atherosclerosis.

  • buy jeans

    11/3/2010 6:19:10 PM |

    The imprecision and uncertainty of conventional total and LDL cholesterol has provided ammunition for some to discount the entire cholesterol concept. And they are right to a degree: cholesterol by itself is indeed a lousy predictor of heart disease. But small LDL is a very reliable predictor of potential for heart disease. Dismissing the entire concept because the standard measurement stinks is not right, either.

  • Mary

    1/25/2011 8:42:22 PM |

    For years I suffered from high cholesterol and was almost permanently on statin medication. I come for a family with a strong history of heart disease and I personally believe that high cholesterol can cause heart disease. Thankfully I now have my cholesterol under control but it has been hard work, and I done it the natural way, as I suffered from the side effects statins cause.

    How To Lower Cholesterol Without Medication

  • Anonymous

    3/12/2011 8:55:30 AM |

    About eighty percent of our cholesterol is produced by the liver and the rest depends on our diet. Foods such as red meat and butter are rich in cholesterol where as those from plant origin have very little or no cholesterol at all. The control of cholesterol in our body is done by the liver. I think,more can be found out from:
    http://www.heart-consult.com/articles/how-cholesterol-affects-heart

  • doug

    5/9/2011 8:52:46 PM |

    exactly!!!!!

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