Cureality | Real People Seeking Real Cures

The battle for preservation of availability of compounded natural hormones goes on.

It started with pharmaceutical manufacturer, Wyeth, who petitioned the FDA to disallow the mixing of pharmaceuticals, especially natural human hormones, by specially trained pharmacists at what are called "compounding pharmacies." These are pharmacies that have special equipment and where trained pharmacists can mix up specific preparations for dispensing. These are available by prescription.

For instance, I have been prescribing natural human testosterone and progesterone for nearly 10 years. I have found service to be excellent, with lots of learning materials provided to patients by the pharmacy. The pharmacists I've spoken to have been courteous and knowledgeable. Compounded hormones are also shockingly less expensive. While a testosterone patch from a pharmaceutical company costs around $4.00 per day, the same quantity of testosterone cream formulated by a compouding pharmacy costs around $0.50 per day--87.5% less.

Wyeth hides behind a smoke screen of concern over quality. But the price differences tells the entire story: they want to eliminate the inexpensive competition and hold us all hostage to the far more expensive, often inferior products that they produce. They'd sooner force a woman to use horse-derived Premarin than to allow her access to human estrogens and progesterone.

To me, this is an outrageous affront to our freedom of choice, both as consumers as well as a physician. If you feel as strongly as I do about opposing the unfair and bullying ways of Wyeth Pharmaceuticals and the FDA, the P2C2 association of compounding pharmacists makes writing a letter to your Senator easy by going to

http://iacprx.convio.net/site/PageServer?pagename=P2C2

Just enter your info and personalize the comments, and the e-mails will be generated for you.

At first, I was skeptical. A book from a nutty author and physician named Duane Graveline kept on coming up in conversations with patients. His book, Lipitor: Thief of Memory , details his personal experience with dramatic changes in memory and thought while taking Lipitor.

Now this is a drug that I've seen used thousands of times. But I've now seen about a dozen people who have had distinct struggles with memory and clarity of thinking while taking Lipitor. Most took doses of 40 mg per day or more, though an occasional person takes as little as 10 mg. The association seems to be undeniable, since it improves after two weeks off the drug, recurs when resumed. Just today, I saw two people where this effect may be an issue.

Curiously, I've not seen it with any other statin agent. Unfortunately, uncovering any scientific data on the issue is a hopeless quest. Either it's very uncommon or, worse, the data has been suppressed.

Any way, I believe that Dr. Graveline was right: Lipitor, in a small number of people, does indeed seem to exert real detrimental effects on the mind.

If you take Lipitor, should you stop it in fear of long-term effects on your mental capacity? I think it's premature to toss the drug out based on this relatively uncommon relationship. This particular effect is likely to be idiosyncratic, i.e., peculiar to an occasional person but does not seem to apply to the majority, probably by some quirk of metabolism or penetrability of the barrier between the blood and nervous system tissue.

If, however, you feel that your thinking and memory have deteriorated on the drug, please speak to your doctor.

How helpful are EKG's for detecting hidden heart disease?

I pose this question because several patients asked this question just this week. It's also a frequent point of confusion and misperception.

Your EKG is nothing more than an expression of the surface electrical activity emitted by heart muscle activity. Multiple (12) leads are attached to the body simply to provide various "views" of this electical activity. EKG, or sometimes "ECG", is short for "electrocardiogram".

What modifies this surface electrical activity? Anything that modifies the electrical activity within the heart itself, or interferes with the detection of the activity. An old heart attack modifies the patterns of electrical conduction in the heart and that can change your EKG. An ongoing heart heart attack likewise. High blood pressure commonly creates changes in the EKG, as does lung disease. A bellyache can change your EKG, as can a stroke. (These non-heart-related phenomena probably are often due to changes in autonomic, or "automatic," nervous system activity.) The heart generates electrical activity in a predictable sequence that generates the heart beat, or "rhythm". EKG's are useful for monitoring heart rhythm, also.

Does having plaque in your coronary arteries have any effect on the EKG? None whatsoever, unless plaque rupture caused heart attack or is about to cause heart attack. So, you can have a horrendous CT heart scan score of, say, 3000, yet maintain a perfectly normal EKG, as long as the heart muscle is normal.

Then why bother with these iffy tests? They are indeed useful to diagnose the cause of active symptoms. For instance, go to the ER with chest pain and an EKG could show changes suggesting that the chest pain is a heart attack. EKG's are also useful for future comparison. Any change in EKG can suggest certain things, like new heart rhythm disturbances unrelated to coronary plaque.

Think of your EKG as just like buying a used car. Say I'm trying to sell you my 1999 Buick Century. It looks pretty good from the outside and I tell you that it has 70,000 miles and runs well. You ask to open the hood, look in the interior and take it out for a drive. I tell you no, you can't do that.

Would you buy the car? Of course you wouldn't. You were permitted only a very superficial examination of the car. You have no idea what's going on inside. Just because the paint job looks brand new doesn't mean the engine and transmission are good.

The same with your EKG: It's a superficial look at one aspect of this used car called your heart. If the EKG is normal, that's good, just like a good exterior on the Buick. But you cannot assume that the heart is otherwise normal.

View the EKG as a simple, superficial test that can only provide minimal reassurance, no matter how often you have it done.

Neal, a 40-year old school principal, and his young wife were terrified on learning of his CT heart scan score of 339, a concerningly high score for any age, particularly age 40.

To make matters worse, all of Neal's plaque was located in the critical left mainstem coronary artery, the shared stem of two of the three coronary arteries. A heart attack in this location is instantly fatal.

So, it was especially gratifying that Neal has set the Track Your Plaque record for largest magnitude of plaque reversal: 51% in his first year.

Studies that show a reduction in heart attack make the news. They talk about 1, 2, up to 6% regression, all achieved with high doses of statin drugs. Yet we are seeing huge, extraordinary quantities of heart disease reversal that haven't yet made headlines, amounts that far exceed those featured in the news. We should be encouraged by experiences like Neal's.

Watch for the upcoming Track Your Plaque newsletter for more details on Neal's story--how he came to the program, how he accomplished this huge effect, and why his experience was such a success. If you haven't yet subscribed, go to the www.cureality.com homepage and click on the upper right hand corner.

Periodically, I'll see a flurry of TV ads for Plavix. It comes with a polished computer-animated cartoon that shows how platelets clump and form a blood clot, causing heart attack.

Imagine there's a pile of oil-soaked rags in a corner of your garage. I come by and tell you to get a good fire extinguisher to keep next to the rag pile in case they spontaneously ignite.

Does that make sense to you?

Wouldn't it be better to get rid of the oily rags and forget about the fire extinguisher?

Plavix is the fire extinguisher. The oil rags are your coronary plaque. The solution is to gain control over plaque behavior. Unfortunately, the TV ads (intentionally, I suspect) give the impression that blood clots just form out of the blue for no reason. Of course that's not true. It requires active, growing, inflamed atheroslcerotic plaque that ruptures, uncovering the "angry" and platelet-adhering material underneath the thin covering or endothelial lining.

Urging everybody to take Plavix is absurd. The TV ads urge many people who have no business taking the drug to take it. There are, without a doubt, groups of people who are better off taking Plavix and aspirin: people who are in the midst of heart attack, people who have unstable plaque, people with recent stents or bypass. Perhaps people at high risk for plaque rupture, e.g., extensive coronary plaque that has continued to grow.

These tactics are consistent with the experiences I've had with the sales representatives from the company (when I used to actually talk to sales reps; my office is now barred from them). The reps very aggressively would urge me to consider having everyone take Plavix. No kidding.

For us, i.e., for people who just have a heart scan score but interested in engaging in a powerful program of prevention and reversal, Plavix rarely provides any advantage. The answer is, just like our oily rag analogy, control the plaque, not put out the fire.

You won't find a lot of scientific validation for this, but it is my firm impression that small LDL, by some crazy means, has the capacity to "turn on" or "turn off" lipoprotein(a), Lp(a).

Recall that Lp(a) is a specific genetic trait, passed to us (if you have it) by mother or father. It falsely elevates LDL cholesterol and escalates heart disease risk more than just about any other known abnormality.

A frequent hint that Lp(a) might be present is a comment I hear often from patients: "My doctor said statin cholesterol drugs don't work for me. I tried them all and my cholesterol won't go down." Or, the result was substantially less than expected. That's because, when Lp(a) is lurking in your cholesterol value, it is unaffected by the statins.

It's been my in-the-trenches observation that, the more fully expressed the small LDL pattern becomes, the worse the Lp(a) behaves. In other words, if small LDL is suppressed effectively, Lp(a) doesn't seem to carry the same dangers as in someone who has plenty of small LDL. I don't know why this is. (I expect that the answer will come from someone like Dr. Marcovina at Stanford, who is at the forefront of Lp(a) structural research. Lp(a) is a complex molecule with several components. How and why it interacts with other particles remains a mystery.)

There are a little bit of data to confirm this. The Quebec Cardiovascular Study has presented some data to this effect, that the combination of small LDL particles and Lp(a) are a particularly lethal combination. We are trying to correlate our data from a CT heart score perspective to discern any statistical relationships.

This raises a very important therapeutic issue if you have Lp(a): the worst thing you can do if you have Lp(a) is become overweight. Excess abdominal fat is a huge trigger to create small LDL particles. Even though being overweight itself has no effect on the measured level of Lp(a), it activates small LDL which, in turn, throws gasoline on the Lp(a) fire.

If you have Lp(a), stay skinny.

I was re-reading some of the details behind the recently announced COURAGE Trial comparing angioplasty/stent in 1100 people compared to "optimal" medical therapy in another 1100. You'll recall that no difference was found.

In particular, over approximately 5 years, 20% of participants in each group died, experienced heart attacks, or strokes. Of those treated with "timal" medical therapy, 32% ended up getting a procedure like stents or bypass anyway due to deteriorating symptoms.

What is "optimal" medical therapy? I bring this up again because the study investigators in COURAGE, as well as in similar trials, say this with a straight face. Optimal medical therapy means aspirin and/or Plavix (the anti-platelet, aspirin-like blood thinner); "aggressive" statin drug therapy to reduce LDL cholesterol to 60-85 mg/dl; and "anti-ischemic" therapy (that reduces angina and the phenomena of poor coronary blood flow) using nitroglycerin preparations, beta blockers, and other drugs.

I do give credit to the investigators for having the courage to perform this trial in a world hell bent on doing procedures and still reporting the neutral outcome. But the notion of "optimal" medical therapy begs for comment.

Indeed, this is regarded as optimal by most practitioners. Some would even argue excessive, based on the low LDL target achieved. Would you be satisfied with a 20% likelihood of heart attack, stroke, or death or 5 years, a 1 in 5 roll of the dice? I would not. Recall that we aim for near-total elimination of risk.

What could have been further "optimized"? Plenty. For instance:

--What is the real LDL, not the fabricated, calculated LDL? The two can be commonly 100 mg/dl different.

--How about raising HDL to 60 mgd/?

--What about reducing the proportion of small LDL particles? After all, small LDL is the number one cause of heart disease in the U.S., not high LDL.

--What is Lp(a)? If you treat LDL with a statin drug, Lp(a) is unaffected and continues to trigger huge plaque growth. You will fail if this is not identified and corrected.

--What is vitamin D3? One of the most powerful facilitators of plaque reversal I know of.

--What are triglycerides? Triglycerides create hidden particles in the blood like intermediate-density lipoprotein, potent triggers for coronary plaque growth. Speaking of intermediate-density lipoprotein, that's another very important pattern to identify, the after-eating persistence of dietary fats.

--Why aren't they taking fish oil? With a 28% reduction in heart attack and 45% reduction in sudden death from heart attack, this alone would have halved the number of "events" in the "optimal" medical treatment group.

Of course, there's more. But the idea that aspirin, statins, and anti-ischemic therapy is somehow optimal is silly and sad at the same time. But that's the bias. The COURAGE Trial does represent a step forward, a step away from the "stent everyone and everything" mentality that motivates my colleagues, aided and abetted by their co-conspirators, the hospitals. But you and I know better. "Optimal" medical therapy, in truth, can mean a far better approach that can dramatically reduce, perhaps eliminate, risks for events like heart attack. The conventional "optimal" medical therapy will suffice only if you're content with a 20% likelihood of heart attack, death or stroke, or a 32% likelihood of an urgent procedure in your future.

For a detailed report on the very important postprandial (after eating) patterns that contribute hugely to heart disease risk, read my recent article in Life Extension Magazine, available (no cost) at:

Uncovering a Hidden Source of Cardiovascular Disease Risk
at http://www.lef.org/magazine/mag2007/mar2007_report_heart_01.htm

For a report on using niacin to reduce risk of heart disease, see another report in the same issue of Life Extension:

Ask the Doctor: Using Niacin to Improve Cardiovascular Health
at
http://www.lef.org/magazine/mag2007/mar2007_atd_01.htm.

Also, keep your eyes open for a lengthy report focused exclusively on the Track Your Plaque program in an upcoming issue of Life Extension. I'll provide links in this Blog when it comes out.

One of the recent questions on our Track Your Plaque Forum related to what to do about a triglyceride level of 101 mg/dl while on fish oil.

Recall that, contary to conventional thinking like that articulated in the ATP-III cholesterol treatment guidelines, we aim to reduce triglycerides to 60 mg/dl or less. This is important to suppress the formation of abnormal triglyceride-containing lipoprotein particles, especially small LDL, reduced HDL, lack of healthy large HDL, VLDL. ATP-III advises a level of 150 mg/dl or less. Unfortunately, triglyceride levels this high guarantee appearance of all these undesirable particles and an increasing heart scan score.

What's better than 4000 mg of fish oil for its 1200 mg of EPA and DHA (omega-3 fatty acids)? More fish oil. In other words, the 4000 mg fish oil providing 1200 mg EPA + DHA is our minimum. A simple increase to 6000 mg to provide 1800 mg EPA + DHA is usually all that is necessary to reduce triglycerides and put a halt to the cascade of abnormal lipoprotein particles that trigger plaque growth. Occasionally, a somewhat higher dose may be required. Doses are best divided into two, with meals (e.g., three capsules twice a day).

Another important issue: An over-reliance on wheat products can also increase triglycerides. This includes any flour product like breads (regardless of whether it's white, whole wheat, or whole grain--they all raise triglycerides), pretzels, bagels, breakfast cereals, and pasta. A dramatic reduction in wheat-containing products will reduce triglycerides substantially, help you reduce your abdominal fat, reduce blood pressure, raise HDL and reduce small LDL, clear your mind, provide more energy, avoid afternoon "fogginess" . . . Huge benefits.

There are two common forms of heart valve disease: aortic valve stenosis (stiffness) and insufficiency (leakiness), and mitral anular calcification.

Both valve issues are regarded as evidence of senescence, or aging--the older you are, the more likely you will have one or both. Both conditions involve progressive calcium deposition and, to some degree, cholesterol deposition. They might be regarded as phenomena of "wear and tear" just like hip arthritis.

There are no known therapies to stall or stop the development of mitral anular calcification. However, several attempts have been made over the years to identify treatments that can slow or stop the progression of aortic valve disease, which is becoming increasingly common and is addressed by surgical valve replacement when severe. The most recent trials have examined whether high-dose Lipitor (80 mg) has any effect (it did not) and high dose Crestor (40 mg), which slowed but did not stop the deterioration of stiff valves.

It's been my suspicion that vitamins D and K2 may play a crucial factor in valve health. After all, vitamin D is the master controller of calcium deposition. Preliminary data also suggest that people who are intentionally made vitamin K deficient with the drug, Coumadin, develop twice the calcium deposition on aortic valves that non-Coumadin takers develop.

I saw a patient Friday, Marianne. In addition to a moderate heart scan score of 379 at age 71, Marianne had a leaky (insufficient) aortic valve. By an echocardiogram 18 months ago, the valve was moderately leaky. I put Marianne on vitamin D, 4000 units, to raise her blood level to 50 ng/ml.

Last week, I asked Marianne to have another echocardiogram. This time, no leakiness whatsoever--none. I have never seen this happen before. Although Marianne is only one example and we don't want to extrapolate too far from the experience of one person, it's hard not to attribute this phenomenal response to vitamin D supplementation.

I wonder what would have happened if we had added vitamin K2, as well?

Anyway, just another potential wonderful effect of vitamin D restoration.

The Fanatic Cook has posted a stinging criticism of the American Heart Association (AHA):

American Heart Association My Fat Translator

Beyond the nonsensical nutritional recommendations (e.g., substitute small French fries for large French fries), she lists the major financial contributors to the AHA, a Who's Who in the pharmaceutical and processed food industry.

"For an organization that brought in close to a billion dollars last year, you'd think they could come up with something a little more pronounced. If I was more cynical I'd say the AHA had an interest in keeping Americans fat . . . or at least dependent on a highly-processed, fast food diet, requiring drugs to tweak lab values."

To be sure, the AHA does a great deal of good in funding research and educating the public about the prevalence of heart and vascular disease. But their fund raising interests have clearly subverted the honesty of their nutritional advice. Sadly, it is the AHA dietary advice that hospital dietitians use in counseling people with heart disease after their heart attack, stent, or bypass surgery. After my patients are discharged from the hospital for any reason, I tell them to please forget everything the nice hospital dietitian told them. It is not okay to eat the factory farm-raised hamburger on the sugar-equivalent enriched flour bun. Low-fat ice cream is not a healthy substitute for full-fat ice cream.

The AHA is no different than the USDA and the American Diabetes Association, "official" organizations that have, in effect, sold out to industry.

Sleep is a fascinating phenomenon.

Virtually all animals, certainly all mammals, sleep. While the form and shape of sleep can vary, sleeping is a universal phenomenon. Even fish sleep, though their eyes remain open.

Sleep disorders like sleep apnea ("apnea" = without breathing) are growing in prevalence nationwide as the country gets fatter and fatter. Our throats assume a smaller diameter, even our tongues get obese. This results in intermittent obstruction to the airway during sleep, causing snoring. It also results in sleep interruption, particularly during attempts to "descend" down to the deepest phases of sleep. Dire health and cardiac consequences can sometimes emerge, such as high blood pressure, higher blood sugar, abnormal heart rhythms, impaired heart muscle function, even sudden death.

We are all familiar with the perceptible effects of sleep deprivation: edginess, crabbiness, diminished attention span, slowed reaction time. I'm not talking about sleep apnea or sleep disorders, but just simple duration of sleep. Data are emerging that both sleep deprivation and sleep excess may trigger undesirable changes in lipids (cholesterol values):

Associations of usual sleep duration with serum lipid and lipoprotein levels.

Kaneita Y, Uchiyama M et al.

STUDY OBJECTIVES: We examined the individual association between sleep duration and a high serum triglyceride, low HDL cholesterol, or high LDL cholesterol level. DESIGN AND SETTING: The present study analyzed data from the National Health and Nutrition Survey that was conducted in November 2003 by the Japanese Ministry of Health, Labour and Welfare. This survey was conducted on residents in the districts selected randomly from all over Japan. PARTICIPANTS: The subjects included in the statistical analysis were 1,666 men and 2,329 women aged 20 years or older. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: Among women, both short and long sleep durations are associated with a high serum triglyceride level or a low HDL cholesterol level. Compared with women sleeping 6 to 7 h, the relative risk of a high triglyceride level among women sleeping <5 h was 1.51 (95% CI, 0.96-2.35), and among women sleeping > or =8 h was 1.45 (95% CI, 1.00-2.11); the relative risk of a low HDL cholesterol level among women sleeping <5 h was 5.85 (95% CI, 2.29-14.94), and among women sleeping > or =8 h was 4.27 (95% CI, 1.88-9.72). On the other hand, it was observed that the risk of a high LDL cholesterol level was lower among men sleeping > or =8 h. These analyses were adjusted for the following items: age, blood pressure, body mass index, plasma glucose level, smoking habit, alcohol consumption, dietary habits, psychological stress, and taking cholesterol-lowering medications. CONCLUSIONS: Usual sleep duration is closely associated with serum lipid and lipoprotein levels.

Triglycerides go up with too little or too much sleep. Note especially the extraordinary association of low HDL cholesterol with sleeping <5 hours (nearly 6-fold increased risk) or sleeping >8 hours (more than 4-fold increased risk).

Why do these effects develop? Does sleep deprivation, for instance, trigger higher adrenaline levels, encourage carbohydrate cravings or binges, make us less likely to engage in physical activity? Cortisol is elevated; could this be a factor? I know that I am a different person when sleep-deprived: irritable, less clear-thinking, quicker to anger, more critical, and I develop carbohydrate cravings. It's curious that triglycerides increase when sleep excess is present; what might that represent?

Anyway, the data are growing: Sleep is an important facet of health, both for maintaining a bright outlook and to discourage development of low HDL and high triglycerides. Though not specifically examined in this study, we know that low HDL/high triglycerides are, as a rule, associated with the undesirable small LDL particle pattern.

As a practical matter, you may also find sleep and waking from sleep more satisfying and restful if you sleep in increments of 90 minutes, e.g., 7 1/2 hours (rather than 7 or 8 hours). This is because the full cycle of sleep, from phase 1 to REM (rapid-eye movement sleep), requires 90 minutes for completion. That doped feeling that sometimes develops when awaking will disappear if you sleep according to your sleep cycle, which is usually 90 minutes long.

There's no doubt that low thyroid function results in fatigue, weight gain, hair loss, along with rises in LDL cholesterol and other fractions of lipids. It can also result in increasing Lp(a), diabetes, and accelerated heart disease, even heart failure.

But how do we distinguish "normal" thryoid function from "low" thyroid function? This has proven a surprisingly knotty question that has generated a great deal of controversy.

Thyroid stimulating hormone, or TSH, is now the most commonly used index of the adequacy of thyroid gland function, having replaced a number of older measures. TSH is a pituitary gland hormone that goes up when the pituitary senses insufficient thyroid hormone, and a compensatory increase of thyroid hormone is triggered; if the pituitary senses adequate or excessive thyroid hormone, it is triggered to decrease release of TSH. Thus, TSH participates in a so-called "negative feedback loop:" If the thyroid is active, pituitary TSH is suppressed; if thyroid activity is low, pituitary TSH increases.

An active source of debate over the past 10 years has been what a normal TSH level is. In clinical practice, a TSH in the range of 0.4-5.0 mIU/L is considered normal. (Lower TSH is hyperthyroidism, or overactive thyroid; high TSH is hypothyroidism, or underactive thyroid.)

The data from a very fascinating and substantial observation called the HUNT Study, however, is likely to change these commonly-held thyroid "rules."

The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study

In this study, over 30,000 Norwegians without known thyroid disease were enrolled. TSH levels and lipid (cholesterol) levels were measured.

In this large and extraordinary observation, increasing TSH levels were associated with increasing levels of LDL cholesterol and triglycerides, and decreasing HDL. At what level of TSH did this relationship start? At TSH levels as low as 1.0!

In other words, there were perturbations in standard lipid measures even with TSH levels ordinarily regarded as "normal," even "perfect."

A subsequent observation from the HUNT Study was even more recently published:

Thyrotropin Levels and Risk of Fatal Coronary Heart Disease: The HUNT Study

Abstract:

Background Recent studies suggest that relatively low thyroid function within the clinical reference range is positively associated with risk factors for coronary heart disease (CHD), but the association with CHD mortality is not resolved.

Methods In a Norwegian population-based cohort study, we prospectively studied the association between thyrotropin levels and fatal CHD in 17 311 women and 8002 men without known thyroid or cardiovascular disease or diabetes mellitus at baseline.

Results During median follow-up of 8.3 years, 228 women and 182 men died of CHD. Of these, 192 women and 164 men had thyrotropin levels within the clinical reference range of 0.50 to 3.5 mIU/L. Overall, thyrotropin levels within the reference range were positively associated with CHD mortality (P for trend = .01); the trend was statistically significant in women (P for trend = .005) but not in men. Compared with women in the lower part of the reference range (thyrotropin level, 0.50-1.4 mIU/L), the hazard ratios for coronary death were 1.41 (95% confidence interval [CI], 1.02-1.96) and 1.69 (95% CI, 1.14-2.52) for women in the intermediate (thyrotropin level, 1.5-2.4 mIU/L) and higher (thyrotropin level, 2.5-3.5 mIU/L) categories, respectively.

Conclusions Thyrotropin levels within the reference range were positively and linearly associated with CHD mortality in women. The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD.

In other words, the findings of this substantial observation suggest that the ranges of TSH usually regarded as normal contribute to coronary events, cardiac death, as well as lipid patterns. While several other studies have likewise shown a relationship of higher TSH/lower thyroid function with lipid abnormalities and overt heart disease, no previous study has plumbed the depth of TSH to this low level and to such a large scale.

I believe that these findings are enough cause to begin thinking seriously about monitoring thyroid function more seriously to uncover "borderline" TSH increases in the "normal" range. While higher TSH levels predict cardiovascular events, does thyroid replacement at these levels reduce it? Critics will say it's a big leap, but I think that it is worth at least considering.

Stay tuned for a lengthy Special Report followed by a full booklet on these issues on the www.cureality.com website.

Copyright 2008 Wiliam Davis, MD

Tne Philadelphia NBC affiliate's website carried this commentary from a colleague of mine:

Mark from the Lehigh Valley is curious about scans that can detect heart disease.

He asked, "I am in my early 50s. My father had a heart attack in his 40s. I am healthy with no symptoms of heart disease, should I consider a heart scan?"

"Well, Mark, occasionally family history needs to be considered more closely. If your father had coronary disease at a relatively young age at the absence of any known risk factor for heart disease for example diabetes, smoking, obesity, high blood pressure, than your level of risk should be considered more closely," Dr. Kevin Shinal, a cardiologist, said.

"There are a number of studies available to access [sic] your level of risk. One such study is a calcium score. A calcium score is a form of a CAT scan that access [sic] the calcium burden or presence of calcium in your coronary arteries. It assigns you a score and score is translated into a level of cardiovascular risk," Shinal said.

But the doctor warned because Mark doesn't have active symptoms, the scan probably wouldn't be covered by insurance.

Was there an understandable answer in there? I certainly couldn't find it.

Why pick on some yokel responding inarticulately to the local media's quest for content? Because this is, all too often, what the public hears: Ill-informed blather from someone who has little or no understanding of the issues. Maybe this doctor wanted his practice group to get some free publicity. "Doctor, could you just answer a few questions from viewers?"

Unfortunately, it's not just local media who are guilty of consulting with know-nothings with only passing knowledge of an issue. National media are guilty of it, too. The need to fill airtime with content is better filled with talking heads who present a compelling story, whether or not it is accurate or insightful, rather than an expert with deep insight into a topic who might not present as pretty a story. I've seen this countless times. A good portion of my day, in fact, is occupied responding to patient questions based on the misinformation presented in some media report.

My message of this brief rant: Be very careful of the messages delivered by the media, even if provided by some supposed "expert." In fact, I regard "experts" in health about as believable as politicians. Sure, sometimes they provide accurate information. But they often do not, or provide information with limited understanding. Or, worse, information intended to serve some hidden agenda.

Were the media to ask me to respond to the question, however, I would say:

"Yes, you should absolutely have a heart scan--yesterday! With your family history, there is no other way to accurately, easily, and inexpensively quantify the amount of coronary atherosclerosis in your heart's arteries. A stress test only uncovers advanced disease. A heart catheterization is overkill and absolutely not indicated in an asymptomatic man. Judging the presence of heart disease from cholesterol values is folly.

"What's left? A CT heart scan. So, yes, you need a CT heart scan ASAP with no doubt whatsoever."

But they didn't ask.

Although Dr. John Cannell's most recent Vitamin D Newsletter concerns the connection between autism and vitamin D, and has nothing to do with coronary plaque reversal, this fascinating discussion between a mother of an autistic boy and Dr. Cannell is so enlightening that I thought that it was still worth passing on.

I also feel very deeply for parents with autistic children, who I see struggle with the developmental difficulties their children encounter. (I even have several patients who are parents of 2 or 3 autistic children.)

As always, Dr. Cannell is at the cutting-edge of converting hard scientific information into practical use. You will note several points or questions raised:

1) Dr. Cannell advocates a powdered capsule form of vitamin D. In my experience, most powdered or tablet forms do not work. But some do. He apparently has success with the brand he specifies.

2) Are there vitamin D-receptor (VDR) genotypes that respond differently? Should there be different 25 (OH) vitamin D blood level targets for different VDR genotypes? Nobody knows yet, but it will be an important question to explore in the future.

3) Is heavy metal toxicity, at least in its milder forms, a surrogate for vitamin D deficiency? (Are chelationists unwittingly treating vitamin D deficiency?)

4) If this is a genuine association, and vitamin D replenishment exerts profound neurologic effects in autistic children, does a similar, though less marked effect, hold in non-autistic children? Will children perform better, learn more effectively, etc. with vitamin D supplementation to normal levels?

5) Vitamin A--Is vitamin A with vitamin D good or bad? This one I do not have an answer to. Reading the literature Dr. Cannell cites didn't help much. (Dr. BG--Any comments? Dr. BG is a vitamin A advocate.)

Perhaps, should the association between autism and vitamin D hold, it raises more questions than it settles. But, true to my experience with vitamin D, every day I stumble on some unique, fascinating effect, all beneficial. We continue to learn new lessons about vitamin D and Dr. Cannell's insights as a practicing psychiatrist deeply concerned with vitamin D issues have helped enormously.

(Sorry, but I did not copy the links to the literature Dr. Cannell cites. To obtain the links, go to the original Vitamin D Newsletter.)

The Vitamin D Newsletter
June 2008

This month we feature a remarkable series of letters from a mother of an autistic son who treated her child with vitamin D. It is the first case report in the medical literature suggesting vitamin D has a treatment effect in autism.

First, a brief case report and then a more detailed exchange of emails between the mother and me.

Case Report:

John is a seven-year old boy living in the northeastern U.S. with a long-standing diagnosis of autism. Symptoms include temper tantrums, repetitive self-stimulatory behavior, impaired language, mood swings, fear of being alone, toileting problems, dysbacteriosis, and impaired muscle strength. John spends a lot of time outdoors starting in the spring and his mother noticed a distinct seasonal variation in his symptoms in that he improved in the summer and regressed in the winter. A 25-hydroxy-vitamin D in April of 2008 was 25 ng/ml and obtained after John had begun to play outside. Due to the seasonality of John's symptoms the mother consulted me. I advised the mother to stop all products containing vitamin A including cod liver oil and begin John on 5,000 IU of vitamin D3 per day for two weeks followed by 2,000 IU per day in the form of powdered vitamin D dissolved in juice. Within a week of starting the vitamin D, John's language began to return and he was no longer as fearful of being alone. At the end of two weeks his language showed further improvement, he began to toilet himself, counted to 10 and knew the spelling of his name. After three weeks language continued to improve and some improvements were noted in his dysbacteriosis. After four weeks of vitamin D treatment, the mother noted improvements in muscle strength as well as continued improvements in language. A repeat 25-hydroxy-vitamin D is pending while John continues taking 2,000 IU of vitamin D per day.

Before you read the series of emails between the mother and me, I'd like to caution that this is only a case report of sorts and does not prove a treatment effect. Spontaneous remissions, while rare in autism, have been reported, thus the supplemental vitamin D may have had nothing to do with his improvement. If the response is due to vitamin D, there is no assurance it will prove lasting. I think it unlikely that older autistic children or individuals with severe autism will show these sorts of apparent improvements. Furthermore, autism is a multifactorial disease with strong genetic roots and it is highly unlikely that treatment of vitamin D deficiency in all autistic children will result in similar improvements. Finally, I did not examine this child, and I am relying on the child's mother to report both his condition and his apparent response to vitamin D treatment. However, the mother agreed to speak with the press about her son and allow for independent confirmation of the apparent treatment response.

Below are the emails, edited for brevity, clarity, and confidentiality.

Dear Dr. Cannell:

I am writing because I believe my son John is strongly affected by vitamin D and I need some advice. John is seven and autistic and weighs 50 pounds. We live in the northeastern part of the United States . He starts spending lots of time outside in May and continues until September. Every year, like clockwork, he has the same patterns of behavior and ability. After about six weeks of sun exposure, every July, he begins feeling much better, seems to be comfortable in his skin, does not have as much self-stimulatory behavior, can eat a variety of foods and has language. This past summer, he was using 14-word sentences. By the end of November, he can't even ask you for a cup of juice. He becomes more exclusive, has emotional highs and lows, has tantrums and is easily frustrated.

His 25(OH)D level on April 15th was 25 ng/ml but he had already been going out in the sun so his level must have been lower in the winter. I have had his genetics tested (Nutrigenomic) and he has mutations in his vitamin D receptors:

VDR Bsm/Taq ++
VDR Fok --
VDR Taq ++

My first question, does it sound like the changes in his behaviors and abilities could be caused by lack of vitamin D? Could you elaborate on the time it would take to get adequate amounts of vitamin D to start seeing positive results? For example, even if he starts going out in the sun in May, it's usually not until July that I see positive changes. Then would it take a month or two to go back to being deficient, thus explaining his 'regression' by the time November comes around. Secondly, I am looking at different forms of vitamin D therapy: a vitamin D lamp, vitamin D3 cream, or oral vitamin D. Can you tell me what might be the best form during the winter months?

Thank you very much for your time and attention.

Jane, Boston MA

Dear Jane:

Yes, it is possible your son's autism is related to vitamin D. Such seasonality has been reported before in autism, both in an individual and in autistic children at a summer camp. Although suggestive, such seasonality does not prove a vitamin D connection. Sun exposure, unless it is full body, takes several months to get vitamin D levels up. If sunblock or clothes are worn sun exposure will not get 25(OH)D levels much above 30 ng/ml. As far as the "mutations" you list, they are actually vitamin D receptor (VDR) polymorphisms and not referred to as mutations although all such changes occurred through mutations at some time in the past. VDR polymorphisms are simply the different structures of the vitamin D receptor that different people have and they are widely distributed. A pilot study of actual VDR receptor mutations did not detect VDR mutations in 24 autistic individuals but they did not assess for VDR polymorphisms. However, a highly significant association exists between one VDR polymorphism and larger head size. Mean head circumference is larger in autism.

Yan J, et al. Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases. Neurosci Lett 2005;380(1-2):37-41.

Handoko HY, et al. Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures. Am J Hum Biol 2006;18(3):415-7.

Lainhart JE, et al. Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism. Am J Med Genet A 2006;140(21):2257-74.

Lainhart JE, et al. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry 1997;36(2):282-90.

I emailed the world's foremost expert on VDR polymorphisms asking him about your son's polymorphisms and his reply, quite technical, is below.

Dear John:

I apologize for the delay in getting back to you regarding VDR polymorphisms. Initial studies by Eisman and coworkers many years ago suggested that several of the polymorphs identified above in the VDR gene (Bsm/Tag) correlated strongly with osteoporosis. Despite the hoopla, subsequent analyses by many different investigators did not really confirm these results, i.e. only a very modest (3%) correlation. This spawned multiple studies searching for correlations between VDR polymorph's and cancer, autoimmune disease and so forth. It is fair to say from all of these studies that the correlation is at best weak, and in most cases non-existent. Part of this may be due to the fact that the Bsm and Taq polymorphs are located in VDR gene introns and as a first approximation cannot affect the VDR protein's function. This is not an absolute statement, however, as our work is now showing that regulatory regions that control the VDR's expression are located within introns as well as upstream. Therefore the possibility exists that these polymorphs could affect expression, although we have not found these regions to contain enhancers yet. This is clearly where gene and disease studies are going. The only polymorph that could affect function is the Fok1 site, which we identified many years ago following our initial cloning and structural analysis of the human VDR gene. The presence of this site leads to the expression of a shorter VDR protein (424 aa) that is purported to have a slight increase in transcriptional activity (10%?) vs the large protein (427 aa). The above analysis suggests that this polymorph is absent, leading to production of the larger perhaps less active protein. On a single patient basis, it is really difficult to conclude anything regarding this finding. Indeed, despite large numbers of patients, the VDR polymorph have not really revealed any significant insight. Given the summer correlations, it is probably more likely that the individual is low in vitamin D3 in winter.

Sincerely,

Professor John Doe

Thus, one of your son's polymorphisms may have less functionality but that should be easily overcome by higher vitamin D levels. The first thing to do is stop all vitamin A, multivitamins containing vitamin A, or cod liver oil and start vitamin D. As you will see below, vitamin A antagonizes the action of vitamin D and he should have plenty of vitamin A if he eats colorful vegetables, colorful fruit, eggs and fortified oatmeal. As far as vitamin D, I think the easiest way to give vitamin D is powdered capsules, not a cream. You can open the capsule and put the powder in about anything, such as juice. To buy the capsules, go toBio Tech Pharmacal and buy both a bottle of the 5,000 and the 1,000 IU capsules. He should take one 5,000 IU capsule a day for two weeks then take 2,000 IU per day. After a month, go to the doctor and have another 25-hydroxy-vitamin D blood test. Do not let your doctor order a 1,25-dihydroxy-vitamin D as it will give you and your doctor false information about your son's vitamin D status. The other option is buying a Sperti vitamin D light. Daily use of the light on both sides of his trunk will raise levels fairly quickly but he should still have a 25(OH)D blood test every month to assure his levels rise to the mid level of normal ranges, about 70 ng/ml. Vitamin D is very safe. Your son would have to take more than 10,000 IU a day for more than a year to have any risk of toxicity. If he improves and his level is 50 ng/ml, the next question is would he improve even more if his level was 70 ng/ml? Some lifeguards have levels of 80-100 ng/ml; normal ranges in the labs in the USA are 30 -100 ng/ml (ideal ranges are 50 -100 ng/ml.) If you have any more questions, let me know. I certainly want to know how he is doing.

Sincerely,

John Cannell

Dear Dr. Cannell:

It has been one week on 5,000 IUs of vitamin D3 daily and already we're getting some language back! We haven't had original language since probably around the end of November. The only language we have had in the past five months has been verbal scripting. Today John has already told me "turn off the TV" and "clean up the water". This is all very exciting. Will it last? I will continue to keep you updated on progress and change in behavior. One more thing, all winter long he was afraid to be by himself anywhere. Now he is starting to be able to be in another room or outside by himself.

Thanks so much,

Jane

Dear Jane:

I can't tell you how happy I am for you. I suspect John will continue to improve. Do you have any parent rating scales or does his treating pediatrician have any objective rating scales? If you have before and after rating scales or his treating doctor does then it becomes important to track his progress on an objective measure. Jane, if you are a member of any autism discussion groups, you should post about this, including doses used. If your son's case is typical, then hundreds of thousands of autistic children may be helped with vitamin D.

John Cannell

Dear Dr. Cannell:

It has been two weeks on 5,000 IU per day and I want to inform you that we are having continued success with language. Continued in the sense that it is consistent, it wasn't just a one day fluke. In addition, he is taking himself to the bathroom; this is another thing that goes away in winter months. I usually have to catch him holding it in and then suggest he go, but now he is going completely by himself. In therapy last week, he started drawing again. He drew a bee and then ran around the room buzzing. Hi All posts by william-davis

Heart Scan Blog Redux: Cheers to flavonoids

13. November 2009 William Davis (32)

Because in Track Your Plaque we've been thinking a lot about anthocyanins, here's a rerun of a previous Heart Scan Blog post about red wine. (Anthocyanins are among the interesting flavonoids in red wine, along with resveratrol and quercetin.)

The case in favor of healthful flavonoids seems to grow bit by bit.

Flavonoids such as procyanadins in wine and chocolate, catechins in tea, and those in walnuts, pomegranates, and pycnogenol (pine bark extract) are suspected to block oxidation of LDL (preventing its entry into plaque), normalize abnormal endothelial constriction, and yield platelet-blocking effects (preventing blood clots).

Dr. Roger Corder is a prolific author of many scientific papers detailing his research into the flavonoids of foods, but wine in particular. He summarizes his findings in a recent book, The Red Wine Diet. Contrary to the obvious vying-for-prime-time title, Dr. Corder's compilation is probably the best mainstream discussion of flavonoids in foods and wines that I've come across. Although it would have been more entertaining if peppered with more wit and humans interest, given the topic, its straightfoward, semi-academic telling of the story makes his points effectively.

Among the important observations Corder makes is that regions of the world with the greatest longevity also correspond to regions with the highest procyanidin flavonoids in their wines.

Regarding the variable flavonoid content of wines, he states:

Although differences in the amount of procyanidins in red wine clearly occur because of the grape variety and the vineyard environment, the winemaker holds the key to what ends up in the bottle. The most important aspect of the winemaking process for ensuring high procyanidins in red wines is the contact time between the liquid and the grape seeds during fermentation when the alcohol concentration reaches about 6 percent. Depending on the fermentation temperature, it may be two to three days or more before this extraction process starts. Grape skins float and seeds sink, so the number of times they are pushed down and stirred into the fermenting wine also increases extraction of procyanidins. Even so, extraction is a slow process and, after fermentation is complete, many red wines are left to macerate with their seeds and skins for days or even weeks in order to extract all the color, flavor, and tannins. Wines that have a contact time of less than seven days will have a relatively low level of procyanidins. Wines with a contact time of ten to fourteen days have decent levels, and those with contact times of three weeks or more have the highest.

He points out that deeply-colored reds are more likely to be richer in procyanidins; mass-produced wines that are usually "house-grade" served at bars and restaurants tend to be low. Some are close to zero.

Wines rich in procyanidins provide several-fold more, such that a single glass can provide the same purported health benefit as several glasses of a procyanidin-poor wine.

So how do various wines stack up in procyanidin content? Here's an abbreviated list from his book:

Australian--tend to be low, except for Australian Cabernet Sauvignon which is moderate.

Chile--only Cabernet Sauvignon stands out, then only moderate in content.

France--Where to start? The French, of course, are the perennial masters of wine, and prolonged contact with skins and seeds is usually taken for granted in many varieties of wine. Each wine region (French wines are generally designated by region, not by variety of grape) can also vary widely in flavonoid content. Nonetheless, Bordeaux rate moderately; Burgundy low to moderate (except the village of Pommard); Languedoc-Roussillon moderate to high (and many great bargains in my experience, since these producers live in the shadow of its northern Bordeaux neighbors); Rhone (Cote du Rhone) moderate to high, though beware of their powerful "barnyard" character upon opening; decanting is wise.

Italy--Much red Italian wine is made from the Sangiovese grape and called variously Chianti, Valpolicella, and "super-Tuscan" when blended with other varietals. Corder rates the southern Italian wines from Sicily, Sardinia, and the mainland as high in procyanidins; most northern varieties are moderate.

Spain--Moderate in general.

United States--Though his comments are disappointingly scanty on the U.S., he points out that Cabernet Sauvignon is the standout for procyanidin content. He mentions only the Napa/Sonoma regions, unfortunately. (I'd like to know how the San Diego-Temecula and Virginian wines fare, for instance.)

The winner in procyanidin content is a variety grown in the Gers region of southwest France, a region with superior longevity of its residents. The wines here are made with the tannat grape within the Madiran appellation; wines labeled "Madiran" must contain 40% or more tannat to be so labeled (such is a quirk of French wine regulation). Among the producers Dr. Corder lists are Chateau de Sabazan, Chateau Saint-Go, Chateau du Bascou, Domaine Labranche Laffont, and Chateau d'Aydie. (A more complete list can be found in his book.)

How does this all figure into the Track Your Plaque program? Can you succeed without red wine? Of course you can. I doubt you could do it, however, without some attention to flavonoid-rich food sources, whether they come from spinach, tea, chocolate, beets, pomegranates, or red wine.

Though my wife and I love wine, I confess that I've never personally drank or even seen a French Madiran wine. Any wine afficionados with some advice?

Can wheat elimination cure ulcerative colitis?

13. November 2009 William Davis (0)

Tammy is a 36-year old mother of three young children. Since age 20, she has suffered with the debilitating symptoms of ulcerative colitis: constant, gnawing abdominal pain; frequent diarrhea, often bloody.

Tammy has had to take several medications, some with significant side-effects, all of which provided only partial relief from the pain and diarrhea. Her gastroenterologist and surgeon were planning a colectomy (removal of the colon) with creation of an ileostomy (rerouting of the small intestine to the abdominal surface, which would require Tammy to wear an ileostomy bag under her clothes for the rest of her life).

Although Tammy had previously tested negative for celiac disease (an allergic sensitivity to the gluten in wheat products), I urged her to attempt a trial of a wheat-free diet. Having witnessed many people experience relief from irritable bowel syndrome, acid reflux, and other common gastrointestinal complaints, all while trying to reduce blood sugar and small LDL, I'd hoped that Tammy would obtain at least some small improvement in her terrible symptoms.

I therefore urged Tammy to try it. After all, what was there to lose? Tammy grudgingly agreed.

She returned 6 months later. Her report: She had lost 38 lbs, virtually all of it within the first 6-8 weeks. Her diarrhea and cramping were not better, but gone. She was down to a single medicine from her former list of drugs.

I am unsure what proportion of people with ulcerative colitis or other inflammatory bowel diseases like Crohn's will experience a result like Tammy's. Perhaps it's only a minority. But I take this another piece of evidence that this enormously destructive thing called wheat has no place in the human diet.

We have no facts or figures on the prevalence of various forms of wheat intolerance in the U.S. When I contacted the Celiac Disease Foundation, they had no figures on the number of fatalities per year in the U.S. from celiac disease. But if there are 2-3 million Americans with celiac disease, there are probably 100 times that many people with various forms of wheat intolerance.

Postprandial pile-up with fructose

12. November 2009 William Davis (20)

Heart disease is likely caused in the after-eating, postprandial period. That's why the practice of grazing, eating many small meals throughout the day, can potentially increase heart disease risk. Eating often can lead to the phenomenon I call triglyceride and chylomicron "stacking," or the piling up of postprandial breakdown products in the blood stream.

Different fatty acid fractions generate different postprandial patterns. But so do different sugars. Fructose, in particular, is an especially potent agent that magnifies the postprandial patterns. (See Goodbye, fructose.)

Take a look at the graphs from the exhaustive University of California study by Stanhope et al, 2009:

From Stanhope KL et al, J Clin Invest 2009. Click on image to make larger.

The left graphs show the triglyceride effects of adding glucose-sweetened drinks (not sucrose) to the study participants' diets. The right graphs show the triglyceride effects of adding fructose-sweetened drinks.

Note that fructose causes enormous "stacking" of triglycerides, meaning that postprandial chylomicrons and VLDL particles are accumulating. (This study also showed a 4-fold greater increase in abdominal fat and 45% increase in small LDL particles with fructose.)

It means that low-fat salad dressings, sodas, ketchup, spaghetti sauce, and all the other foods made with high-fructose corn syrup not only make you fat, but also magnifies the severity of postprandial lipoprotein stacking, a phenomenon that leads to more atherosclerotic plaque.

Track Your Plaque: Safer at any score

11. November 2009 William Davis (0)

Imagine two people.

Tom is a 50-year old man. Tom's initial heart scan score was 500--a concerning score that carries a 5% risk for heart attack per year.

Harry is also 50 years old. His heart scan score is 100--also a concerning score, but not to the same degree as Tom's much higher score.

Tom follows the Track Your Plaque program. He achieves the 60:60:60 lipid targets; chooses healthy foods, including elimination of wheat; takes fish oil at a therapeutic dose; increase his blood vitamin D level to 60-70 ng/ml, etc. One year later, Tom's heart scan score is 400, representing a 20% reduction from his starting score.

Harry, on the other hand, doesn't understand the implications of his score. Neither does his doctor. He's casually provided a prescription for a cholesterol drug by his doctor, a brief admonition to follow a low-fat diet, and little else. One year later, Harry's heart scan score is 200, a doubling (100% increase) of the original score.

At this point, we're left with Tom having a score of 400, Harry with a score of 200. That is, Tom has twice Harry's score, 200 points higher. Who's better off?

Tom with the score of 400 is better off. Even though he has a significantly higher score, Tom's plaque is regressing. Tom's plaque is therefore quiescent with active components being extracted, inflammation subsiding, the artery in a more relaxed state, etc.

Harry's plaque, in contrast, is active and growing: inflammatory cells are abundant and producing enzymes that degrade supportive tissue, constrictive factors are released that cause the artery to pinch partially closed, fatty materials accumulate and trigger a cascade of abnormal responses.

So it's not just the score--the quantity of atherosclerotic plaque present--but the state of activity of the plaque: Is it growing, is it being reduced? Is there escalating or subsiding inflammation? Is plaque filled with degradative enzymes or quiescent?

Following the Track Your Plaque program therefore leads us to the notion that it's not the score that's most important; the most important thing is what you're doing about it. We sometimes say that Track Your Plaque makes you safer at any score.

Triglyceride and chylomicron "stacking"

10. November 2009 William Davis (24)

Continuing the comments started in Grazing is for cattle, here's an interesting study from the Oxford Center for Diabetes, Endocrinology and Metabolism.

Volunteers were fed a test meal breakfast of Rice Krispies, a banana, and a chocolate milkshake (76.4 grams carbohydrates, 51.9 grams fat, 12.2 grams protein). Lunch was served 5 hours later and consisted of a cheese sandwich and a second chocolate milkshake 43.4 grams carbohydrates, 49.6 grams fat, 24.0 grams protein). Frequent blood samples were then assessed over the day. (Don't try this at home: These are obviously very dangerous foods!)

Here's the pattern of triglycerides that was observed (1st dotted vertical line = breakfast, 2nd dotted vertical line = lunch):

Note that triglycerides only begin to decline 3-4 hours after breakfast, only to peak higher after lunch.

Here's the pattern observed for chylomicrons, the "granddaddy" of lipoproteins that derives from intestinal absorption of fatty acids:

Both graphs from Heath RB et al Am J Phyiol Endocrinol Metab 2006.

With chylomicrons, note a similar pattern to triglycerides: Chylomicrons begin to decline at 3-4 hours, only to peak higher after lunch.

This is the first study to examine the effect of sequential meals on such postprandial (after-eating) patterns. But it makes the graphic point that, if insufficient time is permitted between meals, both triglycerides and chylomicrons will "stack" themselves higher and higher. (Chylomicrons are subjected to processing by the enzyme, lipoprotein lipase, to form highly atherogenic, or plaque-causing, chylomicron remnants.)

While not examined in this study, my bet is that "grazing," i.e., eating small meals or snacks frequently, is an extreme instance of triglyceride, chylomicron, and chylomicron remnant stacking. That can only lead to one thing: accelerated heart and vascular plaque.

What is a healthy vitamin D blood level?

9. November 2009 William Davis (32)

When measuring blood levels of vitamin D (as 25-hydroxy vitamin D), what constitutes a desirable level?

There's no study that directly examines this question, no study that enrolled thousands of people and assigned a placebo group and groups receiving escalating doses of vitamin D and/or achieved higher levels of vitamin D, then observed for development of cancer, diabetes, depression, heart disease, multiple sclerosis, osteoporosis, osteoarthritis, etc. Such a study would requires many thousands of participants (particularly to observe cancer and multiple sclerosis incidence), many years of observation, and many tens of millions of dollars. Nope, only a drug company could afford such costs.

So we have to piece together various observations and extrapolate what we believe to be the ideal level of vitamin D. Epidemiologic observations in several cancers (breast, colon, prostate, and bladder) suggest that a 25-hydroxy vitamin D level of 30 ng/ml or higher is desirable (with less cancer incidence above this level). Other data suggest a level of 52 ng/ml or greater is desirable. Unfortunately, much cancer research looked at intake of vitamin D from food and supplement sources, rather than actual blood levels. We also have to factor in the great individual variation in vitamin D metabolism, with a single dose yielding variable blood levels (as much as a 10-fold difference). There's also the variation introduced by vitamin D-receptor variation (genetic polymorphisms).

A new study using vitamin D administration helps chart the desirable levels of vitamin D.

Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.

In this New Zealand study, 42 women (23 to 68 years old) were given 4000 units vitamin D, 39 women given placebo. Median 25-hydroxy vitamin D levels increased from 21 nmol/L (8.4 ng/ml) to 75 nmol/L (30 ng/ml). Both HOMA (a measure of insulin sensitivity) and fasting insulin levels improved, with greatest improvement seen at 25-hydroxy vitamin D levels of 80-119 nmol/L (32-47.6 ng/ml) or greater.

We also know that a vacation on a Caribbean beach in a bathing suit will increase vitamin D blood levels to the 80-110 ng/ml range without ill-effect (at least in young people who maintain the capacity to activate vitamin D in the skin, a phenomenon that declines as we age).

So do we really know the truly ideal level of vitamin D to achieve? I believe that, given the above observations, it is reasonable to extrapolate that the ideal vitamin D blood level likely lies somewhere above 50 ng/ml. We also know that vitamin D toxicity (i.e., hypercalcemia) is virtually unheard of until vitamin D blood levels approach 150 ng/ml, and even then is inconsistent. The health benefits of vitamin D supplementation are so tremendous, that I am not willing to wait for the prospective data to explore this question fully. For now, I aim for a blood level of vitamin D of 60-70 ng/ml (150-175 nmol/L).

Grazing is for cattle

5. November 2009 William Davis (17)

Many dietitians and nutritionists advise many people today to "graze," i.e., to eat small snacks every couple of hours. They argue that it blocks the drop in insulin and blood sugar that can trigger greater appetite and claim it can facilitate weight loss.

This is an absurd notion. Humans are not meant to graze. Humans are meant to find a wild boar or other animal, kill it, gorge on the meat, organs, and fat, then revert to berries, roots, leaves, and other foraged foods until the next kill. A human living in the wild does not have a cupboard or refrigerator full of ready-to-eat snacks to graze on.

The several hours after a meal is the most dangerous for creating coronary atherosclerotic plaque, i.e., the post-prandial period. In other words, eat dinner and, for the next 6-12 hours, your intestinal tract degrades the food; food byproducts are absorbed into the blood or lymph system. The blood is literally flooded with the byproducts of your meal.

Postprandial abnormalities are emerging to be a potent, and much underappreciated, means of causing heart disease and atherosclerosis in other vascular territories (especially carotid arteries and thoracic aorta).

Not eating--i.e., the fasting state--for extended periods is good for you. Encouraging people to graze amplifies atherosclerotic risk, since it creates an abnormal prolonged postprandial state.

The disastrous results of a low-fat diet

4. November 2009 William Davis (16)

Rob was never that committed to following the program in the first place.

I met Rob because of a modest heart scan score and consultation for a cholesterol abnormality. Rob had been cycled through all the statin agents by his primary care physician, all of which resulted in terrible muscle aches that he found intolerable.

I started out, as usual, characterizing his cholesterol abnormality with lipoprotein testing (NMR):

LDL particle number 1489 nmol/L
LDL cholesterol (Friedewald calculation) 143 mg/dl
Small LDL 52% of total LDL
HDL 50 mg/dl
Triglycerides 82 mg/dl

(LDL particle number is the emerging gold standard for LDL quantification, superior to calculated or Friedewald LDL cholesterol for prediction of cardiovascular events.)

Rob is a busy guy. After only a couple of brief visits, life and work got in the way and Rob let his attentions drift away from heart health. Since the information I provided made little impact on his thinking, he reverted to the low-fat diet his primary care doctor had originally prescribed and that he read about in magazines and food packages. He also ran out of the basic supplements I had advised, including fish oil and vitamin D, and just never restarted them.

A couple of years passed and Rob decided that just poking around on his own might not cut it. So he came back to the office. We repeated his NMR lipoprotein analysis:

LDL particle number 2699 nmol/L
LDL cholesterol (Friedewald calculation) 229 mg/dl
Small LDL 81% of total LDL
HDL 53 mg/dl
Triglycerides 78 mg/dl

Two years of a low-fat diet had caused Rob's LDL particle number to skyrocket by 81%, nearly all due to an explosion of small LDL. Recall that small LDL is more susceptible to oxidation, more inflammation-provoking, more adhesive--the form of LDL particles most likely to cause heart disease.

Also, note that, despite the enormous increase in small LDL, HDL and triglycerides remained favorable. This counters the popular rule-of-thumb offered by some that small LDL is not present when HDL is "normal."

Low-fat diets as commonly practiced are enormously destructive. In Rob's case, a low-fat diet caused both calculated Friedewald LDL as well as LDL particle number to increase dramatically. In many other people, low-fat diets increase calculated Friedewald LDL modestly or not at all, but cause the more accurate LDL particle number to increase significantly, all due to small LDL.

I'm happy to say that, once Rob witnessed how far wrong he could go on the wrong program, he's back on Track. (Sorry, pun intended.) He has resumed his supplements and eliminated the food triggers of small LDL--wheat, cornstarch, and sugars.

Dr. David Grimes reminds us of vitamin D

3. November 2009 William Davis (13)

In response to the Heart Scan Blog post, Fish oil makes you happy: Psychological distress and omega-3 index, Dr. David Grimes offered the following argument.

Dr. Grimes is a physician in northwest England at the Blackburn Royal Infirmary, Lancashire. He is author of the wonderfully cheeky 2006 Lancet editorial, Are statins analogues of vitamin D?, questioning whether the benefits of statin drugs simply work by way of increased vitamin D blood levels.

There is a fashionable interest in Omega-3 fatty acids, and these become equated with fish oil.

But fish oil is much more. Plankton synthesise the related squalene (shark oil) which, in turn, is converted into 7-dehydrocholesterol (7-DHC). The sun now comes into play and it converts 7-DHC into vitamin D (a physico-chemical process).

Small fish eat plankton, large fish eat small fish, and we eat large fish. So vitamin D passes through the food chain.

This has been a vital source of vitamin D for the the Inuits and also for the Scots and other dwellers of northwest Europe. (Edinburgh is on the same latitude as Hudson Bay and Alaska, further north than anywhere in China). In these locations there is not adequate sunlight energy to guarantee synthesis of adequate amounts of vitamin D, again by the action of sunlight on 7-DHC in the skin.

When the Scots moved from coastal fishing villages to industrial cities such as Glasgow, they became seriously deficient in vitamin D, and so the emergence of rickets. This was followed by a variety of other diseases resulting from vitamin D deficiency: tuberculosis, dental decay, coronary heart disease, and even multiple sclerosis and depression (the Glasgow syndrome).

And so it was with the Inuits. When their diet changed from fish for breakfast, fish for lunch, fish for dinner, they became deficient of vitamin D and they developed diseases characteristic of industrial cities, where there is indoor work for long hours, indoor activities, and atmospheric pollution.

It is the vitamin D component of fish and fish oils that is important.

I recently saw an elderly lady from Bangladesh living in northwest England. I would have expected her to have a very low blood level of vitamin D, as her exposure to the sun was minimal. However the blood level was 47ng/ml, not 4 as expected. She eats oily fish from Bangladesh every day, showing its value as a source of vitamin D with subsequent good health. I expect her blood levels of omega-3 fatty acids would also be high.

But it is unfashionable vitamin D that is important, not fashionable omega-3.

David Grimes
www.vitamindandcholesterol.com

Excellent point. The health effects of omega-3 and vitamin D are intimately intertwined when examining populations that consume fish.

In this study of Inuits, it is indeed impossible to dissect out how much psychological distress was due to reduced vitamin D, how much due to reduced omega-3s. My bet is that it's both. Thankfully, we also have data examining the use of pure omega-3 fatty acids in capsule (not intact fish) form, including studies like GISSI Prevenzione.

Nonetheless, Dr. Grimes reminds us that both vitamin D and omega-3 fatty acids from fish oil play crucial roles in mental health and other aspects of health, and that it's the combination that may account for the extravagant health effects previously ascribed only to omega-3s.

Why does fish oil reduce triglycerides?

2. November 2009 William Davis (9)

Beyond its ability to slash risk for cardiovascular events, omega-3 fatty acids from fish oil also reduce triglycerides.

There's no remaining question that omega-3s do this quite effectively. After all, the FDA approved prescription fish oil, Lovaza, to treat a condition called familial hypertriglyceridemia, an inherited condition in which very high triglycerides in the 100s or 1000s of milligrams typically develop.

The omega-3 fraction of fatty acids are unique for their triglyceride-reducing property. No other fraction of fatty acids, such as omega-6 or saturated, can match the triglyceride-reducing effect of omega-3s.

But why does fish oil reduce triglycerides?

First of all, what are triglycerides? As their name suggests, triglycerides consist of three ("tri-") fatty acids lined up along a glycerol (sugar) "backbone." Triglycerides are the form in which most fatty acids occur in the bloodstream, liver, and other organs. (Fatty acids, like omega-3, omega-6, mono- or polyunsaturated, or saturated, rarely occur as free fatty acids unbound to glycerol.) In various lipoproteins in the blood, like LDL, VLDL, and HDL, fatty acids occur as triglycerides.

Of all lipoproteins, chylomicrons (the large particle formed through intestinal absorption of fatty acids and transported to the liver via the lymph system) and VLDL (very low-density lipoprotein, very low-density because they are mostly fat and little protein) particles are richest in triglycerides. Thus, we would expect that omega-3s exert their triglyceride-reducing effect via reductions in either chylomicrons or VLDL.

Indeed, that seems to be the case. The emerging evidence suggests that omega-3 fatty acids from fish oil reduce triglycerides through:

--Reduced VLDL production by the liver (Harris 1989)
--Accelerating chylomicron and VLDL elimination from the blood
--Activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma)--Omega-3s ramp up the cellular equipment used to convert fatty acids to energy (oxidation) (Gani 2008)

Combine omega-3 fatty acids from fish oil with wheat elimination and you have an extremely potent means of reducing triglycerides. Read a previous Heart Scan Blog post here to read how a patient reduced triglycerides 93.5% from 3100 mg/dl to 210 mg/dl in just a few weeks using fish oil and wheat elimination.

The battle for natural hormones

Lipitor and memory

EKG's and heart disease

A new Track Your Plaque record

The Plavix Scam

Lipoprotein(a) and small LDL

Optimal medical therapy

Niacin, postprandial patterns

What's better than fish oil?

Valve disease and vitamin D

Fanatic Cook on the American Heart Association

Sleep for heart health

Is normal TSH too high?

Talking heads

Vitamin D Newsletter-Autism and Vitamin D