As if trying to pull meaning out of the medical literature weren’t difficult enough as it is, a new study demonstrates yet another obstacle to easy understanding: the adherer effect.

We’ve all seen the headlines.  Statins improve bone health.  Statins prevent cancer.  Statins make us smarter.  Low-fat diets improve longevity.  All these headlines and others like them are followed by articles describing studies seeming to show that subjects taking certain medications (usually statin drugs, it seems) or following a particular diet have improvements in health and/or longevity.  The promise of these articles is that if we all take the medication or follow the lifestyle choice, we, too, will reduce our risk of [fill in the blank] or live longer.  But will we?

Maybe so.  But not for the reason most people think.

The adherer effect demonstrates that people who adhere to medical or lifestyle regimens end up with better outcomes than those who don’t…even if the regimens are nothing but placebo.

I mentioned this phenomenon in an earlier post.

Almost thirty years ago a study was published in the New England Journal of Medicine looking at this very idea. [The adherer effect]  The study that inspired the article didn’t start out looking at this idea, but one of the investigators noted a key piece of the data and published on it.  The study was looking at clofibrate, a pre-statin cholesterol lowering drug,  and all cause mortality.  Subjects were randomized into two groups – those in one group got the drug, those in the other got the placebo.  After the subjects were on either the drug or the placebo for five years, researchers calculated the mortality from the number of deaths in each group.  Turned out that the five-year mortality of those on clofibrate was 20.0 percent whereas the five-year mortality of those on the placebo was 20.9 percent, or essentially the same.  Taking the drug was no different than taking the placebo, i.e., the drug was worthless. Had one of the researchers not looked a little closer, that would have been the end of the story.

When the data were looked at from the perspective of how many people actually took the drug as prescribed, the researcher discovered that those subjects who took at least 80 percent or more of their clofibrate had a five year mortality of only 15.0 percent, substantially less than the overall five-year mortality.  Those who took their clofibrate sporadically had a five-year mortality of 24.6 percent, significantly higher than those who took it as directed, a piece of data that would seem to confirm the efficacy of clofibrate.  Right?  Not necessarily.  Let’s look at compliance with the placebo.

Turns out that those subjects on the placebo who regularly took their placebo had a five-year mortality of 15.1 percent while those who took their placebo sporadically had a five-year mortality of 28.3 percent.  What this study really showed was that there is something intrinsic to people who religiously take their medicine that makes them live longer.  There was no difference between the drug and placebo in either those who took them regularly or those who took them sporadically, but there was a huge difference in mortality between those who took either drug or placebo on schedule and those who didn’t.

Gary Taubes discussed this same study and the adherer effect in  a long article he wrote for the New York Times Magazine a few years ago:

A still more subtle component of healthy-user bias has to be confronted. This is the compliance or adherer effect. Quite simply, people who comply with their doctors’ orders when given a prescription are different and healthier than people who don’t. This difference may be ultimately unquantifiable. The compliance effect is another plausible explanation for many of the beneficial associations that epidemiologists commonly report, which means this alone is a reason to wonder if much of what we hear about what constitutes a healthful diet and lifestyle is misconceived.

The lesson comes from an ambitious clinical trial called the Coronary Drug Project that set out in the 1970s to test whether any of five different drugs might prevent heart attacks. The subjects were some 8,500 middle-aged men with established heart problems. Two-thirds of them were randomly assigned to take one of the five drugs and the other third a placebo. Because one of the drugs, clofibrate, lowered cholesterol levels, the researchers had high hopes that it would ward off heart disease. But when the results were tabulated after five years, clofibrate showed no beneficial effect. The researchers then considered the possibility that clofibrate appeared to fail only because the subjects failed to faithfully take their prescriptions.

As it turned out, those men who said they took more than 80 percent of the pills prescribed fared substantially better than those who didn’t. Only 15 percent of these faithful “adherers” died, compared with almost 25 percent of what the project researchers called “poor adherers.” This might have been taken as reason to believe that clofibrate actually did cut heart-disease deaths almost by half, but then the researchers looked at those men who faithfully took their placebos. And those men, too, seemed to benefit from adhering closely to their prescription: only 15 percent of them died compared with 28 percent who were less conscientious. “So faithfully taking the placebo cuts the death rate by a factor of two,” says David Freedman, a professor of statistics at the University of California, Berkeley. “How can this be? Well, people who take their placebo regularly are just different than the others. The rest is a little speculative. Maybe they take better care of themselves in general. But this compliance effect is quite a big effect.”

In the same blog post of mine I linked to above, I wrote about another study showing the adherer effect, showing graphically how potent the phenomenon is.

Previously, the study of the adherer effect has been a secondary finding in studies of various drug regimens, but now comes a paper in which the adherer effect is the primary focus of the investigation.  Based on the data in this recent paper, the effect is robust and should be accounted for in the analysis of any data generated when subjects following a particular treatment are compared to those who don’t.

The authors lay out the problem:

The healthy-user effect [the adherer effect] is a hypothetical source of confounding bias that is thought to affect observational studies of drugs, diets, screening procedures, and other health-related behaviors. This bias presumes that patients who initiate and adhere to preventive therapies are more likely to engage in behaviors consistent with a healthy lifestyle than are patients who do not initiate or adhere to such treatments. Aspects of a healthy lifestyle could include diet, exercise, moderation of alcohol, and avoidance of risky behaviors. These characteristics, which are unmeasured in typical pharmacoepidemiological databases, may be associated with morbidity and mortality outcomes in observational studies. Thus, failure to adjust for them can lead to bias in studies of preventive therapies.

The healthy-user bias has been suggested as an explanation for the discrepancy between several experimental and observational studies, including studies of the effects of long-term use of estrogen therapy and vitamin E. It has also been discussed as a potential source of bias in observational studies of the effectiveness of influenza vaccines in the elderly  and the association between use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and reduced risk of hip fracture,  Alzheimer disease,  sepsis,  cancer,  and mortality.  This bias has also been observed in randomized controlled trials in which adherence to placebo was found to be associated with decreased mortality.  Although long suspected as a source of bias, a paucity of empirical data exists on the healthy-user effect.

Here’s how the study was set up.

It was really pretty simple.  The researchers looked at a group of patients who had been prescribed one of a variety of statin drugs and followed their compliance by looking at how many times these subjects picked up their medicines in the year following their prescription.  The typical statin prescription was for 60 days worth of the medication, and all subjects had available to them a full year’s worth of medicines.  The researchers grouped subjects into two groups: one group who took the trouble to go get over 120 day’s worth of the medication (the “more adherent”) and one group of subjects who were dispensed under 120 days of meds (the “less adherent”).

All subjects entered into the study were evaluated after the one year baseline study period during which their effort to follow their prescribed statin regimen sorted them into the categories of more adherent or less adherent.  The researchers were looking to see which subjects – the adherers or the non-adherers – would develop problems that had nothing to do with the statin drugs.

We evaluated a spectrum of events after the 1-year baseline period to assess the healthy-adherer bias. The outcomes were grouped into 4 broad categories: accident events, screening events, other events not expected to be associated with statin exposure, and other events for which a possible association with statin exposure could be expected. We included inpatient and outpatient events as well as primary and secondary diagnoses.

When the data on these 141,086 subjects was crunched, it turned out that the more adherent subjects had significantly fewer accidents, especially motor vehicle and workplace accidents.  The more adherent also had a lower likelihood of developing other disorders that were not likely to be attributed to the effect of the statin drugs.

In other words, whatever characteristic it was that made subjects hang in there with their statin prescriptions also made them less likely to indulge in risky behaviors and less likely to develop all kinds of medical problems.  Why?  Probably because these people were simply more health conscious, kept themselves in better shape, and didn’t act impulsively.

The real take-home message from this study is that the adherer effect significantly affects the outcome of drug and lifestyle intervention studies.  If you see a study that says those subjects using statin drugs developed 20 percent fewer problems (of whatever kind are being studied) than those who don’t use statins, you can be sure that the adherer effect is at work.  This adherer effect is why randomized, double-blind, placebo-controlled studies are needed to determine the efficacy of any drug, and even then the adherer effect should be controlled for.

There is a big note, enclosed in a box and titled Clinical Perspective, at the end of this study that exhorts doctors to consider this adherer effect when looking at data from observational studies.  Here is the note in full.

Clinicians need to read observational studies reporting surprising benefits of drug therapy with a healthy skepticism. Observational studies of preventive medications and health behaviors are susceptible to various sources of bias, including the so-called healthy-user and healthy-adherer biases. In this article, evidence of the healthy-adherer effect is demonstrated by showing that adherence to statins is associated with a reduction in the risk of accidents (eg, workplace or motor vehicle), outcomes that would not be expected to be affected by a statin. The approximate magnitude of the adherer effect was a 15% relative risk reduction. The most likely explanation for this association is that good adherence to statin therapy is a marker for other healthy behaviors, most of which cannot be accounted for in this type of study. In keeping with this explanation, the study also shows that adherence predicts a 7% to 17% increased incidence of medical screening procedures (eg, fecal occult blood testing, mammography). Risk of myocardial infarction, which has been demonstrated to be reduced by statin therapy in randomized placebo-controlled trials, was found in this study to be reduced by 28%. This observed relative reduction must be interpreted as reflecting a combination of the healthy-adherer effect and the drug effect. Clinicians can also learn from this study that patients who follow their advice are also likely to have other healthy behaviors and a lower risk of adverse events.

It is unfortunate, but I doubt that many doctors (or researchers, for that matter) will consider the adherer effect when they read these studies.  I would bet that we will continue to see studies reported as if the positive effects found were a function of the drug or lifestyle regimen studied and not the adherer effect.

To me the saddest part of this study was the statistic that of the 141,086 subjects in this study, 49 percent were women.  The randomized, double-blind, placebo-controlled studies of statins have never shown a benefit in terms of decreased all-cause mortality in women of any age.  Which means that over 70,000 women in this study took a drug that would do them no good, but which could well cause them significant and harmful side effects.

In this study, those who dropped out of their statin regimen because of intolerable side effects would be considered to be less adherent or non adherers.  My guess is that many of these ‘non adherers’ who dropped out because of side effects were really ‘adherers’ by nature.  Had these drop outs due to side effects been controlled for, I would bet that the difference between the less adherent and the more adherent would have been much larger than the data showed.

I figure it’s about time for another grab bag of a post updating everyone on what’s going on at Casa Eades and throwing up a few interesting articles and websites.

The Verdi Requiem

The Santa Barbara Choral Society’s Verdi Requiem was a triumph last weekend.  As you can see from the photo above, MD was pretty whipped when it was over.  Apparently, it’s pretty demanding on soloists, orchestra and chorus.  And, as you can see from the photo above, the listeners don’t have the same burden.  Other photos here.  A recent review of the concert here.

The concert was pretty well attended, although not as well attended as it would have been had the entire city not been consumed with worry about the fire from the week before.  Santa Barbara is just now returning to normalcy.  The receipts from the door covered a little over 40 percent of what it cost to put on the production.  When I heard that figure, I thought the whole thing was a financial disaster, but I learned that that figure is typical for non-profit arts productions.  Around 40 percent of the cost comes from the people who buy tickets – the other 60 percent comes from patrons who sponsor the event.  In other words, the ticket prices are subsidized by the nobless oblige of the wealthy, a large number of whom consider it their obligation to support the arts.  So, next time you go to a great performance that costs you $25 to see, thank a rich person that you didn’t have to pay $60.

Twitter adventures

As anyone who has followed me on Twitter knows, I spend a lot of time reading and posting to Twitter since I first posted about it.  It’s a great way to do mini posts because users of Twitter are limited to 140 characters, so it’s tough to get too verbose.

I was pretty clueless about Twitter until I started using it, so I assume others are clueless as well.  If you are not in the know about this social networking tool and would like to keep up with these mini posts, there are a couple of ways you can do it.  You can sign up for Twitter and follow me (and anyone else you would like to follow).  It takes maybe one minute to sign up for Twitter.  All you need is a working email address and a username and you’re in.  Once you are a Twitteree (or whatever they’re called), and sign up to follow me, you can read these mini posts as I put them up.  If you want to sign up, click here and get started.  If you do start, you will probably find that a bunch of your own friends are using Twitter, so you can keep up with them as well.

The other way you can access these mini posts is by clicking on the little blue bird logo that says FOLLOW ME ON TWITTER.  If you click there, you will go to a page that gives you all the latest mini posts, but you’ll have to keep going back to get the updates as they come in.  Here is a link to the page you will find.

I occasionally Tweet (a Twitter mini post is called a Tweet, a loathsome word if there ever was one, at least when applied to activities of grown humans) on personal stuff, but mainly the Tweets are mini posts on medical articles or other news articles that I think are of interest along with anything else I find that strikes my fancy.

For those of you who do follow me on Twitter, I apologize for any Twitter faux paux I may have committed.  One of the things that most appealed to me about Twitter was the notion that I could put up these mini posts without anyone responding.  But, alas, I was wrong.  I discovered a few days ago that people can respond and several hundred have.  I was taking time from feverishly mini posting by looking around my Twitter home page when I found a highlighted link that said: @DrEades.  When I clicked there, I was appalled to find several hundred responses to Tweets I had made.  I learned that when people respond to Tweets, it ends up in that section.  So, I wasn’t off the hook.  But I couldn’t possibly respond to several hundred people – even at 140 characters a response.  So, if you replied to something I wrote and I didn’t respond, you now know what happened.

I did have a couple of interesting experiences in responding however.  When I discovered the @DrEades section and found the zillion responses to my Tweets waiting there, the most recent one was from a lady who took me to task for one (or several) of my political Tweets.  She wrote that she had always liked my nutritional writing but that my political postings had alienated her.  I decided to reply to her just to see how the whole reply thing worked.  I sent her one of my favorite Thomas Jefferson quotes:

I never considered a difference of opinion in politics, in religion, in philosophy, as cause for withdrawing from a friend.

Then I watched her site and found that she had deleted the Tweet to me, which is how I learned that one could delete these things once they are up.  They can’t be changed, so if you make a grammatical error (which, sadly, I have done a few times) it can’t be fixed, only deleted.  Then she deleted me from her list of people she follows.  I guess the Thomas Jefferson quote alienated her even more.

People are really strange.  I posted a Tweet about an email that I had received a dozen times about how George Bush has a state of the art, energy-efficient ranch house in Crawford, TX while Al Gore has a giant, energy-gobbling house in Nashville.  I always ignored the email because I thought it probably was an urban legend kind of thing.  Then someone sent me a link to the Snopes report on it, which said that the email was true.  I posted the Snopes report on Twitter.  Then I started to wonder what makes Snopes the last word authority on everything, so I started looking into that.  I discovered that Snopes is a husband – wife team, who live in a double-wide house trailer on the outskirts of Los Angeles.  They do all the checking themselves.  I was stunned.  I always figured that Snopes was some kind of outfit with a staff of hundreds that checked out all these things.  The notion that the ultimate authority on everything was just a mom and pop operation who make their living by ads on their snopes.com website.  Now that I know the situation, I’ll be more careful when I accept snopes as the last word on everything.

I put up a Tweet that said basically Who would’ve thought Snopes was a mom and pop operation?  Some guy signed up to follow me on Twitter, and immediately sent a nastygram to @DrEades that said If Snopes is a mom and pop outfit, what does that make the Protein Power blog? A ‘Pop’ outfit?  I replied that the Protein Power blog is a ‘Pop’ operation, but isn’t considered by anyone to be the last word on everything.  He then deleted me from his list of people he followed. As I say, a lot of bizarre people in the weeds out there.

The whole experience has been very strange indeed.  But I’m still working my way through it, probably alienating people right and left.  So join up, follow me, and watch the fun.

Upcoming travel plans

MD and I are leaving late Sunday night for Hong Kong, then to Guangzhou, back to Hong Kong, then to London.  Sadly, the entire trip will be a working trip.  We’re hard at it in our efforts to change the world, and this trip is all about that.  By the time we get back, I should be able to write about what we’ve been working on.

I will take a lot of photos and continue to blog during the trip.  And Tweet.

Comments on the blog

I continue to be mired in comment woes.  I just checked, and I have 78 comments in moderation, some of which have been there for weeks.  It has kind of become a comments graveyard.

I’ve whined about the comment situation for that last two years. I’ve said that I wasn’t going to continue to answer questions and was just going to post the comments as they came in.  My resolve would last for about two days, then I was right back answering all the questions.  Now, I’ve gone into a funk over the whole thing, and have devolved into just ignoring the comments that require answering and letting them stack up, which I hate doing.  But, I’ve been so busy lately that there isn’t much else I can do.

I was reading a book titled Economic Sophisms by one of my heroes, Frederic Bastiat, when I came across the following paragraph that, in a way, applies to the comment situation.

We must admit that our opponents in this argument have a marked advantage over us.  They need only a few words to set forth a half-truth; whereas, in order to show that it is a half-truth, we have to resort to long and arid dissertations.

It’s easy to pen a comment that says, Hi Doc, what are your thoughts on this article? and attach a link.  I have to read the article, pull the actual study, read it, think about it, then write an answer that is considerably longer than the original comment.  What takes a commenter 20 seconds to write ends up costing me an hour or two to come up with an intelligent answer or even an ‘arid dissertation.’

I’m also getting a lot of comments asking for my ideas and recommendations on personal health issues.  People send me lab results and want to know what I think.  Without treating a given individual as a patient, medico-legal restrictions prevent me from answering these kinds of questions.

I never read the comments on blogs that I read, so I must assume that many people don’t read the comments on this blog.  But I end up spending way more time dealing with the comments than I do writing posts.  If I didn’t have to deal with the comments, I would write more posts.

I noticed that Mark Sisson, whom MD and I had lunch with yesterday, has started making posts out of some of his comments in a Dear Readers section of his blog.  He takes several comments that he thinks may be of interest to all his readers, posts them, and throws them out for the combined wisdom of all his readers to deal with. I may start doing this myself and weighing in along with the readers.  If anyone out there has any advice for me on this issue, I’m all ears.

Soda tax in New York

I just read this article this morning.  Was going to make a mini post out of it, but thought it would be better here.

A New York state senator (I’ll leave it to you guess from which party) says that by adding a measly one cent tax to each can of non-diet soda sold, the state of New York can add $100 million per year to its coffers.  If this is true, it means that citizens of and visitors to the state consume 10 billion cans of non-diet soda annually!  The population of New York state is a little over 19 million.  Dividing 10 billion by 19 million calculates out to about 525 cans of non-diet soda per man, woman and child in the state.  That’s almost 90 six-packs per person per year.  Wow!  There have got to be some low-carbers who live there who drink zero six-packs per year, which means that some other poor slob is drinking 180 six-packs per year.  That’s a lot of high-fructose corn syrup.

To my way of thinking, this is an onerous tax.  It moves $100 million from the pockets of the citizenry and puts it in the coffers of the bureaucrats to spend.  And, despite the fact that it sucks off 100 million bucks, the tax isn’t high enough to discourage consumption, so it really has no societal advantage except for transferring funds from the citizens to the government.

Where does your beef come from?

I don’t mean what part of the country.  I mean what part of the cow.  Here is a great site created by the University of Nebraska and the University of Florida showing way more than I (and probably you) need or want to know about beef anatomy.  But if you really do wonder where a flank steak or some other piece of beef comes from on the cow, click here to find out.  A lot of work went into this site.

Gradient gel electrophoresis

For those who hate to pay big bucks to have a lab tell you how much small, dense LDL you have, here’s how you can do it yourself.  That’s right.  With a drinking straw and a few other simple ingredients, you can make your own electrophoresis equipment and test your blood anytime you want for minimal expense.  Warning.  This is a real geek site.  I doubt that many will want to put together their own equipment, but at least it shows what’s involved in making a primitive version and how complex the testing process is.  May make you not feel so bad dropping the money to get the test done professionally.

Feel better immediately

And, finally, here is your feel-good YouTube of the day.  Watch this huge prank (if that’s what you would call it) played on the people in the train station at Antwerp one morning.  Really delightful.  Watch the faces of those watching.

Click here to view the embedded video.

Remember, don’t forget to help me out on this comment issue.  All suggestions will be appreciated.

I don’t know about you guys, but I like these link-o-rama posts because they let me get rid of a bunch of tabs on Firefox and disseminate info that probably isn’t worth an entire post.

First, let me start out by linking to one of my wife’s recent posts.  We’ve had a spate of people writing us through the website asking about cookbooks, of all things.  She did a post a couple of months ago about her favorite cookbooks.  In case you missed it, here it is.

Second, I’m going to start using these link-o-ramas to link to some of my older posts that I think would be of interest to a lot of people now.  One that I thought was pretty good on how to dissect a scientific article didn’t get many readers since I wrote it back when maybe three people read this blog.  The notion that it didn’t get many readers is evidenced by the fact that there are zero comments on it.  So, without further ado, here is Baboon Business.

After all the recent posts about the savagery of the nature, I thought I would throw this item into the mix just to show that nature can be tamed, at least in the short run.  There is a guy who is a fixture in downtown Santa Barbara who has a dog, a cat and a rat as pets.  He is always down on State Street, the main street running through town, with the cat riding on the back of the dog, and the rat riding on the back of the cat.  Here is the YouTube, so you can see for yourselves.

Click here to view the embedded video.

I came across an interesting article titled Is Food the New Sex? in a little journal I get called Policy Review.   The writer of the article posits that our appetites for food and sex have more or less switched positions in our hierarchies of taboos since the 1950s.  She uses a woman who was a housewife in her 30s in the 1950s and her hypothetical granddaughter who is in her 30s today.  The housewife of the 1950s had no taboos on food and all kinds of taboos about sex whereas her granddaughter reads every label and is scared to death of her food, yet expects to live together for a trial run before marriage to her boyfriend and has friends with all sorts of alternative lifestyles.  A fun, but long, article to read.

What follows are a couple of quotes separated by years, but nevertheless related.  So I figured I would post them juxtaposed so that the connection would be obvious.  The first is from Ludwig von Mises (1881-1973), an economist of the Austrian school.

The luxury of today is the necessity of tomorrow. Every advance first comes into being as the luxury of a few rich people, only to become, after a time, an indispensable necessity taken for granted by everyone. Luxury consumption provides industry with the stimulus to discover and introduce new, things. It is one of the dynamic factors in our economy. To it we owe the progressive innovations by which the standard of living of all strata of the population has been gradually raised.

The next quote is from the transcript of a CNBC interview with Warren Buffett last year.  I don’t agree with Mr. Buffett on everything, but I do on this.

…we’ve had a number of recessions in this country; in fact, we had a Great Depression, we had–we’ve got world wars. And throughout, the genius of the American economy, our emphasis on a meritocracy and a market system and a rule of law has enabled generation after generation to live better than their parents did. And, I mean, most of the people in this room, practically all of them last night, lived better than John D. Rockefeller lived. I mean, all kinds of things have happened. And in the 20th century alone, the standard of living of the average American went up seven for one. There’s never been a period like it in history. And that’s not an accident. It’s because we unleash human potential and will continue to do that in the future.

Here is a link to a site containing a video of Gary Taubes, Dr. Jay Wortman, Dr. Alan Einstein and me taken last year at a conference in Phoenix.  We’re all expounding on the problems of the low-fat diet.  It’s the first video in the link.  I haven’t watched the other two, so I can’t tell you what’s in those.

For those of you interested in intermittent fasting, here is an article on the subject from the Los Angeles Times.  I’m working on another post on IF that I hope to have up within the next couple of weeks.

Researchers aren’t sure why the body apparently benefits from a state of mini-starvation. One theory is that the process produces just enough stress in cells to be good. “What our evidence suggests is that nerve cells in animals that are on dietary energy restriction are under mild stress,” Mattson says. “It’s a mild stress that stimulates the production of proteins that protect the neurons against more severe stress.”

What they do know is that occasionally going without food or reducing calories daily makes the body more sensitive to insulin, which helps maintain normal blood sugar levels. And animal studies suggest calorie restriction may reduce the risk of cancer by slowing the growth of abnormal cells.

First I would like the heartily thank everyone who took the time to send me a comment on how to make this blog better both functionally and in content.  I read every single suggestion, and appreciated every one.  I’ll try to incorporate as many of the functional changes as I can within the design framework I have and within the limits of my pocketbook.  To demonstrate my profound gratitude for all the blog topic selections, I’m going to put up a post that absolutely no one asked for. But only because I’ve had it rattling around in my brain for the past week.

One view of the value of epidemiology

A day almost never passes without someone sending a comment my way about some recent study, plucked by the media from the hundreds published that same day, showing that low-carb diets cause brain fog or decreased longevity or cancer of some type or any number of conditions any of us would rather not have.  These comments always  end with the plaintive request, is there any truth to this?

My answer follows: This data comes from an observational study, and, as such, can’t possibly indicate causality.

Since I get these comments so often and answer them the same equally often, I figured it was about time to write a post on what an observational study really is so that I can link to it when I give my standard reply.

I can then add this post to the ones on the glycemic index and relative risk, both of which serve the same purpose.  I can simply link instead of explaining what these terms mean each time I have to use them.

Observational studies – also called prospective or cohort studies and sometimes even epidemiological studies – are the kind most often reported in the media simply because there are so many of them.  These are the studies in which researchers look for disease disparities between large populations of people with different diets, lifestyles, medications, incomes, etc.  If disease disparities are found to exist between groups, then researchers try to make the case that the difference in diet, lifestyle, medication, etc. is the driving force behind the disparity.

We’ve all seen these studies by the score.  We read that a large study population of people is separated into two groups based on blood levels of vitamin C.  One group of subjects has high blood levels, the other group has lower blood levels.  And since every one seems to believe that vitamin C protects against the common cold, the researchers decide to monitor these two groups for a year and find that the group with the highest blood levels of vitamin C has the fewest colds.   These findings are rushed into publication, and soon we read everywhere that vitamin C prevents the common cold.  It all seems so reasonable and so scientific, but the truth is that these studies don’t mean squat.  And the researchers who do them know it, or at least should know it.  The fact that they do know is evident in the weasel words they use in describing their findings.  You’ll read that these data ‘suggest’ or that they ‘imply’ or that this ‘may cause’ that.  The non-technically trained public, however, read these to say that vitamin C prevents the common cold.  And usually the media helps to sway opinion by slanting the story in the same direction.

But, you may ask, why aren’t these studies sound?  If the one group with the greater blood levels of vitamin C had significantly fewer colds, why is it such a stretch to say that vitamin C prevents colds?

I can explain by way of a game I used to play with myself as a child.  I’ve never been one to sleep much even when I was a kid.  I always stayed up late and I always woke up early.  My brain never seemed to slow down.  I was always ruminating on something.  My way of trying to get to sleep was to try to think of everything that could be thought of.  My mind would race, and I would think of my brothers sleeping in the room with me, their beds, my bed, the closet, the tree outside, my dad’s car, the rug on the floor, the moon, and on and on and on.   As I thought faster and faster, continuing to compile things that could be thought of, I would finally hit a quitting point.  Then I would try to figure if there was anything I hadn’t thought of.  Of course, immediately I would think of something. I hadn’t thought of the pigs on my grandfather’s farm.  Or I hadn’t thought of the fire hydrant out front.  Or my father’s shoes.  Or whatever.  Then I would start the game again, this time, of course, starting with the pigs on my grandfather’s farm and going from there.  I would always fall asleep before I had ever thought of everything there was to think of.

Researchers doing observational studies have much the same problem.  They try to think of all the differences between two large populations of subjects so that they can statistically negate them so that only the observation in question – the vitamin C level in the example above – is different between the groups.  Problem is they can never possibly think of all the differences between the groups.  As a consequence, they never have a perfect study with exactly the same number, sex, age, lifestyle, etc. on both sides with the only difference being the study parameter. And so they don’t really ever prove anything.  In fact, we would all probably be a lot better off if all the researchers doing observational studies had followed my lead and fallen asleep mid study.

But I’m being too harsh.  These studies do have some value.  Their value is in generating hypotheses.

The observational study demonstrates a correlation.  In our example above, the correlation is that higher vitamin C levels correlate (in this particular study) with lower rates of colds.  So, from this data, we could hypothesize that vitamin C prevents the common cold.  But at this stage that would be just an hypothesis – not a fact.

Once we have the hypothesis, we can then do a randomize, placebo-controlled trial.   We can recruit subjects, randomize them into two groups that are as equal as possible, especially as vitamin C levels are concerned.  Then we give one group of subjects vitamin C and the other a placebo and watch them for a year.  At the end of the year (or whatever the study period is), we break the codes, see who is on vitamin C and who is on placebo.  We already know how many got colds, so now we compare that to vitamin C intake.  We may find that those who took the vitamin C got significantly fewer colds, so we can say that our study demonstrates that vitamin C prevents the common cold.  If this same study is repeated a number of times with the same outcome, then it can be said to be proven that vitamin C prevents colds. (This study is, of course, hypothetical.)

But these studies are randomized trials, not observational studies.  Observational studies only show correlation, not causation, a fact that everyone doing research and reading about research should have tattooed on their foreheads.

CORRELATION IS NOT CAUSATION

More often than not observational studies are chock full of all kinds of technical-looking graphs, charts and tables.  Many even have complicated equations.  And long statistical analyses of the data derived.  They are like zombies, however.  They give the appearance of scientific life, but they are really scientifically dead.  Irrespective of how many scientific baubles are strewn through them, they are nothing but observational studies, worthwhile only as generators of hypotheses.  They demonstrate only correlation, not causation.

If you want to bear with me, I’ll show you a bizarre observational study that was actually performed that demonstrates everything you need to know about observational studies.

The study was published in 2003 in the prestigious American Journal of Epidemiology.  The title of the study is Shaving, Coronary Heart Disease, and Stroke. (Click here for free full text) This study purports to show that the frequency of shaving correlates with risk for developing heart disease, with those men shaving less having a greater risk.

Here’s the finding that initiated this study.

A case-control study comparing the frequency of shaving in 21 men under 43 years of age who had suffered a myocardial infarction and 21 controls found that nine of the cases but none of the controls shaved only every 2 or 3 days.

Someone noticed that about half of the men in a small group of subjects who had a heart attack shaved once every two or three days.  Another group of men of similar age who hadn’t had a heart attack were designated as controls.  Upon questioning it was discovered that all of the men in the control group shaved every day.  Thus the first hypothesis was born:  Infrequent shaving correlates with heart attack.

The researchers had access to a large population of subjects from another ongoing study called the Caerphilly Study.  Researchers recruited 2,513 men aged 45-59 from this study and gave them comprehensive medical workups including extensive laboratory testing.

Men were asked about their frequency of shaving by a medical interviewer during phase I. Responses were classified into categories ranging from twice daily to once daily, every other day, or less frequently. The 34 men with beards were not classified. These categories were dichotomized into once or twice per day and less frequently.

The men in the study were followed for the next 20 years with follow-up exams periodically to monitor for history of chest pain, heart attack and/or stroke.

Of the 521 men who shaved less frequently than daily, 45.1 percent died during the follow-up period, as compared with 31.3 percent of men who shaved at least daily.

When the data were further refined it was determined that

The age-adjusted hazard ratios demonstrate increased risks of all-cause, cardiovascular disease, and non-cardiovascular-disease mortality and all stroke events among men who shaved less frequently.

So there you have it.  Proof that shaving daily prevents heart disease. Or is it?

The researchers doing this study aren’t so stupid that they really think that the act of shaving itself has anything to do with a man’s risk for developing heart disease.  In fact, they went to great lengths to show that shaving was merely a marker for other things going on that may well have something to do with risk for developing heart disease or increased all-cause mortality.

The one fifth (n = 521, 21.4%) of men who shaved less frequently than daily were shorter, were less likely to be married, had a lower frequency of orgasm, and were more likely to smoke, to have angina, and to work in manual occupations than other men.

And these are just the differences the researchers found.  Had they looked harder, I’m sure they would have found more, just like I did when I played my ‘think of everything that can be thought about’  game with myself as a kid.

But if these researchers had really believed that the data showed that the lack of frequent shaving itself may have been the driving force behind the development of heart disease, they may have designed a randomized clinical trial to show causality.  They could have recruited men without heart disease, randomized them into two groups, instructed the men in one group to shave daily and the men in the other to shave every third day.  Then after 20 years the researchers could tell whether or not shaving protects against heart disease.

But the idea that shaving itself has anything to do with heart disease is so ludicrous that no one would ever do such a study.  We can all see that.  It’s a ridiculous idea.  It should be obvious that the shaving or lack thereof has nothing to do with heart disease or early death; the lack of shaving is merely a marker for all the other conditions that are risk factors for heart disease, i.e., small stature, unmarried, smoking, lower socioeconomic class, etc.  It’s all so easy to see.

But let’s just suppose that we take this same study and substitute the term ‘elevated cholesterol’ for ‘infrequent shaving.’  Now what do we see?  Let’s change one of the quotes from above to reflect this change.  What then?

Of the 521 men who had elevated cholesterol, 45.1 percent died during the follow-up period, as compared with 31.3 percent of men who had low or normal cholesterol.

We nod our heads sagely.  Suddenly we have a study that seems to make sense.  But – and this is important – it doesn’t make any more sense than the shaving study.  Both are observational studies.  We are programmed to think cholesterol is bad and causes heart disease, so this second study appears reasonable to us.  It triggers our confirmation bias.  We don’t believe for a second that shaving has anything to do with heart disease, so we can easily dismiss those findings.  But we are more than ready to believe that the elevated cholesterol caused those men who had it to have heart attacks. But the reality is that both studies are exactly the same – and neither proves anything.

If you’re interested in a longer, more in-depth article on observational studies, take a look at Gary Taubes long piece in the New York Times a few years ago.  I’ve tried to take a little different slant than he did so that my post and his article would cover all the bases.

Cartoon above from: Smith, G. D. et al. Int. J. Epidemiol. 2001 30:1-11

`I quite agree with you,’ said the Duchess; `and the moral of that is–Be what you would seem to be–or if you’d like it put more simply–Never imagine yourself not to be otherwise than what it might appear to others that what you were or might have been was not otherwise than what you had been would have appeared to them to be otherwise.’

`I think I should understand that better,’ Alice said very politely, `if I had it written down: but I can’t quite follow it as you say it.’

Lewis Carroll

If you tell a lie big enough and keep repeating it, people will eventually come to believe it.

Dr. Joseph Goebbels, Nazi minister of propaganda

I’m starting this post with two apropos quotes.  The first, from Alice in Wonderland, because the post will be a little difficult to understand; the second because I just read for the umpteenth time the Big Lie about low-carb diets and wanted to blog about it but couldn’t until I wrote this post first.

Intention-to-treat analysis (ITT) has become the de rigueur way of looking at experimental results that more often than not gives erroneous results.  These erroneous results are then reported as gospel, when in reality they are simply erroneous.  When unbiased, intelligent people (the readers of this blog, for example) consider ITT, they cannot understand how it can be used by scientist trying to make sense out of their data, but, unfortunately, it is in almost every experiment.  Here is how it works.

Let’s say were going to do an experiment comparing two different diets.  We round up 100 subjects and randomize them into two groups of 50.  We put one group, Group A, on one diet, Diet A, and we put the other, Group B, on a different diet, Diet B.  We keep both groups on their respective diets for 8 weeks to see what happens.

At the end of the 8 weeks we find that 30 members of Group A dropped out, but those who hung in there lost an average of 3 pounds per week for a total of 24 pounds each over the course of the study.  We look at Group B and find that no one dropped out of the study and that all the subjects lost an average of 1.2 pounds per week.

What does this data tell us?  It’s pretty simple.  It tells us that Diet A is much more effective, but is more difficult to follow.  It tells us that Diet B is less effective but easier to follow.  Right?  All intelligent people could agree on that.  So that’s how this study would be presented if it were published in a journal, right?  Uh, no.

No?

No.  If published, the conclusion would be that both diets are exactly the same.

Say what?!?!?

Yep.  That’s what the authors would conclude.  Why?  Because they would use an intention-to-treat analysis.  In fact, the peer-review process would probably demand it.

An intention-to-treat analysis demands that all subjects remain in the data pool, even if some have dropped out.  The intention was to treat all the subjects, so the analysis should contain all the subjects, even if some left the study after the first day.  In an ITT, researchers pretend that subjects who chose to abandon the study really didn’t and include them in their final data.  Sounds like something from Through the Looking Glass, doesn’t it?

Let’s look at how this would work in our dietary study above.  The 20 subjects in Group A who followed Diet A lost 24 pounds each.  Multiply this 24 pounds times the 20 subjects who stayed in the study and you find that the group lost 480 pounds over the course of the 8 weeks.  Now divide this 480 pounds by the 50 subjects who started the study, and you get a weight loss of 9.6 pounds for the 8 weeks.  Dividing by 8 gives us an average weight loss of 1.2 pounds per week for all 50 subjects in Group A.  Which is exactly the same as the weight loss in the subjects in Group B.  So, according to the dictates of ITT, the study would show that both diets were equally effective. But, as we’ve seen, they’re not.

If a doctor were recommending a diet to his/her patients based on the actual findings of the study, he/she could reasonably say:  Diet A is very effective but tough to follow, so if you think you can do it, Diet A is definitely the fastest way to lose weight.  If you want something that will help you lose a little weight and is easy to stick to, then try Diet B.

If the same doctor recommends a diet to his/her patients based on the ITT results, he/she would say: Follow whichever diet you want – they’re both the same.

Why, you may ask, could seemingly intelligent people do something so stupid as use ITT to evaluate data? There is a reason, although it has its own problems.

We all know from experience and from talking to a lot of people who have lost weight that a lot of different diets work.  People lose weight on the Ornish diet and they lose weight on the infinitely preferable Protein Power diet.  And many other diets as well.  So, we can reasonably assume that almost any diet will help some people lose weight.  But we want to compare two diets to see which one is really the best.  So, let’s do another experiment.

Let’s take another 100 people and randomize them into two groups of 50, Group C and Group D.  Those subjects in Group C go on Diet C and all of them do well.  They lose an average of 2 pounds per week and all of them stay on the diet. The subjects in Group D go on Diet D, and most don’t do very well. As we all know from experience, it’s tough to stay motivated to stay on a diet if you’re not losing weight.  So, 30 of the subjects in Group D drop out because they’re not losing.  We know that any diet will work for some people, and Diet D is no different.  The 20 who stay in the study are those who are losing on Diet D.  And those 20 Group D subjects lose an average of 2 pounds per week.

In analyzing our data, if we remove from the pool of subjects all those who dropped out of the study, we are left with all 50 people in Group C, who lost an average of 2 pounds per week and only 20 people in Group D, who lost an average of 2 pounds per week.  We would then find that both diets are exactly the same.  Subjects in both groups lost 2 pounds per week.  Therefore both diets are equally effective.

But is that true?  Clearly not.  And that is the problem that ITT was designed to deal with.  But, as we’ve seen above, it brings its own errors.

So, how do we deal with the issue honestly and effectively?  Easy. By explaining the data in two ways.  Most people – researchers included – want to boil an issue down to a single answer, when two answers are required. ITT allows one answer – often incorrect – to two different questions.  ITT is like the old TV show in which the clown Bozo always asked the little kids he interviewed something like this:

So, Bobby, tell me: Do you walk to school or carry your lunch?

Were Bozo adamant on an ITT-type analysis of the question, he could get only one answer.

Going back to our Group A/Group B diet study we can look at the data in two ways:

1. Diet A is extremely effective for those who stick with it. (Called the adherence effect.)

2. Only 40 percent of those attempting Diet A achieve the desired effect. (Called the assignment effect.)

Both of these statements are true.  Both contain valuable information.  But they answer two different questions.  The first answers the question: what happens to people who stick to the diet?  The second answers the question: What happens to people who are placed on the diet?

As Dr. Gerard Dallal writes about ITT

The fraud occurs when the answer to the question of assignment is given as though it were the answer to the question of adherence!

Instead of the conclusion that both Diet A and Diet B show the same results (when, clearly, they don’t), which would be the way it would be presented in a scientific paper demanding ITT, why not present it this way?:

The adherence effect: Subjects following Diet A for 8 weeks lost an average of 3 pounds per week whereas those following Diet B lost 1.2 pounds per week.

The assignment effect: 40 percent of those attempting Diet A remained in the study whereas 100 percent of those following Diet B remained in the study.

Conclusion: Diet A is significantly more effective (3 pounds per week vs 1.2 pounds per week) for those able to remain on the diet.  Diet B is less effective but significantly less difficult to follow than Diet A. (100 percent of subjects on Diet B remained on the diet throughout the study whereas 60 percent of those on Diet A dropped out).

It just ain’t that hard to present it that way.  It provides much more information than the ITT, which attempts to answer two questions with one answer.

Now, let’s look at the big low-carb lie that launched me into this post.  I was reading a book that I intended to review for this blog and came across the following statement:

There is evidence from a variety of sources that [low-carb diets] work for short-term weight loss.  One year after starting a diet, however, there appears to be no significant difference in success rate than that seen on any other common diet plan.

Have you heard that one before?  It’s a specific variant of the old: Studies show that while effective in the short term low-carb diets show no difference in weight loss after one year than do low-fat diets. It’s the Big Lie.

It’s the last refuge argument of low-fat advocates who are getting hammered with all the data showing low-carb diets to be more effective.  Yeah, well, they say, Protein Power may work in the short term, but over a year studies show it’s no better than low-fat.  It’s like a cross thrust in a vampire’s face.

But is it true?  It is if you believe in intention-to-treat analysis.  But what if you believe in a more accurate way of presenting the data?

Let’s briefly look at a few studies published that confirm the idea that there is no difference between low-carb diets and low-fat diets after one year.

The first was published in the Annals of Internal Medicine in 2004.  The conclusion of the authors was that after one year subjects

had more favorable triglyceride and high-density lipoprotein cholesterol levels on the low-carbohydrate diet than on the conventional diet. However, weight loss and the other metabolic parameters were similar in the 2 diet groups.

In the body of the paper, however, one can read the following:

The final 1-year weight change (mean ± SD) was -5.1 ± 8.7 kg in the low-carbohydrate group and -3.1 ± 8.4 kg in the conventional diet group (Figure). The difference in weight loss between the 2 diet groups was not significant (-2.0 kg [CI, -4.9 kg to 1.0 kg]; P = 0.195 before and P > 0.2 after adjustment for baseline variables). The difference in weight loss between the 2 diet groups between 6 months and 1 year was not statistically significant (P = 0.063).

But that’s all ITT blather.  Let’s read the next couple of sentences:

Persons on the low-carbohydrate diet who dropped out lost less weight than those who completed the study (change, -0.2 ± 7.6 kg vs. -7.3 ± 8.3 kg, respectively; mean difference, -7.1 kg [CI, -11.6 kg to -2.8 kg]; P = 0.003). In contrast, weight loss was not significantly different for those on the conventional diet, whether they dropped out or completed the study (change, -2.2 ± 9.5 kg vs. -3.7 ± 7.7, respectively; mean difference, -1.5 kg [CI, -5.7 kg to 2.7 kg]; P > 0.2).

Let’s translate.  Those who dropped out of the low-carb diet but were counted as if they hadn’t lost 0.2 kg (about 0.4 pounds) whereas those who completed the study lost 7.3 kg (about 16 pounds).  Do you think the dropouts skewed the numbers?  I guess so.  And look at the next astounding sentence.  “In contrast, weight loss was not significantly different for those on the conventional diet, whether they dropped out or completed the study…”  So, there was no difference in the results of those following the low-fat diet whether they dropped out or stayed in.  Had the subjects who dropped from the low-fat arm not been included, the results for that diet would have been the same.  Including the subjects who dropped from the low-carb arm, however, dramatically lowered the overall weight loss of the subjects as a group, making them equal to those in the low-fat arm.

It could be accurately stated that those who remained on the low-carb diet for one year lost significantly more weight than those who remained on the low-fat diet. which, of course, refutes the Big Lie that low-carb and low-fat diets provide equal weight loss at one year.

The two other studies used to perpetrate the Big Lie that low-carb diets show no difference in weight loss after one year are the ones by Foster et al and Samaha et al in the May 2003 New England Journal of Medicine.

When analyzed by ITT, both of these studies show no significant difference between low-carb and low-fat diets after a year.  But when looked at from the perspective of those subjects remaining in the study, we see a big difference between the low-carb and the low-fat arms.

In the Foster et al study using a modified version of the Atkins diet, we find a statistically insignificant 1.9 kg difference in weight loss between the two groups by ITT.  But when we eliminate the drop outs and look instead at the data from those subjects who remained on the diets for the entire one year, we find a statistically significant 2.8 kg (over 6 pounds) greater weight loss in those following the low-carb diet.

In the Samaha et al study using the diet from the Protein Power LifePlan, those following the low-carb diet lost a statistically insignificant 2 kg more weight than those following the low-fat diet by ITT.  Eliminating the dropouts, however, gives us a statistically significant 3.6 kg (almost 8 pounds) greater weight loss on the low-carb verses the high-carb diet after one year.**

Intention-to-treat analysis gives us the Big Lie:  Low-carb diets are no more effective than low-fat diets after one year. Dr. Goebbels would have been proud.

The truth, however, is a little different and can be stated thus:

Those who follow low-carb diets for a year lose significantly greater weight than those who follow low-fat diets for a year.

After reading this post you should know more about intention-to-treat analysis than 99.9 percent of the physicians and dietitians practicing in the world today.  Don’t let this knowledge go to waste.  Next time you hear the Big Lie, point out the truth.

** Thanks to Richard Feinman, Ph.D. for the tabulation of these data and for our many conversations on this subject.

I’m putting this post up today and leaving it throughout the weekend because I believe it is so important that everyone watch the videos at the bottom.

These long must-watch videos are in two parts: the first part is by a defense attorney discussing the unbelievable complexity of the law, especially federal law, and the difficulty of simply going through life without knowingly or unknowingly breaking some kind of law.  And he discusses the dangers of talking to the police without a lawyer present.  The second part is a talk by a police detective confirming everything the attorney says and, fascinatingly, discussing his own tricks, learned in over 25 years of police work, to get people to talk to him and even to confess to crimes.

I’ll probably alienate any readers who are involved in law enforcement, which isn’t my intention.  I’m sure that if any law enforcement officials were suddenly under investigation, they wouldn’t say a word without their lawyer present.  The rest of us need these same protections.

I’m not presenting these videos for any criminals who may be reading, but for the average citizen who happens to get crosswise with the police.  Every single police officer I know (and I know a half dozen or so) are hard working, dedicated, responsible, and even kind-hearted folks, but they can make mistakes.  I make mistakes, so I figure they can too.  The officer speaking on the last part of this video says that he doesn’t really interrogate people that he doesn’t think are already guilty.  So, you are basically assumed guilty if you’re under investigation for whatever.  And if the officer is mistaken, you can be in real trouble.  You can’t talk your way out of it; you can only make it worse.  When you watch these videos, you’ll see what I mean.

Martha Stewart spent six months in a federal prison not because she did anything wrong during her alleged insider trading, but because she lied to a federal official.  And it’s easy to lie unintentionally.  Let me give you an example.

When MD and I lived in Little Rock after we had gone into practice, we lived in two different houses.  In the first house, I played a practical joke on her brother out on the front porch that we’ve all laughed about for years.  The joke involved a wallet MD’s dad had left at our house that her brother was coming by to pickup to take back to her father. (The joke involved inside family information and wouldn’t make sense if I described it.  But it was hilarious – to me anyway.  I’m sure her brother may not have felt the same way about it.  Come to think of it, he never came around much after that.)  MD’s father died a couple of years later, and a year or two after that, MD and I moved into the house we lived in for the last 15 years we were in Little Rock.  Not long ago, MD was telling someone visiting from Little Rock about this joke.  As I listened, it dawned on me that MD was telling this story as if it had happened at the last house we lived in.  Later I asked her about where she thought we lived when this happened.  She said ‘on Riverview Point’ (the last house, #2 Riverview Point).  I told her that it had happened in the previous house.  She told me that I was crazy and that I should know better by now than to question her memory.  (She’s right.  She has a unbelievably phenomenal memory.  Probably the best I’ve ever been around.  Whenever I question it, I am almost invariably wrong.  So I seldom question it any longer.)  She said she remembered her brother coming to the door, the joke, and us laughing about it in the Riverview Point kitchen.  I then told her that it couldn’t have happened in the Riverview Point house because her dad had died before we ever moved there.  After a long pause, she said, I know you have to be right, but I remember so clearly that all happening on Riverview Point.

The above story is a benign example of the kind of misremembering that we all have done.  But what if MD were being questioned by the police about the incident and she swore it happened on Riverview Point?  When she would be found to be wrong, it would look like she were intentionally lying.  And if she did so to a federal investigator, she could go to prison.  Remembering incorrectly and lying are two different things, but it’s easy for law enforcement officials trying to make a case to believe that a flaw of memory is an intentional lie. Especially if spoken with authority.

The tragic Jon Benet Ramsey murder took place right after MD and I had moved to Boulder, CO, so we were keenly aware of all that went on with that. Living in Boulder, you couldn’t avoid it. I’ve driven a hundred guests by the Ramsey house, which, by the way, isn’t a mansion as was reported by virtually all the national media, as in ‘the Ramsey mansion.’  It’s smaller than our house, which certainly isn’t a mansion.  The Ramsey house is an upper middle-class house in an upper middle-class neighborhood that sits cheek by jowl with all the other such houses on the street.  There isn’t 30 feet between adjacent houses on the Ramsey’s street, which is certainly not the case for mansions, at least not as I think of mansions.

As I’m sure everyone remembers from the constant media exposure, the Ramsey family wouldn’t speak to the police without their attorney present.  Everyone (including yours truly) figured that one of the Ramsey’s (probably the son) had committed the murder, and that the Ramsey’s were protecting the guilty family member.  Why else wouldn’t they speak with the police?  They were smart.  They did just what the lawyer in this video recommends for all the reasons he recommends.  And it saved their bacon.  I believe that the Boulder police believed that one of the Ramsey’s were guilty, and the Boulder police were under huge pressure to solve the crime.  But the police could never get any traction in the case because of the Ramsey’s attorney.  Had the Ramsey’s spoken freely with the police, one of them may well have been charged with the crime simply because of a slip of the tongue.  A misremembrance that the police categorized as a lie.  As it turns out, DNA evidence has recently exculpated the Ramseys.  But at the time, they were in peril because public opinion had it that one of them was guilty.  And I’m sure the police were predisposed to charge them.

Most clever career criminals know to never speak to the police without an attorney.  The stupid criminals don’t make it long as criminals before they’re locked up.  It’s the non-criminals, the category into which I hope most readers of this blog fall, who need the protections these videos describe.  Don’t think your smart enough or clever enough to intellectually steamroll over an investigator.  They are very, very good at what they do.  It’s their world, and you are totally a fish out of water in that world.

Watch and learn.  I hope you never need the lessons from these videos, but if you do, you’ll be glad you took the time to watch.  Plus, it’s entertaining.  Both speakers are excellent in completely different ways.

In Part I of the 2 video series, Mr. James Duane, a professor at Regent Law School and a former defense attorney, tells you why you should never agree to be interviewed by the police.

Click here to view the embedded video.

In part II, an experienced policeman, Officer George Bruch, who is now a law student, tells you why you should never agree to be interviewed by the police.

Click here to view the embedded video.

Addendum: I came across an article about an Austin, TX attorney’s business card. I don’t know anything about his ethics or ability, but the back of his card gives some pretty sound advice.

I frequently mention in my posts that I find interesting papers by trolling through the medical literature. It dawned on me that maybe others would like to do the same, but really don’t know how to access or search the medical literature. I looked around on some academic sites and found an easy tutorial so that anyone interested can learn.

Before we get to the tutorial, let’s take a look at how I go through the literature. I have a number of journals that I look through every month (or every other month or weekly or however often they are published). Most of these journals are listed in alphabetical order on the Journals Page of our Protein Power website. By clicking on any of these journals you will be taken to the journal’s website and be able to read the abstracts of all the articles. Some of these journals make full text versions of their articles available after a time, usually a year. Most of these journals have an email service for their table of contents that you can sign up for, then you will receive an email listing the table of contents (or TOC, as they refer to it) whenever the newest issue of the journal goes online. If you keep up with these journals, you will be abreast of 90 percent of all the newest nutritional research.

I’m often sent links from articles in the mainstream press about new research. If you find an article you would like to know more about or see if the reported reported it correctly, you can use PubMed (a government-funded data base available free to anyone that contains all the medical literature) to get to the abstract from the journal. Here is an easy way to do it.

Within the last few days I’ve received links from readers about a recent study showing that a lifetime of carb abuse kills of the appetite-suppressing cells in the brain, leading to overeating with aging. (Here are a couple of links.) Usually the press reports have a statement from or somehow identify the lead author of the paper in question. In the case of these reports, the author is identified as Zack Andrews. PubMed can be searched by author. We put Andrews Z in the search line and hit ‘search’ and we come up with a list of papers that include Andrews Z as an author. In this case, the first paper listed is the paper in question. If you click on the highlighted authors’ names, you will be taken to an abstract of the paper. Since this is a recent paper in Nature, you won’t have access to the full text.

If you look at older journals, however, you often will have full text available to you. Here is the link for a famous paper published about 12 years ago that compares the Zone diet to the Protein Power diet. If you look in the upper right-hand corner, you will see a box that says ‘Full Text Free Links.’ Click there and you will be provided with the full-text pdf of this article. You should print this article for a couple of reasons. First, it’s a good article showing the difference between a low-calorie, higher-carb diet (Zone) and a low-calorie, low-carb diet (Protein Power) in terms of numerous parameters. The change that stands out the most is that the PP diet reduced insulin levels by about 50 percent whereas the Zone diet reduced insulin levels by about 8 percent. (I say this study represents the PP diet instead of the Atkins diet or a generic low-carb diet because the carb content is precisely what we recommended in PP.) The other interesting thing about this paper is its title: “Similar weight loss with low- or high-carbohydrate diets.” At the end of the study the weight loss differences were increasing but hadn’t reached statistical significance yet. But virtually every other parameter evaluated changed markedly for the better on the low-carb diet. So why the title? Why not ‘Low-carb diet markedly decreases fasting insulin’ or any of the other titles that would have been accurate. I suspect it’s because this is the title the peer reviewers wanted. Wouldn’t want the title to say anything positive about low-carb diets, now would we?

If you don’t have an author’s name or you don’t have a specific paper in mind, then you have to search PubMed the regular way. Here is a great little tutorial that shows you how to do it. Once you’ve gone through this, you’ll be able to find just about anything you need found in the scientific literature. In the audio sessions, when the woman speaking tells you to go to the Galen Homepage and select UCSF PubMed just go to PubMed and take it from there.

Once you’ve gone through this tutorial and learned how to find articles you want to find, you’ll be better able to keep me on my toes. We’ll both be the better for it.

When I took my parasitology course in medical school I was exposed for the first time to all the loathsome diseases that are unheard of here but are a part of daily life in other parts of the world. Here people go nuts and rush to the emergency room if they find pin worms in their kid’s stool; there having a Loa loa worm creep across your eye is a common occurrence and only a minor bother.

I was fascinated with my study of liver flukes, roundworms, tapeworms and all the other parasites afflicting primarily those in tropical areas. The most vile yet amazing of these creatures was to me Dracunculus medinensis, the Guinea worm. This parasite causes untold misery to those it afflicts, and is now, as this BBC piece relates, on its way to extinction. For people living in areas the Guinea worm infests, I’m sure this is wonderful news.

What the BBC neglected to mention is that the eradication of the Guinea worm has been effected in large measure by none other than our former president, Jimmy Carter. Carter, in my opinion, wasn’t much of a president, but he has been a terrific ex-president when he avoids politics and sticks to humanitarian issues. This Carter Center he and his wife founded has been instrumental in educating people in areas where the Guinea worm is common to take the needed steps to intervene in the parasite’s life cycle and disrupt its ability to reproduce. The BBC reports:

A tropical worm disease that has plagued people since ancient times could be eradicated in less than two years, experts predict.

The World Health Organisation said Guinea worm disease, or dracunculiasis, now only affects around 25,000 people in nine countries.

To have this worm beaten back to only the point at which it affects only 25,000 people is a stupendous achievement. I broke out my old med school parasitology text, which was published in 1975, and found that at that time there were an estimated 48 million people infected with the Guinea worm. From 48 million to 25,000 in about thirty years is a real triumph.

The thing that intrigued me the most about the Guinea worm was its inbred ability to do what it needed to do to reproduce itself. As anyone who has read much of my writing knows, I’m driven by the idea that the best diet for man today is the one he cut his evolutionary teeth on. The forces of natural selection mold our genome in ways that we are barely starting to even think about. Our genome not only responds to the foods we eat by turning on or off particular genes, it affects our thinking and emotions as well. Nowhere is this genomic force more well demonstrated than in the Guinea worm.

Dracunculus medineses is a simple creature in terms of biological complexity with a less than primitive brain. Yet it is driven by incomprehensible forces to do what it needs to do to propagate. It starts its life as a larva wriggling in the water where it is eaten by a water flea. No water flea meal ingestion, the cycle ends. Once in the flea the larva coils itself tightly and becomes inactive. If the flea dies, so does the larva. But if the flea is consumed by a person drinking the water, the larva gets its next big break. The stomach acid dissolves the flea, but not the larva, which makes its way to the small intestine, then through the wall of the small intestine into the body cavity. Over the next year the female finds and mates with a male Guinea worm larva. The male dies and is absorbed into the body of the female. The impregnated female goes through a growth spurt that ends up with her being an adult worm from two or three feet long and about as big around as a piece of spaghetti. Here’s where it gets interesting.

Up to this point the human host of this worm has no symptoms and hasn’t a clue as to what’s about to happen. The pregnant female begins to migrate toward the victim’s feet. How does it know which way that is? It’s a mystery. Once the worm reaches its destination at the under surface of the skin of the foot or ankle it releases a toxic liquid that causes a blister on the surface of the skin. The blister and the toxic liquid that cause it are extremely painful causing an intense, fiery, burning sensation. The person experiencing this torture is driven to submerge the affected foot into water to help reduce the pain. As soon as the foot goes into the water, the female Guinea worm, with uterus poked out the top of the blister, releases thousands of new larva into the water and the cycle starts again.

Once the female has surfaced and released her larva, she can be seen. The age-old method of treatment at this point is to wrap the emerging worm around a stick of matchstick diameter and slowly, very slowly, roll the worm around the stick. It takes several weeks to fully extract the worm. The extraction must be done with extreme care because if the worm breaks during the process a severe inflammatory reaction takes place causing disabling pain and, in some cases, even death.

The worst part of this ordeal is that if you’ve got one Guinea worm, you’ve probably got another ready to erupt at anytime.

By teaching people in Guinea worm infested areas to at least strain their drinking water to remove the water fleas, the life cycle is disrupted. The Carter Center is educating people to do that and to avoid standing in water when the blisters erupt. If the female can’t eject her larvae into the water, the life cycle also comes to a halt.

The take home message of this story is to be aware of urges and drives to eat. If the forces of nature can drive such a simple-brained, primitive creature as the Guinea worm to do all the things it needs to do to reproduce, imagine how strongly these forces work on us infinitely more complex creatures all the time. If a man with his foot on fire from an emerging worm can be trained to go against all his natural inclinations and not plunge his foot in the water, we can be trained not to succumb to our nature-driven urges to go face down in the carbs.

Now, the real reason I wrote this post: I have to expiate for my own sins. My wife bought a box of chocolate candies from a kid trying to raise money for something. She brought them home and put them in a drawer (why she didn’t just give the kid five bucks and say ‘keep the candy’ I don’t know). They’ve been in the same drawer, one in which I almost never look, for several months. Last night MD made ribs for dinner, which I ate along with a few slices of tomato. I felt full and content. Then for whatever reason, the knowledge that those candies were there began to prey on me. Why last night? why not three months ago or anytime in between? I don’t know. It must be one of those drives like the one that drives the Guinea worm to the feet of its victim instead of the hands.

As Hamlet said:

To hold, as ’twere, the mirror up to nature.

Whatever the reason, I opened the box and threw five or six of those suckers back as fast as I could. A paragon of low-carb virtue I was not.

Of course, I felt like crap afterward. Not emotionally, but physically. God only knows how high my blood sugar went. I like to think I’m more complex than a Guinea worm, able to overcome and out think urges installed by my genome, but last night I wasn’t. And I have no one to blame but my genes…and my wife!

Since I seem to be on a roll writing about rear ends (politicians and fatty stools) I might as well go ahead and post this piece now that I’ve gotten all the results in. As near as I can figure, I’ve got about 7,000-8,000 people reading this blog daily, so given the percentage of people who are afflicted with hemorrhoids, this should be of interest to at least a couple of thousand. If you don’t have a hemorrhoid, if you don’t know anyone who has a hemorrhoid, and if you don’t think you will ever get a hemorrhoid, you can quit reading now.

When MD and I were in Dallas a month of so ago visiting our kids, I went to visit (as I usually do when in Dallas) a friend I’ve known for years (let’s call him Jack, not his real name). As we were talking he was squirming around on his couch, looking like he was in some kind of discomfort. I asked him if he was having a problem, and said no. At that point his wife, who was bringing us some coffee, said, “Tell him; he’s a doctor for God’s sake.” Jack then sheepishly told me that he had a bad hemorrhoid that was intensely painful. I asked him all the appropriate questions and diagnosed him as having a thrombosed hemorrhoid that needed treatment.

Jack said he would call is doctor and try to get in. I told him that I had fixed countless thrombosed hemorrhoids, and that if I had the tools I needed, I could fix it for him in a flash. I made a couple of calls and found out that I could get all the necessary equipment at a drugstore nearby. Off we went to gather the stuff. We returned with a latex gloves, a scalpel, a couple of syringes and needles, a bunch of gauze 4X4s for packing after the surgery, and a bottle of xylocaine (an injectible local anesthetic). I recruited Jack’s wife as my assistant, and we got him down on the bed. I had his wife spread his cheeks so that I could get to work. I immediately realized that I had made one of the cardinal errors of doctoring: I had failed to examine the patient before I made the diagnosis.

There are two types of hemorrhoids and two things that can happen with a hemorrhoid. There are internal and external hemorrhoids and these hemorrhoids can be inflamed or thrombosed. Inflamed hemorrhoids are typically kind of tender and itchy–those are the ones that Preparation H and the other topical agents work for because all that needs to be done is to reduce the inflammation and the symptoms pretty much go away. Often, though, the hemorrhoid is thrombosed, which means that it has a blood clot in it. Hemorrhoids are little sacks of tissue around the anal area and just inside, and these sacks contain blood. If the blood clots, the hemorrhoid becomes extremely painful and hurts all the time. It doesn’t really itch as much as it just hurts like the devil.

Here are the two types of hemorrhoids.

I’ve treated so many thrombosed hemorrhoids in my career that I could probably do one in my sleep. To treat them you inject them with a local anesthetic, then slice open the hemorrhoid with a scalpel and remove the clotted tissue with forceps or fingers or a cotton tipped applicator (a Q-tip in non-medical parlance). Once the clot is gone, you pack a bunch of 4X4s into the butt to absorb the blood, and let it heal. The patient gets almost immediate relief and other than a little bleeding for a day or so, the problem is gone.

Once I had  Jack’s cheeks spread, I realized that what he had was not a thrombosed hemorrhoid, but a giant inflamed external hemorrhoid along with a giant inflamed internal hemorrhoid that was strangulated out through his anus. I realized then that I couldn’t fix it with the tools at hand and that he would need see someone skilled in dealing with internal hemorrhoids that usually need to be banded, which is a pretty painful procedure. The doctor puts a little tight band around the base of the hemorrhoid that cuts off the blood supply and the hemorrhoid basically rots off. Had I examined my friend before gathering all the materials I needed, I could have saved him the $20 or so it cost to get it all.

To atone, I told Jack I would find him a doc so that he wouldn’t have to go through going to his primary care doctor, then get referred to someone else to do the banding and spend several days in agony while all the waiting for appointments went on. I looked in the phone book and found a couple of centers specializing in the treatment of hemorrhoids using a technique called infrared coagulation (IRC). I had never heard of this, so I got on Jack’s computer and started searching the medical literature to see what it was all about. I found a bunch of papers including one just recently published in the Journal of the American College of Surgeons that after evaluating all methods available concluded that IRC was the treatment of choice. IRC has equivalent efficacy as compared to banding, but is painless.

Jack called the center, the lady who answered the phone set him up with an appointment that afternoon. I went along as an extremely interested observer.

The center was the epitome of efficiency. A nurse came in and explained the process to Jack and me. The doctor then came in and asked a few pertinent questions about medical history, allergies, bowel habits and history, etc. and took us step by step through the procedure my friend was going to undergo. It was off to the treatment room where another nurse told Jack to take off his pants and shorts, put on a gown and get up on the exam table. The doc came in, got Jack on his side, and performed a digital exam of his rear end. She (the doc was a she) inserted an anoscope, a clear plastice cone-like device open on both ends into Jack’s rear end so that she could see both hemorrhoids. Grabbed a little infrared probe from the machine next to her, stuck the end of it to the base of the hemorroid for just a few seconds, and that was it.

Jack said it felt a little warm but not uncomfortable at all; it was essentially painless. She told him that it took several treatments and that he should feel a little better after each one. He felt significantly better after the first treatment, and now 4 or 5 treatments later, he is cured.

I’m passing all this along for a couple of reasons. First, I want to let anyone with hemorrhoids know that there is a painless alternative. Second, since I only have a database of one, I would like some feedback from anyone else who has had IRC treatment or who knows anyone who has so that I can feel more comfortable recommending it. If my friend’s experience wasn’t the norm, I would like to know.

I’ve read the paper that is the topic of today’s post from beginning to end five times. Not because it is a brilliant, enlightening paper, but because I found it so worthless I kept thinking there was something I was missing. If this paper had been published in the Journal of the American Dietetic Association or some other third tier journal I wouldn’t have thought so much about it. Were it published in a second tier journal such as Metabolism, I would have wondered a little more. But it was published in the October issue of the venerable American Journal of Clinical Nutrition, a first tier journal for sure, and, arguably, the most prestigious nutritional journal in the world.

I’ve decided to use this paper entitled “Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet” to demonstrate how totally meaningless research can find its way to the best of journals thanks to a built-in bias among the “peers”? who are reviewing such research and to show how to interpret a scientific/medical article.

Critically reading a scientific paper is a piece of detective work. One has to discover motives, obfuscations, biases, and sloppy work and put it all together to get the real picture, not just the picture the author of the paper wants to be seen. Just like a good detective who assumes everyone is lying until stories are corroborated, so it is with the scientific literature. One must always corroborate, probe, compare and dig deeply because almost nothing is as it appears on the surface. As Sherlock Holmes says, “These are very deep waters.”? In the case of the study we will in due course explore, the waters are very deep indeed.

But before we start dissecting our study, let’s take a look at how almost all scientific articles are laid out.

Anatomy of a Scientific Article

Scientific articles are composed of the following seven parts: title, abstract, introduction, methods, results, discussion, and references.

Title

The first thing one sees when looking at a scientific article is the title, which is really a mini abstract. It is also the first place the biases of the author(s) can be manifest. When a researcher does a PubMed search the only information supplied are the titles of the various articles the search has identified. Since there are typically anywhere from a hundred to several thousand articles such a search retrieves, the title is the only idea the researcher has as to whether a particular article is of interest. Unfortunately there is no guarantee that the title is an accurate summary of the paper. It can be or it can be totally misleading. One I will always remember was from a paper published in the February 1996 issue of the American Journal of Clinical Nutrition entitled: “Similar weight loss with low- or high-carbohydrate diets.” This was a famous low-carb study done in a metabolic ward in a hospital, so the data are much more reliable than the more-often-used recall diaries. Subjects either followed a low-carb, high-fat 1000 Calorie diet or a high-carb, low-fat 1000 Calorie diet. After six weeks the subjects on the low-carb diet had dropped their blood glucose and triglyceride levels significantly and had reduced their fasting insulin levels by about 50 percent. Every parameter evaluated was significantly better on the low-carb diet except for weight loss. Although all the subjects lost weight, those on the low-carb diet lost a little more, but it didn’t reach the level of statistical significance. This article could have been entitled: “Vast improvement of triglycerides, glucose, and insulin levels on a low-carb diet.” The title would have been more accurate than the one they actually used and much less misleading. But it wouldn’t have fit the authors’ biases. (This is a wonderful article that can be downloaded in full from the above link; it should be read by all.)

Abstract

The abstract is a brief summary of the paper giving the methods, results and conclusions in abbreviated form. Since no one expects the abstracts to be lengthy, the authors can more or less pick and choose the parts of the research paper they want to emphasize while minimizing (or even failing to mention at all) those they would prefer to minimize. Unfortunately, many people read only the abstracts, and so get an incomplete–or even incorrect–impression of the substance of the research report.

Introduction

The introduction to a scientific paper is where the scope of the study is presented. Authors discuss why they chose to do the particular bit of research they did and what they expected to find. They identify other research on the same or similar subjects and identify gaps in the data that they hope their paper will fill. Reading the introduction to a paper gives one the first sense of what the authors are trying to do and a feeling for any biases the authors may have. For instance, if the introduction of a study says something along the lines of “LDL cholesterol is known to be a major risk factor in the development of cardiovascular disease”, it’s pretty obvious that the authors have bought into the lipid hypothesis, a factor that’s important to know in evaluating their study.

Methods and Materials

The methods section of a scientific article is the fine print. Sometimes literally. Many journals set the type for the methods section in a smaller font. It is also figuratively the fine print in that it is the section of the paper that almost no one reads, but that everyone should in order to really understand the paper. The methods section lays out in often tedious detail the protocols of the study and how the researchers actually went about doing the research. By reading the methods section one should have all the information one needs to replicate the study. Unfortunately, authors will often leave out of this section important information that should be listed and that would help immeasurably in understanding the study. In the paper we will discuss shortly there are major pieces of information MIA from the methods section.

Results

This section is where the researchers present the findings of their study. It is usually filled with charts and tables laying out all the data. It is important to study this section carefully in order to compare the actual data with how the researchers interpret this data.

Discussion

In the discussion section the researchers tell us what it all means. From their perspective. It is in this section that the researchers can lay the heavy hand of their bias on the reader. Often the researchers will want a result so strongly that they will resort to nonsensical, meaningless statements. I can’t tell you how many times I’ve read in discussion sections about data that was “trending towards significance.” Reading those words would lead one to believe that the data was meaningful, which is what the writer of those words desperately wants to be the case, but the data aren’t meaningful. A result is either statistically significant or it isn’t. Data can’t “trend toward” significance anymore than a women can “trend toward” being pregnant.

References

This section comes at the end of the article and contains all the citations for other papers referred to. This listing of studies would seem to be a pretty innocuous compilation of papers, but, unfortunately, it is often used to mislead. Many times papers are cited to prove a point, but when the actual paper is studied that point is nowhere to be found. Or sometimes the paper makes the opposite point. It is always good to drill a little deeper into the study by reading some of the supporting papers just to make sure they really do support whatever claims are being made for them.

Now let’s consider the study in question.

Starting with the title–”Arterial endothelial dysfunction in baboons fed a high-cholesterol, high fat diet”–we would assume that this study is going to show us that a high-cholesterol, high-fat diet causes endothelial dysfunction in baboons eating such a diet.

Let me digress a little and make sure we’re all on the same page with endothelial dysfunction. The endothelium is the single layer of cells that lines all the arteries in the body. The endothelium is highly metabolically active tissue constantly producing many substances that when released allow arteries to function properly to distribute blood throughout the body. The endothelium can send signals that make the arteries relax and reduce blood pressure or constrict and increase it; these cells can send signals to increase or decrease the accumulation of platelets, can send signals that attract inflammatory cells, and produce nitric oxide, a powerful vascular regulator. Anything that causes the endothelium to not perform its many tasks properly causes endothelial dysfunction. Endothelial dysfunction is thought to be the first step in the progression to overt vascular disease.

The title leads us to believe that a high-cholesterol, high-fat diet leads to endothelial dysfunction, at least in baboons. And, most people will connect the dots and conclude that baboons are primates and humans are primates, so therefore a high-cholesterol, high-fat diet will cause endothelial dysfunction in humans.

Moving along, what does the abstract tell us?

First, it tells us that

Endothelial dysfunction signals the initiation and progression of atherosclerosis.

I’ll buy that; that’s what we discussed above.

Then the abstract contains this strange statement:

Elevated LDL-cholesterol concentrations have been suggested to induce endothelial dysfunction, but direct in vivo evidence for the relation is still lacking.

In other words, we (the authors) believe in the lipid hypothesis, but realize that there really hasn’t ever been any direct evidence showing that it’s true. The implication is that this paper is going to remedy that.

The objective of the study:

We examined the hypothesis that a high-cholesterol, high-fat (HCHF) diet can directly cause endothelial dysfunction in vivo.

A summary of the results:

We found that the HCHF diet induced a high inflammatory status [my italics], as indicated by increased concentrations of interleukin 6, tumor necrosis factor (TNF-alpha), and monocyte chemoattractant protein 1.

And the authors’ conclusions:

Our results show that an HCHF diet can directly induce inflammation and endothelial dysfunction.

A quick read through of the abstract pretty much confirms what we’ve figured out just from the title alone. These folks are going to show us that a high-cholesterol, high-fat diet fed to baboons causes endothelial dysfunction, which is the first step towards the development of serious cardiovascular disease.

If you were like the many people and read only the abstract, you might be going around telling others that you just read a study that proves fat and cholesterol cause heart disease.

The introduction starts off with a pretty strange statement.

It is well known that not every individual with known atherogenic risk factors, such as hypercholesterolemia, develops atherosclerosis. Moreover, these known risk factors explain only 50% of the difference between healthy and clinically affected persons.

And

No studies have documented the interactions between circulating environmental risk factors [LDL-cholesterol and other lipids] for atherosclerosis and the arterial wall in living human subjects.

These researchers are throwing down the gauntlet. They are saying, the lipid hypothesis has never been proven, but with this paper, we may change all that. We’re gonna by God show that eating a high-cholesterol, high-fat diet will cause endothelial dysfunction.

When we get into the Methods and Materials Section we start to get our first hint that a little fudgaroo is going to take place.

Although the intent of the in vivo experiments was to identify functional changes in ECs [endothelial cells] after an atherogenic diet [presupposes here that a high-fat, high-cholesterol diet is atherogenic, alerting us to their bias], such experiments cannot determine the specific components that are responsible for these changes. Therefore, we also designed an in vitro challenge experiment.

Translation: We didn’t get the results we were looking for in the original study, so we decided to torture the data a little until it gave us the confession we wanted. In this case they didn’t really torture the data, they decided to fiddle with the baboon endothelial cells until they got a result they could live with, one that fit their bias. I’ve elected to ignore the “in vitro challenge” from the scope of this blog because I think it was a desperation measure done to have something to report despite the fact that it was meaningless.

Here is another admission buried in a large paragraph:

The baboons selected for this study were previously classified as high responders because their serum LDL-cholesterol concentrations increased after an HCHF diet.

The baboons chosen for the experiment were those that had previously been shown to respond to a high-fat, high-cholesterol diet by increasing their levels of LDL-cholesterol. Hmmm.

Here is the most stunning piece of information of all. It is stunning by its omission of probably the single most important piece of information needed to intelligently analyze this study.

The baboons had been fed a normal unpurified stock diet for monkeys (SWF Primate Diet; Harlan Teklad, Madison, WI) for >40 wk before the 7-wk HCHF dietary challenge. Both diets were fed ad libitum.

There it is. This is a study about how a diet affects the endothelium, and, with the exception of one table, you have just read the entirety of the information provided on the diet provided. I searched the Harlan Teklad website in vain for a description of the SWF Primate Diet. The table (which if I were a more skilled blogger could include for you here) shows the macronutrient differences between the two diets, but doesn’t tell anything about the composition. Was the added cholesterol oxidized? Were there trans fatty acids. Was there high-fructose corn syrup? Sucrose? We don’t know because the authors decided not to include this monumentally important information in a nutritional/dietary study.

The table does show one interesting fact that isn’t commented upon in the paper. The high-cholesterol, high-fat diet contains 23% more calories per gram than does the baseline diet. And since the animals consumed the diet ad libitum, does this mean that on the HCHF diet they ate 23% more? We don’t know. But if they did consume more, how do we know that whatever abnormalities are found aren’t a consequence of excess calories and not of the cholesterol and/or fat. Don’t know; can’t tell.

In my mind this one giant omission invalidates the entire study.

To continue. After having been fed the SWF Primate Diet (whatever that is) for 40+ weeks the baboons are switched to a high-cholesterol, high-fat diet. The day of the dietary changeover the researchers take blood from the baboons and surgically remove a segment of their left femoral arteries (the femoral artery is the large artery running through the thigh) to provide a baseline for any changes that might take place. Three weeks after starting the high-fat, high-cholesterol diet researchers once again draw blood, then after a total of seven weeks on the high-fat diet a final blood sample is taken and a segment of the right femoral artery is harvested to compare with the left one removed seven weeks earlier.

What did the researchers find?

The HCHF diet substantially changed the lipoprotein profile in the baboons.

How?

Total cholesterol concentrations were dramatically increased (85.6%; P < 0.0001) after 3 wk of the HCHF diet.

Okay, but is this a surprise? These baboons were chosen for this study because they responded to such a diet by increasing their cholesterol levels. But how do we even know that this cholesterol elevation wasn’t a caloric phenomenon and had nothing to do with the added fat and cholesterol in the diet?

The authors said the HCHF diet substantially changed the lipoprotein profile. What else changed besides total cholesterol?

We observed a significant increase in serum oxLDL-cholesterol [oxidised LDL-cholesterol] concentrations at the 3rd week of the HCHF diet compared with basal concentrations (54.9%, P = 0.03), but the concentration increase at the 7th week of the dietary challenge (19.6%) was not significant (P = 0.11). No statistically significant changes in the concentration of triacylglycerols [triglycerides] or the ratio of total cholesterol to HDL cholesterol were observed during the HCHF dietary challenge.

So we had a little blip of oxLDL-cholesterol at the three week mark, which could easily be attributed to an acute change in the diet, but nothing after the seven weeks? No changes in triglycerides, no change in the cholesterol/HDL ratio? I thought these guys said the HCHF diet substantially changed the lipoprotein profile. Other than a change in total cholesterol, which really isn’t part of a lipoprotein profile, it doesn’t look to me like it changed it at all.

Did the diet cause any inflammatory changes? Any changes in antioxidant status? C-reactive protein?

Our results showed that the following 4 patterns of proinflammatory changes occurred when baboons were fed the HCHF diet: 1) MCP-1 concentrations significantly increased and remained high until the end of the 7-wk dietary challenge; 2) IL-6 and TNF-alpha concentrations were dramatically increased after 3 wk of the dietary challenge but decreased to below baseline concentrations by the end of the challenge; 3) soluble TNF-alpha receptor II concentrations were significantly lower than baseline concentrations after 7 wk of the dietary challenge but not after 3 wk; and 4) the total antioxidant status and the concentrations of IFN-gamma , IL-1β¸, and CRP did not change significantly during the entire dietary challenge period. The concentrations of other endothelial dysfunctional markers, ie, soluble VCAM-1 and soluble ICAM-1, did not change significantly during the full 7-wk HCHF challenge.

So, other than a doubling of MCP-1 nothing happened. No inflammatory changes whatsoever. No changes in antioxidant status. No changes in CRP (C reactive protein).

What is MCP-1? MCP-1 (monocyte chemoattratant protein 1) is a cytokine that attracts monocytes (a type of white blood cell) to an area in response to an infection other immunologic insult. What does it mean in this study? Who knows since we don’t know what the caloric content of the high-cholesterol, high-fat diet was. It’s unlikely to be much of a factor, however, since virtually no other inflammatory parameters were changed. Generally during inflammation a whole host of markers change, not simply a single one while all the others remain normal. Since a couple of other cytokines (IL-6 and TNF-alpha) increased at the three week mark but returned to baseline or below after seven weeks it is possible that MCP-1 has a longer trajectory back to normal and if evaluated after, say, ten weeks, would also have returned to baseline. This, of course, is speculation on my part, but certainly reasonable given that no other measured cytokines were out of line after the seven weeks.

How about changes in the arteries themselves?

We examined the femoral artery macroscopically and microscopically; no atherosclerotic lesions, including early fatty streaks, were observed after the 7-wk HCHF challenge.

So, let’s see what we’ve got. After 7 weeks on an indeterminate high-cholesterol, high-fat diet the baboon subjects that were chosen because they had already proven to be hyper responders to fat and cholesterol in the diet increased their cholesterol levels and had a doubling of MCP-1. That’s it. No other lipid changes, no changes in other inflammatory parameters, and no visible (by either eyeball or microscope) changes in the arteries. We can attribute the elevated cholesterol levels to the fact that these baboons were chosen specifically because of their tendency to increase their cholesterol levels when following a high-fat, high-cholesterol diet.

So, what it all boils down to is nothing much at all.

But, you wouldn’t know that by reading the Discussion Section of the paper.

Consistent with our previous observations [when they determined which baboons were hyper responders], the HCHF diet can effectively increase total blood cholesterol and non-HDL cholesterol concentrations in baboons.

Our results show that the HCHF diet also results in gross systemic inflammatory responses, as indicated by markedly elevated cytokine concentrations.

Oh really?

After several paragraphs explaining why there were no elevations of all the cytokines and other inflammatory markers they were looking for, the authors conclude with

In summary, our results clearly show that the HCHF diet resulted not only in increased serum cholesterol concentrations but also in inflammation and endothelial dysfunction.

So they would have us believe.

As Huang Po, a Buddhist teacher from long, long ago put it:

The foolish reject what they see, not what they think. The wise reject what they think, not what they see.

The authors of this paper saw very little conclusive data in this study. It’s pretty obvious what they thought.